Major Neurocognitive Disorder: Dementia

By
Dr Aguocha Grace U.
MBBS, MPH, FMCPsych
 OUTLINE:
• Definition.
• Introduction.
• Epidemiology.
• Aetiology.
• Clinical features.
• Types.
• Course and prognosis.
• Management.
• Recent advancement.
• Complications.
• Conclusion/Prevention.
• References.
 Definition of Dementia
• It refers to a disease process marked by progressive cognitive impairment or decline
in clear consciousness.
• It can be defined as an acquired persistent impairment of intellectual function
sufficient to interfere with social or occupational function, without impairment of
consciousness. The word ‘acquired’ distinguishes dementia from developmental
impairment of intellect, mental retardation. On the other hand, ‘persistent’
distinguishes dementia from the transient impairment of organic confusional states.
‘Persistent’ implies only a longer time-course and does not exclude the possibility of
successful treatment if dementia is due to certain causes, unfortunately rare.
• It is a clinical condition characterized by progressive decline from a previous level of
cognitive functioning with impairment in 1 or more cognitive domains (memory,
executive functions, attention, language, social cognition and judgement,
visuoperceptual or visuospatial abilities) in clear consciousness.
 Definition cont’d
• Is a syndrome characterized by progressive, usually irreversible, global
cognitive deficits.
• Is an acquired global impairment of intellect, memory and personality
but without impairment of consciousness. It is usually but not always
progressive.
• Dementia is a general term used for progressive loss of brain
functions that affect the ability to live and increase dependence.
 Introduction
• Dementia is derived from the Latin word ‘demens’ (being out of one’s mind).
• It is not a single illness but a group of symptoms (Syndrome) caused by
damage to the brain. The symptoms include: loss of memory, mood changes
and confusion.
• Of profound burden to the family, care giver, and society.
• The critical clinical points of dementia are the identification of the disorder,
and the clinical work up of its cause.
• An underlying cause can be reversible if treatment is initiated early, before
irreversible damage occurs.
 Introduction cont’d
• Although dementia is a global or generalized disorder, it often begins
with focal cognitive or behavioural disturbances.
• It is NOT attributable to old age/NOT part of/same as normal ageing.
 Dementia is NOT the same as
normal ageing
Normal Elder Dementia Patient
May forget part of an experience Forgets entire experiences
Remembers the experience later Usually does not remember even later
Understands written/spoken directions Slowly loses ability to understand any direction
Can use reminder notes Loses ability to use reminder notes
Can take care of self Loses the ability to take care of self
 Epidemiology of Dementia
• The prevalence of dementia rises with increasing age.
• The prevalence is about 1% at age 60 years; 5% in the general population older
than 65 years of age; 20-40 % in the general population older than 85 years of age;
15-20% in outpatient general medical practices; and 50% in chronic care facilities.
• Doubles every 5 years till 95 years.
• By 2050, it is predicted that there will be more than 18 million people living with
dementia.
• The male to female prevalence is about 11-21%.
• Black Americans are twice as likely as whites to develop dementia.
• Of all patients with dementia, 50-60% have the most common type of dementia,
dementia of the Alzheimer’s type.
 Epidemiology cont’d
• The second most common type of dementia is the Vascular, which
accounts for about 15-30% of all dementia cases; about 15-20% may
have co-existing Vascular and Alzheimer’s dementia.
• Lewy body dementia 7-28%, while frontotemporal 10-15%.
• Globally about 47.5 million are living with dementia, with over 2/3rd
residing in low middle income countries, including Africa.
• Medical comorbidities, sleep disorders, and traumatic brain injury are
associated with increased risk of dementia while increased years of
education, cognitive, and physical activities throughout the lifespan
reduces the risk of disease.
 Epidemiology cont’d
• Average survival after diagnosis varies between 4-10 years, and is
influenced by factors like age at diagnosis, sex, psychotic features,
motor system involvement, and medical comorbidities.
• Healthy individuals ie without comorbidities, survival can extend to
15-20 years.
• The burden of dementia is poorly understood in Nigeria due to poor
mental health access, low socio-economic status, and delay in seeking
medical care, etc.
• Asa Auta, Ezejimofor et al study done in South West showed a
prevalence of 4.9%, being higher in women when compared to men.
 Epidemiology cont’d
• Increased prevalence with advancing age, 3.9% in persons 60-90 years
to 11% in ages more than 90.
• Alzheimer’s dementia had the highest prevalence of about 2% while
others were about 1%.
 Aetiology
• The possible aetiologies of dementia is grouped into:
• The non-degenerative, and
• The degenerative.
 Aetiology: Non-degenerative
• Traumatic: subdural haematoma, posttraumatic dementia, dementia
pugilistica.
