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Dementia: An Overview

Article in Journal of Pharmaceutical Technology Research and Management · May 2014

DOI: 10.15415/jptrm.2014.21003

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DOI: 10.15415/jptrm.2014.21003

Dementia: An Overview
Nitin Bansal1* and Milind Parle2

1
Department of Pharmacology, ASBASJSM College of Pharmacy, BELA
(Ropar) Punjab-140111, India
2
Department of Pharmaceutical Sciences, Guru Jambhwshawar University
of Science & Technology, Hisar, Haryana-125001, India
*
Email: [email protected]

Abstract: Dementia is a neurodegenerative disorder characterized by

progressive and continuous loss of cognitive functions. The neuropsychiatric
symptoms include apathy; agitation and depression. As the disorder progresses,
the patient gradually becomes dependent on others to perform routine daily
activities. Various underlying diseases or disorders are the root cause of the
syndrome of dementia. Each of these disorder or disease is characterized by
a specific signs and symptoms in combination with a presumed underlying
neuropathology. Alzheimer’s disease is the most prevalent cause of dementia.
The second most prevalent cause is vascular dementia. In this review, the
clinical types, pathophysiology and pharmacotherapy is summarized.

Keywords: Amnesia, Alzheimer’s disease, Cognition, Dementia, Memory

1. INTRODUCTION

L
earning and memory are two fundamental cognitive functions that confer
us the ability to accumulate knowledge from our experiences (Liu et al.,
2009). Learning refers to acquisition of any new information about the
event in particular surroundings and subsequent retrieval of this information is
referred to as memory (Okano et al., 2000). Memory, one of the most complex Journal of Pharmaceutical
functions of the brain, comprises of multiple components such as perception/ Technology, Research and
sensation, registration, consolidation, storage, retrieval and decay/forgetting Management
Vol. 2, No. 1,
(Lindebooma and Weinstein, 2004; Parle et al., 2006). Memory may be sensory May 2014
(registration), short-term memory and long-term memory (Nader, 2000). pp. 29–45
Consolidation refers to the process of conversion of short-term memory to long-
term memory (Robbins and Murphy, 2006). Sensory memory (registration) is
defined as a process of sensory perception and an ability to retain the perceived
sensory signals in the sensory areas of the brain for relative short interval of ©2014 by Chitkara
time, following actual sensory experience. The incoming information first University. All Rights
enters sensory memory, which holds an exact copy of what is seen or heard, for Reserved.

29
Bansal, N. a few seconds or less. For instance, look at a flower and then close your eyes.
Parle, M. An icon, of fleeting mental image of the flower will persist for about one-half
second (Iconic memory). Similarly, information you hear is held in sensory
memory as an echo (Echonic memory) for up to 2 seconds (Schweickert,
1993; Nader, 2000). In general, sensory memory holds information just long
enough so that some of it can be transferred to the second memory system.
Short-term memory (STM) holds small amounts of information for relatively
brief periods; it is also called as working memory. It operates through central
executive, visuo-spatial sketchpad and phonological loop. A central executive
coordinates the material to focuss on reasoning and decision-making. The visuo-
spatial sketchpad concentrates on visual and spatial information, while the
phonological loop is responsible for holding and manipulating material related
to speech, work and numbers (Ellis and Nathan, 2001). STM can be prolonged
by rehearsal, the more time STM is rehearsed, the greater its chances of being
stored in LTM. Long-term memory has the capacity to hold the information
for months to years, it may be classified into declarative (explicit) and non-
declarative (implicit) memory (Budsen and Price, 2005).
Declarative memory is a deliberate process to remember factual information
such as names, faces and dates. It is stored in medial temporal lobe (mainly
hippocampus) and diencephalons (Shaprine & Eichenbaum 2000; Budsen and
Price, 2005). Non-declarative memory is unintentional recollection of earlier
experiences (Nelson et al., 1992). It operates spontaneously without conscious
efforts and it is stored in striatum, neocortex, amygdala and cerebellum. The
CA1 (Deadwyler and Hampson, 1999) and CA3 neurons (Deadwyler and
Hampson, 1999; Ramirez-Amaya et al., 1999) of hippocampus are responsible
for spatial learning and memory (Gilbert, 2000). Declarative memory is
divided into semantic memory and episodic memory. Semantic memory deals
with general knowledge and facts about the world e.g. mathematical figures
and historical dates (Budsen and Price, 2005) and episodic memory refers to
biographical details of an individual such as accident and memorable events
(Budsen and Price, 2005). Procedural memory is a form of non-declarative
memory and it refers to skills and habits such as riding a bicycle (Budsen and
Price, 2005). Priming and perceptual learning, simple classical conditioning
and non-associative learning are other forms of non-declarative memory
(Budsen and Price, 2005).

