DEMENTIA

Organic mental disorders are caused by either a demonstrable cerebral disease, brain injury
or other insults leading to cerebral dysfunction.
Common symptoms of organic mental disorders
Following are the common symptoms seen in organic mental disorders:
A. Cognitive impairment: In organic mental disorders one or more of cognitive functions
are impaired. Frequently patient presents with disorientation (to time, place and person),
impaired attention and concentration, disturbances in memory (especially recent memory
resulting in anterograde amnesia), etc. As organic mental disorders commonly have
disturbances of cognition, they are also known as cognitive disorders.
B. Disturbances of consciousness:
 The consciousness has different levels ranging from alertness to coma. Usually the
term “alertness” is used when one is aware of the internal and external stimuli and can
respond to them. the patients with organic mental disorders usually have disturbances
of consciousness which can be of varying severity.
 The term “somnolence or lethargy” is used when patient tends to drift off to sleep
when not actively stimulated.
 The next level is “obtundation” in which patient is difficult to arouse and when
aroused appears confused.
 The next level is “stupor or semi coma” in which patient is mute and immobile. When
stimulated persistently and vigorously he may groan or mumble.
 Finally, in “coma,” patient is totally unarousable and remain with their eyes closed.
 Various other terms such as “confusional state”, “clouding of consciousness” and
“altered sen sorium” are used to describe the disturbances of consciousness in
delirium.
C. Hallucinations:
 these patients most commonly have visual hallucinations
although auditory, olfactory, gustatory and tactile hallucinations can also be present.
D. Delusions:
 The delusions are usually transient. Complex delusions are rare

The organic mental disorders are classified in the following groups:

A. Delirium
B. Dementia
C. Amnestic disorder
 DIMENTIA
 Dementia is defined as a progressive impairment of cognitive functions in the absence
of any disturbances of consciousness. The Dementia is defined as a progressive
impairment of cognitive functions in the absence of any disturbances of
consciousness.
 The prevalence of dementia increases with age, with prevalence of around 5% in the
population older than 65 years and prevalence of20–40% in the population older than
85 years.
 Prevalence of dementia increases with age, with prevalence of around 5% in the
population older than 65 years and prevalence of 20–40% in the population older than
85 years.
 The underlying cause of dementia can be permanent or reversible.
 Of all patients with dementia, 50 to 60 percent have the most common type of
dementia, dementia of the Alzheimer's type (Alzheimer's disease).
 Alzheimer's disease is a degenerative brain disease and the most common form of
dementia. Dementia is not a specific disease. It's an overall term that describes a
group of symptoms.

Clinical features
I. Cognitive impairment
II. Functional impairment
III. Neuropsychiatric symptoms

I. Cognitive impairment
Dementia is acquired cognitive decline in multiple areas resulting in functional impairment;
AD(Alzheimer’s disease) is one cause of dementia and the core clinical symptom of AD is
cognitive loss. Cognitive decline is manifested as amnesia, aphasia, agnosia, and apraxia (the
4As).
(a) Amnesia
 Memory loss in AD is early and inevitable. Characteristically, recent memories are
lost before remote memories. However, there is considerable individual variation,
with some patients able to recall specific and detailed events of childhood and others
apparently having few distant memories accessible.
 With disease progression, even remote and emotionally charged memories are lost.
 The discrepancy between recent and remote memory loss suggests that the primary
problem is of acquisition or retrieval of memory rather than a destruction of memory.
  Although as the disease progresses it is likely that all memory processes are impaired.
Retrieval of remote memory is assumed to be preserved for longer because of
rehearsal over life.
(b) Aphasia
 Language problems are found in many patients at presentation, although the language
deficits in AD are not as severe as those of the fronto-temporal degenerations and may
only be apparent on detailed examination.
 Word-finding difficulties (nominal dysphasia) are the earliest phenomena observed
and are accompanied by circumlocutions and other responses, for example repetitions
and alternative wordings.
 As the disorder progresses, syntax is affected and speech becomes increasingly
paraphasic. Although harder to assess, receptive aphasia, or comprehension of speech,
is almost certainly affected.
 In the final stages of the disorder, speech is grossly deteriorated with decreased fl
uency, preservation, echolalia, and abnormal non-speech utterances.
(c) Agnosia
 Patients with AD may have difficulty in recognizing as well as naming objects. This
can have implications for care needs and safety if the unrecognized objects are
important for daily functioning.
 One particular agnosia encountered in AD is the loss of recognition of one’s own face
(autoprosopagnosia). This distressing symptom is the underlying cause of perhaps the
only clinical sign in AD—the mirror sign. Patients exhibiting this will interpret the
face in the mirror as some other individual and respond by talking to it or by apparent
fearfulness.
 Auto prosopagnosia can present as an apparent hallucinatory experience, until it is
realized that the ‘hallucination’ is fixed in both content and space, occurring only
when self-reflection can be seen.
(d) Apraxia
 Apraxia is inability to perform learned motor functions. For example, patient may
start having difficulties in functions like buttoning the shirt or combing the hair
 Strategies to avoid such tasks are often acquired as the disease progresses, and it is
only when these fail that the dyspraxia becomes apparent.
Other cognitive impairment
 There appear to be no cognitive functions that are truly preserved in AD. Visuospatial
diffi culties commonly occur in the middle stages of the disorder and may result in
topographical disorientation,
 wandering, and becoming lost. Difficulties with calculation, attention, and cognitive
planning all occur.
II Functional impairment
  Although the cognitive decline in AD is the core symptom, it is the functional
deterioration that has the most impact on the person themselves and it is the functional
loss that necessitates most of the care needs of patients with AD, including nursing-
home residency.
 Increasingly, abilities to function in ordinary life (activities of daily living (ADLs))
are lost, starting with the most subtle and easily avoided and progressing to the most
basic and essential. In general, functional abilities decline alongside cognitive
abilities.
 Functional abilities are related to gender; for example, cooking abilities are rehearsed
more frequently in women, and home-improvement skills in men.
 This is exploited in the Functional Assessment Staging (FAST) Scale; in the original
form, this is a seven-point scale of functional impairment, with stage 1 as no
impairment and stage 7 as severe AD.
 ADLs are divided into those that relate to self-care and those that concern
instrumental activities. Instrumental ADLs, those related to the use of objects or the
outside world, are lost first and can be subtle.A change in the ability to use the
telephone properly or to handle finances accurately may not be apparent.
 Self-care ADLs include dressing and personal hygiene and are also lost gradually; for
example, untidiness in clothing progresses to diffculties in dressing.Personal hygiene
becomes poor as dentures are not cleaned and baths taken less often, before finally
assistance is required with all self-care tasks.
III Neuropsychiatric symptoms
(a) Mood
The depression in elderly patients may mimic symptoms of dementia and hence is
known as pseudodementia . A depressed patient may get a low score on MMSE, as
depressed individual lacks motivation to solve the questions. Hence low score on
MMSE should be carefully interpreted, if depression is suspected.
 The relationship between AD and depression is complex.
 depression occurs as part of dementia, depression can be confused with dementia
since cognitive impairments are found in depression.
 The term pseudodementia is used to describe the condition in which depression causes
cognitive deficits that masquerade as dementia. Patients will often present with
difficulties in memory and concentration and deny depressive symptoms. Causes of
pseudodementia include the following: Increased stress and depression alter the
hypothalamic-pituitary axis causing cognitive impairment.
  A major depressive episode is found in approximately 10 per cent of patients, minor
depressive episode in 25 per cent, some features of depression in 50 per cent, and an
assessment of depression by a carer in up to 85 per cent.
 It is commonly believed that depression is more common in the early than in the later
stages of AD, although this may reflect the difficulties of assessing depression in the
more severely affected and least communicative patients.
 severely affected patients in nursing homes may be particularly prone to depression.
 Elation, disinhibition, and hypomania all occur in AD but are relatively infrequent,
elevated mood being found in only 3.5 per cent of patients by Burns et al.
 The underlying cause of mood change in AD is not known. However, loss of
serotonergic and noradrenergic markers accompanies cholinergic loss; some studies
have found a greater loss of these markers at post-mortem in AD patients with
depression than in non-depressed patients.
(b) Psychosis
 Psychotic symptoms occur in many patients, although, as with depression, there is an
inherent difficulty in determining the presence of delusions or hallucinatory
experiences in the moderately to severely demented.
 In community-based surveys, between 20 and 70 per cent are reported to suffer from
some form of psychotic symptom with delusions being more common than
hallucinations.( Delusions are frequently paranoid and the most common delusion is
one of theft.
  Hallucinations are only somewhat less frequent than delusions the median of one
series of studies being 28 per cent. Visual hallucinations are reported more commonly
than auditory ones, and other modalities are rare.
 Most studies of the non-cognitive symptomatology of AD precede the wide
recognition and accepted criteria of dementia with Lewy bodies, one of the cardinal
symptoms of which is visual hallucinations.
 persecutory ideas or intrusive illusionary experiences, are common in AD as are
misidentifi cation syndromes. Capgras’ syndrome may occur, but frequently the
symptom is less fully evolved with the patient mistaking one person for another.
 Failure to recognize one’s own face may be due to visuospatial difficulties or to a true
misidentifi cation syndrome—distinguishing between the two is difficult.
 Various factors have been associated with psychosis in AD,An association with
polymorphic variation in serotonin receptors has been reported.
 The relationship between psychosis and dementia severity is not as clear cut as that
between functional ability and dementia severity.
 Psychosis can occur at any stage of the disease process, although most studies find the
maximal rate of psychosis in those with at least moderate dementia.
 underlying psychosis accounts for much of the behavioural disturbance and
aggression encountered in AD.
(c) Personality
 Changes in personality are an almost inevitable concomitant of AD.
 may occur, often with an exaggeration of less favourable traits.
 Family members have described the loss of personality as a ‘living bereavement’—
the body remains, but the person once known has gone.
 Personality change is most frequently one of loss of awareness and normal
 responsiveness to the environment.
 Individuals may become more anxious or fearful, there is a fl attening of affect, and a
withdrawal from challenging situations.
 Catastrophic reactions are short-lived emotional reactions that occur when the patient
is confronted, and cannot avoid, such a challenging situation.
 Less commonly, personality changes may be of disinhibition with inappropriate
sexual behaviours or inappropriate affect.
 Aggressiveness is, as noted above, often accompanied by psychosis, but it may be part
of a more general personality change.
(d) Other behavioural manifestations
 Behavioural complications in AD have become a target of therapy.
 Behaviours exhibited in AD include wandering, changes in eating habit, altered sleep
or circadian rhythms, and incontinence.
 These behaviours are closely linked to disease severity and occur to some extent in
the majority of patients with AD.
 Wandering may be a manifestation of topographical confusion, a need for the toilet, or
it may refl ect hunger, boredom, or anxiety. Sleep is frequently disturbed, with many
 patients exhibiting altered sleep–wake cycles and others experiencing increased
confusion towards evening (‘sundowning’).
 A central defect in the regulation of circadian rhythms underlying these phenomena is
postulated. Excessive or inappropriate vocalizations (grunting and screaming) occur
in the late stages.
TYPES OF DIMENTIA