• Neoplasm/Tumor: primary or metastatic (eg. Meningioma, or metastatic
breast or lung cancer).
• Cardiac, vascular, and anoxia: multi infarct, Binswanger’s disease (diffuse
white matter disease)(subcortical arteriosclerotic encephalopathy),
hemodynamic insufficiency eg. hypoperfusion or hypoxia.
• Infection: acquired immune deficiency syndrome (AIDS), neurosyphilis,
prion disease 9eg, Creutzfeldt-Jakob disease, bovine spongiform
encephalitis, Gerstmann-Straussler syndrome).
 Non-degenerative Aetiology
cont’d
• Metabolic derangement: Vitamin deficiencies(eg. Vitamin B12, folate),
Endocrinopathies 9eg. Hypothyroidism), Chronic metabolic disturbances (eg.
Uremia).
• Drugs and toxins: alcohol, heavy metal poisoning, irradiation, carbon monoxide).
• Physiologic: normal pressure hydrocephalus.
• Psychiatric: cognitive decline in late-life schizophrenia, pseudodementia of
depression.
• Demyelinating diseases: multiple sclerosis.
• Miscellaneous: Wilson’s disease, Huntington’s disease, Neuroacanthocytosis, etc.
• Medications: morpine, fentanyl, etc.
 Degenerative/Irreversible
• Dementia due to Alzheimer’s disease.
• Dementia due to Lewy body disease.
• Frontotemporal dementia.
• Dementia due to Huntington’s disease.
• Dementia due to Creutzfeldt Jakob disease.
 Clinical Features Of Dementia
• The presenting complaint is usually of: poor memory.
• Other features include: disturbances of behavior, language, personality, mood,
or perception.
• The clinical picture is much determined by the patient’s premorbid personality.
• Those with good social skills may continue to function adequately despite
sever intellectual deterioration.
• Forgetfulness: usually early and prominent, sometimes difficult to detect in the
early stages.
• Impaired attention and concentration: common and non-specific.
• Difficulty with new learning: most conspicuous feature.
 CFs of Dementia cont’d
• ‘Organic orderliness’: loss of flexibility and adaptability in new situations,
with the appearance of rigid and stereotyped routines; and when taxed
restricted abilities, sudden explosions of rage or grief (‘catastrophic
reaction’) occur or are frequent.
• As dementia worsens, neglect of self ensues, and neglect of social
conventions.
• Disorientation is common: for time occurs first, and later, for place and
person.
• Thereafter, behavioural change: aimless, stereotypies and mannerisms may
appear.
• Thought affected: slow, impoverished in content, and perseverative. False
 CFs of Dementia cont’d
• ideas, often persecutory in nature, gain ground easily. In the later stages,
thinking becomes grossly fragmented and incoherent, and reflects in
the patient’s speech. Eventually the patient may become mute.
• Mortality is increased, with death often following bronchopneumonia
and a terminal coma.
• Behavioural, affective, and psychotic features often accompany the
cognitive deficits during dementia.
• The balance of these core symptoms and signs, together with some
additional features, forms the basis for the clinical differentiation
between the various causes of dementia.
 Table 2: Clinical features that help to
distinguish between major causes of dementia
Prominent symptoms and signs Other clinical features
Alzheimer’s disease Memory loss especially short-term, Relentlessly progressive, survival 5-
dysphasia and dyspraxia, sense of 8 years
smell impaired early on,
behavioural changes (wandering)
Vascular dementia Personality change, labile mood, Stepwise progression,Hx of
preserved insight hypertension, Signs of
Cerebrovascular disease,commoner
in men and smokers
Dementia with Lewy bodies Fluctuating alertness, visual Frequent adverse reactions to
hallucination, falls and faints, antipsychotics
parkinsonism
 Table 2: CFs cont’d
Prominent symptoms and signs Other clinical features
Frontotemporal dementia Prominent behavioural change, Onset usually before the age of 70
expressive dysphasia, early loss of years
insight, early primitive reflexes
Prion disease Myoclonic jerks, seizures, Often early onset, rapid onset and
cerebellar ataxia, psychiatric progression, transmissible
symptoms (vCJD)
Normal-pressure hydrocepalus Mental slowing, apathy, Commonest in 50-70 years age
inattention, urinary incontinence, group, commonest reversible
problems walking (gait apraxia) dementia
 Clinical Features Of Dementia
cont’d
• MEMORY: forgetting recent events, misplacing personal items, asking
repetitive questions, missing appointments.
• VISUOSPATIAL: navigational problems/getting lost; difficulty locating
items; problems visually recognizing faces or objects; problems
comprehending words or sentences; effortful or non-fluent speech;
grammar errors or omissions; spelling errors; and problems reading
and writing.
