APPROACH TO A PATIENT

WITH DEMENTIA

DR ROBIN GARGJUNIOR RESIDENT

DEPTT. OF MEDICINE

DEMENTIA- “OUT OF ONE’S MIND” DEMENTIA- the disease with acquired deterioration in

cognitive/ intellectual abilities, without impairment of consciousness, that impairs the successful performance of activities of daily living.

Cognitive impairment represents a decline from previous level of functioning.

Episodic memory, the ability to recall events specific in time & place, is the cognitive function most commonly lost.

In addition to memory, dementia may erode language, visuospatial, praxis, calculation, judgement & problem solving abilities.

MAJOR NEUROCOGNITIVE DISORDER DSM- V (DIAGNOSTIC AND STATISTICAL MANUAL)A. Evidence of significant cognitive decline from a previous level of

performance in one or more area of cognitive domains ( complex attention, executive function, learning and memory, language, perceptual-motor or social cognition) based on :

1. Concern of the individual , a knowledgeable informant or the clinician that there has been a significant decline in cognitive function; and

2. Substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing or , in its absence , another quantified clinical assessment.

B. The cognitive deficits interfere with independence in everyday activities. C. The cognitive deficits do not occur exclusively in the context of a

delirium. D. The cognitive deficits are not better explained by another mental

disorder (e.g., major depressive disorder, schizophrenia).

EPIDEMIOLOGY

~ 5 to 8 % of persons age 65 to 70 years

~ 10 % of persons age >70 years

20-40% of persons age>85 years

• Alzheimer's disease is most common cause of dementia 50-75%

• Vascular dementia is second most frequent cause.

• Dementia with lewy bodies is also common in 15- 30% of patients.

Alzheimer’sDisease

•Early onset•Normal onset

Vascular (Multi-infarct)

Dementia

Lewy Body

Dementia

DEMENTIA

Other Dementias•Metabolic•Drugs/toxic•White matter disease•Mass effects•Infections•Parkinson’s

Fronto-Temporal

Lobe Dementias

ETIOLOGYNEURO-DEGENERATIVE

Alzheimer's Ds ; Parkinson’s Ds dementia & Dementia with Lewy Bodies, Fronto-temporal dementia

VASCULAR Multi-Infarct; Diffuse white matter ds(Binswanger’s)NEUROLOGICAL MS, Huntington’s ds, MSA, Hereditary ataxias, Prion Ds

(Creutzfeldt jakob & GSS), ALS-parkinsonism-dementia complex of Guam, Adult Down’syndrome with Alzheimer ds, Brain tumour

ENDOCRINE Hypothyroidism; Cushing syndrome; Adrenal insufficiency; Hypo and Hyperparathyroidism

NUTRITIONAL Def. of Vit.B12(SACD),Thiamine(Wernicke’s), Niacin(Pellagra)

INFECTIOUS HIV; Neurosyphilis; JC virus(PMLE), TB, Fungal, protozoal, Whipple

METABOLIC Hepatic/ Renal Insufficiency; Wilson’s Ds

TRAUMATIC & DIFFUSE BRAIN DAMAGE

Chronic Subdural Haematoma; Dementia pugilistica(chronic traumatic encephalopathy),Postencephalitis, Postanoxia,NPH, Intracranial hypotension

TOXIC AGENTS Alcoholism; Heavy Metals(Pb,Hg,As,Al); Drug/medication intoxication(Sedatives, tranquilizers & analgesics)

PSYCHIATRIC Depression(Pseudodementia),Schizophrenia,Conversion disorderMISCELLANEOUS Sarcoidosis,Vasculitis,CADASIL,Acute intermittent porphyria

o Symptoms-major changes in memory, language & perceptual deficits, apraxia .Lack of extrapyramidal features

o Areas affected-temporal cortex (medial), parietal cortex, and frontal lobe cortex

o Examples-Alzheimer’s Ds Dementia with Lewy Bodies Frontotemporal Dementia Vascular Dementia

o Symptoms-behavioral changes, impaired affect and mood, motor slowing, executive dysfunction, less severe changes in memory.extra pyramidal features

o Areas affected- thalamus, striatum, midbrain, striatofrontal projections

o Examples - Parkinson’s disease, progressive supranuclear palsy, NPH, Huntington’s disease, Creutzfeldt-Jakob disease, vit. Deficiency, thyroid ds, metabolic, dementia pugilistica