ICD-10 includes four dementia categories: (1) dementia in Alzheimer's disease; (2)
vascular dementia; (3) dementia in diseases classified elsewhere in the ICD (e.g.,
dementia in Pick's disease, Huntington's disease, Parkinson's disease,
Creutzfeldt-Jakob disease); and (4) unspecified dementia.

1.Alzheimer’s disease
 Alois Alzheimer, a German psychiatrist and neuropathologist, described the salient
features of what is now known as Alzheimer’s disease in 1906.
 Alzheimer’s disease is the most common cause of dementia, accounting for 50–60 per
cent of cases worldwide.
Pathology
  Post-mortem (and more recently neuroimaging) investigations have shown that a
brain affected by Alzheimer’s is significantly smaller than age-matched controls, with
widened sulci and enlarged ventricles. There is cell loss, shrinkage of the dendritic
tree, proliferation of astrocytes, and increased gliosis. There are two key histological
findings.
 Amyloid plaques are areas of dense, insoluble beta-amyloid peptide surrounded by
abnormal neuritis filled with highly phosphorylated tau protein.
 Neurofibrillary tangles are made up of helical filaments of the microtubule-
associated protein, tau, in a highly phosphorylated state. These are found throughout
the
cortical and subcortical grey matter (Figure 26.1).

 Beta-amyloid is derived from a larger protein, APP, which is encoded by the APP gene
on chromosome 21. Mutations in this gene have been found which produce an early-
onset autosomal dominant form of Alzheimer’s, although this is exceptionally rare.
Mutations in the presenilin genes, which encode proteins involved in the cleavage of
APP to beta-amyloid, also cause an autosomal dominant form of the disease. The
exact method by
 The plaques and tangles occur initially in the hippocampi, and then spread more
widely. The occipital lobe and cerebellum tend to remain relatively unscathed.
Prevalence
  The prevalence in developed countries of moderate and severe Alzheimer’s disease is
about 5 per cent of individuals aged 65 years and over, and 40 per cent of those aged
over 85 years.
 Therefore, as life expectancy increases in developing countries so the number of
patients with Alzheimer’s disease increases. About 80 per cent of these demented
people live in the community rather than institutions.
 The disease is more common in men.
Aetiology
The cause of Alzheimer’s disease is unknown.
Some of the known risk factors are
 Age
 Family history
 APP, presenilin, or apoE4 gene mutation carrier
 Previous head injury
 Down’s syndrome
 Hypothyroidism
 Parkinson’s disease
 Cardiovascular disease (including hypertension)
 Low level of education, lower IQ
 Genetic factors play a role, especially in those with early onset of the disease.
A family history of Alzheimer’s is the single most important risk factor; first-degree relatives
of those with late-onset Alzheimer’s disease have a risk of developing the disorder that is
three times that of the general population.
Course
 There is a progressive decline, the rate of which is not necessarily steady. Incidental
physical illness may cause a superimposed delirium resulting in a sudden
deterioration in cognitive function from which the patient may not recover fully.
Death occurs usually within 5–8 years of the first signs of the disease, and is most
frequently from bronchopneumonia.