• EXECUTIVE FUNCTIONS: problems organizing, multitasking or
maintaining focus; distractibility; difficult reasoning, problem solving;
calculation.
 CLINICAL FEATURES cont’d:
• BEHAVIOURAL/PSYCHOLOGICAL: depression; screaming; aggression
(verbal and physical); wandering; personality changes; catastrophic
reactions; anxiety; irritability; poor impulse control; delusion
9persecutory); hallucination (more of visual than auditory); poor
personal care.
• MOTOR: restlessness; poor balance incoordination; tremor.
• SLEEP DISTURBANCE.
• WEIGHT LOSS.
• BLADDER/BOWEL INCONTINENCE.
 Types of Dementia: Based on
Their Putative Neuroanatomical
basis
• Two (2) types: Subcortical and Cortical dementia.
• Subcortical dementia: develops in the region of the brain called the
subcortex. This is located underneath the cortex of the brain.
• Cortical dementia: is an umbrella term describing damage to parts of
the brain in the cerebral cortex. Symptoms include memory loss, a
decline in thinking skills, and personality changes. Examples,
Alzheimer’s disease, frontotemporal dementia.
• Table 3 below shows the features of cortical and subcortical
dementias
Table 3: Features of cortical and
subcortical dementias
Subcortical dementia Cortical dementia
Memory impairment Moderate Severe, early
Language Normal Dysphasias, early
Mathematical skills Preserved Impaired, early
Personality Apathetic, inert Indifferent
Mood Flat, depressed Normal
Coordination Impaired Normal
Cognitive and motor speed Slowed Normal
Abnormal movements Common, choreiform, or tremor rare
 Types of Dementia: Based on
Age
• Two (2) types: Presenile and senile dementia.
• Presenile dementia: Or early-onset dementia. Occurring in those
under 65 years.
• Senile dementia: Or late-onset dementia. Begins later in life.
 TYPES OF DEMENTIA: Due To
Aetiology
• Dementia due to Alzheimer’s disease (AD).
• Vascular dementia.
• Dementia of Lewy bodies.
• Frontotemporal dementia.
• PLUS:
• Others – traumatic brain injury (TBI), HIV, prion disease, Parkinson’s
disease, and Huntington’s disease.
 Dementia due to Alzheimer’s
disease (AD)
• In 1907, Alois Alzheimer first described the extracellular amyloid positive
senile plaques and intracellular tau positive neurofibrillary tangles of
Alzheimer’s disease in brain in a woman: unusual neuropathological
features.
• Emil Kraepelin, his colleague, named it Alzheimer’s disease.

• It is the most common cause of dementia, affecting an estimated 5.7 million

Americans which is expected to triple by 2050 because of aging population.
• Incidence is said to be higher in African Americans than Asian Americans;
More in women than men.
 Alzheimer’s Dementia(AD)
cont’d
• Onset is insidious with memory impairment.
• Language impairment.
• Deterioration in visuospatial abilities, loose bearing in familial
environment, and constructional apraxia.
• Neuropsychiatric manifestation: agitation, delusion, aggression,
hallucination, wandering, loss of normal circadian sleep pattern.
• Physical signs: unlike patients with vascular dementia, AD may not
show obvious physical signs till late stage when they may become
mute, be confined to bed and assume decorticate position.
 Alzheimer’s Dementia: Possible
Protective Factors
• Smoking.
• Non-steroidal anti-inflammatory drugs (NSAIDs).
• Vitamin E.
• Higher level of pre-morbid education.
• Oestrogen (eg. Hormone replacement therapy [HRT]).
 AD: Risk Factors
• Could be – environmental or medical.
• Medical comorbidities – diabetes, obesity (obesity paradox).
• Lifestyle choices – sedentary, smoking.
• Vascular risk factors – cardiovascular injury.
• Sleep disturbance, depression.
• Traumatic brain injury.
• Low educational attainment.
• Others – increasing age, family history of Down’s syndrome, women
due to hormonal factors, hypothyroidism.
 AD: Genetic Risk Factors
• The estimated heritability of Alzheimer’s dementia is 60-80%. Thus,
genetic factors play a major role in determining a person’s risk to
develop Alzheimer’s disease (AD).
• Some studies have indicated that as many as 40% of patients have a
family history of dementia of AD.
• Additional support for genetic influence is the concordance rate for
monozygotic twins, which is higher than the rate for dizygotic twins.
• The transmission is said to be autosomal dominant though rare.
 AD: Genetics
• The primary genetic risk factor is Apolipoprotein E (APOE) e4 allele, brain cholesterol
transporter increases the risk of AD by increased aggregation and reduced clearance
of the amyloid beta polypeptide.