2 AMNESIA VS DEMENTIA
Amnesia is a condition in which memory is disturbed. Often this condition is
reversible e.g. alcohol/wine-induced amnesia. Amnesia may develop either a an
consequence of various neurological problems such as stroke, multiple cerebral

30
infarcts, head trauma and Alzheimer’s disease or consumption of alcohol (Fama Dementia: An
et al., 2004; McIntosh and Chick, 2004), chronic drug abuse (Vik et al., 2004) Overview
and certain chemical agents utilization (Chun, 2005). The memory impairment
in amnesia is usually global, being both anterograde and retrograde (Cipolotti
et al., 2001). Anterograde amnesia, is an inability to form new memories (Park
et al., 2007), where as retrograde amnesia, is failure to retrieve old memories
(Anand et al., 2007). Damage to the hippocampus, fornix, mamillary bodies,
anterior and medial thalamic nuclei or basal forebrain can result in anterograde
amnesia. Some authors have reported that severe anterograde amnesia is
caused by bilateral lesions in medial temporal lobe structures (Di Gennaro et
al., 2006), anteromedian thalamus (Carrera et al., 2004) or fornix (Poreh et al.,
2006). Cases of anterograde amnesia were also developed by a unilateral lesion
in mamillary body (Kupers et al., 2004), anterior medial thalamus (Summers,
2002), or hippocampus (Park et al., 2007).
Dementia refers to a syndrome that is characterized by progressive
deterioration of cognitive functions. The neuropsychiatric symptoms include
apathy; agitation and depression. As the disorder progresses, the patient
gradually becomes dependent on others to perform routine daily activities.
Various underlying diseases or disorders are the root cause of the syndrome of
dementia. Each of these disorder or disease is characterized by a specific signs
and symptoms in combination with a presumed underlying neuropathology.
Alzheimer’s disease is the most prevalent cause of dementia. The second most
prevalent cause is vascular dementia (Chen et al., 2009). It is often difficult
to distinguish between subtypes of dementia. However, most dementias are
progressive, irreversible and incurable. The risk factors and protective factors
associated with dementia are listed in Table 1. The main risk factor for dementia
is age. Prevalence is 2 % in those aged 65-69 years compared with 20% in
those aged 85-89. The terms senile and pre-senile dementia have been used to
differentiate between patients under or over 65 years but these are no longer in
common use because the two types share some etiological features. Dementia
is estimated to affect 24.3 million people worldwide. There are 4.6 million new
cases of dementia every year and it is suggested that this figure will double every
20 years, reaching over 80 million by 2040 (Husband and Worsely, 2006).

3 CLINICAL TYPES AND PATHOPHYSIOLOGY OF DEMENTIAS

Dementia, according to the Diagnostic and Statistical Manual of Mental
Disorders IV (DSM-IV), is a syndrome that may be caused or characterized
by multiple cognitive deficits, which include memory impairment and at least
one of the following: aphasia, apraxia, agnosia or disturbance in executive
functioning. Social or occupational function is also impaired. A diagnosis of

31
Bansal, N. Table 1: Risk factors and protective factors of dementia
Parle, M.
Risk factors Protective factors
Age ++ Apolipoprotein ε2 allele ++
Women + Low cholesterol level +/-
Low education + Statins +/-
First degree relative + Antihypertensive drug treatment +
Down’s syndrome + Moderate alcohol consumtion +/-
Hormone replacement therapy
Head trauma + +/-
(estrogen)
Apolipoprotein ε4 allele ++ Aspirin -
Aluminum level +/- Nonsteroidal anti-inflammatory drugs +/-
Dietary factors (vitamin E,
Hypertension + +/-
antioxidants)
Lifestyle (active life, leisure
Depression + activities, social support and +/-
network)
Mild cognitive impairment ++
Heart disease/atrial fibrillation +
Cigarette smoking ++
Diabetes mellitus ++
Excessive alcohol
+
consumption (3 drinks/day)
Hyperlipidemia +
Hyperhomocysteinemia, low
+
serum folate levels
Previous mental decline +/-
Note: ++=confirmed; +=notable; +/-=controversial; -=negative. Adapted from
Lobo and Saz, 2005

