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Laura A. Rabin,1,2 Colette M. Smart,3,4

and Rebecca E. Amariglio5,6
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1
Department of Psychology, Brooklyn College and The Graduate Center of the City University
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of New York, Brooklyn, New York 11210; email: lrabin@brooklyn.cuny.edu

2
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461
3
Department of Psychology, University of Victoria, Victoria, British Columbia V8W 2Y2,
Canada; email: csmart@uvic.ca
4
Institute on Aging and Lifelong Health, University of Victoria, Victoria, British Columbia
V8P 2Y2, Canada
5
Department of Neurology and Center for Alzheimer Research and Treatment, Brigham and
Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115
6
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston,
Massachusetts 02114; email: ramariglio@mgh.harvard.edu

Annu. Rev. Clin. Psychol. 2017. 13:369–96 Keywords

The Annual Review of Clinical Psychology is online at cognitive complaints, dementia, early detection, mild cognitive
clinpsy.annualreviews.org
impairment, preclinical Alzheimer’s disease, subjective cognitive decline
https://doi.org/10.1146/annurev-clinpsy-032816-
045136 Abstract
Copyright  c 2017 by Annual Reviews. Older adults with subjective cognitive decline (SCD) in the absence of ob-
All rights reserved
jective neuropsychological dysfunction are increasingly viewed as at risk for
non-normative cognitive decline and eventual progression to Alzheimer’s
disease (AD) dementia. The past decade has witnessed tremendous growth
in research on SCD, which may reflect the recognition of SCD as the ear-
liest symptomatic manifestation of AD. Yet methodological challenges as-
sociated with establishing common assessment and classification procedures
hamper the construct. This article reviews essential features of SCD associ-
ated with preclinical AD and current measurement approaches, highlighting
challenges in harmonizing study findings across settings. We consider the
relation of SCD to important variables and outcomes (e.g., AD biomarkers,
clinical progression). We also examine the role of self- and informant-reports
in SCD and various psychological, medical, and demographic factors that
influence the self-report of cognition. We conclude with a discussion of in-
tervention strategies for SCD, ethical considerations, and future research
priorities.

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 CP13CH15-Rabin ARI 13 April 2017 9:58

Contents
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370
TERMINOLOGY AND CONCEPTUALIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
MEASUREMENT AND CLASSIFICATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
RELATION OF SUBJECTIVE COGNITIVE DECLINE TO KEY
BIOMARKERS, CLINICAL PROGRESSION, AND COGNITIVE
OUTCOMES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
Relation of Subjective Cognitive Decline to Neuroimaging and Biomarkers
of Preclinical Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
Subjective Cognitive Decline in APOEε4 Carriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
Relation of Subjective Cognitive Decline to Clinical Progression . . . . . . . . . . . . . . . . . . 379
Annu. Rev. Clin. Psychol. 2017.13:369-396. Downloaded from www.annualreviews.org

Relation of Subjective Cognitive Decline to Objective Cognition . . . . . . . . . . . . . . . . . . 379

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ROLE OF SELF- AND INFORMANT-REPORTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381

INTERRELATIONSHIPS OF SUBJECTIVE COGNITIVE DECLINE
WITH OTHER VARIABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
Personality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384
Physical Health Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385
Demographic Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385
INTERVENTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
ETHICAL CONSIDERATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 388
FUTURE DIRECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 388

INTRODUCTION
Subjective cognitive decline (SCD) refers to individuals’ perceived decline in memory and/or
other cognitive abilities relative to their previous level of performance, in the absence of objec-
tive neuropsychological deficits ( Jessen et al. 2014a). There is accumulating evidence that older
individuals with SCD have an increased likelihood of biomarker abnormalities consistent with
Alzheimer’s disease (AD) pathology and an increased risk for future pathologic cognitive decline
and dementia ( Jessen et al. 2014a). In addition to representing a harbinger of non-normative cog-
nitive decline, SCD can affect emotional and social functioning and overall quality of life ( Jenkins
et al. 2015). Effective intervention to delay or prevent pathologic cognitive decline may best be
targeted at the earliest symptomatic disease stages, such as SCD, in which cognitive functioning is
still relatively preserved. As such, it is critical to find sensitive, low-cost methods for early detection
of individuals at risk for incident AD dementia. Research efforts are focused on determining how,
when, and why older adults complain about perceived cognitive changes, and whether reliable
and valid differences exist in the subjective and objective presentations of individuals with SCD as
compared to clinically normal older adults without SCD.
In this article, we review the essential features of SCD and summarize key findings on its
relation to AD biomarkers, clinical progression, objective cognition, and Apolipoprotein E (APOE)
genetic status. Though SCD is associated with numerous other conditions—including non-AD
forms of dementia, psychiatric disorders, medication or substance effects, and even normal aging
( Jessen et al. 2014a)—in this review we focus on SCD associated with preclinical AD. We describe

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current approaches to the assessment and classification of SCD and highlight key challenges in
harmonizing procedures across research studies and settings. We also consider the relation and
relative value of self- and informant-reports in SCD. We then review the association of various
psychological, medical, and demographic factors on self-reported SCD and consider nonpharma-
cologic interventions in SCD. We conclude with a discussion of ethical considerations and key
issues that researchers must tackle to refine the construct of SCD and propel the field forward.

TERMINOLOGY AND CONCEPTUALIZATION

Reisberg and colleagues (1982) introduced the concept of SCD in the early 1980s in an attempt
to define stages of AD according to the Global Deterioration Scale, a rating scale based on data
obtained during clinical interviews with older adults and their informants. They characterized stage
2 as subjective complaints of memory deficit in the context of intact objective memory. Stage 2
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criteria also required intact functioning in employment or social situations and an appropriate
level of concern about symptoms. Reisberg (1986) theorized that subjective cognitive impairment
preceded mild cognitive impairment (MCI), the symptomatic predementia phase of AD, and
he surmised that this stage would presage the emergence of MCI symptoms by approximately
15 years.
The concept of SCD then hit a relative plateau until its reemergence in the literature after
2005. Various terms have been utilized to characterize it, such as (subjective) cognitive complaints,
(subjective) memory complaints, (subjective) memory concerns, subjective memory impairment,
subjective cognitive impairment, subjective memory loss, subjective memory deterioration, and
subjective cognitive decline. Beyond nomenclature, significant diversity in assessment strategies
exists with respect to the subjective report measures used and the thresholds applied for determin-
ing when an individual’s condition meets criteria for “significant” cognitive concerns and warrants
classification as SCD. Additionally, participants have been studied in diverse settings, including
population-based cohorts, volunteer samples, and medical help-seeking samples, and these set-
tings affect how complaints are expressed and reported. Furthermore, there has been uncertainty
about whether self- or informant-report data are most useful in identifying very early AD-related
cognitive decline ( Jessen et al. 2014a).
An international effort to establish common standards for SCD has addressed these and other
challenges in defining and conceptualizing SCD. In 2014, a working group of AD researchers
with a particular interest in SCD (the Subjective Cognitive Decline Initiative; SCD-I) published
consensus terminology and a conceptual framework for research on SCD in AD ( Jessen et al.
2014a). The Global Deterioration Scale stage 2 criteria correspond well to the concept of SCD
associated with preclinical AD (also referred to as pre-MCI SCD) recently introduced by the
SCD-I ( Jessen et al. 2014a). The SCD-I presented a broad definition of SCD (see the sidebar
titled Research Criteria for Pre-MCI SCD), along with specific features that increase the likeli-
hood of preclinical AD in the affected individuals (referred to as SCD plus; see the sidebar titled
Features That Increase the Likelihood of Preclinical AD in Individuals with SCD: SCD Plus).
The group also presented a working model for how objective and subjective cognitive decline
are hypothesized to track the progression of disease pathology and clinical states. As shown in
Figure 1, cognitive decline is proposed to begin after a relatively stable period of cognitive per-
formance in the presence of increasing AD pathology. After cognitive performance falls below
a normal, demographically adjusted threshold, an MCI diagnosis becomes appropriate and cog-
nitive decline progresses steadily toward dementia. SCD is depicted by a bar shaded from white
to red, which corresponds to the later stages of preclinical AD. SCD is thus conceptualized as a
pre-MCI condition in which the threshold for impairment on objective tests has yet to be reached.

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RESEARCH CRITERIA FOR PRE-MCI SCD

The following research criteria for pre-MCI SCD are adapted from Jessen et al. (2014a) with permission from
Elsevier.

Inclusion Criteria
 Self-experienced persistent decline in cognitive capacity compared with a previously
normal status and unrelated to an acute event.
 Normal age-, gender-, and education-adjusted performance on standardized cognitive
tests that are used to classify MCI or prodromal AD.

Exclusion Criteria
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 Mild cognitive impairment, prodromal AD, or dementia.

 Condition can be explained by a psychiatric disorder or neurological disease (apart from
AD), medical disorder, medication, or substance use.

Notably, by the stage of MCI and AD dementia, SCD becomes attenuated (as depicted by the
fading red bar), suggesting that insight diminishes as the disease progresses. One implication is
that the predictive power of SCD is strongest at the late preclinical stage of AD, when the ability to
detect objective cognitive impairment is poor due to the limited sensitivity of standard neuropsy-
chological tests ( Jessen et al. 2014a). On the other end of the spectrum, the sensitivity of SCD
may decrease as insight diminishes across the late MCI/dementia stages. In fact, Jessen and col-
leagues (2014b) have speculated that the predictive power of subjective cognitive reports increases
and the predictive power of objective tests decreases as prediction moves to the earliest disease
stages. This may be related to successful compensation in the very early disease stages, which
yields unimpaired cognitive test performance despite the subjective experience of impairment

FEATURES THAT INCREASE THE LIKELIHOOD OF PRECLINICAL AD IN

INDIVIDUALS WITH SCD: SCD Plus

The following are features that increase the likelihood of preclinical AD in individuals with SCD and are adapted
from Jessen et al. (2014a) with permission from Elsevier. Molinuevo and colleagues (2017) offer in-depth discussion
about these criteria and provide recommendations for their implementation in research settings.
 Subjective decline in memory rather than in other domains of cognition
 Onset of SCD within the last 5 years
 Age at onset of SCD ≥ 60 years
 Concerns (worries) associated with SCD
 Feeling of performing worse than others of the same age group
 Confirmation of cognitive decline by an informant
 Presence of the APOEε4 genotype
 Biomarker evidence for AD (defines preclinical AD)

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Onset of Impairment
decline in on standardized
cognitive cognitive
performance tests

Subjective cognitive decline (SCD)

Cognitive performance

Subjective cognitive symptoms

Ob
jec
tive
cog
niti
ve
dec
line
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Mild cognitive impairment/

Preclinical Alzheimer’s disease Dementia
prodromal Alzheimer’s disease
Progression of disease pathology and clinical states

Figure 1
Working model of the course of cognitive decline in relation to progression of Alzheimer’s disease (AD) pathology. Subjective
cognitive decline (SCD) as a diagnostic entity (red bar), defined by self-experienced cognitive decline, occurs in the late stage of
preclinical AD. Those with SCD likely experience subtle cognitive decline (left blue dotted line) not detectable on standardized testing.
At some critical point, underlying disease burden contributes to a level of cognitive decline for which the individual can no longer
compensate, heralding the onset of mild cognitive impairment (MCI) and manifestation of impairment on standardized tests (right blue
dotted line). At the MCI stage, SCD as a diagnostic entity is no longer present (red bar ends) but self- or informant-reports of cognitive
difficulties/decline are present. These subjective cognitive symptoms are depicted by a gradient shaded from light to dark gray across
the disease stages. In the earliest stages, the individual does not report cognitive complaints (light gray bar) until underlying pathology
begins to impinge upon perceived cognitive function (dark gray bar). As objective cognitive impairment (blue solid line) progresses, the
gray bar slowly fades, suggesting that self-reports of cognitive difficulty recede as late MCI and dementia ensue, consistent with
anosognosia. However, informant-reports of cognitive difficulty persist, and become more accurate than self-reports, in late MCI and
dementia, which is why the gray bar fades but does not disappear. Adapted with permission from Jessen et al. (2014a).

( Jessen et al. 2014b). It also raises the possibility that more sensitive tests of cognition could
capture the subtle cognitive changes associated with the SCD stage.
In summary, SCD is considered among the earliest clinical manifestations of AD, and it is
thought to occur prior to cognitive impairment, when individuals have sustained only mild neu-
ronal damage and are able to functionally compensate ( Jessen et al. 2014a). SCD is etiologically
heterogeneous and phenomenologically complex, and research has been hampered by a lack of
common terminology and research procedures. To address these issues, the SCD-I recently pro-
posed a common framework that includes research criteria for SCD and a model that charts its
course in relation to AD progression. Future work is required to validate tenets of the proposed
model: for example, the idea that SCD has differential predictive value across stages of objective
impairment.