• Individuals who carry at least a copy of the APOE e4 allele have an increased chance
of developing atherosclerosis, which is an accumulation of fatty deposits and scar-like
tissue in the lining of the arteries. This progressive narrowing of the arteries increases
the risk of heart attack and stroke.
• Other genetic variants have been implicated as well in the aetiology of ADx. Of the
genetic variants so far associated with Adx, three (3) rare single-gene variants are
known to cause the disease: Amyloid precursor protein (APP) on chromosome 21;
Presenilin 1 (PSEN1) on chromosome 14; Presenilin 2 (PSEN2) on chromosome 1.
• Persons with Down’s syndrome (trisomy 21) who live longer, have the risk of
developing dementia.
 Neuropathology of Alzheimer’s
Dementia
• There is deposition of beta amyloid, neuritc plaques, and
neurofibrillary tangles in the cerebral cortex and many subcortical
regions.
• Amyloid precursor protein (APP)[transmembrane proteins] coded on
chromosome 21 is cleaved by proteases (beta and gamma secretases)
producing insoluble beta amyloid.
• Beta amyloid activates macrophages and microglia, producing
inflammation that accelerates neuronal damage. Beta amyloid is
toxic.
• Oxidative stress appears to increase the rate of neuronal death.
 Neuropathology of ADx cont’d
• Senile/neuritic plaques (a core of beta amyloid surrounded by
dystrophic neurites, immune activated microglia and reactive
astrocytes. The neuritic plaques are found in several regions (cortex,
limbic structures, striatum, diencephalon) and increase with disease
progression.
• Neurofibrillary tangles (NFT), bundles of phosphorylated tau proteins
[pr associated with microtubules] with other cytoskeletal proteins are
an early pathological change. Severity of dementia is proportional to
the density. It can be seen in cortex, hippocampus, substantia nigra,
and locus ceruleus.
 Neuropathology of ADx cont’d
• It is not unique to AD, can be seen in Down’s syndrome, brain of normal
ageing people, dementia pugilistica [punch drunk syndrome/chronic
traumatic encephalopathy].
• Neuronal loss in hippocampus, cortex, proliferation of astrocytes [gliosis],
loss of synapsis.
• On gross examination/macroscopically ie post mortem of AD brain reveals
atrophy of the medial temporal lobes, hippocampus, and cerebral cortex.
• Also, ventricular enlargement, widened sulci, shrunken brain, flattened
gyri.
• Microscopically, senile plaques, neurofibrillary tangles.
Pic 1: Showing the Normal and AD
neurons and brain.
Pic 2: Showing Amyloids Infiltrating
The Wall of A Small Vessel (below)
 Neurotransmitters (NT)
• Prior to the amyloid hypothesis, the prevailing view was the cholinergic
hypothesis of Alzheimer’s disease.
• NTs implicated in ADx especially acetylcholine ie its severe and widespread
loss in the cerebral cortex. The loss occurs because of pathology and
atrophy in the cells of origin, in the nucleus basalis of Meynert.
• The cholinergic deficits may correlate/explain previously some of the
cognitive impairment, they are no longer considered to have a primary
causal role.
• Decreased central cholinergic function leads to a relative
hyperdopaminergic condition correlating with the emergence of psychotic
symptoms.
 Neurotransmitter cont’d
• Cholinergic pathology may in fact be of more relevance in dementia
with Lewy bodies.
• Depletion of other NTs like serotonin, norepinephrine and tryptophan.
• Excessive stimulation by the NT, glutamate, that may damage neurons
is also implicated.
 Vascular Dementia
• The primary cause of vascular dementia, formerly referred to as multi-
infarct dementia, is presumed to be multiple areas of cerebral vascular
disease, resulting in a symptom pattern of dementia.
• Most commonly seen in men, especially those with preexisting
hypertension or other cardiovascular risk factors.
• The second commonest cause of dementia, of comparable prevalence to
dementia with Lewy bodies.
• The prevalence increases with age, approximately doubling every 5 years.
• There appear to be geographical differences, with high rates reported in
China, Japan, and the Russian Federation.
 Vascular Dementia cont’d
• Onset usually in the late 60’s or the 70’s.
• Often relatively acute, and follows a stroke.
• The course is usually a stepwise progression, with periods of
deterioration that are sometimes followed by partial recovery for a
few months.
• About 50% of the patients die from ischaemic heart disease, and
others from cerebral infarction or renal complications.
• Shorter survival when compared with Alzheimer’s dx.
 Vascular Dementia cont’d
• It affects primarily small and medium sized cerebral vessels, which
undergo infarction and produce multiple parenchymal lesions spread
over wide areas of the brain.
• The infarction can be from occlusion of vessels from atherosclerotic
plaques or thromboemboli from distant origins.