dementia should not be made during the course of a delirium. (A dementia and
a delirium may both be diagnosed if the dementia is present at times when the
delirium is not present.)
Dementia may occur due to both anatomical and biochemical changes in
the brain. The behavioral and psychological symptoms of dementia include
agitation/irritability/mood labiality, anxiety, apathy, delusion, depression
symptoms, disinhibition, euphoria, hallucinations, loss of appetite and sleep
disturbances (Tampi et al; 2011). Dementia has been etiologically associated
with numerous heterogeneous conditions listed in Table 2 and is categorized in
few subtypes according to its causes.

32
 Table 2: Disorders that may produce dementia syndrome Dementia: An
Overview
DEGENERATIVE DISORDERS METABOLIC DISORDERS
Cortical Anoxia
Alzheimer’s disease Cardiac disease
Frontotemporal dementia Pulmonary failure
Dementia with Lewy bodies Anemia
Subcortical Chronic renal failure
Parkinson’s disease Uremia encephalopathy
Huntington’ s disease Dialysis dementia
Wilson’s disease Hepatic failure
Thalamic dementia Portosystemic encephalopathy
Others Acquired hepatocerebral degeneration
Multiple sclerosis Endocrinopathies
VASCULAR DEMENTIA Thyroid, parathyroid disturbances
Multi-infarct dementia Cushing’s syndrome
Multiple large-vessel occlusions Recurrent hypo- or hyperglycemia
Strategic infarct dementia Porphyria
Lacunar state Vitamin deficiency states
Binswanger’s disease Thiamine (B1), Cyanocobalamin (B12)
Chronic ischemia Folate, Niacin
HYDROCEPHALIC DEMENTIAS Other chronic metabolic abnormalities
Communicating, normal pressure Hypo-or hyper-natremia
Non-communicating Hematological conditions
CNS INFECTION-ASSOCIATED
TOXIC CONDITIONS
DEMENTIAS
Alcohol related
HIV-associated dementia
Drugs
Creutzfeldt- Jakob disease
Polydrug abuse
Neurosyphilis
Psychotropic agents
Chronic meningitis
Anticonvulsants
Viral encephalitis
Solvents and other inhalants
Progressive multifocal
Anticholinergic compounds
leukoencephalopathy
Antineoplastic therapies
Fungal meningitis (cryptococcal)
Corticosteroids, NSAIDs
Antihypertensives
NEOPLASTIC DEMENTIAS
Cardiac medications
Meningioma
Metals
Glioblastoma
Lead, mercury, arsenic
Metastases
Nickel, aluminum
Paraneoplastic syndromes
Industrial agents and pollutants
TRAUMATIC CONDITIONS
Carbon monoxide
Posttraumatic subdural hematoma
Organophosphate insecticides
Dementia pugilistica
Organochlorine pesticides
CHRONIC INFLAMMATORY
Perchloroethylene, toluene
CONDITIONS
Trichloroethane, trichloroethylene
Systemic lupus erythematous
Hydrocarbon inhalants
Other collegen-vascular disorders
PSYCHIATRIC DISORDERS
Depression

33
Bansal, N. • Cortical dementia: dementias in which predominant involvement of
Parle, M. dysfunction is in cortex region
• Subcortical dementia: dementias having predominant involvement of
the white and grey matter structures such as basal ganglia, thalamus and
frontal lobe projections.
• Mixed dementia: describes dementia involves both cortical and subcortical
regions.