2. Vascular dementia
Vascular dementia (also known as multi-infarct dementia) is the second most common cause
of dementia, accounting for 15–20 per cent of cases. It is a clinical syn drome caused by a
variety of different cerebro vascular pathologies, including but not confined to infarctions.
Pathology
Vascular dementia is associated with ischaemic and nonischaemic changes in the brain. Both
large and small blood vessels may be involved. Neuroimaging has identified that in patients
with vascular dementia the following typically occur:
● multiple infarctions and ischaemic lesions in the white matter;
 ● atrophy of old infarcted areas;
● infarcts tend to be bilateral;
● lesions involve the full thickness of the white matter;
● changes in blood flow in unaffected regions;
● the entire brain is smaller and the ventricles expanded.
Clinical features
 Vascular dementia usually presents in the late sixties or early seventies, with a more
sudden onset than Alzheimer’s disease. Patients may present after a stroke, or due to a
sudden unexplained decline in function.
 Unlike Alzheimer’s, emotional and personality changes tend to occur early, before
memory loss becomes apparent. The symptoms are characteristically fluctuating, and
episodes of confusion are common, especially at night.
 Depression is a prominent feature. Fits, transient ischaemic attacks, or other signs of
cerebral ischaemia may occur.
 On examination there may be focal neurology, often upper motor neuron deficits, and
signs of cardiovascular disease elsewhere.
Diagnosis
The diagnosis from Alzheimer’s disease is difficult to make with certainty unless there is a
clear history of stroke or neurological localizing signs .
Suggestive features are patchy defects of cognitive function, stepwise progression of the
condition, and the presence of hypertension and of arteriosclerosis in peripheral or retinal
vessels.
Prevalence
The prevalence of vascular dementia is 1–4 per cent of individuals aged 65 and over,
depending mainly upon geographical location. Incidence is 6–12 per 1000 per year over 70
years. It is more common in men than women.
Aetiology
Risk factors include:
● personal history of cardiovascular disease, including hypertension and high
cholesterol;
● smoking;
● family history of cardiovascular or cerebrovascular disease;
● atrial fibrillation;
● diabetes mellitus;
● coagulopathies;
 ● polycythaemia;
● sickle-cell anaemia;
● carotid disease.
Prognosis
From the time of diagnosis the lifespan averages 4–5 years, although the variations are wide.
About half the patients die from ischaemic heart disease, while others die from cerebral
infarction or renal complications
3. Lewy body disease
Frederick Lewy was a German neuropathologist who worked with Alzheimer, and in 1912
described the spherical neuronal inclusion bodies found in some patients with dementia.
These ‘Lewy bodies’ are characteristic of
Lewy body disease, which has three main clinical manifestations:
1 Parkinson’s disease;
2 dementia with Lewy bodies
3 autonomic failure associated with degeneration of sympathetic neurons in the spinal cord.
There is a cross-over between the three syndromes, as many patients with Parkinson’s
develop both dementia and autonomic dysfunction in their latter years.
Pathology
 There is usually a mixture of Lewy bodies and Alzheimertype amyloid plaques and
tangles. Lewy bodies are dense, intracytoplasmic inclusions made of phosphorylated
neurofilament proteins, associated with ubiquitin and alpha-synuclein.
 These are primarily found in the basal ganglia, and later spread into the cortex.
Neuronal loss is prominent, and there is a slight reduction in total brain volume. The
significance of the Alzheimer’s-like pathology is unknown.
Clinical features
● Dementia—relative sparing of memory, with fluctuatingcognitive ability and level
of consciousness is typical.
● Parkinsonism—postural instability and shuffling gait; only 20 per cent have a
tremor.
● Visual hallucinations.
● Falls.
● Depression.
● Sleep disorders—daytime somnolence.
Prevalence
Lewy body dementia accounts for 10–15 per cent of dementia cases. The prevalence is 0.7
per cent in over 65s, rising to 5.0 per cent in over 85s. It is more common in men than
women.
Aetiology
The cause of Lewy body dementia is unknown, but once again family history is a key risk
factor, and rare familial types have been found. No environmental risk factors have been
identified.
Course and prognosis
 Life expectancy for Lewy body dementia is 4–10 years, with the rate of cognitive
decline similar to that in Alzheimer’s. Frequently, the early stages are only recognized
in retrospect, but function can be much more impaired than in other dementias due to
pronounced parkinsonism affecting movement.
 Perceptual and behavioural disturbance can be severe in the later stages of the illness,
with antipsychotic medications often needed. A high proportion of these patients will
enter residential care by this stage.
Treatment
 The principles of treatment remain as previously outlined, but there are a couple of
specific points relating to Lewy body dementia. Parkinsonism should be treated with
l-DOPA and other antiparkinsonian medications.
 Anticholinergics should be avoided as there is evidence that they can increase
confusion and visual hallucinations in these patients. If needed, atypical
antipsychotics should be used before typical antipsychotics, because Lewy body
dementia carries a higher risk of neuroleptic malignant syndrome than other
condition.
4. FRONTOTEMPORAL DIMENTIA
5. HIV-associated dementia
Clinical features
 The onset of HIV-associated dementia is usually insidious.
  Early cognitive symptoms include forgetfulness, loss of concentration, mental
slowing, and reduced performance on sequential mental activities of some complexity
(the subject misses appointments, or needs lists to recall ordinary duties.
 Early behavioural symptoms include apathy, reduced spontaneity and emotional
responsivity, and social withdrawal (the subject becomes indifferent to his or her
personal and professional responsibilities; his or her work production decreases, as
well as the frequency of social interactions; the subject complains of early
fatiguability, malaise, and loss of sexual drive).
 Depression, irritability or emotional lability, agitation, and psychotic symptoms may
also occur.
 Early motor symptoms include loss of balance and coordination, clumsiness, and leg
weakness; the subject is less precise in normal hand activities, such as writing and
eating, drops things more often than usual, trips and falls more frequently, and
perceives the need to exercise more care in walking.
 Routine mental status tests, in this early stage, may be normal or show only slowing
in verbal or motor responses and/or difficulty in recalling a series of objects after 5
min or more. Neurological examination may show tremor (best seen when the patient
sustains a
 posture, such as holding the arms and fingers outstretched), hyperrefl exia
(particularly of the lower extremities), ataxia (usually seen only on rapid turns or
tandem gait), slowing of rapid alternating movements (of the fingers, wrists, or feet),
frontal release signs (snout refl ex, palmar grasp), dysarthria.
 In the late stages of the disease, there is usually a global deterioration of cognitive
functions and a severe psychomotor retardation.
 Speech is slow and monotonous, with word-fi nding diffi culties and possible
progression to mutism. Patients become unable to walk, due to paraparesis, and
usually lie in bed indifferent to their illness and their surroundings. Bladder and bowel
incontinence are common.
 Myoclonus and seizures may occur.
 The level of consciousness is usually preserved, except for occasional
hypersomnolence.
Classification
The WHO criteria for HIV-associated dementia(2) are as follows:
1. The research criteria for dementia of the ICD-10 are met, with some modifications:
(a) decline in memory may not be severe enough to impair activities of daily living;
(b) decline in motor function may be present, and is verified by clinical examination
and, when possible, formal neuropsychological testing;
(c) the minimum requested duration of symptoms is 1 month;
(d) aphasia, agnosia, and apraxia are unusual.
2. Laboratory evidence for systemic HIV infection is present.
3. No evidence of another aetiology from history, physical examination, or laboratory tests
should be present (specifically, cerebrospinal fluid analysis and either computed tomography
(CT) or magnetic resonance imaging (MRI) should be done to exclude active central nervous
system opportunistic processes).
possible presence of a depressive ‘pseudodementia’ also should be considered

Brain imaging
 CT or MRI scans can show ventricular enlargement with cortical atrophy,
 T2-weighted MRI scans can show hyperintensities.
 With functional brain imaging, patients with AIDS dementia complex have been
found to have hypermetabolism of the basal ganglia and limbic regions.
 In cortical regions, adult patients with AIDS dementia complex have been reported to
have increased metabolism in frontal, temporal, and parietal cortex,
 whereas children with HIV have been reported to have diffuse hypometabolism in
right temporo-occipital regions
Epidemiology
 There has been a decrease in the incidence of HIV-associated dementia after the
introduction of highly active antiretroviraltherapy (HAART):
 However, the incidence seems to have increased again in 2003.(7) A postmortem
neuropathologic study reported that, while severe HIV encephalopathy was not
detected anymore in the HAART era, the prevalence of mild and moderate
encephalopathy increased,probably reflecting the longer survival time after initial
HIV infection.
 Pathogenesis
 HIV crosses the blood-brain barrier by a Trojan-horse-type mechanism, using the
macrophages it infects. Once in the brain, it infects glial cells. Infected and activated
macrophages and microglia release neurotoxins which lead to neuronal damage and
apoptosis. It is possible that direct effects of viral proteins on neurones also contribute
to neurodegeneration.
 Post-mortem studies have revealed the presence of HIV in frontal lobes, subcortical
white matter and the basal ganglia.
Course and prognosis
 In the pre-HAART era, HIV-associated dementia often progressed rapidly to severe
deterioration and death, especially in patients with advanced systemic disease. Today,
many patients present an attenuated form which is slowly progressive or static.
 The mean survival, which was 5 months in 1993–1995, increased to 38.5 monthsin
1996–2000.
 Prominent psychomotor slowing, a history of intravenous drug use and low CD4 T-
lymphocyte count seem to predict a more rapid progression.
Available treatments
  Antiretrovirals are not always successful in crossing the blood brain barrier, have been
able to reduce the incidence and modify the course of HIV-associated dementia.
 There is evidence that they can improve specific aspects of cognitive functioning,
such as psychomotor speed performance, in people with HIV-associated dementia.
 The optimal HAART regimen for the treatment of HIV-associated dementia has not
been established.
 Neuroprotective drugs whose beneficial effect on cognitive performance in patients
with HIV infection has been preliminarily documented include the monoamine
oxidase inhibitor deprenyl
 Other investigational drugs include memantine and nitroglycerin, nimodipine,
pentoxifylline and lexipafant.
 The psychostimulant methylphenidate has been found to be useful in treating apathy
and cognitive slowing in patients with HIV associated dementia, with relatively mild
side effects.
 AIDS patients with depressed mood have been found to respond to tricyclic
antidepressants and selective serotonin reuptake inhibitors (SSRIs) as well as HIV-
seronegative subjects. There is a preliminary evidence that SSRIs (or at least some of
them) are better tolerated than tricyclic antidepressants, except in patients with
diarrhoea.
Management
 Patients with HIV-associated dementia often have additional disease processes which
may aggravate the cognitive impairment, including secondary infections and
metabolic disturbances. These conditions should be adequately diagnosed and
managed.
 An appropriate HAART regimen should be implemented and constantly monitored
(taking into account that cognitive dysfunction may have a negative impact on
adherence to treatment).
 If psychotic symptoms, behavioural dyscontrol, or mood disturbances are present, the
same strategies which are used for other people with these problems should be
implemented, taking into account that HIV-infected patients have an increased
sensitivity to the side effects of antipsychotics and antidepressants,
 Psychosocial interventions in HIV-associated dementia should include maintenance of
a structured daily schedule, titration of external stimuli, restriction to familiar
environments, frequent orienting interactions with signifi cant others, and monitoring
ofpersonal and fi nancial affairs.
 Psychoeducational intervention with families and significant others is also essential.