• Many studies have highlighted the relationship between stroke and
dementia. About 10% of patients develop dementia before their first
stroke; 10% develop dementia shortly after their first stroke; and
about 33% develop dementia after a recurrent stroke.
• Risk factors include: increasing age, hypertension, diabetes mellitus,
 Vascular Dementia cont’d
• atherosclerotic heart disease, hypertriglyceridemia and
hyperlipidemia.
 Vascular Dementia: Clinical
Features
• Sudden onset, gradual progression.
• One or more strokes.
• Has a fluctuating course.
• Emotional and personality changes may appear first, followed by
impairments of memory and intellect that characteristically progress in
stages.
• Depression is frequently seen.
• Episodes of emotional lability and confusion are common, especially at
night.
• Transient ischaemic attacks or mild strokes may recur from time to time.
 Vascular Dementia: CFs cont’d
• Behavioural changes and anxiety are more common than in
Alzheimer’s disease.
• Insight is often maintained until a late stage.
• The diagnosis is difficult to make with confidence unless there is a
clear history of strokes or localizing neurological signs.
• Suggestive features are patchy psychological deficits, erratic
progression, and relative preservation of personality.
• Signs of hypertension, of arteriosclerosis in peripheral and retinal
vessels are seen on physical examination; and there may be
neurological signs such as rigidity, akinesia, and brisk reflexes as well.
 Vascular Dementia: CFs cont’d
• Some patients may have a combination of AD and VD.
• No particular clinical presentation: patients with large territory
strokes may have stepwise decline and hemiparesis, while those
with cerebral small vessel disease may present with an insidious
onset of cognitive decline with gait disturbance and parkinsonism.
• Patients with vascular cognitive impairment tend to perform worse
on tests of executive function compared to memory function.
• In addition to the cognitive impairment, there may be focal or
lateralising signs like dysarthria, hemiparesis, aphasia, etc.
 Vascular Dementia
• Some genetic disorders are associated with the development of
vascular dementia. Cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopaty [CADASIL]. It is related to
mutation on chromosome 19 with recurrent ischaemic attacks.
• Deposition of osmophilc materials on vascular smooth muscle.
Cognitive impairment, migraine headache and stroke.
• Imaging studies with MRI can identify the microinfarcts.
 Lewy Body Dementia
• It is an umbrella term for a clinical diagnosis of both Parkinson’s
disease dementia and dementia with Lewy body.
• It is the 3rd most common degenerative dementia after Alzheimer’s
disease.
• Parkinson’s disease dementia: dementia occurring in the context of an
established diagnosis of Parkinson’s disease.
• Dementia with Lewy bodies: dementia associated with some
combination of fluctuating cognition, recurrent visual hallucinations,
rapid eye movement [REM] sleep behavior disorder and Parkinson’s
starting with or after the dementia diagnosis.
 Lewy Body cont’d
• Seen in persons over 65 years with intraneural cytoplasmic
eosinophilic inclusions [lewy bodies] in cerebral cortex neurons that
stain with alpha synuclein antibodies. About 30% of Dementia.
• Male : Female; 1.5 : 1 (more in males).
• The concentration of the Lewy bodies correlates with the degree of
the dementia.
• Visual processing, attention, executive functioning are more impaired
than memory.
 Lewy Body Dementia cont’d
• They usually experience sudden change in cognition, hallucinations,
REM sleep behavior disorder, parkinsonism.
• They often experience repeated falls, autonomic dysfunction like
orthostatic hypotension, urinary incontinence, delusions, depression.
• There is also reduced acetylcholine which correlates with the
cognitive impairment.
• Cholinesterase inhibitors reduce the cognitive impairment.
• 50% of individuals with Lewy body dementia have severe sensitivity to
neuroleptic medications so these should be used with great caution in
managing their psychotic symptoms.
 Lewy Body Dementia cont’d
• Neuropathology/Post mortem: the characteristic histopathological
feature is the presence of lewy bodies (neuronal alpha synclein
inclusions) in the cerebral cortex, and substantia nigra (as in
Parkinson’s disease).
• There is a significant overlap with Alzheimer’s Dx, with dementia with
Lewy bodies often exhibiting abundant senile plaques and widespread
reductions in choline acetyltransferase in the neocortex; however,
neurofibrillary tangles are rare: neuronal loss
• Brain atrophy is less marked than in Alzheimer’s disease, especially in
the hippocampus.
 Frontotemporal Dementia
• Also known neuropathologically as Frontotemporal lobar degeneration.
• It is a neurodegenerative disease that encompasses pick’s disease.
• Also called frontal lobe disorders, frontotemporal disorders, etc
• It constitutes about 15-20% of irreversible dementias.