3.1. Cortical Dementias

3.1.1 Alzheimer’s disease
Alzheimer’s disease (AD) accounts for around 60 per cent of all cases of dementia
(Fratiglioni et al., 2007). AD is a progressive neurodegenerative condition that
may be of presenile or senile onset depending on whether the occurrence of
disease is before or after the age of 65 years. Clinically, the patient presents
itself as a progressive dementia of insidious onset with subtle personality
alterations eventually resulting in complete anomia, agnosia and apraxia. The
disease is occasionally accompanied by steep disturbance, anxiety, aggression
and agitation (Cummings, 2004). Histopathological evidence of senile plaques
and neurofibrillary tangels, either at autopsy or under rare circumstances, when
biopsy is obtained, constitutes the most reliable diagnosis. Senile plaques are
the clusters of degenerative nerve endings containing extracellular deposits
of β-amyloid. Neurofibrillary tangles are microscopic paired helical filaments
mainly made up of phosphorylated tau proteins (Kamphuis and Wurtman,
2009). Neocortex and hippocampus are the major regions characterized by
these abnormalities. In fact, severity of cognitive impairment in AD correlates
with the density of these plaques in neocortex. Biochemically, AD affects
some of the selective neurotransmitters and neuromodulators. There has been
a considerable deficiency of acetylcholine in brain of virtually all the patients
of AD, who have been studied (Shah et al., 2008). The serotonergic and
noradrenergic systems also seem to be affected particularly when the onset of the
disease is before the age of 75 years. Putative pathogenic mechanisms include
glutamate neurotoxicity, free radical production, aluminum accumulation,
apoptosis and inflammation (Silvestrelli et al., 2006).

3.1.2. Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) accounts for 15 to 20 per cent of dementia
cases. The disease seems to lie somewhere between AD and Parkinson’s
disease. DLB has distinct microscopic features: patients present with Lewy
bodies and amyloid plaques in the subcortical and cortical regions of the brain.

34
Neurofibrillary tangles are less commonly seen. Lewy bodies are eosinophilic Dementia: An
cytoplasmic inclusions that are distinct from neurofibrillary tangles. They Overview
contain a protein called alpha-synuclein, which is normally responsible for
synaptic plasticity. Alpha- synuclein also appears to regulate the size of
presynaptic vesicular pools of neurotransmitters and, therefore, influences
neurotransmission. In DLB, heavily phosphorylated alpha-synuclein becomes
cross linked to form the insoluble complexes that are Lewy bodies. Lewy bodies
also contain a variety of inflammatory markers (eg. interleukins), proteases,
BA and lipids. Lewy body development is accompanied by neuronal loss with
specific deficits in cholinergic and dopaminergic neurotransmission (Husband
and Worsley 2006).

3.1.2. Fronto-temporal dementia

FTD, sometimes also referred to as fronto-temporal lobar degeneration
(FTLD), is the second commonest cause of dementia in younger people (<
65 years) (Ratnavalli, 2002), and produces focal atrophy of the frontal and/
or anterior temporal lobes, with concomitant cognitive features (Neary et al.,
2005). Two major presentations are recognized:
(i) A behavioural variant (bvFTD)- bvFTD is characterised by a prominent
change in personality and social behaviour, with apathy and/or disinhibition,
emotional blunting, stereotyped or ritualised behaviours, loss of empathy
alterations in appetite and food preference with limited or no insight. These
changes reflect involvement of orbital and mesial frontal lobes (Sjogren
and Andersen, 2006).
(ii) A language variant, which in turn is divided in two different patterns:
semantic dementia (SD) and progressive non-fluent aphasia (PNFA).
In SD, there is a profound loss in conceptual knowledge (or semantic
memory) causing anomia and impaired comprehension of words, objects,
or faces. In PNFA, by contrast, there is a gradual loss of expressive
language abilities with impairments in phonological (sound-based) and
grammatical aspects of language production. Repetition of multisyllabic
words and phrases is impaired but, in contrast to SD, word comprehension
and object recognition are well preserved (Lillo and Hodges, 2009).

3.2 Subcortical dementias

3.2.1 Parkinson’s disease
The one-third patients with Parkinson’s disease are prone to subcortical and
progressive dementia. The neurodegeneration is not only confined to substantia
nigra but spread to other subcortical nuclei including the limbic system and the

35
Bansal, N. cerebral cortex. Furthermore, the underlying neurochemical deficits associated
Parle, M. may be losses of cholinergic, dopaminergic and noradrenergic innervations
(Kulisevsky and Pagonabarraga, 2009; Hindle, 2010).