MEASUREMENT AND CLASSIFICATION

Classification of SCD is based largely on the interpretation of subjective report data in the context
of normal neuropsychological functioning and activities of daily living. There is, however, no stan-
dardized assessment or consensus about optimal self- and informant-report instruments, and no

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a b
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Figure 2
Higher levels of cognitive complaints are associated with decreased gray matter density in the (a) left and (b) right hippocampi across
the entire sample (N = 120, p < .001). Adapted with permission from Saykin et al. 2006.

common thresholds for establishing SCD positivity on existing measures. In fact, classification of
participants is highly diverse, with no two SCD-I working group studies using the same approach
(Molinuevo et al. 2017). By way of example, in an early study of SCD, Saykin and colleagues
(2006) created a cognitive complaint index for their volunteer/physician-referred participants,
a composite measure consisting of cognitive items from nine self- and informant-report ques-
tionnaires, with scores calculated as the percentage of all items endorsed in a positive/impaired
direction. The authors determined that greater than 20% endorsement of items or complaints was
required to meet the threshold for SCD in the context of intact objective cognition. As expected,
those with SCD and MCI scored similarly on this measure (endorsing 30% and 35% of items,
respectively), and both groups scored significantly higher than clinically normal older adults (10%
endorsement). Those with SCD also showed a pattern of reduced gray matter density similar to
those with MCI in bilateral medial temporal, frontotemporal, and other neocortical areas, and the
cognitive complaint index itself was inversely related to gray matter density in medial temporal
and other regions (Figure 2), establishing a neural basis for cognitive complaints in nondemented
older adults.
Saykin and colleagues (2006) utilized quantitative measures in a categorical classification that
applied a flexible cutoff score to define the presence of SCD. Whereas these authors provided
specific information about their classification approach, many other studies fail to provide details
about the subjective report measures utilized or the method used to collect, score, or quantify self-
report data to establish the presence of SCD (e.g., Marini et al. 2011, Perrotin et al. 2015, Striepens
et al. 2010, van Harten et al. 2013, Visser et al. 2009). Further, whereas most studies attempt to
categorize individuals as either having SCD or not, others have used more continuous, dimensional
approaches. As an example of the latter, using data from the Nurses’ Health Study (a longitudinal
community-based study), Amariglio and colleagues (2011) administered telephone cognitive tests
and seven dichotomously scored subjective memory questions to over 16,000 participants. The
authors created a continuous variable for total number of complaints, and their results indicated
that an increase in cognitive complaints was associated with greater objective impairment, with
each additional complaint adding an approximate 20% increase in odds of cognitive impairment.

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Research has not identified or assessed all the classification approaches in use, precluding
conclusions about their relative merits and drawbacks. From a psychometric standpoint, however,
there needs to be sufficient use of a measure across populations and settings to identify scores that
reliably discriminate among groups. Unfortunately, complaints are quantified using a large number
and variety of measures. Rabin and colleagues (2015) conducted a review of study instruments used
by 19 SCD-I working groups to ascertain SCD (comprising a total of 34 self-report measures and
640 cognitive self-report items). Results revealed vast heterogeneity in every dimension examined,
including number of subjective report instruments and items used, mode of administration, key
structural and content features of items, and format, scaling, and timeframe of response options.
Such variation in measurement characteristics can influence the nature of responses and calculated
rates of SCD (Tandetnik et al. 2015). Strikingly, SCD questions presented limited overlap, with
75% of the items being used uniquely in a single study (Rabin et al. 2015). There was also
little evidence for the psychometric quality of the measures, most of which were designed for
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populations other than individuals affected by SCD (e.g., large-scale longitudinal studies that
monitor progression to MCI and dementia). Furthermore, the majority of reviewed items tapped
memory, which might not be the sole complaint of individuals with SCD associated with preclinical
AD; items from other domains may have better discriminant or predictive validity at this early
stage of decline (Amariglio et al. 2011). Finally, SCD-I working group members reported that
instrument selection decisions were often based on practical considerations beyond the study of
SCD, such as availability and brevity of measures, which raises questions about their validity for
the study of SCD (Rabin et al. 2015).
An additional concern with focusing on numerical differences is that various community-based
studies have revealed that the base rate of cognitive complaints is relatively high in the typical
older adult population and could simply represent complaints about normal aging (e.g., Cooper
et al. 2011, Jonker et al. 2000, Slavin et al. 2010). Thus, endorsement of a large number of
complaints in a community sample may result in false positive diagnoses of SCD; this may sit
in opposition to the endorsement of similar complaints by individuals presenting to a memory
clinic, where complaints are more likely to reflect non-normative age-related changes. Moreover,
because subjective report measures are largely atheoretical with regard to the experience of SCD,
there is a risk of false positive identification (i.e., type I error) of individuals with SCD based simply
on the number of complaints reported (Rabin et al. 2015).
Despite these limitations, quantitative approaches remain a cornerstone of clinical neuropsy-
chological assessment and research. Sophisticated methods from measurement science may pro-
vide a way to ascertain quantitative differences in cognitive complaints by persons with and without
SCD. Gifford and colleagues (2015b), for example, administered 57 self-report items to partici-
pants with SCD, MCI, and clinically normal controls. Factor analysis identified a unidimensional
latent trait of SCD, whereas item response theory and computer adaptive test modeling reduced
the 21-item pool to 9 items that robustly represented the latent trait and differentiated controls
from MCI cases. Item content included complaints about recalling phone numbers and birth-
days (i.e., semantic knowledge), recalling items to buy at the store (i.e., prospective memory), and
an overall perception of memory impairment and actual memory decline over time. One limi-
tation was that the items pertained exclusively to memory. SCD-I working group studies have
also employed item response theory to establish item equivalence across multiple SCD measures,
enhancing the power to identify subsets of items associated with AD biomarkers and clinical pro-
gression. Ultimately, the goal of the SCD-I item analysis project is to establish a core set of items
to be used in clinical trials that seek to enroll cognitively intact participants with an increased likeli-
hood of abnormal AD biomarkers and a risk of progression to MCI and AD dementia (Sikkes et al.
2015).

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In contrast to quantitative approaches, qualitative methods may help uncover the unique
first-person experience of individuals with SCD without assuming that SCD varies from MCI
and AD dementia only by a matter of degree (Buckley et al. 2015a). Buckley and colleagues
(2015c) undertook a review of the qualitative literature pertaining to the subjective experience of
cognitive change. Fifty-eight studies were eligible for inclusion, and the results revealed distinct
patterns of experience for clinically normal older adults with complaints about cognitive decline
as compared to those with MCI and AD dementia. In terms of complaint themes, clinically
normal older adults typically mentioned memory issues, including word- and name-finding
difficulties. Cognitive lapses were often reported as co-occurring, with causal attributions related
to stress or anxiety or age-related factors. Furthermore, clinically normal older adults frequently
reported anger, frustration, or annoyance with perceived memory lapses, reflecting a preserved
insight and conscious awareness of cognitive difficulties. In interpreting these findings, it should
be acknowledged that the term SCD was used as a symptom rather than as a diagnostic entity, and
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most studies focused on individuals with MCI. Also, studies used an array of sampling strategies
that make it difficult to generalize across studies.
Other studies have attempted to incorporate qualitative features into categorical classification
approaches for SCD. In the German study on Aging, Cognition and Dementia in primary care
patients (AgeCoDe; see Jessen et al. 2014b), a general practice registry-based study, participants
were assessed at home with the question “Do you feel like your memory is becoming worse?”
Response options included no; yes, but this does not worry me; and yes, this worries me. Those
reporting a memory decline with worry (concern), in the context of intact objective cognition,
were rated as having SCD. In an alternative classification approach by the same researchers,
those reporting memory decline without associated concerns were rated as SCD-C, and those
reporting a memory decline with associated concerns were rated as SCD+C (Koppara et al.
2015b). In one study, Jessen and colleagues (2010) classified participants at baseline and 1.5-
and 3-year follow-up intervals. Subjective memory impairment with worry was associated with
the greatest risk for conversion to any dementia. Recently, AgeCoDe researchers investigated
the possible modifying role of temporal stability of the SCD report on AD dementia risk in
cognitively normal older adults. SCD with worry consistently reported over time was associated
with greatly increased risk of AD dementia (Wolfsgruber et al. 2016). Together, these findings
suggest that qualitative features of the SCD report (i.e., concern and longitudinal stability) have
predictive validity for AD dementia over and above complaints per se.
In summary, there is no current consensus on how to assess or classify SCD, and the approaches
used exhibit vast heterogeneity. Some studies apply binary classifications (SCD/no SCD) based on
questionnaire items, composite scores, or qualitative features of subjective reports. Others treat
the number of cognitive complaints as a continuous variable, which may be useful in capturing
features such as frequency and severity of the cognitive complaint. For comparability and replica-
bility, it seems worthwhile to establish operationalized criteria that minimize subjective judgment
and maximize the use of valid and reliable instruments with well-defined cutoffs. In an emerging
field such as SCD, however, different studies adopt varying objectives, participant populations,
and measures. Cultural and linguistic variables also affect SCD reporting, and admittedly we have
yet to truly understand the development of SCD symptoms within the SCD phase. Therefore, the
SCD-I has recently argued for flexibility in classification. Instead of proposing a single approach,
the SCD-I recently published recommendations for how to assess SCD in research settings
and how to report information from each study to ensure consistency (Molinuevo et al. 2017).
The group also recommended that future research should attempt to use a short set of identical
questions (harmonized methodology) to define the boundaries between SCD and MCI and

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should identify subjective report items with optimal sensitivity and specificity for detection of
preclinical AD (Molinuevo et al. 2017).

RELATION OF SUBJECTIVE COGNITIVE DECLINE TO KEY

BIOMARKERS, CLINICAL PROGRESSION, AND COGNITIVE
OUTCOMES

Relation of Subjective Cognitive Decline to Neuroimaging and Biomarkers

of Preclinical Alzheimer’s Disease
Cross-sectional associations between SCD and brain-based biomarkers in otherwise clinically
normal older individuals have been demonstrated across a range of studies. Primarily, studies have
examined SCD in relation to biomarkers of AD at the preclinical phase, which include evidence
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of amyloidosis and neurodegeneration ( Jessen et al. 2014a, Sperling et al. 2011). Biomarkers of
amyloidosis include reductions in cerebral spinal fluid (CSF) Aβ42 and increased amyloid tracer
uptake on positron emission tomography (PET). Biomarkers of AD-related neurodegeneration
include atrophy in medial temporal lobes and paralimbic and temporoparietal cortices revealed by
structural magnetic resonance imaging (MRI), decreased fluorodeoxyglucose 18F (FDG) uptake
on PET with a temporoparietal pattern of hypometabolism, and elevated CSF tau ( Jack et al.
2010, Sperling et al. 2011).
Many of the earliest biomarker studies investigated the relationship between SCD and the
medial temporal lobe. In particular, reductions in left hippocampal volume (van der Flier et al.
2004) and bilateral entorhinal cortex volume ( Jessen et al. 2006) were observed in individuals
with SCD compared to individuals without memory complaints. Furthermore, individuals with
SCD manifest a pattern of brain atrophy in medial temporal and frontotemporal regions more
consistent with MCI than clinically normal elderly do (Saykin et al. 2006). More recent imaging
studies have revealed that SCD is associated with decreased hippocampal volume (specifically in
the CA1 and subiculum subfields) (Perrotin et al. 2015), an AD-like pattern of gray matter atrophy
(Peter et al. 2014), and cortical thinning in the medial temporal lobe (Meiberth et al. 2015).
Several studies have employed FDG-PET imaging to identify brain regions that show ab-
normal glucose metabolism in SCD. Results have been somewhat paradoxical. One study found
reduced parietotemporal and parahippocampal glucose metabolism (Mosconi et al. 2008), whereas
another showed increased metabolism in the right medial temporal lobe (Scheef et al. 2012). Taken
together, parietotemporal regions are vulnerable in early AD, and hyperactivity may reflect com-
pensation that precedes eventual hypometabolism.
Imaging techniques using PET with Pittsburgh Compound B (PiB) have allowed for quantifica-
tion of amyloid burden in vivo (Klunk et al. 2004). Using this technique, researchers have associated
greater amyloid with a greater number of memory complaints on questionnaires (Amariglio et al.
2012), worse self-reported memory compared to age-matched peers (Perrotin et al. 2012), and
reports of current memory difficulty (Rowe et al. 2010). Additionally, memory clinic patients with
normal cognitive functioning were found to have higher amyloid burden than clinically normal
controls from a separate research cohort (Snitz et al. 2015a). These findings are in contrast to
other studies that have not found associations between amyloid and SCD (Buckley et al. 2013,
Chetelat et al. 2010, Rodda et al. 2010).
Efforts to study amyloidosis and neurodegeneration simultaneously have shown that both
biomarkers independently associate with greater subjective memory complaints in clinically nor-
mal older individuals (Amariglio et al. 2015b). Furthermore, when individuals are staged based on
biomarker status, SCD is associated with advancing stages of preclinical AD, such that individuals

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who exhibit both amyloidosis and neurodegeneration report the highest number of memory com-
plaints. Findings that investigate biomarker relationships between SCD and amyloid and neuronal
injury using CSF are somewhat less clear, but allude to a similar pattern (Colijn & Grossberg 2015).
In a study investigating CSF markers across diagnostic groups, an AD-like profile was more com-
mon in SCD individuals compared to normal controls (Visser et al. 2009). Another study found
that SCD individuals who were APOEε4 carriers were more likely to have a CSF AD-like profile,
although this did not apply to the entire SCD group (Mosconi et al. 2008). A study with a smaller
sample, however, did not find differences in CSF profiles between SCD individuals and healthy
controls (Antonell et al. 2011).
In summary, converging findings suggest that SCD is associated with AD biomarkers across a
range of modalities. SCD biomarker profiles may reflect an intermediate stage between clinically
normal older adults and MCI individuals (i.e., a pre-MCI condition), which is in keeping with how
SCD is currently conceptualized ( Jessen et al. 2014a). Associations between SCD and biomarkers
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further validate the concept of SCD as a stage prior to the onset of clinical impairment along the
early AD trajectory. More practically, identifying SCD may help to enrich secondary prevention
trials aiming to recruit individuals who are biomarker positive but do not have clinical symptoms
(Buckley et al. 2016b). As imaging modalities improve and expand, and as SCD criteria are more
clearly delineated, we may expect further refinement in characterizing the association between
SCD and brain-based biomarkers.