• It is most common in men especially those who have a first degree relative with
the condition.
• It is inherited in an autosomal dominant pattern linked mutant gene on
chromosome 17 which codes for tau.
• It has an insidious onset at average age of 58 years range 20-90 with fatal
progression in 4 years.
• There is no cholinergic deficit unlike in AD.
 Frontotemporal Dementia
cont’d
• They display slow decline in their social skills, and emotional function.
• Prominent behavioural and personality disorder with mild cognitive
impairment.
• Progressive decrease in speech output, echolalia.
• Apathy, disinhibition, loss of sympathy or empathy, compulsive habits,
change in eating habits, motor neuron disease.
• Sparing of memory and visuospatial function.
• Features of Kluver-Bucy syndrome [hyperorality, hypersexuality,
placidity] are also common here.
 Frontotemporal Dementia
cont’d
• Computed Tomography [CT] Scan show frontal and temporal lobe
atrophy.
• There is also neuronal loss, gliosis, and neuronal pick bodies.
 Course and Prognosis
• The classic course of dementia is an onset in the patients 50s or 60s, with
gradual deterioration over 5-10 years, leading to death.
• The age of onset and the rapidity of deterioration vary among different
types of dementia.
• The average survival expectation for patients with dementia of the
Alzheimer’s type is approximately 8 years, with a range of 1-20 years.
• Persons with an early onset of dementia or with a family history of
dementia, the disease is likely to have a rapid course.
• A gradual onset of symptoms is most commonly associated with
dementia of the Alzheimer’s type, vascular dementia, endocrinopathies,
brain tumors, and metabolic disorders.
 Course and Prognosis cont’d
• Conversely, the onset of dementia resulting from head trauma,
cardiac arrest with cerebral hypoxia, or encephalitis can be sudden.
• The symptoms of the early phase can be subtle, they become
conspicuous as the dementia progresses, and the family members
may then bring the patient to a physician.
• Death typically results from motor impairment which may lead to
aspiration pneumonia.
 Clinical Evaluation
• The aim is to rule out potentially reversible causes of cognitive decline
by reviewing medical comorbidities, medication and substance use,
and environmental exposures.
• Neurodegenerative diseases typically have an insidious onset and
gradual progression while non-degenerative are usually acute onset.
• History, mental state examination [clouding of consciousness,
depression, psychosis], mini mental status examination, physical
examination [gait, focal signs, parkinsonism], investigation.
 Diagnosis:
• DIAGNOSTIC CRITERIA – DSM 5:
• Evidence of significant cognitive decline from the previous level of
performance in one or more cognitive domain.
• Cognitive deficit interfere with independence in everyday activities.
• Cognitive deficit do not occur in the context of delirium.
• Cognitive deficit not better explained by another mental disorder.
- With or without behavioural disturbance.
 Investigations
• BIOPSYCHOSOCIAL MODEL
• Biological:
• Full blood count [FBC], Erythrocyte sedimentation rate [ESR].
• Liver function test [LFT].
• Renal function test [RFT].
• Vitamin B12.
• Thyroid function test [TFT], T4.
• Retroviral screening [RVS]/
• Syphilis [VDRL].
• Urinalysis.
 Investigations cont’d
• Biological Cont’d
• CT/MRI to exclude structural lesions such as neoplasms, subdural
haematomas, and normal pressure hydrocephalus
• Hallmark of MRI in ADx is: of medial temporal atrophy and cortical
atrophy.
• MRI can also show infarctions [small or large].
• Electroencephalogram [EEG], slow wave activity especially in
dementia with lewy bodies.
 Investigations Cont’d
• Psychological:
• Mini mental state examination, [MMSE].
• Abbreviated mental test score, [AMTS].
• Alzheimer’s disease assessment scale-cognitive score.
• Clock drawing test.
 Mini mental state examination
• 1st developed by Folstein Folstein in 1975.
• For screening/assessing an individual’s cognitive state (dementia) in
primary health setting.
• Detect severity cognitive impairment, has predictive failure.
• May not really differentiate between types of dementia.
• If the scores are stable over 2 years, reconsider diagnosis because dementia
produces a progressive decline.
• It may over or under estimate in elderly and poorly educated.
• Its specificity and sensitivity for dementia is about 80%.
• Ensure patient has no visual or hearing difficulties.
