DementiaDementia

Prof AK DaifProf AK Daif

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WHAT IS DEMENTIAWHAT IS DEMENTIA??• An acquired syndrome of decline in memory and other

cognitive functions sufficient to affect daily life in an alert patient

• Progressive and disabling

• NOT an inherent aspect of aging

• Different from normal cognitive lapses

Dementias – classificationDementias – classificationBased on siteBased on site

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DSM-IV DIAGNOSTIC CRITERIA FOR DSM-IV DIAGNOSTIC CRITERIA FOR ADAD

• Development of cognitive deficits manifested by both• impaired memory

• aphasia, apraxia, agnosia, disturbed executive function

• Significantly impaired social, occupational function• Gradual onset, continuing decline• Not due to CNS or other physical conditions (e.g., PD,

delirium)

• Not due to an Axis I disorder (e.g., schizophrenia)

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NORMAL LAPSES NORMAL LAPSES vs vs

DEMENTIADEMENTIA• Forgetting a name

• Leaving kettle on

• Finding right word

• Forgetting date or day

• Not recognizing family member

• Forgetting to serve meal just prepared

• Substituting inappropriate words

• Getting lost in own neighborhood

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Mild Cognitive Mild Cognitive ImpairmentImpairment

“Mild Cognitive Impairment (MCI) is a state between normal cognition and dementia, characterized by deficits not

explainable by age, educational background, or medical illness.”

Kryscio RJ, Schmitt FA, et al. Risk factors for transitions from normal to mild cognitive impairment and dementia. Neurology 2006; 66: 828-32.

• MCI is common (5-25%)• MCI carries an increased risk of dementia and of death

– If the deficits exist primarily in memory and executive function, risk of progression to dementia is higher

• 10-15% per yr rate of development of dementia and AD compared to 1-7% per yr for those without MCI

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DIFFERENTIAL DIAGNOSIS DIFFERENTIAL DIAGNOSIS FOR DEMENTIAFOR DEMENTIA

• Alzheimer’s disease• Vascular (multi-infarct) dementia• Dementia associated with Lewy bodies• Delirium• Depression• Other (alcohol, Parkinson's disease [PD], Pick’s

disease, frontal lobe dementia, neurosyphilis)

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ASSESSMENT: ASSESSMENT: HISTORY/PHYSICALHISTORY/PHYSICAL

• Ask both the patient & a reliable informant

• Current condition• Medical history• Current medications • Patterns of alcohol use or

abuse• Living arrangements

• Neurologic status• Functional Status• Mental Status• ie. Folstein, MiniCog, • Neuropsych testing

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Evaluation of DementiaEvaluation of Dementia

• Standard laboratory studiesStandard laboratory studies– Complete blood count

• Anemia, infection

– Comprehensive metabolic panel • Glucose, electrolytes, renal or hepatic failure

– Thyroid function tests

• Studies done in suspect casesStudies done in suspect cases– Estimated sedimentation rate – Serology for syphilis, HIV, lyme disease– Screen for heavy metals

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ASSESSMENT: BRAIN IMAGINGASSESSMENT: BRAIN IMAGING

• Use imaging when:– Onset occurs at age < 65 years– Symptoms have occurred for < 2 years– Neurologic signs are asymmetric– Clinical picture suggests normal-pressure hydrocephalus

• Consider:– Noncontrast computed topography head scan– Magnetic resonance imaging– Positron emission tomography

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Evaluation of DementiaEvaluation of Dementia

• Radiologic/Neuro-Imaging studiesRadiologic/Neuro-Imaging studies• Carotid dopplers • CT Scan, MRI of Brain

– Linear/volumetric measurement is not recommendedLinear/volumetric measurement is not recommended• PET and SPECT imaging not recommended for routine

use in the diagnosis of dementia– “Little evidence to support the routine useroutine use of PET in pts with

suspected or established dementia” JAGs 51: 2003 Clinical criteria accurate in 90%

*PET scan may help clarify Alzheimer’s vs. other types dementias in those *PET scan may help clarify Alzheimer’s vs. other types dementias in those already fully evaluatedalready fully evaluated

*SPECT scan may help identify early dementia but studies are limited*SPECT scan may help identify early dementia but studies are limited

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Potential Reversible CausesPotential Reversible Causes

• Neoplasms• Metabolic disorders• Trauma • Toxins• Infections• Autoimmune

disorders• Drugs

• Nutritional disorders• Psychiatric disorders• Normo-pressure

Hydrocephalius (NPH)

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Distinguishing DementiaDistinguishing Dementia

• Delirium versus Dementia– Acute onset– Cognitive fluctuations over hours or days– Impaired consciousness and attention– Altered sleep cycles

• Depression versus Dementia– Demonstrate motivation during cognitive testing– Express cognitive complaints that exceed measured

deficits– Maintain language and motor skills

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SPECIFIC SPECIFIC DEMENTIAS…DEMENTIAS…

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Alzheimer’s DementiaAlzheimer’s Dementia

• Dementia NOT caused by other medical/mood or CNS disorder– Definitive diagnosis is on brain biopsy/autopsy

• Neurofibrillary tangles and senile plaques• Reduced cerebral production of choline acetyl transferase• Decreased Acetylcholine synthesis• Marked cholinergic deficit

– DSM-IV criteria• Cognitive deficits including impaired memory, executive function and

aphasia/apraxia/agnosia• Gradual onset, continuing decline; impaired social/occupational

function

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SYMPTOMS & SIGNS OF ADSYMPTOMS & SIGNS OF AD

• Memory impairment• Gradual onset, progressive cognitive decline• Behavior and mood changes• Difficulty learning, retaining new information• Aphasia, apraxia, disorientation, visuospatial dysfunction• Impaired executive function, judgment• Delusions, hallucinations, aggression, wandering

Alzheimer's diseaseAlzheimer's disease

• CT scanning aids diagnosis by excluding multiple infarction or a mass lesion.