CORTICAL VS. SUBCORTICAL DEMENTIA

CORTICAL SUBCORTICAL

MIXED Both cortical and sub-cortical area involved. Example: vascular dementia, Dementia with Lewy

bodies, Corticobasal degeneration, Neurosyphilis

REVERSIBLE DEMENTIA

D = Delirium E = Emotions (Depression) & Endocrine Disease M= Metabolic Disturbances E = Eye & Ear Impairments N = Nutritional Disorders, NPH T = Tumors, Toxicity, Trauma to Head(SDH) I = Infectious Disorders A= Alcohol, Arteriosclerosis

IRREVERSIBLE DEMENTIA Alzheimer’s Vascular Lewy Body Dementia Parkinson’s Frontotemperal Dementia Huntington’s Disease Cruzefeldt Jakob Disease Leukoencephalopathies

DIAGNOSTIC APPROACHCOGNITIVE IMPAIRMENT ?

DETERIORATION FROM APREVIOUSLY HIGHER LEVEL ?

CONSCIOUSNESS ALTERED?

MULTIPLE COGNITIVE FUNCTIONSINVOLVED ?

DEMENTIA

YES

YES

YES

NO

NO

YES

NO

MENTALRETARDATION

DELIRIUM

APHASIAAMNESTIC , etc

SERIOUS INTERFERRENCE WITH DAILY ACTIVITIES??

YES

NO MILD COGNITIVE IMPAIRMENT(MCI)

HOW TO DIAGNOSE A CASE OF DEMENTIA

Focussed History

Symptoms analysis

Focussed physical examination

Cognitive and neuropsychiatric examination

Laboratory evaluation

FOCUSSED HISTORY Chronology of the problem - Mode of onset – acute(Delirium) vs gradual - Progression -slow (AD) -stepwise (Vascular dementia) -rapid (CJD,FTD) -progression with fluctuations(DLB) - Duration of symptoms

CLINICAL SYMPTOMS COGNITIVE IMPAIRMENT

FUNCTIONAL IMPAIRMENT

NEURO-PSYCHIATRIC MANIFESTATIONS

BEHAVIOURAL DISTURBANCES

MOOD CHANGES

ANXIETY

PERSONALITY CHANGES

PSYCHOSIS

SLEEP DISTURBANCES

COGNITIVE IMPAIREMENT

o Memory impairment (Episodic; Immediate,recent or remote; Anterograde vs retrograde amnesia)o Aphasia (impairment of naming, comprehension or fluency)o Apraxia (impaired ability to carry out learned motor activities despite intact motor function)o Agnosia (failure to recognize or

identify objects despite intact sensory function)o Impairment in executive

functioning (disturbances in planning, organizing, sequencing, and abstracting, problem solving)o Impaired visuo-spatial

functioning (interference with dressing, eating or even walking, failure to solve simple problems or copy geometric figures or clock reading)

Each of the cognitive deficits results in a significant impairment in functioning that represents a decline from a previous level of functioning.

Difficulties with job performance if the patient is still working. Difficulties in driving, shopping & housekeeping.

Difficulties in social functioning disengagement from usual activities & interests, trouble maintaining social relationships & social roles, and difficulty performing activities of daily living.

FUNCTIONAL IMPAIRMENT

The Neuropsychiatric Inventory (NPI) A useful tool developed to assess psychopathology

Evaluates 12 neuropsychiatric disturbances:

NEURO-PSYCHIATRIC MANIFESTATIONS

• Delusions• Hallucinations• Agitation• Dysphoria• Anxiety• Apathy• Irritability

• Euphoria• Disinhibition• Aberrant Motor Behaviour• Night-time Behaviour

Disturbance• Appetite & Eating

Abnormalities

Apathy, disinhibition, compulsivity, loss of empathy for others & overeating suggests FTD.

Agitation, aggressive behavior, uncooperative behavior, and wandering.