Subjective Cognitive Decline in APOEε4 Carriers

Studying the impact of APOE on SCD is complicated by the fact that knowledge of family history
may influence self-reported memory concerns. Individuals with a family history of AD dementia
are more likely to be APOEε4 carriers. Thus, in addition to increased genetic risk for AD de-
mentia, these individuals may have a heightened awareness of their cognition, having witnessed
family members decline, and therefore may be more likely to express concern about cognitive
function. Indeed, participants recruited for memory studies from the community have shown a
higher preponderance of APOEε4 than the overall population, even in those without clinical im-
pairment (Rodriguez-Gomez et al. 2015). Knowledge about one’s genotype can influence both
objective and subjective cognition. In one study, APOEε4 carriers who knew their genotype re-
ported greater memory complaints and performed worse on objective memory measures than
APOEε4 carriers who did not know their status (Lineweaver et al. 2014). By contrast, individuals
who were APOEε4 noncarriers and who knew their genotype reported fewer memory complaints
than APOEε4 noncarriers who did not know their genotype. The groups showed no differences
in objective performance.
Studies that have investigated whether APOEε4 carrier status is associated with SCD have been
mixed in their findings. Whereas some studies have shown that APOEε4 carriers report greater
memory concerns (Dik et al. 2001, Laws et al. 2002, Mosconi et al. 2008), others have not found
a difference by genotype status (Bartley et al. 2012, Buckley et al. 2013, Harwood et al. 2004,
Lautenschlager et al. 2005). A recent study reported that the odds of having SCD are higher in
cognitively intact individuals who are APOEε4 carriers and who are also above the age of 70 (Krell-
Roesch et al. 2015). There is also evidence that the relationship between biomarkers and SCD may
be affected by APOEε4 status. In a number of studies, the relationship between SCD and amyloid
burden is enhanced in APOEε4 carriers (Rowe et al. 2010, Zwan et al. 2015). Additionally, the
relationship between SCD and biomarkers such as hippocampal volume (Striepens et al. 2011),
changes in hippocampal volume (Stewart et al. 2011), and glucose metabolism and increased levels
of AD biomarkers in the CSF (Mosconi et al. 2008) is stronger in APOEε4 carriers, although
another study did not find that APOEε4 affected the relationship between SCD and biomarkers
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of neurodegeneration (Risacher et al. 2015). Finally, a few studies have shown that self-reported
cognitive concerns predict longitudinal cognitive decline more rapidly in APOEε4 carriers than in
noncarriers (Dik et al. 2001, Samieri et al. 2014). Additional research is required to elucidate the
impact of APOE genotype on AD vulnerability among those with SCD and to clarify the possible
moderating role of age and knowledge of APOE status.

Relation of Subjective Cognitive Decline to Clinical Progression

The earliest research on SCD consisted of longitudinal community-based studies that investigated
whether a memory complaint at baseline predicted progression to dementia, with mixed findings
(Geerlings et al. 1999, Schmand et al. 1996, Schofield et al. 1997, Tobiansky et al. 1995). Many of
these studies were conducted prior to the formulation of the concept of MCI, and it is likely that
some SCD participants met criteria for MCI. The relevance of memory complaints at the MCI
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stage is less clear than in SCD, as awareness of deficits begins to erode (Roberts et al. 2009). Thus,
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interpretation of early longitudinal studies should consider this methodological limitation. More
recent studies have found that SCD predicts dementia, but over longer follow-up periods (Kaup
et al. 2015, Koppara et al. 2015b, Reisberg et al. 2010, van Oijen et al. 2007, Wang et al. 2004), in
individuals with significant concern or worry ( Jessen et al. 2010) or in SCD participants recruited
from memory clinics rather than community-based samples (Nunes et al. 2010, van Harten et al.
2013, Visser et al. 2009).
There is also ongoing investigation of the role of SCD in predicting longitudinal outcomes in
the context of biomarker positivity. PET imaging of Aβ positive, clinically normal individuals has
shown that “high” levels of SCD predicted an approximately five times greater rate of progression
to MCI or dementia as compared to “low” levels of SCD, but they did not predict decline in
episodic memory over 3 years (Buckley et al. 2016a,b). In SCD individuals with CSF evidence of
preclinical AD, cognitive decline on tests of memory, executive functioning, and global cognition
was observed, but not progression to clinical diagnosis over 2 years (van Harten et al. 2013).
Additionally, SCD individuals demonstrated a decline in memory performance that was associated
with baseline differences in glucose metabolism in AD-vulnerable brain regions (Scheef et al. 2012).
In summary, whereas early longitudinal studies were equivocal, recent research with well-
characterized samples, longer follow-ups, and complementary biomarker information has been
more successful in predicting clinical outcomes. In the short term, for example during the
timeframe of a clinical trial, SCD may not be a powerful predictor of longitudinal outcomes,
but it nonetheless contributes predictive ability in combination with other risk factors, such as
biomarker positivity.

Relation of Subjective Cognitive Decline to Objective Cognition

Objective cognitive testing remains the gold standard for assessment of current cognitive function.
This is complicated by the fact that, by definition, individuals with SCD score within normal
limits on clinical neuropsychological testing typically used to make a clinical diagnosis. One key
discriminating point between the measurement of subjective and objective cognitive performance
is that neuropsychological tests assess performance at a single point in time, whereas subjective
decline captures longitudinal change ( Jessen 2014). Therefore, for some older adults with SCD,
average neuropsychological test scores will actually reflect stable functioning (no decline), whereas
for others average scores will reflect a subtle decline from a higher baseline level ( Jessen 2014).
Moreover, the ability to detect impairment with neuropsychological tests is best at high levels of
impairment but decreases as one approaches the normal ability range. Mild cognitive difficulties
are more difficult to distinguish from normal ability due to issues of test sensitivity and the adequacy

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of normative datasets for older adult populations ( Jessen et al. 2014a,b; Mitrushina et al. 2005;
Puente & Puente 2013).
The limitations inherent to sole reliance upon clinical neuropsychological tests to assess cog-
nition have led researchers to pursue alternative assessment methods. In one study, memory clinic
patients with SCD showed subtle cognitive deficits on an experimental, short-term memory bind-
ing task compared to normal controls, though both groups performed similarly on standardized
memory tests (Koppara et al. 2015a). In another study, community-dwelling older adults with SCD
scored significantly lower than clinically normal older adults on long-term, naturalistic subtasks
of a clinical prospective memory test despite intact performance on traditional episodic memory
tests (Rabin et al. 2014). Smart & Krawitz (2015) examined performance on the Iowa Gambling
Task, which was developed as an experimental measure but is available for administration as a
neuropsychological test (Bechara 2007). SCD and clinically normal groups did not differ on the
test based on standardized clinical scoring, but novel statistical analyses of trial-to-trial responding
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indicated that SCD individuals discounted prior outcomes in making decisions, which suggests
either difficulties in updating/working memory or rapid forgetting of trial-to-trial information.
Research is required to replicate these findings and to identify the task-specific features and cog-
nitive domains that confer sensitivity to subtle changes associated with SCD. Another approach
is to use advanced psychometric techniques (e.g., item response theory) or composite measures to
increase the sensitivity of traditional measures to subtle cognitive change (Rentz et al. 2013). Fi-
nally, ecological momentary assessments, which utilize mobile technology for frequent cognitive
assessments in natural environments (Kremen et al. 2012, Scott et al. 2015, Trull & Ebner-Priemer
2013), may be better than traditional assessments at capturing subtle perceived cognitive failures
as they occur in real time. Momentary assessments also enable investigation of real-time relations
between cognition and other relevant variables (e.g., stress, pain, mood), which may be important
in explaining variation in subjective cognition. Importantly, accuracy of momentary reports may
be higher than that of retrospective reports (Solhan et al. 2009).
Longitudinal studies have more reliably found relationships between subjective and objective
cognitive tests, due in part to their ability to capitalize on individual- rather than group-level change
to detect decline over time (Hertzog & Pearman 2014). For example, in two separate studies, SCD
predicted cognitive decline longitudinally, but the combination of SCD and APOEε4 carriage led
to even steeper decline (Dik et al. 2001, Samieri et al. 2014). Using a continuous SCD measure,
two additional studies found that greater memory complaints predicted steeper decline on an
episodic memory test (Hohman et al. 2011) and a global cognitive measure (Dufouil et al. 2005).
Another study found that SCD individuals, particularly those with concerns about their memory,
demonstrated steeper episodic memory decline longitudinally, but not declines in verbal fluency
or working memory (Koppara et al. 2015b).
Recent work has attempted to characterize the dynamic relationship between serial assessments
of subjective and objective measures longitudinally. Significant change-on-change associations be-
tween longitudinal changes on objective and subjective measures have been found (Amariglio et al.
2015a, Parisi et al. 2011). Other studies have explored the interplay between objective and subjec-
tive measures and their possible temporal directions of mutual influence. In a population-based
study of older adults utilizing latent growth curve models to analyze yearly change scores in
memory complaints and objective memory, Snitz and colleagues (2015b) found that lower mem-
ory complaints predicted subsequent stronger memory performances (consistent with practice
effects), but that lower memory performance predicted subsequent decline in memory complaints
(consistent with anosognosia). Of interest, results for language and executive function domains
were the opposite of those for memory, with lower objective scores in these domains associating
with subsequent increases in memory complaints.

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In summary, valid detection of cognitive decline by objective testing at the SCD stage poses
challenges, though novel assessment approaches may capture cross-sectional associations. At more
advanced disease stages, neuropsychological testing becomes a more valid marker of impairment.
Longitudinal studies have more reliably found relationships between SCD and cognitive decline.
Not surprisingly, research has revealed complex temporal dynamic relationships between subjec-
tive and objective cognition that vary according to disease stage and level of objective impairment.
This work has also uncovered differences in how memory complaints track with objective cognition
in nonmemory domains, with possible implications for the design of SCD measures.