6. The nature of dementia in Parkinson’s disease

 Parkinson’s disease has been regarded as a neurological condition mainly affecting
motor function and arising from specific lesions in the brain stem.
 The recognition of dementia in Parkinson’s disease is of importance in management
but the possibility that motor and cognitive functions may be located in the same
region of the brain is of theoretical importance
  There have been numerous reports of the impairment of specifi c cognitive functions
in patients with Parkinson’s disease.
 The impairments identified included deficits in memory, language, visuospatial
functioning, abstract reasoning, slowness in intellectual tasks, and difficulty in
shifting from task to task. These deficits are widespread among patients with
Parkinson’s disease and can occur at an early stage of the disorder.
 A proportion of patients with Parkinson’s disease show impairment of a range of
cognitive functions akin to the global impairment seen in Alzheimer’s disease.
However, the pattern of impairment is frequently less severe than in
Alzheimer’sdisease where the pathological changes in the brain are known to be
widespread.
 Cummings suggested that cognitive impairment in Parkinson’s disease takes three
forms:
o one which is relatively mild and meets the criteria for subcortical dementia,
o a more severe form showing wider impairment of cognitive function but
neuropathologically distinct from Alzheimer disease
o and a severe form which shows neuropathological changes in both the
subcortical region of the brain, and in the cortex, the latter of Alzheimer type.
 More recently the debate has shifted to whether dementia in Parkinson’s disease,
dementia with Lewy bodies and Alzheimer’s disease should be viewed as a spectrum,
or as separate conditions with varying degrees of clinical and pathological overlap.

Prion disease
 Prion diseases are rare, fatal neurodegenerative disorders caused by misfolded prion
proteins (PrP) in the brain. This can lead to memory loss, behavior changes, and
movement problems.
 The unusual type of self-replicating microbe can initiate prion diseas. In prion disease,
the normal cellular prion protein (PrPc) gets misfolded and becomes pathogenic and
propagates further in the neighboring cells and tissues and can infect other organisms.
 Patients presented at a mean of 62 years with a dementia with prominent
neuropsychiatric manifestationsand progressive motor decline (ataxia and/or
parkinsonism)
 Approximately 1.5 million per year mortality rate has been reported due to the most
frequent Sporadic CJD (sCJD) .
 Globally, only 5–15% cases of genetic prion diseases have been reported which occur
due to the mutation in prion protein gene (PRNP) located on human chromosome 20.
The human prion diseases, also known as the subacute spongiform encephalopathies, have
been traditionally classified into
I. Creutzfeldt–Jakob disease (CJD)
II. Gerstmann–Sträussler syndrome (GSS)
III. Kuru
IV. Fatal familial insomnia (FFI)
Although rare, affecting about 1–2 per million worldwide per annum, remarkable attention
has been recently focused on these diseases
Biology
 Prions are small infectious pathogens containing protein but apparently lacking
nucleic acid
 The “protein only”hypothesis proposes that the pathological prion protein(PrPSC) is a
conformational isoform of a normal host protein(PrPC), which is found
predominantly on the outer surface of neurons, attached by a glycosylphosphatidyl-
inositol (GPI)anchor.
 Prions can be transmitted between members of different species. This phenomenon is
known as the violation of the species barrier
 The determining factor seems to bethe degree of similarity between the two species of
prions.This fact became cause of a great deal of anxiety caused bythe outbreak of
epidemic bovine spongiform encephalopathy (BSE, or mad cow disease).

1. Kuru
 Kuru reached epidemic proportions amongst a defi ned population living in the
Eastern Highlands of Papua New Guinea. The earliest cases are thought to date back
to the early part of the century.
 Kuru affected the people of the Fore linguistic group and their neighbours with whom
they intermarried. Kuru predominantly affected women and children (of both sexes),
with only 2 per cent of cases in adult males and was the commonest cause of death
amongst women in affected villages.
 It was the practice in these communities to engage in consumption of dead relatives as
a mark of respect and mourning. Women and children predominantly ate the brain and
internal organs, which is thought to explain the differential age and sex incidence.
 Preparation of the cadaver for consumption was performed by the women and
children such that other routes of exposure may also have been relevant.
 The disease has gradually declined in incidence although a small number of cases
have been documented in recent years with incubation periods which may exceed 50
years.
 Kuru affects both sexes and onset of disease has ranged from age 5 to over 60. The
mean clinical duration of illness is 12 months with a range of 3 months to 3 years; the
course tends to be shorter in children.
 The central clinical feature is progressive cerebellar ataxia. In sharp contrast to CJD,
dementia is usually absent, even in the latter stages, although in the terminal stages
many patients have
 their faculties obtunded. The occasional case in which gross dementia occurs is in
marked contrast to the clinical norm.
 A prodrome and three clinical stages are recognized:
(a) Prodromal stage
Kuru typically begins with prodromal symptoms consisting of headache, aching of limbs, and
joint pains, which can last for several months.
(b) Ambulatory stage
 Kuru was frequently self-diagnosed by patients at the earliest onset of unsteadiness in
standing or walking, or of dysarthria or diplopia. At this stage there may be no
objective signs of disease. Gait ataxia however worsens and patients develop a broad-
based gait, truncal
 instability, and titubation(While standing still, the patient's body may swagger back
and forth and from side to side, known as titubation. Patients will not be able to walk
from heel to toe or in a straight line.).
 A coarse postural tremor is usually present and accentuated by movement; patients
characteristically hold their hands together in the midline to suppress this.
 Standing with feet together reveals clawing of toes to maintain posture. This marked
clawing response is regarded as pathognomonic of kuru.
 Patients often become withdrawn at this stage and occasionally develop a severe
reactive depression. Prodromal symptoms tend to disappear. Astasia and gait ataxia
worsen and the patient requires a stick for walking.
 As ataxia progresses the patient passes from the fi rst (ambulatory) stage to the second
(sedentary) stage. The mean clinical duration of the fi rst stage is around 8 months and
correlates closely with total duration.
(c) Sedentary stage
 At this stage patients are able to sit unsupported but cannot walk.
 Attempted walking with support leads to a high steppage, wide based gait with reeling
instability, and flinging arm movements(intermittent, sudden, violent, involuntary,
flinging, or ballistic high amplitude movements) in an attempt to maintain posture.
 Hyperreflexia(Hyperreflexia is the presence of hyperactive stretch reflexes of the
muscles.) is seen although plantar responses(The plantar reflex is a reflex elicited
when the sole of the foot is stimulated with a blunt instrument. The reflex can take
one of two forms.) usually remain flexor (a muscle that allows you to bend part of
your body) with intact abdominal reflexes.
 Clonus is characteristically short-lived(If muscles twitch or jerk repeatedly, this is
known as 'clonus', for example when a foot taps repetitively on the floor)
 There is no paralysis, although muscle power is reduced. Obesity is common at this
stage but may be present in early disease associated with bulimia.
 Characteristically, there is emotional lability and bizarre uncontrollable laughter,
which has led to the disease being referred to as ‘laughing death’. There is no sensory
impairment.
 In sharp contrast to CJD, myoclonic jerking is rarely seen. EEG is usually normal or
may show non-specific changes.
 This stage lasts around 2–3 months. When truncal ataxia reaches the point where the
patient is unable to sit unsupported, the third or tertiary stage is reached.
(d) Tertiary stage
  Hypotonia and hyporeflexia develop and the terminal state is marked by flaccid
muscle weakness. Plantar responses remain flexor and abdominal reflexes intact.
 Progressive dysphagia(worsening difficulty in swallowing) occurs and patients
become incontinent(lacking self restrained)of urine and faeces.
 Inanition(lack of nourishment) and emaciation(thin and weak) develop. Transient
conjugate eye signs and dementia may occur.
 Primitive reflexes develop in occasional cases.
 Brainstem involvement and both bulbar and pseudobulbar signs occur.
 Respiratory failure and bronchopneumonia eventually lead to death.
 The tertiary stage lasts 1–2 months