3.2.2 Huntington’s disease

Huntington’s disease (HD) is an autosomal dominant disorder with an average
course of 15 to 20 years. It typically affects patients between 30 and 50 years
of age and has a prevalence of between four and seven per 100,000 worldwide
(Roze et al., 2010). The main and initial symptom of HD is “fidgety”
movements (chorea) but cognitive decline, attention deficit and depression
follow. Development of bipolar disease and schizophrenia is common in patients
with HD. The gene mutation responsible has been identified as a polymorphic
trinucleotide repeat in chromosome 4p. This is responsible for producing mutant
forms of the Huntington protein. This is normally found in cell cytoplasm but,
in HD, it is seen in nuclei. The mechanism of neurodegeneration as a result of
this genetic mutation is unclear and the net result is a deficit in GABAeric and
increased dopaminergic activity (Krobitsch and Kazantsev, 2011).

3.2.3. Wilson’s disease

The characteristic extrapyramidal signs are seen in the patients with Wilson’s
disease. The symptoms of depression, disinhibition, personality changes and
reduced impulse control are common; however the cognitive deficits are usually
mild. The psychopathological features observed here are by virtue of abnormal
and destructive deposition of copper in the basal nuclei; due to an inherited
defect in the copper-carrying serum protein ceruloplasmin (Shimizu, 2004).

3.2.4. Normal pressure hydrocephalus

The characteristic triad of clinical symptoms of this neuropsychiaric syndrome
includes motoric and psychopathological features i.e. an early abnormal
gait (resembling the steps of spastic paraparesis); subcortical dementia with
particularly severe apathetic features and urinary incontinence (that may not
appear until late in the course. The cognitive difficulties appear with the onset
of the incident. The neuropsychiatric deficits are due to the tissue destruction
by stretching as a result the chronic hydrocephalus (Kazui, 2008).

3.3 Mixed dementias and dementia in disseminated brain diseases

3.3.1 Vascular dementia

Vascular dementia (VaD) remains the second most common form of dementia
(upto 20% of all cases) in the elderly after AD (Roman, 2002). It is the result

36
of brain injury produced by cerebrovascular disease, either hemorrhagic or Dementia: An
ischemic, or by hypoperfusive lesions resulting from cardiac disease or Overview
circulatory failure (Roman, 2005). The high prevalence of VaD in the aging
population is a reflection of the fact that stroke and ischemic heart disease
(IHD) are the two leading causes of morbidity and mortality in the elderly. The
small brain infarcts leads to cognitive deterioration when they have enough
cumulative effects on critical areas of the brain, results VaD. Depending
upon the nature, extent and site of neuropathological lesion, the VaD may be
categorized into several subtypes such as-
(i) Large vessel vascular dementia
(a) Multi-infarct dementia:- Multiple large complete infarcts localized in
cortico–subcortical area, mainly in white mater, are responsible for
dementia.
(b) Strategic infarct dementia:- Single brain infarct, often lacunar in size,
damages functionally critical areas of the brain (e.g. angular gyrus,
thalamus, basal forebrain, posterior cerebral artery, and anterior
cerebral artery territories).
(ii) Small-vessel vascular dementia:-
(a) Subcortical: It is involved in Binswanger disease, CADASIL (Cerebral
Autosomal Dominant Arteriopathy with Subcortical Infarcts and
Leukoencephalopathy), and characterized by multiple lacunes with
extensive perifocal incomplete infarctions.
(b) Cortical and subcortical: It is involved in hypertensive, arteriolosclerotic
angiopathy, amyloid angiopathies and collagen-vascular disease.
(iii) Hypoperfusive vascular dementia:-
Ischemic-hypoxic dementia is a characteristic of diffuse anoxic-ischemic
encephalopathy, and characterized by restricted injury due to selective
vulnerability i.e. mesial temporal lobe sclerosis, incomplete white-matter
infarction and border-zone infarction.
(iv) Hemorrhagic vascular dementia:
Hemorrhagic dementia, occur mainly in traumatic subdural hematoma,
subarachnoid hemorrhage, cerebral hematoma and venous thrombosis.