ROLE OF SELF- AND INFORMANT-REPORTS

SCD is defined by self-experienced cognitive decline. Informant confirmation has been hypoth-
esized to increase the likelihood that an individual is along the preclinical AD spectrum, but it is
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not currently required for classification ( Jessen et al. 2014a). Although a detailed discussion of the
merits and drawbacks of subjective report data is beyond the scope of this review, certain consider-
ations warrant mention. The common approach of assessing subjective cognition with self-report
questionnaires is associated with practical advantages such as brevity, ease of administration, and
low cost. Global retrospective self-reports of cognition, however, are limited by recall biases and
the inability to capture subtle perceived changes that occur over time and across environments and
contexts (Stone & Shiffman 1994). In addition, such measures require older adults to characterize
their cognition by aggregating experiences into an average state, introducing additional bias (Hill
et al. 2015), and they can be affected by intellectual and educational variables. Accuracy of infor-
mant reporting, particularly in clinically normal individuals, can also vary depending on the nature
of the relationship between participants and informants and the frequency or intensity of their
interaction. Additionally, informant-reports may be influenced by epiphenomena such as the af-
fective state of the patient or informant, a tendency to deny or magnify problems, or misjudgment
of the degree of impairment (Mackinnon & Mulligan 1998). Finally, older adults who have study
informants may represent a subgroup of individuals with effective social networks, which are asso-
ciated with a reduced risk of dementia loss of functional capacity (Bourne et al. 2007, Fratiglioni
et al. 2004). These participants may differ in meaningful ways from those lacking informants.
With these issues in mind, we consider the relation and relative value of self- and informant-
report in SCD. Self- and informant-reports tend to be dynamic, with convergence and then
divergence occurring around the MCI stage. For example, Buckley and colleagues (2015b) found
that self-reported concerns aligned with informant concerns, particularly in clinically normal
individuals who had a high number of concerns. By the advanced MCI stage, greater informant
concerns diverged from self-reported concerns. Rueda and colleagues (2015) corroborated these
findings and suggested that self-reported cognition might be valid in normal older adults and
early MCI, with informant-reports being more accurate in late MCI and beyond. In studies of
individuals with cognitive impairment, self- and informant-report have not typically been related
(Chung & Man 2009, Jorm et al. 1994), further suggesting that alignment of self- and informant-
report depends on disease stage.
Studies that have examined self- and informant-reports in relation to performance have
also found differences by disease stage. In one study, those with greater informant-reported
concerns relative to self-reported concerns performed worse on objective cognitive measures
(Rattanabannakit et al. 2016). Other studies have shown that informant-report is more consis-
tently associated with cognitive performance in individuals with clinical impairment (Buckley
et al. 2015b, Caselli et al. 2014, Jorm et al. 1994, Rattanabannakit et al. 2016, Rueda et al. 2015,
Slavin et al. 2010). In terms of the relationship between subjective report and AD biomarkers, some

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Correlation between subjective and objective cognitive performance

0.6
Reporter type
Self

Correlation (95% confidence interval)

Informant
Self and informant
0.4

0.2
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0.0
0 12 24 36 48
Month

Figure 3
Pearson’s correlation coefficients are plotted over time, by reporter type of the subjective cognitive report
instrument, Cognitive Function Instrument (CFI), with 95% confidence intervals. Signs for the correlations
are inverted. Initially, self report more strongly associated with objective performance on the modified
Alzheimer’s Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (mADCS-PACC), but this
pattern was eventually surpassed by informant-report. Adapted with permission from Amariglio et al. (2015).

studies using PET amyloid imaging found a relationship between self-report and amyloid burden
in clinically normal individuals, but no relationship with informant-report (Amariglio et al. 2012).
By contrast, another study found an association between both self- and informant-report with
amyloid imaging (Rueda et al. 2015). Using CSF biomarkers, informant-report was more strongly
related to Aβ42 and tau levels compared to self-report (Rueda et al. 2015, Valech et al. 2015).
Additionally, the relationship between hippocampal volume and subjective ratings was stronger
for informant- than for self-report (Rueda et al. 2015).
In terms of clinical progression, several studies have found that informant-report predicted AD
dementia more reliably than self-report (Carr et al. 2000, Rabin et al. 2012), but other studies have
found that the initial superiority of self-report in predicting progression compared to informant-
report reverses as individuals move towards clinical impairment (Amariglio et al. 2015a, Caselli
et al. 2014; see also Figure 3). There is also some evidence that informant-reports of decline
predict executive function task performance over and above self-reports (Mulligan et al. 2016),
and that informant- (as opposed to self-) report items tapping executive function more broadly
are predictive of clinical progression (Rabin et al. 2010, 2012). Future research is required to
determine whether specific subsets of self- or informant-complaint items associate with clinical
and cognitive outcomes.
In summary, research suggests that the accuracy of self- and informant-report is dynamic
along the early AD spectrum. Self-report may be most meaningful at the preclinical stage, but
as individuals approach MCI, informant-report may relate more strongly to objective cognitive
performance and progression to AD dementia. Therefore, self- and informant-report represent
complementary approaches, and their combination could offer the best predictive ability for AD
(Amariglio et al. 2015a; Gifford et al. 2014, 2015a; Rabin et al. 2012).

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INTERRELATIONSHIPS OF SUBJECTIVE COGNITIVE DECLINE

WITH OTHER VARIABLES
SCD has garnered significant interest in large part because of its association with preclinical AD
dementia. Some research has found that as many as 60% of individuals with SCD decline to MCI
and AD over a 15-year period (Reisberg & Gauthier 2008). However, this means that SCD is
unspecific, with the remaining 40% of older adults (approximately) presenting with SCD due to
conditions other than AD. Just as objective cognitive status is multiply determined, so is subjective
cognitive status. Below we explore factors consistently known to influence self-report of cognition
and, consequently, the expression of SCD.

Depression
Depression can present differently in older adults than in people of other age groups and may in-
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clude symptoms of perceived or actual cognitive impairment (Steffens & Potter 2008). The widely
used Geriatric Depression Scale (Yesavage et al. 1982), for example, contains items such as “Do
you feel you have more problems with memory than most?” According to the cognitive model of
depression, individuals with depression commonly exhibit information-processing biases, includ-
ing an attentional bias toward negative information (Peckham et al. 2010). Many older adults are
aware of age-related changes in cognition, but for those with depression there may be a hyper-
sensitivity to perceived cognitive failures, which could result in an overreporting of complaints.
Thus, for some individuals, addressing the underlying symptoms of depression through either
pharmacologic or psychotherapeutic avenues may significantly reduce cognitive complaints.
Originally, the SCD-I working group recommended that researchers exclude persons with
clinically significant depression and other psychiatric conditions ( Jessen et al. 2014a), presumably
because depression is known to influence cognitive complaints and may obfuscate the predictive
power of complaints in relation to incipient AD. However, emerging research suggests that this
may not be the optimal strategy, because the relationships between depression, SCD, and risk for
cognitive decline are more complex and nuanced than previously believed. For some individuals,
an occurrence of earlier depressive episodes has been shown to confer increased risk for later
pathologic cognitive decline (Butters et al. 2008). Conversely, the emergence of first-episode late-
life depression may be a prodrome for incipient AD and other dementias. This is corroborated
by recent reviews that suggest that late-life depression is associated with increased risk of all-
cause dementia, including AD (DaSilva et al. 2013, Diniz et al. 2013). Moreover, depression
has been shown to be associated with objective changes to brain structure and function (Butters
et al. 2008), including gray matter abnormalities within frontal-subcortical and limbic networks
(Sexton et al. 2013) and white matter integrity (Allan et al. 2016). These types of brain changes,
and their associated cognitive impairments, are often associated with non-AD dementias such
as vascular dementia and movement disorders (Attix & Welsh-Bohmer 2013). Together, these
findings suggest that the exclusion of persons with depression from studies on SCD could result
in an incomplete understanding of the mechanisms by which SCD predicts future decline and
dementia. An alternative approach might be to include such persons in research while quantifying
depression and other psychiatric symptoms as potential moderator variables. The presence of
psychiatric comorbidities may give rise to different subtypes of SCD that have different trajectories
toward pathologic cognitive decline.

Anxiety
Anxiety may influence reports of perceived cognitive impairment. Previous literature was likely
to classify many individuals with SCD as the “worried well,” given that their cognitive concerns

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were reported in the context of normal clinical-neuropsychological function (Boone 2009). This
notion is corroborated by studies questioning the reliability of the relationship between subjective
cognitive complaints and objective cognitive impairment (Cargin et al. 2008, Jorm et al. 1994,
Rami et al. 2014). However, given the number of individuals with SCD who are estimated to
decline to AD and (possibly) other dementias, the presence of anxiety or worry is no longer a
reason to assume that someone may not decline to dementia over time. Some researchers have
shown that worry or concern specific to cognitive function is associated with concurrent (Mulligan
et al. 2016, Smart et al. 2014, Smart & Krawitz 2015) and future risk of cognitive decline ( Jessen
et al. 2010).
Furthermore, much like with depression, emerging research is demanding a more nuanced
investigation of the relationships between anxiety, SCD, and future cognitive decline. For example,
Pietrzak et al. (2015b) followed a clinic-based sample over an approximate 4.5-year period to
examine the relationships between amyloid burden, anxiety, and progression to MCI and dementia
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in clinically normal older adults. They found that positive Aβ status at baseline was associated
with greater cognitive decline over the study period. This association was moderated by anxiety,
such that in the positive Aβ group, higher levels of anxiety were associated with significantly more
pronounced slopes of decline compared to lower levels of anxiety. In a related study (Pietrzak et al.
2015a), those with rapidly declining cognition also had elevated subjective memory impairment in
conjunction with higher amyloid and greater levels of anxiety. In terms of potential mechanisms
to explain these findings, it is possible that anxiety is a marker of underlying dysfunction of the
hypothalamic-pituitary-adrenal (HPA) axis; high stress in midlife, typically associated with HPA
axis dysfunction, has been shown to predict greater risk for AD in later life ( Joshi & Pratico 2013).
Both stress and HPA axis function are associated with cortisol production. Popp and colleagues
(2015) found elevated CSF cortisol concentrations in persons with MCI-AD and AD dementia as
compared to those with other variants of MCI and normal cognition. Moreover, higher baseline
levels of CSF cortisol were associated with faster clinical progression and cognitive decline in
the MCI-AD subgroup. With HPA axis dysfunction increasingly recognized as a risk factor for
cognitive decline, in future research it will be important to determine whether (and how) anxiety
in SCD is a sign of early HPA axis dysfunction and serves as a prodromal marker of incipient AD.

Personality
Existing literature suggests associations between certain personality factors—particularly higher
neuroticism and lower conscientiousness—and increased risk of MCI and dementia (Duberstein
et al. 2011, Low et al. 2013), although the precise mechanisms underlying these associations remain
unclear. For example, in older adult samples, higher neuroticism scores have been associated with
structural brain changes (Kapogiannis et al. 2013), including in areas associated with AD such as the
medial temporal cortex ( Jackson et al. 2011). Conversely, higher levels of conscientiousness have
been associated with greater volumes in prefrontal and medial temporal areas ( Jackson et al. 2011)
and larger dorsolateral prefrontal and smaller frontopolar cortices (Kapogiannis et al. 2013). In
many studies on SCD, personality—particularly neuroticism—is controlled for rather than specif-
ically evaluated for its impact on cognitive complaints. Two recent studies have directly examined
the relationships between SCD and personality. Smart and colleagues (2015) found that lower
levels of conscientiousness, as measured by the Big Five Inventory, discriminated between clini-
cally normal older adults with and without SCD. Integrating the use of preclinical AD biomarkers,
Snitz and colleagues (2015c) found that neuroticism moderated the relationship between cogni-
tive complaints and amyloid burden, such that only individuals higher in neuroticism showed the
predicted positive association between complaints and amyloid burden.

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The precise mechanisms by which personality associates to SCD and cognitive decline remain
unclear. Many of the studies assessing personality use cross-sectional comparisons of age groups,
and there are limited data tracking within-person longitudinal changes in personality. Thus the
question remains: Do existing personality traits confer increased risk of decline, or do changes
in cross-sectional measures of personality represent emergent symptoms of cognitive decline
(Duberstein et al. 2011, Friedman et al. 2014)? Previous research assumed that personality was
relatively stable over the adult lifespan (Costa & McCrae 1994); thus, certain personality traits
were presumed to be stable individual differences that conferred increased risk for later cognitive
decline. More recent research suggests that changes in personality traits continue in mid and later
life, albeit to varying degrees compared to early adulthood (Roberts & Mroczek 2008, Srivastava
et al. 2013). In order to better understand the relationship between personality and SCD, future
longitudinal studies are needed, including repeated administration of personality measures in
conjunction with assessment of neuropsychological status and biomarkers.
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Physical Health Concerns

In populations with chronic health difficulties, cognitive complaints may be more highly associated
with physical health symptoms than with objective impairment (Boone 2009). With increasing age
comes greater likelihood for chronic physical health difficulties, accounting in part for the relatively
high frequency of cognitive complaints within the clinically normal older adult population ( Jonker
et al. 2000, Slavin et al. 2010). Chronic pain, for example, is highly prevalent in older adults (Reid
et al. 2015) and could influence self-report of cognitive complaints via the direct experience of
pain symptoms, the effect of pain medication on cognition, and the comorbidity of depression
and anxiety (Allaz & Cedraschi 2015, Gibson 2015, Goesling et al. 2013). Unmanaged vascular
risk factors such as hypertension, hypercholesterolemia, and type II diabetes have been related to
greater cognitive complaints, possibly due to vascular cognitive impairment, even in the absence
of stroke (Sahathevan et al. 2011). Moreover, type II diabetes and related factors, such as sleep
and metabolic function, can cause transient fluctuations in cognitive status (McConnell 2014).
Individuals may report cognitive complaints but appear within normal limits on clinical assessment
due to the transitory nature of such cognitive fluctuations. Thus, assessment of physical health is
necessary to ascertain the etiologic factors influencing the presentation of SCD, with attention to
the conditions that could influence perceived cognitive function and the possible iatrogenic effects
of the medications used to manage these conditions. Finally, assessment of mood and personality
is also essential, given both their relationships to chronic medical conditions and their potentially
additive effects in the reporting of cognitive complaints.