Agitation, particularly worsening in the evening hours, is common.

These symptoms account for substantial caregiving burden and are often the trigger for moves to higher levels of care.

BEHAVIOURAL DISTURBANCES

10% Dementia pts in early course have Major Depression.

50% Alzheimer’s pts have depressive symptoms.

Depressive symptoms, emotional lability, & irritability may be related to psychological reactions to the awareness of losing one's memory & anticipation of increasing functional impairment.

Suicidal ideation and behavior may also occur – esp in mildly impaired.

MOOD CHANGES

~ 60% of pts encounter anxiety

Manifest as fear of being alone, patients will search for their caregivers so as not to be alone.

Some patients exhibit “catastrophic reactions” when confronted with their cognitive limitations or when facing changes in routine or environment.

ANXIETY

Disinhibition

Impulsivity

Making inappropriate jokes

Being overly familiar with strangers

Disregarding social norms

Loss of judgement & reasoning

Inappropriate sexual remarks or behaviors

PERSONALITY CHANGES

o Delusions are common, usually with common themes of theft, infidelity or misidentification in late stages of AD.

o In late stages, 10% of AD patients develop Capgras’ syndrome, the delusion that a caregiver has been replaced by an impostor.

o Visual hallucinations & Capgras’ syndrome are early features in DLB.

PSYCHOSIS

SLEEP DISTURBANCES

REM sleep behavior disorder(RBD) is common in DLB.

ADVANCING DEMENTIA

ALTERED SLEEP-WAKE CYCLES

DISRUPTED AND FRAGMENTED SLEEP in ~50%

H/o movement disorders ( myoclonus in CJD) H/o seizures may indicate strokes or neoplasm but can

also occur in AD(particularly early age of onset AD) H/o gait disturbance is common in vascular dementia,

PD/DLB & NPH. H/o recurrent head trauma could indicate chronic SDH,

chronic traumatic encephalopathy(dementia pugulistica or punch-drunk syndrome), intracranial hypotension or NPH.

H/o alcohol abuse causing malnutrition & thiamine deficiency which causes Wernicke’s encephalopathy (confusion,ataxia & diplopia) & irreversible Korsakoff’s syndrome(unable to recall new information,confabulation).

H/o veganism, bowel irradiaton, gastric surgery, chronic antihistamine therapy predispose to B12 deficiency(SACD).

OTHER IMPORTANT POINTS IN HISTORY

Past H/o HTN & DM important in vascular dementia. H/o high risk sexual behaviors & IV drug abuse can lead to CNS

infection esp HIV or syphilis. Occupational History for heavy metal intoxication. H/o chronic drug intake esp. sedatives & analgesics. Family History for HD & familial forms of AD, FTD, DLB or prion

disorders.

ALZHEIMER’S DISEASE(AD) – Patients usually begin with memory symptoms but other early symptoms include difficulty with managing money, driving, shopping, following instructions, finding words or navigation.

FRONTOTEMPORAL DEMENTIA(FTD) – Suggested by personality change, disinhibition and weight gain or compulsive eating. Other suggestive points may include prominent apathy, loss of empathy for others, loss of executive function or progressive abnormalities in speech. There is relative sparing of memory or visuospatial abilities.

DEMENTIA WITH LEWY BODIES(DLB) – Suggested by early visual hallucinations, parkinsonism, proneness to delirium, REM sleep behaviour disorder(RBD) or Capgras syndrome.

VASCULAR DEMENTIA – History of sudden stroke with irregular stepwise progression.

CREUTZFELDT- JAKOB DISEASE – Rapid progression of dementia in association with motor rigidity and myoclonus.

PHYSICAL EXAMINATION Neurological examination-mobility and balance assessment Focal neurological deficits Extra-pyramidal signs Vision & hearing screening Cardiac and pulmonary evaluation

Alzheimer’s Disease – Initially neurological examination is normal. Motor system involvement occurs later in course.

Frontotemporal Dementia – Patients develop axial rigidity, supranuclear gaze palsy or a motor neuron disease.

Dementia with Lewy bodies – Initial symptoms may include new onset of a parkinsonian syndrome but it often starts with visual hallucinations or dementia.