3.3.2 Infection associated dementia

HIV dementia: HIV dementia (HIVD) is likely to become more common,
considering the rise in HIV infection. It is estimated that up to 30 percent
of patients with HIV will develop HIVD. HIVD is a subcortical dementia
where patients present with poor cognitive flexibility, reduced response times,

37
Bansal, N. apathy and emotional lability. The pathological mechanism involved in HIVD
Parle, M. appears to be apoptosis in neuronal cells as a result of various neurotoxic
chemicals (proteases, cytokines etc) shed from infected macrophages and glial
cells within the CNS. There is some evidence to suggest that treatment with
antiretroviral agents could reduce the incidence of HIVD and, in patients who
have developed the dementia, possibly stop or slow progression (Sharma and
Bhattacharya, 2009).

Creutzfeldt-Jakob Disease: It is a dementia with an extremely rapid course,

caused by transmissible infectious agent, the prion. Cognitive deterioration is
progressive, widespread and accompanied by pyramidal and extrapyramidal
signs i.e myoclonic jerks, ataxia and muscle rigidity. Death generally occurs
in 6-12 months. The pathological changes are widespread in the cortex and
the subcortical structures. Spongiform change in neurons is characteristic and
neuronal loss and astrocytic proliferation occur (Dupiereux et al., 2009).

Neurosyphilis: It may evolve into different types of dementia if left untreated.

The most severe form is general paresis, often evident 15-20 years after the
original infection. The dementia may be easily recognized in the advanced
state by characteristic signs, such as pupillary abnormalities, dysarthria, tremor
of the tongue and hypotonia (Nagano and Abe, 2004).
Chronic meningitis caused by chronic bacterial or fungal infections,
can eventually cause progressive dementia, with fluctuations in arousal and
cognitive performance, apathy, lethargy, disorientation and cranial nerve
abnormalities (Herta et al., 2005).
Herpes simplex encephalitis may cause major neurological and cognitive
sequelae (Cyngiser, 2008).

3.3.3 Metabolic and toxic dementias

Metabolic and toxic dementias form a heterogenous group of diseases of
special interest to the psychiatrist because they are potentially reversible
and relatively frequent in medical settings (Craft, 2009). Dementia in these
conditions has predominantly subcortical features but may have mixed
characteristics. Progression of dementia is usually dependent on the chronicity
of the metabolic or toxic condition, and the further course tends to be disease-
specific. Hippocampal neurons are probably most vulnerable to anoxic injury
but are also vulnerable to severe hypercholesterolemia and to repeated or severe
episodes of hypoglycemia (Yaffe et al., 2004). Hypothyroidism can produce
subcortical damage through a mechanism of relative cerebral hypoxia. Vitamin
B12 deficiency has been associated with disseminated degeneration in areas of

38
cortical white matter, the optic tracts and the cerebeller peduncles (Osimani et Dementia: An
al., 2005). In pellagra, nicotinic acid and probably other vitamin B deficiencies Overview
may lead to neuronal destruction (Hillborn and Marttila, 2010). Alcoholic
dementia is one possible complication of chronic alcoholism (Hulse et al.,
2005). This situation may be a result of associated malnutrition, especially of
B vitamins and particularly thiamine. Thiamine (vitamin B1) deficiency causes
Wernicke’s encephalopathy. Prolonged untreated thiamine deficiency can result
in an irreversible dementia/amnestic syndrome (Korsakoff’s psychosis) (Phaf
et al., 2000). Dementing syndromes may also occur in chronic intoxication
with medications (prescribed or abused by patients). The onset is accidental,
and physicians should be alert to the possibility of this reversible dementia.
Elderly patients are more vulnerable to developing the dementing syndrome
(Bassil & Morley, 2010).

3.3.4 Neoplastic-associated dementia:

Neoplastic diseases (depending upon tumor location, extent as well as rapidity of
tumor growth) essentially may produce any kind of neuropsychiatric symptoms.
Meningioma tumor present in frontal lobe is associated with symptoms like
cognitive loss with apathy, negativism and akinesia. Limbic encephalopathy is
a complication of small cell lung carcinoma and may manifest with dramatic,
sudden onset of memory loss. A full dementia syndrome may eventually
develop (Staropoli, 2008).