Demographic Factors
Of all the demographic factors studied, epidemiological research suggests that advancing age
remains the most powerful predictor of risk for development of AD dementia (Alzheimer’s Assoc.
2016b). Bearing in mind that SCD is estimated to span approximately 15 years prior to the onset
of manifest AD symptoms (Reisberg et al. 2008), an older age of presentation associated with
SCD may suggest a greater likelihood of preclinical AD, particularly with the presence of relevant
biomarkers ( Jessen et al. 2014a). However, studies have shown that SCD at younger ages is also
more predictive of AD risk (Wang et al. 2004, Zwan et al. 2015), suggesting that SCD at a younger
age may be more clinically meaningful in terms of predictive utility and long-term management
and care. Future research might establish whether there is an optimal age range in which SCD is
useful for predicting risk of disease progression.

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Emerging literature suggests that education levels have a complex influence on SCD and its
meaning for risk of future cognitive decline. Two previous studies have found that, in persons
with SCD, higher levels of education were associated with greater risk of decline to AD dementia
( Jonker et al. 2000, van Oijen et al. 2007). It is possible that highly educated individuals are more
sensitive to subtle declines in cognitive function and are therefore more likely to subjectively detect
a change. Furthermore, whereas a certain degree of underlying brain pathology might give rise to
clinical symptoms in less-educated individuals, persons with higher cognitive reserve may be able
to compensate for longer periods of time and thus appear clinically normal. In support of this,
recent work suggests a relationship between SCD and amyloid burden that is stronger in those
with more years of education (Aghjayan et al. 2016).
Linguistic and cultural factors may also influence the report of cognitive complaints. Little is
known about different cross-cultural expressions of SCD, though one can speculate that cognitive
complaints may be more or less socially sanctioned in different cultures. In one of the few studies to
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explore race and SCD, the relationship of objective memory performance and memory complaints
was significant in Caucasians but not in African Americans matched for socioeconomic status
characteristics ( Jackson et al. 2016). Within-culture studies of SCD, particularly within non-
English-speaking and non-European cultures, are key to understanding the meaning of SCD in
these populations. Knowledge of the base rate of cognitive complaints among clinically normal
older adults in these populations would provide a reference point against which to interpret the
meaning of complaints. Similarly, neuropsychological constructs may be differentially expressed
across cultures. For example, North American tests of mental function often emphasize the speed
of completion of tasks, a potential representation of cultural values not intrinsic to the cognitive
process (Sternberg 1998). Additionally, cross-cultural investigations will help to derive complaint
items that are most reliable and clinically meaningful for a given cultural group.
In summary, classification of SCD rests primarily on self-report of perceived cognitive decline,
but such self-reports are multiply determined. A comprehensive biopsychosocial approach to
characterizing individuals is needed to understand the factors that contribute unique and shared
variance to SCD. Such an approach could illuminate unique profiles or subtypes of SCD that are
associated with highest risk for incipient AD dementia, as well as identify individuals that may
respond to different interventions (e.g., for depression or chronic pain).

INTERVENTION
Individuals with SCD represent important targets of intervention for several reasons. For individ-
uals who do have preclinical AD, prevention-intervention could slow the rate of incipient decline
to prolong and preserve cognitive and functional abilities. At this very early stage of decline, it is
presumed that individuals have sufficiently intact cognitive function that can be harnessed toward
either compensation or restitution of function (Sohlberg & Mateer 2001). For example, in the case
of mild memory perturbations, older adults could be taught strategies to compensate for these
difficulties without changing the underlying memory system per se (Troyer 2001, Wiegand et al.
2013). Alternatively, other cognitive functions such as attention could be enhanced and recruited
to improve perceived memory function (Smart et al. 2016). Conversely, for individuals present-
ing with SCD within the context of mood/anxiety, personality, and health concerns, intervention
could improve psychological functioning and overall quality of life.
Within the field of dementia, significant time and economic resources have been directed to-
ward the development and implementation of pharmacologic interventions, with overall modest
effects on cognitive function and minimal behavioral benefits (Tan et al. 2014). However, the
use of similar medications in SCD raises concerns. For one, pharmacologic trials are costly to

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implement and maintain. Furthermore, given the heterogeneity of possible etiologies of SCD,
clinical trials may include individuals without preclinical AD who are being administered med-
ications for use in AD dementia, the benefits of which are uncertain or unproven. This is no
small matter, given that many of these medications have significant side effects (Tan et al. 2014).
However, for individuals who have SCD associated with depression, anxiety, or physical health
concerns, empirically supported pharmacologic management of these symptoms may positively in-
fluence perceived or actual cognitive function and, in turn, reduce reports of cognitive complaints.
Cognitive and behavioral interventions for SCD may be more useful than medication. From
an economic standpoint, there already exist empirically supported treatments whose efficacy and
effectiveness could be tested in SCD populations (Smart et al. 2016). For example, the field of
cognitive rehabilitation arose to meet the needs of individuals with acquired brain injury (Sohlberg
& Mateer 2001), and knowledge continues to mount regarding the efficacy of such interventions on
cognitive, behavioral, and emotional functions (van Heugten et al. 2012). Cognitive rehabilitation
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is currently being implemented in older adults with MCI (Huckans et al. 2013) and AD dementia
(Choi & Twamley 2013), and likewise it could be tailored for SCD. Moreover, with regard to
individuals with SCD associated with psychological or medical comorbidities, there already exists
substantial literature on empirically supported cognitive and behavioral treatments for older adults
with depression (Bridle et al. 2012, Simon et al. 2014), anxiety (Hall et al. 2016), and physical
health symptoms such as chronic pain (Makris et al. 2014, Park & Hughes 2012). Development
of new interventions specific to SCD is likely to cost less than development of new medications,
as is their subsequent implementation, which can occur with a wider range of professionals than
physicians alone. There are theoretical reasons for which nonpharmacologic interventions in SCD
are worthwhile pursuits. Individuals with SCD are by definition aware of and concerned about
subtle changes in cognition ( Jessen et al. 2014a), which suggests that they would be motivated to
participate in interventions to improve their functioning. Moreover, given that individuals with
SCD are hypothesized to be early in the trajectory of AD-related cognitive decline, they could
potentially benefit maximally from the interventions they receive, as opposed to those who are
more impaired.
Smart and colleagues (2017) conducted a systematic review and meta-analysis of controlled
trials of nonpharmacologic interventions for SCD. Target participants were older adults (ages
55+) with SCD broadly defined, with or without clinically normal controls, and with cognitive,
behavioral, or psychosocial outcome variables. Eleven studies were eligible for inclusion in the
systematic review, and meta-analyses were conducted on 9 of the 11 studies that had cognitive
outcome data, revealing a small effect size for all nonpharmacologic interventions on cognition
(d = 0.22). Although still small, the effect was greater for those studies that explicitly involved
cognitive training methods (d = 0.37). The systematic review revealed a great diversity of in-
tervention methods. Although no definitive conclusions could be made about the efficacy of a
particular type of intervention, given the results of the meta-analysis and the fact that the majority
of interventions (8/11) used some form of cognitive training, findings suggest that nonpharma-
cologic interventions are a worthwhile pursuit in persons with SCD and can result in short-term
benefits in cognition. Most studies (7/9) included only immediate postintervention assessment,
which is unsurprising as the field attempts to establish proof of principle that such interventions
have measurable benefit on cognitive function in persons with SCD. That said, given that the most
compelling question is whether these interventions can slow or alter the trajectory of cognitive
decline in persons with SCD, this underscores the need for future studies to conduct longitu-
dinal follow-up assessment following intervention. For researchers and clinicians interested in
implementing intervention trials in persons with SCD, Smart et al. (2017) also provided detailed
recommendations on best practices in this area.

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ETHICAL CONSIDERATIONS
The ethical context for a research and clinical agenda on SCD warrants attention. With an aging
baby boomer generation, the ensuing decades will see a rapid increase in the proportion of older
adults in the general population and a similar increase in the number of individuals at risk to develop
AD dementia. As such, interest in the topic of SCD and its clinical and societal impact is only likely
to increase over time. Zeal in the pursuit of this topic should be tempered by an appreciation of the
possible ethical implications of such research. For example, aggressive assessment of older adults
in the community could trigger a health crisis in the “worried well,” creating unnecessary anxiety
in individuals who are otherwise aging normally (Fox et al. 2013). Conversely, in participants
classified with SCD, researchers should carefully consider on an individual basis the amount of
clinical disclosure to be given and the psychological impact of such information. For example,
individuals may be asked to report their level of complaints or concern about cognitive decline in
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detail, without ever being given a diagnostic label of SCD or being told the implications of such a
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diagnosis. This is important given that some, but not all, individuals with SCD will develop AD
dementia, and AD itself is presently an incurable condition.
Research has already been conducted assessing the psychological risks and benefits of disclosing
APOEε4 status to individuals who are currently asymptomatic—see Schicktanz and colleagues
(2014) for an overview of relevant ethical issues. At a minimum, researchers should consider at the
outset how much information will be provided to participants about their SCD status and consider
the factors that may increase psychological risk for adverse outcomes following the receipt of this
information, specifically current or prior history of depression (Draper et al. 2010). With the
rapidly increasing number of older adults in the population and the projected increases in rates
of diagnosis of AD dementia (Alzheimer’s Assoc. 2016a), researchers are understandably eager to
identify those at risk as early as possible to institute secondary prevention-interventions to delay
future decline. One must also consider issues of distributive justice, however, if such efforts mean
that health care and research monies are disproportionately diverted away from individuals already
diagnosed with dementia who are currently in need of intervention and support (Schicktanz et al.
2014).

FUTURE DIRECTIONS
The last decade has seen a burgeoning interest in the topic of SCD. For the field to maximize its
contributions to the understanding of preclinical AD, several important issues must be resolved.
First, researchers need to adopt standard terminology and assessment practices specifying
whether SCD is being used as a diagnostic entity or a descriptor. Further refinement of the
construct is needed to support this clarification, including standardized research and operational/
diagnostic criteria to facilitate the comparison of study findings, data pooling and meta-analytic
work, and collaborative multicenter research efforts. Readers are referred to Jessen et al. (2014a)
and Molinuevo et al. (2017) for proposed diagnostic criteria and operational guidelines. As
previously noted, the SCD-I supports some flexibility in the classification of SCD, and individual
studies may still vary in their major aims and approach to SCD. It is incumbent on researchers to
clarify how they operationalize SCD within a given study and why they choose a given approach.
This effort will move the field forward by allowing for synthesis across relevant types of studies
(e.g., community samples, clinic samples, etc.). Rigorous classification reporting will also help
delineate which interventions work under which conditions. The potential value of SCD as an
enrichment strategy for preclinical AD prevention trials differs from that of current strategies
(genetic risk factors, causal mutations, Aβ PET scan status). SCD is a behavioral phenotype

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independent of specific biological hypotheses. As such, it may bear more fruit as a broader and
more general risk enhancement strategy applicable to a wide range of possible intervention trials.
Second, given that individuals with SCD have normal neuropsychological functioning, classifi-
cation primarily rests on subjective reports. To increase the predictive validity of SCD as a marker
for preclinical AD, a multimethod approach to objective assessment is crucial and must include
not only neuroimaging but also novel and challenging assessments of cognition. Particularly in
community samples, where there may be a higher rate of false positives, convergent evidence
from multiple methods may increase the likelihood of accurate designation of SCD associated
with preclinical AD.
Third, future research is likely to benefit from a multimethod approach not only in the as-
sessment of key outcomes, but also in the assessment of complaints themselves. As noted above, a
great diversity of methods are currently employed to assess complaints (Rabin et al. 2015), which
likely reflects differing aims among the various studies. The field is likely to advance more expedi-
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tiously if greater multicenter collaboration with core common items to assess SCD is undertaken.
Harmonization of existing datasets using advanced statistical procedures can provide clues as to
which items might comprise such a common core.
Fourth, harmonized observational studies are needed to (a) better understand the complex and
heterogeneous natural history of SCD, (b) differentiate features of SCD associated with preclinical
AD from SCD due to other etiologic factors, and (c) ultimately improve the prediction of clinically
meaningful outcomes.
Finally, for intervention trials, studies should again rigorously delineate how individuals with
SCD were recruited and classified. Researchers should specify the target variable of interest (e.g.,
cognitive complaints, objective cognitive function), include measures that are sensitive and specific
to ascertaining changes in these variables, and employ interventions that specifically target those
variables of interest. Researchers are further encouraged to draw on the rich body of knowledge
that already exists within the field of cognitive rehabilitation to design novel interventions or tailor
existing protocols.