Progressive supranuclear palsy(PSP) is a/w unexplained falls, axial rigidity, dysphagia & supranuclear vertical gaze deficits.

Corticobasal syndrome(CBS) features asymmetric rigidity, dystonia, myoclonus, apraxia of one limb, alien limb phenomenon(limb exhibits unintended motor actions such as grasping, groping, drifting or undoing), pyramidal signs, nonfluent aphasia, executive dysfunction or a behavioural disorder.

Hemiparesis or other focal neurological deficits suggest vascular dementia or brain tumour.

Dementia with myelopathy and peripheral neuropathy suggests Vitamin B12 deficiency.

Peripheral neuropathy may also indicate another vitamin deficiency, heavy metal intoxication, thyroid dysfunction, Lyme ds or vasculitis.

Dry, cool skin, hair loss and bradycardia suggest hypothyroidism.

In the elderly, Hearing impairment or visual loss may produce confusion and disorientation misinterpreted as dementia.

COGNITIVE & NEUROPSYCHIATRIC EXAMINATION

Folstein Mini-Mental Status Examination (MMSE)

Earliest deficits on cognitive testing:- AD- Episopic memory loss FTD- Deficits in executive control or language function PDD/DLB- Deficits in visuospatial function Vascular dementia-Mixture of executive comtrol & visuospatial

deficits, with prominent psychomotor slowing

MMSE

SCORE RANGE

24-30 Normal18-23 Mild10-17 Moderate< 10 Severe

INVESTIGATIONSASSESSMENTS RATIONALE

Labs: Complete blood count, serum electrolytes, renal and thyroid function and vitamin B12 level

Rule out correctable or contributory causes of dementia

Imaging: Computed tomography without contrast or magnetic resonance imaging(MRI)

Rule out infarcts, primary & metastatic neoplasms, subdural hematomas, NPH, diffuse white matter ds or regional pattern of atrophy.

PET and SPECT Temporal-parietal hypoperfusion or hypometabolism in AD & frontotemporal deficits in FTD.

Amyloid Imaging, Pittsburgh Compound-B(PiB) & 18F-AV-45(florbetapir)

Radioligands for detecting brain amyloid a/w amyloid angiopathy or neuritic plaques of AD

Lumbar Puncture Indicated when CNS infection or inflammation are possibilities. Presence of low AB42 & mildly elevated CSF tau is highly suggestive of AD.

EEG Can suggest CJD(repetitive bursts of diffuse high amplitude sharp waves or periodic complexes) or underlying nonconvulsive seizure disorder.

Brain Biopsy Only to diagnose vasculitis, potentially treatable neoplasms or unusual infections.

TREATMENT Major goals are to treat reversible causes. e.g. thyroid replacement

for hypothyroidism, vitamin therapy for thiamine & B12 deficiency, antimicrobials for infections, ventricular shunting for NPH, appropriate treatment for CNS neoplasms etc.

Symptomatic treatment in irreversible causes. Drugs used in Alzheimer’s Ds are cholinesterase inhibitors(donepezil,

rivastigmine, galantamine); NMDA receptors blockers(memantine). SSRIs are commonly used for depressive symptoms(e.g.

escitalopram) Seizures can be treated with levetiracetam. Antipsychotics such as quetiapine can be used for patients with

agitation, aggression & psychosis but all antipsychotics should be used with caution due to their untoward side effects.

DEMENTIA - SUB TYPES

ALZHEIMER’S DISEASE (AD) About 70% of all cases of dementia in elderly Incidence increases with age Occurs in up to 20-40% of persons >85 years old Risk factors include old age, family history, female sex, ApoE4 allele,

HTN,DM,elevated homocysteine & cholesterol levels, decreased folic acid level, low intake of fruits, vegetables, low levels of exercise.

Characterized by:Progressive loss of cortical neuronsFormation of neuritic plaques (beta-amyloid is major component)

and intraneuronal neurofibrillary tangles (hyperphosphorylated tau protein is major constituent)

Decrease in cortical levels of neurotransmitters esp. Ach & nicotinic cholinergic receptors.