Kuru is a disease that was once epidemic among a specific population in Papua New Guinea. It
primarily affected the Fore linguistic group and neighboring communities who practiced cannibalism as
a sign of respect and mourning. Kuru predominantly impacted women and children who consumed the
brains and internal organs of the deceased. Although the disease has declined, cases with incubation
periods exceeding 50 years have been documented.
The main clinical feature of Kuru is progressive cerebellar ataxia, but unlike other similar diseases,
dementia is usually absent, especially in the later stages. Kuru has distinct stages:
1. Prodromal Stage: Begins with symptoms like headaches, limb aches, and joint pains lasting
several months.
2. Ambulatory Stage: Patients experience unsteadiness in standing or walking, along with
dysarthria and diplopia. Gait ataxia worsens, and a characteristic clawing of the toes occurs. A
coarse postural tremor is common, and patients may become withdrawn.
3. Sedentary Stage: Patients can sit unsupported but cannot walk. Attempted walking with
support results in a high-stepping, wide-based gait with flinging arm movements. Emotional
lability, uncontrollable laughter, hyperreflexia, and muscle weakness are notable features. This
stage lasts 2-3 months.
4. Tertiary Stage: Hypotonia and hyporeflexia develop, along with progressive dysphagia and
incontinence. Patients become emaciated, and brainstem involvement with bulbar and
pseudobulbar signs occurs. Respiratory failure and bronchopneumonia lead to death. This stage
lasts 1-2 months.
Kuru is a unique disease with distinct clinical characteristics associated with its history of cannibalistic
practices in the affected communities.

2. Gerstmann-Sträussler-Scheinker syndrome (GSS)

 GSS is inherited in an autosomal dominant pattern with virtual complete penetrance.
Its diagnosis cannot be made from the usual laboratory or imaging studies.
  Demonstration of PRNP gene mutations appears to be a sensitive and highly specific
way to diagnose GSS. Neuropathology, although less used in practice, can also be
useful.
 The degree of dementia in GSS varies among affected families and individuals within
the same family. Part of the variability of expression of this illness may be due to
differences in the underlying PRNP mutation or the associated polymorphisms in
codon 12915.
3. Fatal familial insomnia (FFI)
 FFI was first identified in Italian families, but kindreds have now been reported
throughout the world.
 Although rarely, sporadic cases are also described. Disease onset is earlier and
duration is shorter in those who are homozygous formethionine at codon . It is a
rapidly fatal disease in which patients characteristically develop progressive insomnia
withloss of the normal circadian pattern, along with dysautonomia and endocrine
disturbances.
 Patients characteristicallydevelop progressive insomnia with loss of the normal
circadiansleep-activity pattern, which may manifest as a dream-like
 confusional state during waking hours. Inattention, impairedconcentration and
memory, confusion, and hallucinations are frequent, but overt dementia is rare.
 Methionine-homozygous patients are more likely to have hallucinations and
myoclonus as prominent disease features, while methionine heterozygous patients are
more likely to develop early problems with ataxia, bulbar signs, and nystagmus.
 Dysautonomia is characterized by hyperhidrosis, hyperthermia, tachycardia, and
hypertension. Endocrine disturbances include decreased ACTH secretion, increases in
cortisol secretion, and loss of the normal diurnal variations in levels of growth
hormone, melatonin, and prolactin.
 Fluorodeoxyglucose PET showing decreased glucose utilization in the thalamus may
be detectable even before the development of clinical symptoms. Sleep studies
demonstrate adramatic reduction in total sleep time and disruption of thenormal sleep
architecture. Genetic studies are now the diagnostic procedure of choice for diagnosis
of this condition.
 Neuronal loss and gliosis that is maximal within thethalamus are, however, consistent
findings.
4. Creutzfeldt-Jakob Disease
 Creutzfeldt-Jakob disease (CJD) is a rare form of dementia that affects one in every
5,000 people across the world. In CJD symptoms get worse very quickly, with 90% of
patients dying within a year of their diagnosis.
 Creutzfeldt-Jakob Disease Invariably fatal, this transmissible, rapidly progressive
disorder occurs mainly in middle age or older and is manifest early on by fatigue, flu-
like symptoms, and mild cognitive impairment or focal findings such as aphasia or
apraxia.
  Subsequent psychiatric manifestations include mood lability, anxiety, euphoria,
depression, delusions, hallucinations, or marked personality changes.
 Progression of disease occurs over months leading to dementia, akinetic mutism,
coma, and death.
 Other common neurological findings are generalized startle myoclonus, cortical
blindness, and extrapyramidal and cerebellar signs.
 The rates of Creutzfeldt-Jakob disease range from 0.25 to 2 cases per million persons
a year worldwide.
 The infectious agent self-replicates and can be transmitted to humans by inoculation
with infected tissues and sometimes by ingestion in food.
 Iatrogenic transmission has been reported via transplantation of contaminated cornea
or to children via contaminated supplies of human growth hormone. Household
contacts are not at greater risk than the general population, unless there is direct
inoculation.
 Because of an epidemic of a newly recognized prion disease, bovine spongiform
encephalopathy (mad cow disease), among cattle in the United Kingdom and because
of the unexpected recent emergence of cases of an atypical form of Creutzfeldt-Jakob
disease among teenagers in the United Kingdom, fears exist that transmission to
humans may have occurred as a result of eating infected meat.
 Diagnosis requires pathological examination of the cortex, which reveals the classic
triad of spongiform vacuolation, loss of neurons, and glial cell proliferation.
 Genetic susceptibility is a factor in disease risk, indicated by a common
polymorphism of the human prion protein. An immunoassay for Creutzfeldt-Jakob
disease in the CSF is currently under development, showing promise in supporting the
diagnosis of Creutzfeldt-Jakob disease in patients with dementia.
 EEG abnormalities, although not specific for Creutzfeldt-Jakob disease, are present in
nearly all patients: a slow and irregular background rhythm with periodic complex
discharges.
 Computed tomography (CT) and MRI studies may reveal cortical atrophy later in the
course of disease; SPECT and PET reveal heterogeneously decreased uptake
throughout the cortex. There is no known treatment for Creutzfeldt-Jakob disease.