DISCLOSURE STATEMENT
The authors are not aware of any affiliations, memberships, funding, or financial holdings that
might be perceived as affecting the objectivity of this review.

ACKNOWLEDGMENTS
L.A.R. was supported by the National Institutes of Health (NIH) (NIA/NIGMS grant
SC2AG039235) and PSC-CUNY (Award #68859–00 46). C.M.S. was supported by Alzheimer
Society of Canada Young Investigator Award #1216. R.E.A. was supported by Alzheimer’s Associ-
ation grant NIRG-12–243012 and NIH grant K23AG044431. The authors thank Rose Bergdoll,
Donald Brodale, and Dr. Rachel Buckley for assistance with manuscript editing.

LITERATURE CITED
Aghjayan SL, Buckley RF, Vannini P, Rentz DM, Jackson JJ, et al. 2016. The influence of demographic factors
on subjective cognitive concerns and beta-amyloid. Int. Psychogeriatr. 29:645–52
Allan CL, Sexton CE, Filippini N, Topiwala A, Mahmood A, et al. 2016. Sub-threshold depressive symptoms
and brain structure: a magnetic resonance imaging study within the Whitehall II cohort. J. Affect. Disord.
204:219–25

www.annualreviews.org • Subjective Cognitive Decline 389

 CP13CH15-Rabin ARI 13 April 2017 9:58

Allaz A-F, Cedraschi C. 2015. Emotional aspects of chronic pain. In Pain, Emotion and Cognition: A Complex
Nexus, ed. G Pickering, S Gibson, pp. 21–34. New York: Springer. 1st ed.
Alzheimer’s Assoc. 2016a. Prevalence. Chicago: Alzheimer’s Assoc. http://www.alz.org/facts/#prevalence
Alzheimer’s Assoc. 2016b. Risk Factors. Chicago: Alzheimer’s Assoc. http://www.alz.org/alzheimers_
disease_causes_risk_factors.asp
Amariglio RE, Becker JA, Carmasin J, Wadsworth LP, Lorius N, et al. 2012. Subjective cognitive complaints
and amyloid burden in cognitively normal older individuals. Neuropsychologia 50:2880–86
Amariglio RE, Donohue MC, Marshall GA, Rentz DM, Salmon DP, et al. 2015a. Tracking early decline in
cognitive function in older individuals at risk for Alzheimer’s disease dementia: the Alzheimer’s Disease
Cooperative Study Cognitive Function Instrument. JAMA Neurol. 72:446–54
Amariglio RE, Mormino EC, Pietras AC, Marshall GA, Vannini P, et al. 2015b. Subjective cognitive concerns,
amyloid-beta, and neurodegeneration in clinically normal elderly. Neurology 85:56–62
Amariglio RE, Townsend MK, Grodstein F, Sperling RA, Rentz DM. 2011. Specific subjective memory
complaints in older persons may indicate poor cognitive function. J. Am. Geriatr. Soc. 59:1612–17
Annu. Rev. Clin. Psychol. 2017.13:369-396. Downloaded from www.annualreviews.org

Antonell A, Fortea J, Rami L, Bosch B, Balasa M, et al. 2011. Different profiles of Alzheimer’s disease cere-
Access provided by University of New England on 03/10/18. For personal use only.

brospinal fluid biomarkers in controls and subjects with subjective memory complaints. J. Neural Transm.
118:259–62
Attix DK, Welsh-Bohmer KA. 2013. Geriatric Neuropsychology: Assessment and Intervention. New York: Guilford
Bartley M, Bokde AL, Ewers M, Faluyi YO, Tobin WO, et al. 2012. Subjective memory complaints in
community dwelling healthy older people: the influence of brain and psychopathology. Int. J. Geriatr.
Psychiatry 27:836–43
Bechara A. 2007. Iowa Gambling Task. Lutz, FL: Psychol. Assess. Resour.
Boone KB. 2009. Fixed belief in cognitive dysfunction despite normal neuropsychological scores: neurocog-
nitive hypochondriasis? Clin. Neuropsychol. 23:1016–36
Bourne VJ, Fox HC, Starr JM, Deary IJ, Whalley LJ. 2007. Social support in later life: examining the roles of
childhood and adulthood cognition. Pers. Individ. Differ. 43:937–48
Bridle C, Spanjers K, Patel S, Atherton NM, Lamb SE. 2012. Effect of exercise on depression severity in older
people: systematic review and meta-analysis of randomised controlled trials. Br. J. Psychiatry 201:180–85
Buckley RF, Ellis KA, Ames D, Rowe CC, Lautenschlager NT, et al. 2015a. Phenomenological characteriza-
tion of memory complaints in preclinical and prodromal Alzheimer’s disease. Neuropsychology 29:571–81
Buckley RF, Maruff P, Ames D, Bourgeat P, Martins RN, et al. 2016a. Subjective memory decline predicts
greater rates of clinical progression in preclinical Alzheimer’s disease. Alzheimers Dement. 12(7):796–804
Buckley R, Saling MM, Ames D, Rowe CC, Lautenschlager NT, et al. 2013. Factors affecting subjective
memory complaints in the AIBL aging study: biomarkers, memory, affect, and age. Int. Psychogeriatr.
25:1307–15
Buckley R, Saling M, Ellis K, Rowe C, Maruff P, et al. 2015b. Self and informant memory concerns align in
healthy memory complainers and in early stages of mild cognitive impairment but separate with increasing
cognitive impairment. Age Ageing 44:1012–19
Buckley RF, Saling MM, Fromann I, Wolfsgruber S, Wagner M. 2015c. Subjective cognitive decline from a
phenomenological perspective: a review of the qualitative literature. J. Alzheimers Dis. 48(Supp. 1):25–40
Buckley RF, Villemagne VL, Masters CL, Ellis K, Rowe C, et al. 2016b. Conceptualization of the utility of
subjective cognitive decline in clinical trials of preclinical Alzheimer’s disease. J. Mol. Neurosci. 60(3):354–
61
Butters MA, Young JB, Lopez O, Aizenstein HJ, Mulsant BH, et al. 2008. Pathways linking late-life depression
to persistent cognitive impairment and dementia. Dialogues Clin. Neurosci. 10:345–57
Cargin JW, Collie A, Masters C, Maruff P. 2008. The nature of cognitive complaints in healthy older adults
with and without objective memory decline. J. Clin. Exp. Neuropsychol. 30:245–57
Carr DB, Gray S, Baty J. 2000. The value of informant versus individual’s complaints of memory impairment
in early dementia. Neurology 55:1724–26
Caselli RJ, Chen K, Locke DE, Lee W, Roontiva A, et al. 2014. Subjective cognitive decline: self and informant
comparisons. Alzheimers Dement. 10:93–98
Chetelat G, Villemagne VL, Bourgeat P, Pike KE, Jones G, et al. 2010. Relationship between atrophy and
beta-amyloid deposition in Alzheimer disease. Ann. Neurol. 67:317–24

390 Rabin · Smart · Amariglio

 CP13CH15-Rabin ARI 13 April 2017 9:58

Choi J, Twamley EW. 2013. Cognitive rehabilitation therapies for Alzheimer’s disease: a review of methods
to improve treatment engagement and self-efficacy. Neuropsychol. Rev. 23:48–62
Chung JC, Man DW. 2009. Self-appraised, informant-reported, and objective memory and cognitive function
in mild cognitive impairment. Dement. Geriatr. Cogn. Disord. 27:187–93
Colijn MA, Grossberg GT. 2015. Amyloid and tau biomarkers in subjective cognitive impairment. J. Alzheimers
Dis. 47:1–8
Cooper C, Bebbington P, Lindesay J, Meltzer H, McManus S, et al. 2011. The meaning of reporting for-
getfulness: a cross-sectional study of adults in the English 2007 Adult Psychiatric Morbidity Survey. Age
Ageing 40:711–17
Costa PT Jr., McCrae RR. 1994. Set like plaster: evidence for the stability of adult personality. In Can Personality
Change? ed. TF Heatherton, JL Weinberger, pp. 21–40. Washington, DC: Am. Psychol. Assoc.
DaSilva J, Gonçalves-Pereira M, Xavier M, Mukaetova-Ladinska EB. 2013. Affective disorders and risk of
developing dementia: systematic review. Br. J. Psychiatry 202:177–86
Dik MG, Jonker C, Comijs HC, Bouter LM, Twisk JW, et al. 2001. Memory complaints and APOE-epsilon4
Annu. Rev. Clin. Psychol. 2017.13:369-396. Downloaded from www.annualreviews.org

accelerate cognitive decline in cognitively normal elderly. Neurology 57:2217–22

Access provided by University of New England on 03/10/18. For personal use only.

Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF. 2013. Late-life depression and risk of vascular de-
mentia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies.
Br. J. Psychiatry 202:329–35
Draper B, Peisah C, Snowdon J, Brodaty H. 2010. Early dementia diagnosis and the risk of suicide and
euthanasia. Alzheimers Dement. 6:75–82
Duberstein PR, Chapman BP, Tindle HA, Sink KM, Bamonti P, et al. 2011. Personality and risk for
Alzheimer’s disease in adults 72 years of age and older: a six-year follow-up. Psychol. Aging 26:351–62
Dufouil C, Fuhrer R, Alperovitch A. 2005. Subjective cognitive complaints and cognitive decline: consequence
or predictor? The epidemiology of vascular aging study. J. Am. Geriatr. Soc. 53:616–21
Fox C, Lafortune L, Boustani M, Brayne C. 2013. Debate & analysis: the pros and cons of early diagnosis in
dementia. Br. J. Gen. Pract. 63(612):e510–12
Fratiglioni L, Paillard-Borg S, Winblad B. 2004. An active and socially integrated lifestyle in late life might
protect against dementia. Lancet Neurol. 3:343–53
Friedman HS, Kern ML, Hampson SE, Duckworth AL. 2014. A new life-span approach to conscientiousness
and health: combining the pieces of the causal puzzle. Dev. Psychol. 50:1377–89
Geerlings MI, Jonker C, Bouter LM, Ader HJ, Schmand B. 1999. Association between memory complaints
and incident Alzheimer’s disease in elderly people with normal baseline cognition. Am. J. Psychiatry
156:531–37
Gibson SJ. 2015. The pain, emotion, and cognition nexus in older persons and in dementia. In Pain, Emotion
and Cognition: A Complex Nexus, ed. G Pickering, S Gibson, pp. 231–47. New York: Springer
Gifford KA, Liu D, Carmona H, Lu Z, Romano R, et al. 2015a. Inclusion of an informant yields strong
associations between cognitive complaint and longitudinal cognitive outcomes in non-demented elders.
J. Alzheimers Dis. 43:121–32
Gifford KA, Liu D, Lu Z, Tripodis Y, Cantwell NG, et al. 2014. The source of cognitive complaints predicts
diagnostic conversion differentially among nondemented older adults. Alzheimers Dement. 10:319–27
Gifford KA, Liu D, Romano RR, Jones RN, Jefferson AL. 2015b. Development of a subjective cognitive
decline questionnaire using item response theory: a pilot study. Alzheimers Dement. Diagn. Assess. Dis.
Monit. 1:429–39
Goesling J, Clauw DJ, Hassett AL. 2013. Pain and depression: an integrative review of neurobiological and
psychological factors. Curr. Psychiatry Rep. 15:421
Hall J, Kellett S, Berrios RE, Bains MK, Scott S. 2016. Efficacy of cognitive behavioral therapy for generalized
anxiety disorder in older adults: systematic review, meta-analysis, and meta-regression. Am. J. Geriatr.
Psychiatry 24(11):1063–73
Harwood DG, Barker WW, Ownby RL, Mullan M, Duara R. 2004. No association between subjective
memory complaints and apolipoprotein E genotype in cognitively intact elderly. Int. J. Geriatr. Psychiatry
19:1131–39
Hertzog C, Pearman A. 2014. Memory complaints in adulthood and old age. In The SAGE Handbook of Applied
Memory, ed. TJ Perfect, DS Lindsay, pp. 423–43. London: SAGE

www.annualreviews.org • Subjective Cognitive Decline 391

 CP13CH15-Rabin ARI 13 April 2017 9:58

Hill NL, Mogle JM, Munoz E, Wion R, Colancecco EM. 2015. Assessment of subjective cognitive impairment
among older adults. J. Gerontol. Nurs. 41:28–35
Hohman TJ, Beason-Held LL, Lamar M, Resnick SM. 2011. Subjective cognitive complaints and longitudinal
changes in memory and brain function. Neuropsychology 25:125–30
Huckans M, Hutson L, Twamley E, Jak A, Kaye J, Storzbach D. 2013. Efficacy of cognitive rehabilitation
therapies for mild cognitive impairment (MCI) in older adults: working toward a theoretical model and
evidence-based interventions. Neuropsychol. Rev. 23:68–80
Jack CR, Wiste HJ, Vemuri P, Weigand SD, Senjem ML, et al. 2010. Brain beta-amyloid measures and
magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment
to Alzheimer’s disease. Brain 133:3336–48
Jackson J, Balota DA, Head D. 2011. Exploring the relationship between personality and regional brain volume
in healthy aging. Neurobiol. Aging 32:2162–71
Jackson JD, Rentz DM, Aghjayan S, Buckley RF, Meneide TF, et al. 2016. Subjective cognitive concerns are as-
sociated with objective memory performance in Caucasian but not African-American persons. Alzheimers
Annu. Rev. Clin. Psychol. 2017.13:369-396. Downloaded from www.annualreviews.org
Access provided by University of New England on 03/10/18. For personal use only.