NORMAL BRAIN CELLS

Neurotransmitters (ACh)– being sent – message being

communicated to the next cell

NORMAL BRAIN CELLS

Once the message is sent, then enzymes lock onto the messenger

chemicals and take them out of circulation so a new message can be

sent

plaques tangles

Less neurotransmit

ter Further to go to get to the next cell

Enzymes (AChE) – get to them BEFORE they

deliver their message

BRAIN CELLS WITH ALZHEIMER’S

Alzheimer’s drugs provide FAKE messenger

chemicals that distract the enzymes. They attach

to the Fake ACh & the message can get thru

(Cholinesterase inhibitors)

WHAT DO ALZHEIMER’S DRUGS DO?

CLINICAL MANIFESTATIONS Begin with memory impairment language

visuospatial skills Anosognosia - unaware of difficulties Cognitive decline-driving, shopping, house-keeping, job difficulties Language impaired- naming, comprehension then - fluency Apraxia – learned seq. motor task can’t perform Visuospatial deficits Late stages- Delusions, capgras’ syndrome,loss of judgement & reasoning,

disinhibition, disrupted sleep-wake patterns. End stage - rigid, mute, incontinent & bed-ridden, hyperactive DTRs,

myoclonic jerks. Death resuls from malnutrition,. Secondary infections, pulmonary emboli,

heart ds or, most commonly, aspiration.

AD DIAGNOSIS Neuroimaging- CT/MRI shows posterior predominant cortical

atrophy & atrophy of medial temporal memory structures (entorhinal cortex & hippocampus).

PET – Hypometabolism in posterior temporal-parietal cortex. It can also detect presence of fibrillar amyloid in the brain.

EEG- Normal or non-specific slowing Lumbar Puncture- CSF shows low AB42 & mildly elevated

tau.

Treatment- Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) & NMDA glutamate receptor blockers(memantine).

The Changing Brain in Alzheimer’s Disease

No one knows what causes AD to begin, but we do know a lot about what happens in the brain once AD takes hold.

Pet Scan of Normal Brain

Pet Scan of Alzheimer’s Disease Brain

AD and the Brain

Slide 19

VASCULAR DEMENTIA

Multi-infarct dementia- recurrent strokes -step wise progression -H/o HTN,DM,CAD MRI- multiple areas of infarction Diffuse white matter disease (Binswanger’s ds,

leukoaraiosis) -lacunar infarction, microangiopathy -dementia may be insidious in onset & progress slowly -confusion, personality changes, psychosis , emotional lability -pyramidal signs & cerebellar signs + , -gait disorder, urinary incontinence, dysarthria -MRI- B/L T2 signal hyperintensities in subcortical white matter

FRONTOTEMPORAL DEMENTIA

Often begins with marked behavioral disturbances, unlike AD Behavioral variant FTD-Apathy,disinhibition,compulsivity,loss of

empathy & overeating, deficits in executive control Semantic variant PPA- Inability to decode word,object,person-

specific & emotion meaning. Nonfluent/agrammatic variant PPA- Prominent motor speech

impairment. Memory & visuo spatial skills spared. May be accompanied by motor neuron disease. MRI- Focal atrophy of frontal, insular and/or temporal cortex Disease is subtyped according to protein composition of neuronal &

glial inclusions, which contain- tau, TDP-43 or FUS

FTLD spectrum containing tau deposition includes Pick’ s disease, Progressive supranuclear palsy syndrome(PSP-S) & Corticobasal Syndrome(CBS).

PSP-S(Steele-Richardson-Olszewski syndrome)- It involves degeneration of brainstem,basal ganglia,limbic structures & selected area of cortex. It is characterized by falls, personality changes, supranuclear vertical gaze palsy, axial dystonia with hypererect posture,dysarthria,dysphagia & symmetric axial rigidity.

Corticobasal syndrome(CBS) is dementia movement disorder a/w atrophy in perirolandic cortex & basal ganglia. Patients present with asymmetric rigidity, dystonia, myoclonus, apraxia of one limb, alien limb phenomenon(limb exhibits unintended motor actions such as grasping, groping, drifting or undoing), pyramidal signs, nonfluent aphasia, executive dysfunction or a behavioural disorder.