Prognosis and treatment of Prion disease

 Prion diseases are always fatal, regardless of any current treatment effort. Care for
patients with prion disease is therefore mainly supportive.
 Isolated case reports of stabilization or improvement following treatment with
amantadine, acyclovir, interferons, polyanions, vidarabine, and methisoprinol have
not been replicated.
  Quinacrine and chlorpromazine, which were found to inhibit PrPSc formation in a
cultured neuroblastoma cell line(ScN2a) chronically infected with prions, also failed
to showany benefit when used in humans.
 Finally, Flupirtine maleate, a centrally acting nonopioidanalgesic that has displayed
cytoprotective activity in vitroin neurons inoculated with a prion protein fragment did
notshow significant effect on survival time compared with placebo. However, patients
performed significantly better on thecognitive part of the Alzheimer Disease
Assessment Scale(ADAS-Cog) and on the Mini Mental Status Examination,but the
difference did not reach statistical significance.
 Caregiver’s impressions were also significantly better in the flupirtine-treated group.
 As already mentioned, however, at this moment, prionic diseases are incurable and
invariably fatal.

AETIOLOGY OF DIMENTIA

APOLIPOPROTEINE GENOTYPE
 A gene that plays an important role in cases of late-onset Alzheimer’s disease is the
APOE (apolipoprotein) gene on chromosome 19.This gene codes for a blood protein
that helps carry cholesterol through the bloodstream.
 We know that differing forms (genetic alleles) of APOE differentially predict risk for
late-onset Alzheimer’s disease. Three such alleles have been identified, and everyone
inherits two of them, one from each parent.
 One of these alleles, the APOE-E4 allele, significantly enhances risk for late-onset
disease. Thus a person may inherit zero, one, or two of the APOE-E4 alleles, and his
or her risk for Alzheimer’s disease increases correspondingly.
 For example, having two APOE-E4 alleles results in a sevenfold
increase in a
 person’s chances of developing the disease.
 Another such allele, APOE-E2, seems to convey protection against late-onset
Alzheimer’s disease. The remaining and most common allele form, APOE-E3, is of
neutral significance. The alleles differ in how efficient they are in clearing amyloid,
with APOE-E2 being most efficient and APOE-E4 least efficient .
 APOE-E4 has been shown to be a significant predictor of memory deterioration in
older individuals with or without clinical dementia.
 The APOE-E4 allele is relatively uncommon in Chinese people compared to its
frequency in people from Europe or North America. In contrast, people of African
descent are especially likely to have this allele
 The APOE-E4 allele (which can be detected by a blood test) is overrepresented in all
types of Alzheimer’s disease including the early-onset and late-onset forms.
Approximately 65 percent of patients have at least one copy of the APOE-E4 allele
 Exciting as they are, however, these discoveries still do not account for all cases of
Alzheimer’s disease, not even all late-onset cases
  Many people who inherit the most risky APOE pattern (two APOE-E4 alleles) do not
succumb to the disorder. One study found that only 55 percent of people who had two
APOE-E4 alleles had developed Alzheimer’s disease by age 80 (Myers et al., 1996).
 And others with Alzheimer’s disease have no such APOE-E4 risk factor. In addition,
substantial numbers of monozygotic twins are discordant for the disease (Bergem et
al., 1997; Breitner et al., 1993).
 Why should this be? Current thinking is that our genetic susceptibility interacts with
other genetic factors and with environmental factors to determine whether we will
succumb to any particular disorder

THE CHOLINERGIC HYPOTHESIS

 At post-mortem there is evidence of significantly greater neuronal loss in the
cholinergic nucleus basalis of Meynert and loss of cholinergic markers.
 These observations led to the cholinergic hypothesis, which stated that the cognitive
impairment of AD was due to a disorder predominantly affecting cholinergic
neurones.
 It was this hypothesis that led to the development of pharmacological strategies to
rectify cholinergic loss and the introduction of the first compounds specifically
designed for and effi cacious in AD.
 However, the cholinergic hypothesis was something of a simplification as other
neurotransmitter systems (e.g. serotonergic and noradrenergic) are also affected in AD
THE PRESENILIN GENES
 Mutations in presenilin-1 (PS-1) and presenilin-2 (PS-2), two very similar genes on
chromosome 14 and chromosome 1 respectively, also cause early onset autosomal
dominant AD.
 The proteins encoded by these genes are part of the γ-secretase complex that
metabolizes APP to β-amyloid
 Mutations in the presenilin genes result in an increase in the production of β-amyloid
probably through interfering with the normal γ-secretase complex.
TANGLE FORMATION AND TAU PHOSPHORYLATION
 The neurofibrillary tangles (NFs) are intraneuronal aggregates of tau protein. The tau
protein present in tangles is in a highly phosphorylated form and has abnormal
functioning.
 Normally, tau protein binds and stabilizes microtubules, which are essential for axonal
transport, however in Alzheimer’s this function is deranged.
 The neurofibrillary tangles are widely distributed in cortical structures and
hippocampus, but always spare cerebellum
 Multiple studies have established that amount and distribution of NFs correlates with
the duration and severity of dementia .
 Both senile plaques and neurofibrillary tangles can be present in elderlies without any
dementia. However in patients with dementia, these findings are extensive and wide
spread.
 The neuropathological diagnosis of Alzheimer disease requires extensive presence of
both senile plaques (extracellular deposits) and neurofibrillary tangles (intracellular
inclusions)
 MANAGEMENT OF DEMENTIA
Management of dementia involves both non-pharmacologic and pharmacologic approaches
with the aim of reducing suffering caused by cognitive and related symptoms while delaying
cognitive decline.
Goals of Treatment:
1. Improving Quality of Life: The primary objective is to enhance the quality of life for
AD patients. However, assessing quality of life in dementia can be difficult, as
patients may exhibit different perceptions and experiences.
2. Managing Conflicts: Balancing the patient's quality of life with the needs and well-
being of caregivers and family members is essential. Conflicts of interest and ethical
issues may arise, and resolving them is part of the treatment process.

Non-Pharmacologic Management:
1. Specialist Referrals: Complex cases may benefit from referrals to specialists like
geriatric nurse practitioners, social workers, occupational or speech therapists, and
others.
2. Cognitive Activities: Engaging in cognitive activities such as reading and playing
mentally stimulating games can help maintain cognitive function.
3. Attention to the Environment Patients with cognitive losses are sensitive to their
surroundings and seem to do best with optimal stimulation. Understimulation may
cause withdrawal; overstimulation may cause confusion and agitation. Familiar and
constant surroundings maximize the patient's existing cognitive functions. Daily
routines often increase a patient's sense of security; memory and orientation can be
facilitated by prominent displays of clocks and calendars, a night light, checklists, and
diaries. Medication schedules should be simplified, if possible. If moves cannot be
avoided, it helps to place familiar objects (e.g., photographs and furniture) in the new
environment and to create a homelike atmosphere. The availability of newspapers,
radio, and television can be useful in maintaining a patient's contact with and
awareness of the outside world.
4. Music and Art Therapy: These approaches can improve cognitive function and
overall quality of life.
5. Reminiscence Therapy: Focusing on early-life stories and events through
psychotherapy can improve psychological well-being.
 6. Physical Exercise: Both aerobic and non-aerobic exercises have shown positive
effects on cardiovascular health and cognitive function.
7. Social Activities: Participating in social activities, support groups, and interactions
with trained pets can be beneficial.
8. Diet: Eating a brain-healthy diet, such as one rich in nuts, berries, leafy greens, and
fish, is recommended.
9. Family Intervention Psychotherapeutic intervention with family members is a
critical aspect of treatment. Education and counseling about the nature of the patient's
illness help relatives cope with the anger and puzzlement they often experience when
the patient with dementia behaves in peculiar, disturbing, and uncharacteristic ways.
Relatives may need reassurance that their emotional reactions are common and that
talking about them can bring relief. Many relatives also need help in grieving the loss
of the patient who now behaves like a stranger rather than the person they once knew.
Pharmacologic Management:
Numerous pharmacological treatments are currently available for Alzheimer's disease, each
targeting specific symptoms such as agitation or memory loss.These treatments can alleviate
symptoms and enhance the quality of life for patients but do not have the capability to halt or
reverse the progression of the disease itself.
1. Cholinergic Enhancement: One approach to improving memory function involves
boosting cholinergic activity in the brain, given that Alzheimer's patients often have
reduced levels of choline acetyltransferase, suggesting a cholinergic deficit. Trials of
cholinergic agonist agents have shown temporary memory improvement in both
young and elderly volunteers.
2. Cholinesterase Inhibitors: The FDA has approved short-term treatment with two
reversible cholinesterase inhibitors, tacrine and donepezil. These drugs have modest
effects on memory and cognition and may also reduce behavioral symptoms.
Prolonged cholinergic therapy might even delay disease progression, although tacrine
can cause reversible liver enzyme elevations.
3. Treatment of Behavioral Symptoms: Available therapies can sometimes effectively
manage behavioral symptoms associated with dementia, such as depression, agitation,
and anxiety. Antidepressant medications with minimal anticholinergic effects are
preferred over tricyclic drugs. However, caution is advised when using lithium in
patients with underlying neurological diseases.
4. Antipsychotic Medications: Antipsychotic drugs are effective in treating psychotic
symptoms and agitation. The choice of a specific agent depends on its adverse effect
profile. While a meta-analysis shows that antipsychotic drugs have a significantly
greater effect than a placebo, the magnitude of the effects is relatively small.
Clinicians should be cautious about the risk of tardive dyskinesia in elderly patients.
5. Benzodiazepines: Benzodiazepines have been employed to treat agitation in
dementia. However, they have undesirable adverse effects, including confusion,
memory impairment, and agitation complicated by ataxic gait. Short-acting
 benzodiazepines that do not require liver metabolism are considered safer, while long-
acting agents should be avoided. Benzodiazepines may be useful for treating
insomnia, but other potential causes of insomnia should be assessed and addressed
before considering pharmacological agents for sleep.