Dement. 12(7 Suppl.):P1173

Jenkins A, Tales A, Tree J, Bayer A. 2015. Are we ready? The construct of subjective cognitive impairment
and its utilization in clinical practice: a preliminary UK-based service evaluation. J. Alzheimers Dis.
48:S25–31
Jessen F. 2014. Subjective and objective cognitive decline at the pre-dementia stage of Alzheimer’s disease.
Eur. Arch. Psychiatry Clin. Neurosci. 264(Suppl. 1):S3–7
Jessen F, Amariglio RE, van Boxtel M, Breteler M, Ceccaldi M, et al. 2014a. A conceptual framework for
research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimers Dement. 10:844–52
Jessen F, Feyen L, Freymann K, Tepest R, Maier W, et al. 2006. Volume reduction of the entorhinal cortex
in subjective memory impairment. Neurobiol. Aging 27:1751–56
Jessen F, Wiese B, Bachmann C, Eifflaender-Gorfer S, Haller F, et al. 2010. Prediction of dementia by
subjective memory impairment: effects of severity and temporal association with cognitive impairment.
Arch. Gen. Psychiatry 67:414–22
Jessen F, Wolfsgruber S, Wiese B, Bickel H, Mösch E, et al. 2014b. AD dementia risk in late MCI, in early
MCI, and in subjective memory impairment. Alzheimers Dement. 10:76–83
Jonker C, Geerlings MI, Schmand B. 2000. Are memory complaints predictive for dementia? A review of
clinical and population-based studies. Int. J. Geriatr. Psychiatry 15:983–91
Jorm AF, Christensen H, Henderson AS, Korten AE, Mackinnon AJ, Scott R. 1994. Complaints of cognitive
decline in the elderly: a comparison of reports by subjects and informants in a community survey. Psychol.
Med. 24:365–74
Joshi YB, Pratico D. 2013. Stress and HPA axis dysfunction in Alzheimer’s disease. In Studies on Alzheimer’s
Disease, ed. D Pratico, P Mecocci, pp. 159–65. New York: Springer
Kapogiannis D, Sutin A, Davatzikos C, Costa P Jr., Resnick S. 2013. The five factors of personality and
regional cortical variability in the Baltimore longitudinal study of aging. Hum. Brain Mapp. 34:2829–40
Kaup AR, Nettiksimmons J, LeBlanc ES, Yaffe K. 2015. Memory complaints and risk of cognitive impairment
after nearly 2 decades among older women. Neurology 85:1852–58
Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, et al. 2004. Imaging brain amyloid in Alzheimer’s
disease with Pittsburgh Compound-B. Ann. Neurol. 55:306–19
Koppara A, Frommann I, Polcher A, Parra MA, Maier W, et al. 2015a. Feature binding deficits in subjective
cognitive decline and in mild cognitive impairment. J. Alzheimers Dis. 48(Suppl. 1):S161–70
Koppara A, Wagner M, Lange C, Ernst A, Wiese B, et al. 2015b. Cognitive performance before and after the
onset of subjective cognitive decline in old age. Alzheimers Dement. 1:194–205
Krell-Roesch J, Woodruff BK, Acosta JI, Locke DE, Hentz JG, et al. 2015. APOE epsilon4 genotype and the
risk for subjective cognitive impairment in elderly persons. J. Neuropsychiatry Clin. Neurosci. 27:322–25
Kremen WS, Lachman ME, Pruessner JC, Sliwinski M, Wilson RS. 2012. Mechanisms of age-related cognitive
change and targets for intervention: social interactions and stress. J. Gerontol. A Biol. Sci. Med. Sci. 67:760–
65

392 Rabin · Smart · Amariglio

 CP13CH15-Rabin ARI 13 April 2017 9:58

Lautenschlager NT, Flicker L, Vasikaran S, Leedman P, Almeida OP. 2005. Subjective memory complaints
with and without objective memory impairment: relationship with risk factors for dementia. Am. J.
Geriatr. Psychiatry 13:731–34
Laws SM, Clarnette RM, Taddei K, Martins G, Paton A, et al. 2002. APOE-epsilon4 and APOE-491A
polymorphisms in individuals with subjective memory loss. Mol. Psychiatry 7:768–75
Lineweaver TT, Bondi MW, Galasko D, Salmon DP. 2014. Effect of knowledge of APOE genotype on
subjective and objective memory performance in healthy older adults. Am. J. Psychiatry 171:201–8
Low LF, Harrison F, Lackersteen SM. 2013. Does personality affect risk for dementia? A systematic review
and meta-analysis. Am. J. Geriatr. Psychiatry 21:713–28
Mackinnon A, Mulligan R. 1998. Combining cognitive testing and informant report to increase accuracy in
screening for dementia. Am. J. Psychiatry 155:1529–35
Makris UE, Abrams RC, Gurland B, Carrington Reid M. 2014. Management of persistent pain in the older
patient: a clinical review. JAMA 312:825–37
Marini S, Bagnoli S, Bessi V, Tedde A, Bracco L, et al. 2011. Implication of serotonin-transporter (5-HTT)
Annu. Rev. Clin. Psychol. 2017.13:369-396. Downloaded from www.annualreviews.org
Access provided by University of New England on 03/10/18. For personal use only.

gene polymorphism in subjective memory complaints and mild cognitive impairment (MCI). Arch. Geron-
tol. Geriatr. 52:e71–74
McConnell H. 2014. Laboratory testing in neuropsychology. In Clinical Neuropsychology: A Pocket Handbook
for Assessment, ed. MW Parsons, TA Hammeke, PJ Snyder, pp. 53–73. Washington, DC: Am. Psychol.
Assoc. 3rd ed.
Meiberth D, Scheef L, Wolfsgruber S, Boecker H, Block W, et al. 2015. Cortical thinning in individuals with
subjective memory impairment. J. Alzheimers Dis. 45:139–46
Mitrushina M, Boone KB, Razani J, D’Elia LF. 2005. Handbook of Normative Data for Neuropsychological
Assessment. New York: Oxford Univ. Press
Molinuevo JL, Rabin LA, Amariglio R, Buckley R, Dubois B, et al. 2017. Implementation of subjective
cognitive decline criteria in research studies. Alzheimers Dement. 13:296–311
Mosconi L, De Santi S, Brys M, Tsui WH, Pirraglia E, et al. 2008. Hypometabolism and altered cerebrospinal
fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints. Biol. Psychiatry
63:609–18
Mulligan BP, Smart CM, Ali JI. 2016. Relationship between subjective and objective performance indicators
in subjective cognitive decline. Psychol. Neurosci. 9:362–78
Nunes T, Fragata I, Ribeiro F, Palma T, Maroco J, et al. 2010. The outcome of elderly patients with cognitive
complaints but normal neuropsychological tests. J. Alzheimers Dis. 19:137–45
Parisi JM, Gross AL, Rebok GW, Saczynski JS, Crowe M, et al. 2011. Modeling change in memory perfor-
mance and memory perceptions: findings from the ACTIVE study. Psychol. Aging 26:518–24
Park J, Hughes AK. 2012. Nonpharmacological approaches to the management of chronic pain in community-
dwelling older adults: a review of empirical evidence. J. Am. Geriatr. Soc. 60:555–68
Peckham AD, McHugh RK, Otto MW. 2010. A meta-analysis of the magnitude of biased attention in depres-
sion. Depress. Anxiety 27:1135–42
Perrotin A, de Flores R, Lamberton F, Poisnel G, La Joie R, et al. 2015. Hippocampal subfield volumetry and
3D surface mapping in subjective cognitive decline. J. Alzheimers Dis. 48(Suppl. 1):S141–50
Perrotin A, Mormino EC, Madison CM, Hayenga AO, Jagust WJ. 2012. Subjective cognition and amyloid
deposition imaging: a Pittsburgh Compound B positron emission tomography study in normal elderly
individuals. Arch. Neurol. 69:223–29
Peter J, Scheef L, Abdulkadir A, Boecker H, Heneka M, et al. 2014. Gray matter atrophy pattern in elderly
with subjective memory impairment. Alzheimers Dement. 10:99–108
Pietrzak RH, Lim YY, Ames D, Harrington K, Restrepo C, et al. 2015a. Trajectories of memory decline in
preclinical Alzheimer’s disease: results from the Australian Imaging, Biomarkers and Lifestyle Flagship
Study of ageing. Neurobiol. Aging 36:1231–38
Pietrzak RH, Lim YY, Neumeister A, Ames D, Ellis KA, et al. 2015b. Amyloid-β, anxiety, and cognitive
decline in preclinical Alzheimer disease. JAMA Psychiatry 72:284–91
Popp J, Wolfsgruber S, Heuser I, Peters O, Hull M, et al. 2015. Cerebrospinal fluid cortisol and clinical
disease progression in MCI and dementia of Alzheimer’s type. Neurobiol. Aging 36:601–7

www.annualreviews.org • Subjective Cognitive Decline 393

 CP13CH15-Rabin ARI 13 April 2017 9:58

Puente AE, Puente AN. 2013. Assessment of neuropsychological functioning. In APA Handbook of Testing
and Assessment in Psychology, Vol. 2: Testing and Assessment in Clinical and Counseling Psychology, ed. KF
Geisinger, pp. 133–52. Washington, DC: Am. Psychol. Assoc.
Rabin LA, Chi SY, Wang C, Fogel J, Kann SJ, Aronov A. 2014. Prospective memory on a novel clinical task
in older adults with mild cognitive impairment and subjective cognitive decline. Neuropsychol. Rehabil.
24:863–93
Rabin LA, Saykin A, Brown M, Wishart H, Flashman L, et al. 2010. Complaints associated with current cognitive
functioning and progression to dementia: predictive value of patient and informant report items. Presented at
Midyear Meet. Int. Neuropsychol. Soc., Krakow, Poland
Rabin LA, Smart CM, Crane PK, Amariglio RE, Berman L, et al. 2015. Subjective cognitive decline in older
adults: an overview of self-report measures used across 19 international research studies. J. Alzheimers
Dis. 48(Suppl. 1):S63–86
Rabin LA, Wang C, Katz MJ, Derby CA, Buschke H, Lipton RB. 2012. Predicting Alzheimer’s disease:
neuropsychological tests, self-reports, and informant reports of cognitive difficulties. J. Am. Geriatr. Soc.
Annu. Rev. Clin. Psychol. 2017.13:369-396. Downloaded from www.annualreviews.org

60:1128–34
Access provided by University of New England on 03/10/18. For personal use only.