Treatment of FTD is symptomatic. SSRIs can be used.

PARKINSON’S DISEASE DEMENTIA AND DEMENTIA WITH LEWY BODIES

When dementia occurs after an established diagnosis of Parkinson’s Disease, the term used is Parkinson’s Disease Dementia(PDD).

When dementia precede or co-emerge with parkinsonism, it is referred to as Dementia with Lewy Bodies(DLB).

DLB is characterized by visual hallucinations,parkinsonism,fluctuating alertness, falls, capgras syndrome & REM sleep behavior disorder(RBD).

Better memory but severe visuospatial deficit. Patients sensitive to adverse effects of neuroleptics Lewy bodies are found in brainstem, substantia nigra, limbic system

and cortex. Lewy bodies are intraneuronal cytoplasmic inclusions containing

alpha-synuclein. Cholinesterase inhibitors provide significant benefit.

NORMAL PRESSURE HYDROCEPHALUS

Triad1. Dementia: typically subcortical with executive impairment2. Gait instability(ataxic or apractic)3. Urinary incontinence

Walk with “feet stuck to floor”. Symptoms progress over weeks to months. It is a communicating hydrocephalus with a patent aqueduct of

sylvius. LP opening pressure falls in high normal range. Cause is obstruction to normal CSF flow over cerebral convexities &

delayed resorption into venous system. CT shows enlarged lateral ventricles with little or no cortical

atrophy, although sylvian fissures may appear propped open(so called “boxcarring”), which can be mistaken for perisylvian atrophy.

CRUETZFELDT-JAKOB DISEASE(CJD)

Rapidly progressive prion disorder a/w dementia, focal cortical signs, rigidity & myoclonus.

90% has myoclonus vs 10% in AD Death <1 year after first symptom appear. EEG- diffuse slowing and abnormal periodic complexes. MRI- Cortical ribboning & basal ganglia hyperintensities on

FLAIR MRI. CSF- detect specific amino acid sequence (PrPSc)

CASE 1 70 yr old female present with progressive memory loss for

past 1 yr. She also complaints of difficulty in naming objects and driving car and house keeping. for the past 1 month she has difficulty in dressing ,eating and gets agitated easily and wanders around at night.

MMSE – 15/30 Neurological exam- normal Vision & hearing- normal

CASE 2 76 yr old male presented in neuro opd with c/o progressive

memory loss, emotional lability, gait disturbance for past 5 months

h/o of 3 episodes of cerebrovascular accidents + recent attack 7 months back h/o HTN,DM,CAD+ O/E- incresed tone in all limbs,power 3+ in RT.UL &LL. 4+ in

LT side, B/L extensor plantar

CASE 3 55 YR old woman presented with 2yr history of progressive

alteration in social behavior. The pt had h/o social disinhibition, abusive language, euphoria. there are complaints of excessive food intake and weight gain for past 1 yr and pt was taken to psychiatrist once.

o/e- vitals stable..neurological exam –WNL MMSE-18/30

CASE 4 82 yr old male came to opd with c/o progressive decline in

memory for the past 6-8 months. He also complaints of having decreased sleep and occasional nightmares. He occasional sees his deceased wife at times.

o/e- vitals stable ,rigidity of limbs+ - gait- slow stepping gait, bradykinesia+

MMSE- 21/30

WHAT IS THE DIAGNOSIS?

CASE 5 65 YR old male presented to neuro opd with c/o gait

disturbance for past 1 yr. On history taking his son complained his father is having memory loss for past 6 months and it is progressing.

The pt also c/o of urinary incontinence+ Neurolog exam- no focal deficits MMSE- 23/30

CASE 6 50 YR old woman was admitted with c/o progressive memory

loss and gait problem ,slurred speech within one month; The pt also had behavioral problem – insomnia, agitation,aggression duration of 3 weeks.the pt also c/o abnormal jerky hand movements for past 1 month

o/e- limb & gait ataxia +, reflexes-exagg. - tone increased all limbs, plantar b/l extensor - no focal weakness

MMSE- 16/30

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