3.3.5 Dementia following traumatic brain injury:

Traumatic brain injury may cause variety of cognitive difficulties. The severe
trauma with loss of consciousness is called as post-traumatic amnesia.
Dementia pugilistica called as dementia of boxers, commonly starts with signs
of ataxia, dysarthria and Parkinson’s like extrapyramidal signs before cognitive
effects are appreciated (Dekosky et al., 2010).

3.3.6 Psychiatric disorders associated dementia:

The relationship between dementia and depression is complex. Pseudodementia
is a term used to describe the condition of depressed patients who perform
poorly on cognitive tasks because of lack of interest and motivation. However,
dementia syndrome of depression (DSD) occurs during episodes of severe
mood disorders (Korczyn and Halperin, 2009).
A wide variety of medications have been proposed to treat different types
of dementia. Table 3 enlists the common pharmacotherapeutic options to
delay symptom progression and to improve quality of life for the patient of
dementia.

39
Bansal, N. Table 3: Pharmacotherapy of Dementia
Parle, M.
Drug Mode of action Evaluation/Comments Reference
Precursors to Acetylcholine Shah et
Not effective alone/high
(ACh): Increase amount of al.,2008;
dose difficult to tolerate by
Choline, Lecithin, ACh Scarpini et al.,
the patient
glycerophosphorylholine 2003
Acetylcholinesterase
Clinical modest effects on Summer,
inhibitors: Tacrine,
Prevent the isolated cognitive measures. 2006;
donepezil, physostigmine,
breakdown of ACh May decrease negative Trinh et al.,
metrifonate, galanthamine,
behaviors. 2003
rivastigmine
Cholinergic agonists: Some subjective Caccamo et
Muscarinic agonist
Bethanecol improvement. al., 2009
ACh release modulators: K+-channel blockers Solntseva et
Fampridine, Linopridine Serotonin receptor Effective in animal model of al., 2003;
Ondensetron antagonist cognitive impairment Esbenshade et
Captopril ACE inhibitor al., 2008
Safe; may be useful in AD,
Thomas and
NMDA-receptor VaD and mixed dementia.
Memantine Grossberg,
partial antagonist However, additional data is
2009
needed.
Other therapeutic agents
Modest clinical effect,
Ergoloid mesylates: Metabolic Olin et al.,
possibly due to mood
Nicergoline, hydergine enhancement 2001
elevation.
Increase blood flow
to brain, affect nerve
Some clinical trials have
growth factor, Prevent Pike et al.,
Estrogen shown improvement in
atrophy of cholinergic 2009
cognition function
neuron, reduce
oxidative stress
May prevent Reduced prevalence of AD
Nonsteroidal anti- degeneration if in rheumatoid groups vs.
Wyass, 2006;
inflammatory drugs immune/inflammatory control and some groups
Stewart, 1997
(NSAIDs) effects cause plaque taking anti-inflammatory
and tangle formation medication.
May attenuate rate Based on animal studies,
of degeneration NIA workgroup concluded Tuszynski,
Nerve growth factor
of remaining ACh strong rationale for clinical 2007
neurons trials
Inhibits calcium
influx that occurs with Less deterioration on some
Tomassoni et
Nimodipine cellular changes, may memory tests, minimal
al., 2008
slow progression of cognitive benefits.
disease
Irreversible MAO-B Improvements in sone
inhibitor, acts as cognitive testing, was
Shah et al.,
Selegiline (L-deprenyl) asn antioxidant and comparable to vitamin
2008
increases adrenergic E in delaying disease
stimulation progression.

40
 Drug Mode of action Evaluation/Comments Reference Dementia: An
Antioxidant, traps free Zandi et al.,
Overview
Delayed Alzheimer’s
Vitamin E radicals, may inhibit 2004; Parigi et
progression.
lipid peroxidation al., 2006
Neuroprotective/
Some minimal benefits on
Acetyl-l-cartnitine promotes ACh Nalecz, 2004
cognitive tests.
synthesis
Many studies show
Enhances brain Farlow, 2009;
Nootropic agents: piracetam, increases cognitive tests and
metabolism, possibly Winnicka et
oxiracetam, aniracetam some symptoms, minimal
neuroprotective al., 2005
benefits.
HMG-CoA reductase
inhibitor, antioxidant, Mechanism of affecting
Schreurs,
Statins anti-inflammatory, learning and memory not
2010
improve endothelial known
dysfunction

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