Rami L, Mollica MA, Garcia-Sanchez C, Molinuevo JL. 2014. The Subjective Cognitive Decline Question-
naire (SCD-Q): a validation study. J. Alzheimers Dis. 41:453–66
Rattanabannakit C, Risacher SL, Gao S, Lane K, Brown SA, et al. 2016. The Cognitive Change Index as
a measure of self and informant perception of cognitive decline: relation to neuropsychological tests.
J. Alzheimers Dis. 51:1145–55
Reid MC, Eccleston C, Pillemer K. 2015. Management of chronic pain in older adults. BMJ 350:1–10
Reisberg B. 1986. Dementia: a systematic approach to identifying reversible causes. Geriatrics 41:30–46
Reisberg B, Ferris SH, de Leon MJ, Crook T. 1982. The Global Deterioration Scale for assessment of primary
degenerative dementia. Am. J. Psychiatry 139:1136–39
Reisberg B, Gauthier S. 2008. Current evidence for subjective cognitive impairment (SCI) as the pre-mild
cognitive impairment (MCI) stage of subsequently manifest Alzheimer’s disease. Int. Psychogeriatr. 20:1–
16
Reisberg B, Prichep L, Mosconi L, John R, Glodzik-Sobanska L, et al. 2008. The pre-mild cognitive impair-
ment, subjective cognitive impairment stage of Alzheimer’s disease. Alzheimers Dement. 4:S98–108
Reisberg B, Shulman MB, Torossian C, Leng L, Zhu W. 2010. Outcome over seven years of healthy adults
with and without subjective cognitive impairment. Alzheimers Dement. 6:11–24
Rentz DM, Parra Rodriguez MA, Amariglio R, Stern Y, Sperling R, Ferris S. 2013. Promising developments
in neuropsychological approaches for the detection of preclinical Alzheimer’s disease: a selective review.
Alzheimers Res. Ther. 5:58
Risacher SL, Kim S, Nho K, Foroud T, Shen L, et al. 2015. APOE effect on Alzheimer’s disease biomarkers
in older adults with significant memory concern. Alzheimers Dement. 11:1417–29
Roberts B, Mroczek D. 2008. Personality trait change in adulthood. Curr. Dir. Psychol. Sci. 17:31–35
Roberts JL, Clare L, Woods RT. 2009. Subjective memory complaints and awareness of memory functioning
in mild cognitive impairment: a systematic review. Dement. Geriatr. Cogn. Disord. 28:95–109
Rodda J, Okello A, Edison P, Dannhauser T, Brooks DJ, Walker Z. 2010. (11)C-PIB PET in subjective
cognitive impairment. Eur. Psychiatry 25:123–25
Rodriguez-Gomez O, Abdelnour C, Jessen F, Valero S, Boada M. 2015. Influence of sampling and recruitment
methods in studies of subjective cognitive decline. J. Alzheimers Dis. 48(Suppl. 1):S99–107
Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, et al. 2010. Amyloid imaging results from the Australian
Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol. Aging 31:1275–83
Rueda AD, Lau KM, Saito N, Harvey D, Risacher SL, et al. 2015. Self-rated and informant-rated everyday
function in comparison to objective markers of Alzheimer’s disease. Alzheimers Dement. 11:1080–89
Sahathevan R, Brodtmann A, Donnan GA. 2011. Dementia, stroke, and vascular risk factors: a review. Int. J.
Stroke 7:61–73
Samieri C, Proust-Lima C, Glymour MM, Okereke OI, Amariglio RE, et al. 2014. Subjective cognitive
concerns, episodic memory, and the APOE epsilon4 allele. Alzheimers Dement. 10:752–59e1
Saykin AJ, Wishart HA, Rabin LA, Santulli RB, Flashman LA, et al. 2006. Older adults with cognitive com-
plaints show brain atrophy similar to that of amnestic MCI. Neurology 67:834–42

394 Rabin · Smart · Amariglio

 CP13CH15-Rabin ARI 13 April 2017 9:58

Scheef L, Spottke A, Daerr M, Joe A, Striepens N, et al. 2012. Glucose metabolism, gray matter structure,
and memory decline in subjective memory impairment. Neurology 79:1332–39
Schicktanz S, Schweda M, Ballenger JF, Fox PJ, Halpern J, et al. 2014. Before it is too late: professional
responsibilities in late-onset Alzheimer’s research and pre-symptomatic prediction. Front. Hum. Neurosci.
8:921. https://doi.org/10.3389/fnhum.2014.00921
Schmand B, Jonker C, Hooijer C, Lindeboom J. 1996. Subjective memory complaints may announce dementia.
Neurology 46:121–25
Schofield PW, Marder K, Dooneief G, Jacobs DM, Sano M, Stern Y. 1997. Association of subjective memory
complaints with subsequent cognitive decline in community-dwelling elderly individuals with baseline
cognitive impairment. Am. J. Psychiatry 154:609–15
Scott SB, Graham-Engeland JE, Engeland CG, Smyth JM, Almeida DM, et al. 2015. The Effects of Stress on
Cognitive Aging, Physiology and Emotion (ESCAPE) project. BMC Psychiatry 15:146
Sexton CE, McKay CE, Ebmeier KP. 2013. A systematic review and meta-analysis of magnetic resonance
imaging studies in late-life depression. Am. J. Geriatr. Psychiatry 21:184–95
Annu. Rev. Clin. Psychol. 2017.13:369-396. Downloaded from www.annualreviews.org
Access provided by University of New England on 03/10/18. For personal use only.

Sikkes SAM, Rabin LA, Crane PK. 2015. Harmonization of international subjective cognitive decline (SCD)
questionnaires: Which cognitive complaints relate to clinical outcomes? Alzheimers Dement. 11(Suppl.
7):307–8
Simon SS, Cordás TA, Bottino CMC. 2014. Cognitive behavioral therapies in older adults with depression
and cognitive deficits: a systematic review. Int. J. Geriatr. Psychiatry 30:223–33
Slavin MJ, Brodaty H, Kochan NA, Crawford JD, Trollor JN, et al. 2010. Prevalence and predictors of
“subjective cognitive complaints” in the Sydney Memory and Ageing Study. Am. J. Geriatr. Psychiatry
18:701–10
Smart CM, Karr JE, Areshenkoff CN, Rabin LA, Hudon CA, et al. 2017. Non-pharmacologic interven-
tions for older adults with subjective cognitive decline: systematic review, meta-analysis, and preliminary
recommendations. Neuropsychol. Rev. https://doi.org/10.1007/s11065-017-9342-8
Smart CM, Koudys J, Mulligan BP. 2015. Examining conscientiousness in older adults with subjective cognitive
decline: Are we really measuring personality? Alzheimers Dement. 11(Suppl. 7):583
Smart CM, Krawitz A. 2015. The impact of subjective cognitive decline on Iowa Gambling Task performance.
Neuropsychology 29:971–87
Smart CM, Segalowitz SJ, Mulligan BP, Koudys J, Gawryluk J. 2016. Mindfulness training for older adults with
subjective cognitive decline: results from a pilot randomized controlled trial. J. Alzheimers Dis. 52:757–74
Smart CM, Segalowitz SJ, Mulligan BP, MacDonald SW. 2014. Attention capacity and self-report of subjective
cognitive decline: a P300 ERP study. Biol. Psychol. 103:144–51
Snitz BE, Lopez OL, McDade E, Becker JT, Cohen AD, et al. 2015a. Amyloid-beta imaging in older adults
presenting to a memory clinic with subjective cognitive decline: a pilot study. J. Alzheimers Dis. 48(Suppl.
1):S151–59
Snitz BE, Small BJ, Wang T, Chang CC, Hughes TF, Ganguli M. 2015b. Do subjective memory complaints
lead or follow objective cognitive change? A five-year population study of temporal influence. J. Int.
Neuropsychol. Soc. 21:732–42
Snitz BE, Weissfeld LA, Cohen AD, Lopez OL, Nebes RD, et al. 2015c. Subjective cognitive complaints,
personality and brain amyloid-beta in cognitively normal older adults. Am. J. Geriatr. Psychiatry 23:985–93
Sohlberg MM, Mateer CA. 2001. Cognitive Rehabilitation: An Integrative Neuropsychological Approach. New
York: Guilford
Solhan M, Trull TJ, Jahng S, Wood P. 2009. Clinical assessment of affective instability: comparing EMA
indices, questionnaire reports, and retrospective recall. Psychol. Assess. 21:425–36
Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, et al. 2011. Toward defining the preclinical stages
of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association
workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7:280–92
Srivastava S, John OP, Gosling SD, Potter J. 2013. Development of personality in early and middle adulthood:
set like plaster or persistent change? J. Pers. Soc. Psychol. 84:1041–53
Steffens DC, Potter GG. 2008. Geriatric depression and cognitive impairment Psychol. Med. 38:163–75
Sternberg RJ, Kaufman JC. 1998. Human abilities. Annu. Rev. Psychol. 49:479–502

www.annualreviews.org • Subjective Cognitive Decline 395

 CP13CH15-Rabin ARI 13 April 2017 9:58

Stewart R, Godin O, Crivello F, Maillard P, Mazoyer B, et al. 2011. Longitudinal neuroimaging correlates of
subjective memory impairment: 4-year prospective community study. Br. J. Psychiatry 198:199–205
Stone AA, Shiffman S. 1994. Ecological momentary assessment in behavioral medicine. Ann. Behav. Med.
16:199–202
Striepens N, Scheef L, Wind A, Meiberth D, Popp J, et al. 2010. Volume loss of the medial temporal lobe
structures in subjective memory impairment. Dement. Geriatr. Cogn. Disord. 29:75–81
Striepens N, Scheef L, Wind A, Meiberth D, Popp J, et al. 2011. Interaction effects of subjective memory
impairment and ApoE4 genotype on episodic memory and hippocampal volume. Psychol. Med. 41:1997–
2006
Tan CC, Yu JT, Wang HF, Tan MS, Meng XF, et al. 2014. Efficacy and safety of donepezil, galantamine,
rivastigmine, and memantine for the treatment of Alzheimer’s disease: a systematic review and meta-
analysis. J. Alzheimers Dis. 41:615–31
Tandetnik C, Farrell MT, Cary MS, Cines S, Emrani S, et al. 2015. Ascertaining subjective cognitive decline:
a comparison of approaches and evidence for using an age-anchored reference group. J. Alzheimers Dis.
Annu. Rev. Clin. Psychol. 2017.13:369-396. Downloaded from www.annualreviews.org
Access provided by University of New England on 03/10/18. For personal use only.

48:S43–55
Tobiansky R, Blizard R, Livingston G, Mann A. 1995. The Gospel Oak Study stage IV: the clinical relevance
of subjective memory impairment in older people. Psychol. Med. 25:779–86
Troyer A. 2001. Improving memory knowledge, satisfaction, and functioning via an education and intervention
program for older adults. Aging Neuropsychol. Cogn. 8:256–68
Trull TJ, Ebner-Priemer U. 2013. Ambulatory assessment. Annu. Rev. Clin. Psychol. 9:151–76
Valech N, Mollica MA, Olives J, Tort A, Fortea J, et al. 2015. Informants’ perception of subjective cogni-
tive decline helps to discriminate preclinical Alzheimer’s disease from normal aging. J. Alzheimers Dis.
48(Suppl. 1):S87–98
van der Flier WM, van Buchem MA, Weverling-Rijnsburger AW, Mutsaers ER, Bollen EL, et al. 2004.
Memory complaints in patients with normal cognition are associated with smaller hippocampal volumes.
J. Neurol. 251:671–75
van Harten AC, Visser PJ, Pijnenburg YA, Teunissen CE, Blankenstein MA, et al. 2013. Cerebrospinal
fluid Aβ42 is the best predictor of clinical progression in patients with subjective complaints. Alzheimers
Dement. 9:481–87
van Heugten C, Gregório GW, Wade D. 2012. Evidence-based cognitive rehabilitation after acquired brain
injury: a systematic review of content of treatment. Neuropsychol. Rehabil. 22:653–73
van Oijen M, de Jong FJ, Hofman A, Koudstaal PJ, Breteler MM. 2007. Subjective memory complaints,
education, and risk of Alzheimer’s disease. Alzheimers Dement. 3:92–97
Visser PJ, Verhey F, Knol DL, Scheltens P, Wahlund LO, et al. 2009. Prevalence and prognostic value of
CSF markers of Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild
cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol. 8:619–27
Wang L, van Belle G, Crane PK, Kukull WA, Bowen JD, et al. 2004. Subjective memory deterioration and
future dementia in people aged 65 and older. J. Am. Geriatr. Soc. 52:2045–51
Wiegand MA, Troyer AK, Gojmerac C, Murphy KJ. 2013. Facilitating change in health-related behaviors
and intentions: a randomized controlled trial of a multidimensional memory program for older adults.
Aging Ment. Health 17:806–15
Wolfsgruber S, Kleineidam L, Wagner M, Mösch E, Bickel H, et al. 2016. Differential risk of incident AD
dementia in stable versus unstable patterns of subjective cognitive decline. J. Alzheimers Dis. 54(3):1135–46
Yesavage JA, Brink T, Rose T, Lum O, Huang V, et al. 1982. Development and validation of a geriatric
depression screening scale: a preliminary report. J. Psychiatr. Res. 17:37–49
Zwan MD, Villemagne VL, Dore V, Buckley R, Bourgeat P, et al. 2015. Subjective memory complaints in
APOEε4 carriers are associated with high amyloid-beta burden. J. Alzheimers Dis. 49:1115–22

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Annual Review of
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Contents Volume 13, 2017

Clinical Psychology Training: Accreditation and Beyond

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Personal Sensing: Understanding Mental Health Using Ubiquitous
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Brain Mechanisms of the Placebo Effect: An Affective Appraisal
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Schooling and Children’s Mental Health: Realigning Resources to
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Psychological Treatments for the World: Lessons from Low- and
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Controversies in Narcissism
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Irritability in Children and Adolescents
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Trait Impulsivity and the Externalizing Spectrum
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Subjective Cognitive Decline in Preclinical Alzheimer’s Disease
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Child Maltreatment and Risk for Psychopathology in Childhood
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