The treatment process in AD involves multiple components:

Patient Management: This aspect includes the assessment and diagnosis of AD. Discussing
the diagnosis and prognosis with the patient can be challenging, especially in the early stages
when patients may have limited insight. Managing mood and behavioral disturbances is a
critical part of patient care, with a focus on accurately assessing these disturbances and
implementing behavioral interventions. The use of anti-psychotic medication is generally
reserved as a last resort due to limited efficacy and potential adverse effects. Specific drug
treatments, such as cholinesterase inhibitors and memantine, target cognitive impairment.
Family Management: Providing information and support to the patient's family and
caregivers is essential. Caregivers often play a central role in the patient's care and well-
being. They may experience stress and burden, making it crucial to offer support services and
educational resources. Genetic counseling may be considered for families with a history of
familial AD to address concerns about inheritance.
Environment Management: Creating a comfortable, stimulating, and safe environment for
AD patients is a core component of treatment. Social services play a critical role in achieving
this goal. Care can often be provided at home with appropriate support, such as home-
delivered meals and home-help services. Day care centers and respite care can offer relief to
caregivers while maintaining the patient's independence. Safety issues, especially for patients
living alone, should be addressed to prevent accidents and ensure the well-being of the
patient.
In summary, dementia management involves a combination of non-pharmacologic
and pharmacologic approaches, tailored to the individual's needs and symptoms. Caregiver
support and education are crucial components of effective dementia care, and safety measures
should be in place to ensure the well-being of both patients and caregivers. While
medications can provide modest benefits, they should be used cautiously, and the focus
should be on improving the overall quality of life for individuals with dementia and their
families.

INVESTIGATION OF DEMENTIA
Diagnosis include comprehensive assessment involving history, examination, assessment of
function, global assessment, and investigations.
History
Diagnosis of AD is described as a positive process rather than one of exclusion. It highlights
the significance of obtaining a careful informant history, focusing on the pattern and timing
of onset and progression. Family history interviews, such as the Cambridge Mental Disorders
of the Elderly Examination (CAMDEX), are mentioned as valuable tools for research
purposes. It is also important to consider risk factors for AD, including family history and
vascular risk factors, as well as late-onset disorders, and emphasizes the importance of
avoiding the term "sporadic" dementia.
Examination
The examination phase involves assessing the mental state, cognitive impairments, and
screening tests like the Mini Mental State Examination. Physical examinations are also
important to identify underlying physical illnesses that can complicate the diagnosis.
Assessment of function
Assessment of function is described as crucial, involving both informant history and direct
observation. The instrumental activities of daily living (ADLs) are lost before basic ADLs
and mentions the role of occupational therapists in assessing functional abilities. The FAST
Scale is introduced as a tool for staging the severity of functional decline in AD.
Global assessment
Global assessment, driven by regulatory agencies like the United States Food and Drug
Administration, is discussed as a valuable addition to clinical trials and practice. Two scales,
the Clinician's Interview of Change and the Clinical Dementia Rating, are mentioned as
widely used for global assessment.
Routine investigations
 Routine biochemistry, thyroid function tests, vitamin B12, folate estimations, and a
full blood count are recommended as part of dementia screening. Neuroimaging is
recommended in all cases by expert guidelines, and serves two purposes—to exclude
reversible causes of dementia and to contribute towards a definitive diagnosis. Thus,
using structural imaging with CT or, increasingly, with magnetic resonance imaging
(MRI), the hippocampal atrophy of AD, the frontal predominant atrophy of FTD and
the lesions of vascular dementia can be identified, adding to the specificity of
diagnosis.
 In practice, neuroimaging is often omitted particularly when patients present with a
typical history of a slowly progressive dementia of many years standing.
 Functional scanning (single-photon emission CT (SPECT) in particular) can be useful
where regional dementias are suspected, and MRI should be the imaging modality of
first choice where vascular dementia is a possibility.
 An EEG is nearly always non-specifically abnormal even in the early stages of AD, in
contrast with fronto-temporal degenerations where an EEG remains unaffected at a
broadly equivalent severity. This can help to distinguish the conditions, particularly
where there is neuroimaging evidence of regional insufficiency
In summary, the clinician should consider a comprehensive and multifaceted approach to
diagnosing AD and related dementias, encompassing history, examination, assessment of
function, global assessment, and investigations to ensure an accurate and thorough evaluation
of patients.
 Cognitive screening and assessment

Clock drawing
Numerous versions of the clock-drawing test have been devised, with many scoring
algorithms [Brodaty and Moore, 1997]. Patients are typically asked to draw a clock face with
numbers and hands (indicating a dictated time). It was designed as a quick and acceptable
screening test for dementia. It is fast, requires no training and most scoring methods are fairly
simple. It shows fairly good sensitivity and specificity as a screening test. It assesses only a
very narrow part of cognitive dysfunction seen in dementia, and many other conditions (e.g.
stroke) will affect it directly.

Mini-Cog
The Mini-Cog [Borson et al. 2000] is a very short test (3 min) suitable for primary care
screening for dementia. It incorporates the clock-drawing test, adding a three-item delayed
word recall task. It showed comparable sensitivity and specificity to the Mini-Mental State
Examination (MMSE) in classifying community cases of dementia [Borson et al. 2003].
General Practitioner assessment of Cognition
The General Practitioner assessment of Cognition (GPCOG) [Brodaty et al. 2002] was
designed for use in primary care and includes nine direct patient cognitive items, and six
informant questions assessing change over several years. In total, it takes about 6 min. It has
strong performance on sensitivity and specificity versus MMSE in detecting dementia in a
typical primary care population [Ismail et al. 2009].

Memory Impairment Screen

The Memory Impairment Screen is a very brief four-item scale taking under 5 min to
administer, and showing good sensitivity and specificity in classifying dementia [Buschke et
al. 1999]. It lacks executive function or visuospatial items. Its use is likely to be confined to
primary care, as an alternative to GPCOG, 6-CIT, clock-drawing, Mini-Cog or AMTS.