 MMSE Form
Orientation Year,month,day,date, season 5
Country, state, LGA, Hometown, 5
Village
Registration Examiner names 3 objects, Patient 3
repeats the objects, 1 point for
each
Attention Serial 7 ie 100 – 7, stop after 5 5
subtractions Or spell world
backwards
Recall Ask the names of the objects 3
learned earlier
Language Name a pencil and a watch 2
Repeat:’No ifs, and or buts’ 1
Give a 3 stage command 3
 MMSE Form cont’d
Language Ask patient to read and obey a 1
written command
Ask patient to write a sentence 1
[with a subject and verb]
Copying Ask patient to copy intersecting 1
pentagon
Total score 30
 MMSE: Result Interpretation
Score Description Stage
30-26 Normal Could be normal
25-20 Mild Early
19-10 Moderate Middle
9-0 severe late
 Social Investigation
• In collaboration with the social worker who visits the patient’s
residence to make enquiries about the patient’s living circumstances,
relevant family members and care givers, economic stability, extent of
coping for patient and care givers, health care access and quality,
medicolegal matters.
• Also, patients level of interaction with people around him/her.
 Management of Dementia
• Aim:
• Identify causes, especially the reversible ones and treat immediately.
• Slow down the rate of progression for non-reversible causes.
• Care giver psychoeducation and training to reduce burden of care.
• Manage other medical comorbidities.
• Maximize functional performance and quality of life, while reducing
the period of disability.
• Prepare patient for end of life process.
 Management Cont’d
• Is multidisciplinary: Psychiatrist, neurologist, clinical psychologist,
geriatrician, social worker, genetic counselor, occupational therapist
physical instructor, psychiatric trained nurse, etc.
• N/B:
• Neurodegenerative diseases typically have an insidious onset with a
slow gradual progression.
• An acute change in mental status should raise a concern for non
neurodegenerative course.
• Genetic counselling for early onset if a genetic cause is identified.
 Treatment of Dementia
• Pharmacological:
• Acetylcholinesterase inhibitors [ACHEI] eg donepezil, galantamine,
and rivastigmine.
• N-methyl-D-aspartate receptor antagonist eg memantine.
• Selective serotonine reuptake inhibitors [SSRI] eg citalopram.
• Atypical antipsychotics eg risperidone, quetiapine, olanzapine.
• Melatonin.
• Benzodiazepine eg diazepam.
 Treatment Cont’d:
Pharmacological
• Others still controversial:
• Vitamins eg Vit E.
• Gingko biloba.
• Estrogen and hormone replacement therapy.
• Statins.
• Non-steroidal anti inflammatory drugs [NSAIDs].
• Vaccine.
 Acetylcholinesterase Inhibitors
• Main stay of treatment.
• They inhibit the hydrolysis of acetylcholine [a chemical messenger
important for learning and memory].
• Improves cognitive function and behavioural problems and often
slows the rate of progression.
• Side effects: gastrointestinal upset, dizziness, urinary frequency,
muscle cramps, and vivid dreams.
• Rare but serious adverse effects for rivastigmine include: increased
pulmonary and gastric secretions, so caution in patients with
gastrointestinal bleeding, and gastric ulcer disease.
 N-methyl-D-aspartate receptor
antagonist
• Example: Memantine.
• It inhibits the excitotoxic glutamate thus used to improve cognition
and behavioural symptoms.
• Start at low dose then titrate up gradually.
 Selective Serotonin Reuptake
Inhibitor
• Example: Citalopram, Escitalopram.
• May be used for compulsivity, and overeating in frontotemporal
dementia, depression, and agitation.
 Atypical Antipsychotics
• Example: Risperidone, quetiapine, olanzapine, etc.
• Can be used in low dose for agitation and psychosis.
 Benzodiazepines
• Example: Diazepam, Nitrazepam, etc.
• Used for agitation and anxiety.
 Acetamides
• Example: Melatonin.
• Used for REM sleep disorder.
 Non-Pharmacological
• Mainly for the behavioural/psychological signs and symptoms, and
care giver support.
• Ensure you have obtained a good understanding of the behavior
[frequency, degree of risk, potential triggers].
• The behaviours can represent the patients attempt to communicate
an unmet need to the care giver.
• It should be tailored to suite the patient, caregiver and environment.
• Appropriate intervention must be individual based, taking into
account intellectual capacity, physical and mental health, socio-
cultural background, premorbid personality factors.
 Non-Pharmacological Cont’d
• Physical activity: structured exercise program like walking indoor or
outdoor.
• Sensory enhancement: music, bright light therapy, massage.
• Social interaction: with people and pets which can be video recorded
and played to patient.
• Purposeful engagement: games, music, arts and craft, technology.
• Environmental design: label rooms, bathrooms and common areas
appropriately. Prominent display of calender, photograph with names
of persons close to patient.
 Non-Pharmacological Cont’d
• Reinforcing desired behavior with rewards.
• Staff/caregiver education: psychoeducate regarding the illness,
symptoms and progression, appropriate responses to delusional
thoughts, self care, stress management and coping strategies.