Mini-Mental State Examination

The MMSE [Folstein et al. 1975] is by some way the best known and most widely used
measure of cognition in clinical practice worldwide. This scale can be easily administered by
clinicians or researchers with minimal training, takes around 10 min and assesses cognitive
function in the areas of orientation, memory, attention and calculation, language and visual
construction. Patients score between 0 and 30 points, and cutoffs of 23/24 have typically been
used to show significant cognitive impairment. It is widely translated and used. A
standardized version [Molloy et al. 1991] improves its reliability, and is probably most
important for research settings. The MMSE is unfortunately sometimes misunderstood as a
diagnostic test, when it is in fact a screening test with relatively modest sensitivity. It has
floor and ceiling effects and limited sensitivity to change. This in theory should limit its
wider use in detecting change in clinical work and in research studies, though in these
contexts it is still widely used, and even advocated [NICE, 2006].

Montreal Cognitive Assessment

The Montreal Cognitive Assessment [Nasreddine et al. 2005] was originally developed to
help screen for mild cognitive impairment (MCI). It takes minimal training and can be used
in about 10 min by any clinician. It assesses attention/concentration, executive functions,
conceptual thinking, memory, language, calculation and orientation. A score of 25 or lower
(from maximum of 30) is considered significant cognitive impairment. It performs at least as
well as MMSE, including in screening for dementia. It has been widely translated. As it
assesses executive function, it is particularly useful for patients with vascular impairment,
including vascular dementia.

Addenbrookes Cognitive Assessment

The ACE [Mathuranth et al. 2000] and its commonly used revision the ACE-R [Mioshi et al.
2006] was originally developed as a screening test for dementia which, unlike the MMSE,
would rely less on verbal than on executive abilities. It takes 15–20 min to administer and
includes the items which lead to a MMSE score. It has been shown to have very high
reliability and excellent diagnostic accuracy, and it is a practical option for clinical services
intent on precision in diagnoses.

All India Institute of Medical Sciences (AIIMS) comprehensive neuropsychological battery

in Hindi-adult Form
The AIIMS comprehensive neuropsychological battery in Hindi (adult form) is a
comprehensive battery of tests which is normed for those aged 15–80 years. It is based on the
Luria-Nebraska Neuropsychological Battery [8]. It consists of 160 items divided into ten
basic scales and four secondary scales. It is the only indigenously developed Indian test in
Hindi [18].

PGI battery of brain dysfunction

The PGI Battery of brain dysfunction consists of five sub tests – PGI memory scale, Bhatia’s
Short Scale, Verbal adult intelligence scale, Nahor-Benson test of Perceptual Acuity, and
Bender Visual Motor Gestalt Test. This test battery gives a global measure of cognitive
dysfunction based on 19 test variables. It has established norms for the age group of 20–59
years. It was developed in 1990 and estimates well-accepted or validated psychological
concepts of (a) intelligence, (b) memory, and (c) gestalt formation or perceptual acuity. It
gives a profile of current cognitive functioning of the subject [19].
The Luria-Nebraska Neuropsychological Battery
 developed in the late 1970s, is a standardized assessment tool used in clinical and
research settings. It was initially based on the work of Russian neurologist and
neuropsychologist A. R. Luria but was standardized and quantified by Charles J.
Golden and his collaborators.

 The battery consists of 269 items, each scored on a 2- or 3-point scale, with higher
scores indicating poorer performance. These items are organized into 11 content
scales, covering various aspects of neuropsychological functioning. There are also
derived scales, such as Pathognomonic and Left Hemisphere scales, reflecting brain
damage sensitivity and sensorimotor asymmetries.

 Additional scales, including right and left hemisphere, localization, factor, and double
discrimination scales, have been developed based on different scoring methods for the
same 269 items. These scales are expressed as T scores with a mean of 50.

 The assessment also incorporates age and education corrections, using a computed
critical level for abnormal performance. Extensive factor analysis supports the
homogeneity of the scales.

 The theoretical foundations of the Luria-Nebraska battery are primarily based on

empirical validity, quantification, and the application of established psychometric
procedures. It aims to discriminate between brain-damaged patients and normal
controls, distinguish between different neurological disorders, and determine the
localization of brain damage. The battery follows clinical inference methods
suggested by Reitan, including performance level, patterns, and comparisons.

 Despite its association with Luria's name, the battery's development was not directly
tied to Luria's methods or theories. Instead, it serves as a standardized psychometric
instrument with established validity and reliability for specific purposes in English-
speaking countries, using selected test items that were not exclusive to Luria's work.

The NIMHANS Neuropsychological Battery

There are two approaches of NIMHANS Neuropsychological Battery
I) The first approach was proposed by Dr. C.R Mukundan. The battery constitutes tests, some
of which are adapted for the local patient population and some developed on the basis of
principles of cerebral localisation and lateralisation of higher mental functions. This is a
loosely packed battery from which appropriate tests can be chosen according to diagnostic
needs and used along with other tests to form an integrated interpretation. The various tests
included are:
Brain Behaviour
Inter-relationship Tests for Eliciting Frontal Lobe Dysfunction
1) Attention
– Spontaneous arousal of attention
– Distraction
– Excessive broadening/ narrowing of attention
2) Tests of visual search
– Visual scanning of numbers
– Visual scanning of pictures
– Visual exploration test
3) Mental set- Psychomotor perseveration
4) Psychomotor deficits
– Test of Optic-kinaesthetic organisation
– Test of optic-spatial organisation
– Kinetic melody disturbance
5) Deficits in working memory
– Test of mental control
– Delayed response tests
6) Deficits of ideational and design fluency test
7) Deficits in visuospatial planning tasks
– Bender gestalt test
– Alexander passalong test
– Object assembly test
– Maze tests
8) Frontal Amnesia
9) Expressive speech disturbances
10) Changes in voluntary activity, personality and affect

Tests for Eliciting Temporal Lobe Dysfunction

1) Deficits of visual integration
– Block design test
– Object assembly test
2) Verbal and Visual learning and memory functions test
– The verbal learning and memory functions test
– Visual learning and memory functions test
3) Benton’s visual retention test
4) Test of comprehension
5) Presence of nominal aphasia
6) Presence of conduction aphasia
– Sentence repetition test
7) Recent history of cognitive, emotional and personality changes
Tests for Eliciting Parietal Lobe Dysfunction
1) Tests for visuospatial perception
– Bender gestalt test
– Block design test
– Spatial comparison test
– Spatial comparison using verbal report of differences
2) Presence of
– Apraxia (ideomotor, ideational and constructional)
– Agnosia (Visual object agnosia, prospagnosia, finger agnosia, autotopagnosia,
hemisomatagnosia, simultagnosia, visual inattention, astereognosia and left-right
disorientation)
II) The second approach was developed by Dr. Shobhani Rao et.al in 2004:This approach is
more quantitative and the tests are organised on the basis of various neuropsychological
functions. Performance on neuropsychological tests is influenced by socio-demographic
variables such as age, education, and the test-taking attitude of the population. For example,
the Indian population has wide variation with reference to education hence normative data
collected elsewhere will be invalid in an Indian context, has seen the development of many
tests in the recent past, these tests may have to be changed, as they may not have carry
meaning to our population. For the above two reasons, we need to collect normative data for
our population. The present study is the outcome of an endeavour to collect normative data
for 18 widely used tests, which assess various domains and are in current international usage.
The various tests included are:
Tests of Speed: can be categorised into
1) Motor speed - Finger tapping tests and
2) Mental speed -Digit Symbol Substitution Test
Tests of Attention:
3) Focused attention-Colour trails test
4) Sustained attention- digit vigilance test
5) Divided attention- the triads test
Tests of executive functions:
6) Phonemic fluency-controlled oral word association test (COWA)
7) Category Fluency-Animal names test
8) Design fluency-design fluency test
Working memory:
9) N back test (Verbal working memory and Visual working memory)
10) Self ordered pointing test
Planning
11) Tower of London test
Set shifting
12) Wisconsin card sorting test (WCST)
Response inhibition
13. Stroop test-NIMHANS version
Verbal comprehension
14) Token test
Tests of verbal Learning and memory:
15) Rey’s Auditory verbal learning test
16) Logical memory test
Visuo constructive ability
17) Complex figure test
18) Design learning test