• Harmless compulsions may not be discouraged.
• Adult structured day programs to give caregiver some respite.
• Institutionalization: long term care when the mental and physical
health of the caregiver is at risk.
 Medicolegal
• Driving: implicit memory but with time, doctor has the right to report
to traffic authorities.
• Financial affairs: during early stage of dementia when competence is
preserved; can transfer power/letter of attorney; trustworthy family
member if not Curatorship.
• Testamentary capacity: mental sanity/ability to make a will.
 Differential Diagnosis
• Normal pressure hydrocephalus:
• Characterized by an increase in intracranial CSF content without a
gross anatomic obstruction to flow.
• It occurs insidiously without increasing CSF pressure.
• It can be idiopathic or secondary to some condition.
• Rare condition and can be seen in persons above 70 years.
• Triad of: insidious gait abnormality [wide based shuffling gait],
urinary incontinence, and cognitive impairment.
• CT Scan shows enlarged ventricle not in keeping with the widening of
 Differential Diagnosis cont’d
• the sulci.
• Incontinence in dementia is LATE.
• VP shunt may improve cognition.
• Mild Cognitive Impairment:
• There is cognitive impairment that represents a decline from the
previous level of performance but does not interfere with the daily
activities and can function independently.
• It is a high risk for dementia.
• Parkinson’s disease.
 Differential Diagnosis cont’d
• Delirium:
• Is an acute and reversible change in cognition which occurs with altered
consciousness.
• Toxic metabolic encephalopathies:
• Altered states of consciousness due to chemical imbalance.
• Usually an acute onset.
• With deteriorating course.
• Pseudodementia:
• Psychiatric problem especially depression co-existing with cognitive
impairment.
 Differential Diagnosis cont’d
• Alcohol induced amnestic disorder.
• Beclouded dementia:
• Delirium that develops in a patient who already has dementia.
 Recent Advancements
• In recent years, major progress has been made in developing and
validating CSF and imaging of AB and tau, the core molecular features
that define AD neuropathology in living persons.
• Reduction in levels of AB and increase in total tau and phosphorylated
tau.
• AB and p=tau are associated with amyloid plaques and neurofibrillary
pathology, respectively, while increase in t-tau are a non specific
marker of neurodegeneration and can be seen in other conditions
associated with rapid neuronal death. [Creutzfeldt-JAKOB disease,
acute ischemia, and traumatic brain injury].
 Recent Advancements cont’d
• Direct detection of amyloid plaques in living people using PET
[Positron emission tomography] ligands that bind to neurotic plaques.
Research findings, not clinical.
• The biomarkers have helped establish the existence of a prolonged
preclinical phase of AD.
• Set backs include patient access, and cost.
 Recent Advancement cont’d
• Shows 80-90% sensitivity and specificity in discriminating between
Alzheimer’s dementia, healthy controls and progression in mild
cognitive impairment.
• Other markers:
• Temporoparietal hypometabolism on 18F-FDG PET scan.
• Measurement of hippocampal volume.
• Biomarkers for prediction of progression to AD in persons with mild
cognitive impaiment.
 Complications
• Depression: patient and caregiver.
• Wandering/missing.
• Caregiver burnout.
• Malnutrition.
• Falls.
• Aspiration pneumonia.
• Suicide.
 Conclusion
• Dementias are heterogenous group of clinical syndromes with memory
impairment and other cognitive functions in clear consciousness.
• Prevalence increases due to rapid population ageing.
• The use of pharmacological and non-pharmacological treatment
provides a good benefit.
• For prevention of dementia:
• Be physically active.
• Get enough sleep.
• Eat healthy diet.
 Conclusion cont’d
• Avoid alcohol and tobacco.
• Stay mentally alert by learning new hobbies, reading, or solving
crossword puzzles.
• Manage health problems including diabetes, high blood pressure, and
high cholesterol, very well.
 References
• Kaplan and Sadock: Synopsis of Psychiatry; Benjamin James Sadock, Virginia Alcott Sadock,
11th Edition. Wolters Kluwer, New York London.
• Clinical Neurology: A Modern Approach. Anthony Hopkins. Oxford University Press, 1993;
Chapter 11: pg 163.
• Oxford Handbook of Psychiatry. David Semple/Roger Smyth. 3 rd edition; p 132, Oxford
University Press.
• Clinical Neurology For Psychiatrists by David Myland Kaufman; 6th edition, Saunders
Elsevier Philadelphia page 111-158.
• Continuum lifelong learning in Neurology American Academy of neurology February 2019,
vol 25.
• Emedicine. Medscape. Com.
• Clinical Psychiatry, Robert E Hales, 4th edition American Psychiatry publishing, Washington
DC London UK.
Thank you for
Listening