• MRI shows bilateral temporal lobe atrophy.

• SPECT usually shows temporoparietal hypoperfusion.

The brain in ADThe brain in AD

microscopic view:

neurofibrillary tangles and protein deposits

macroscopic view:

neuronal loss appears as atrophy

2020PET scan in Alzheimer’s disease

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PROGRESSION OF ADPROGRESSION OF AD

Mild Impairment• Disorientation for date• Naming difficulties• Recent recall problems• Mild difficulty copying

figures• Decreased insight• Social withdrawal• Irritability• Mood change• Problems managing

finances

Moderate• Disorientation for date and

place• Comprehension difficulties• Impaired new learning,

calculating skills• Getting lost in familiar areas,

wandering• Not cooking, shopping, banking• Delusions, hallucinations• Agitation, restlessness, anxiety,

aggression• Depression• Problems with dressing and

grooming• Aphasia and apraxia

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PROGRESSION OF ADPROGRESSION OF AD

Severe Impairment• Nearly unintelligible verbal output• Remote memory gone• Unable to copy or write• Unable to feed*• No longer grooming or dressing• Incontinent• Unable to Walk

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Other Dementias……..Other Dementias……..

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DSM-IV DIAGNOSTIC CRITERIA DSM-IV DIAGNOSTIC CRITERIA FOR VASCULAR DEMENTIAFOR VASCULAR DEMENTIA

• Development of cognitive deficits manifested by both

• impaired memory• aphasia, apraxia, agnosia, disturbed executive function

• Significantly impaired social, occupational function• Focal neurologic symptoms & signs or evidence of

cerebrovascular disease• Stepwise Deterioration (after each event)

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Multi-infarct dementia Multi-infarct dementia (MID)(MID)

• This is an overdiagnosed condition which accounts for less than 10% of cases of dementia.

• MID is caused by multiple strokes - SILENT STROKES• Dementia occurs ’stroke by stroke‘, with progressive focal

loss of function.• Clinical features of stroke profile – hypertension,

diabetes, etc. – are present. More often in males.• Diagnosis is obtained from the history

and confirmed by CT or MRI scan (the presence of multiple areas of infarction).

• Treatment: Maintain adequate blood pressure control, anti-platelet aggregants (aspirin).

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DEMENTIA ASSOCIATED WITH DEMENTIA ASSOCIATED WITH

LEWY BODIESLEWY BODIES• Dementia

• Visual hallucinations

• Parkinsonian signs

• Alterations of alertness or attention

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DLB-Other FeaturesDLB-Other Features

• Neuroleptic Sensitivity (ie Olanzapine)

• Falls

• Early incontinence

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OTHER DEMENTIASOTHER DEMENTIAS• Alcoholic Dementia

– Direct effects of alcohol, Secondary effects of alcohol,Wernicke-korsakoff syndrome

• Toxic Metal and Gas Exposure– Common exposures: lead, mercury, manganese, arsenic,

carbon monoxide & carbon disulfide

• Vitamin Deficiencies– Vitamins B12, folate, niacin, and thiamine

– More severe B12 deficiency: subacute combined degeneration

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Organic causes of dementiaOrganic causes of dementia

• Organ Failure (liver, kidneys)

• Endocrine (hypothyroidism, diabetes)

• Inflammatory (Lupus)

• Neurodegenerative causes (multiple sclerosis & Huntington’s Chorea)

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• May appear similar to Alzheimer’s…..• Early treatment may reverse cognitive

changes before they become permanent• Triad of symptoms: gait instability, urinary

incontinence and dementia – Wide-based, shuffling gait with poor coordination– Incontinence follows gait change, includes urgency– Slow thinking/response, decreased spontaneity

• Enlarged ventricles on MRI– But no evidence of atrophy: Alzheimer’s shows large

ventricles due to brain atrophy

Normal-Pressure Normal-Pressure HydrocephalusHydrocephalus

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Parkinson DementiaParkinson Dementia

• Age Onset: 50 to 80; survival 8-15 yrs• Dementia occurs later in the disease, mild to

mod.• Slowness of thought• Neuropsychiatric symptoms common• Dysphagia, dysphonia

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Frontotemporal DementiaFrontotemporal Dementia

• Diagnostic criteria similar to Alzheimer’sBUTBUT

• Onset typically younger (less than 65 years)• Predominant changes/disturbances in behavior

– Personality change is a hallmark– Changes occur early and progress

• Non-fluent, expressive aphasia common– Words remain but are presented in nonsensical format

• Frontal and/or temporal atrophy on MRI• Early absence of neurologic signs, neurologic signs occur

with progression

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Structural Structural Changes in Changes in MRI:MRI:

Fronto-Fronto-temporal temporal dementiasdementias

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Parkinson Plus DementiasParkinson Plus Dementias

• Dementia occurs early

Additional physical symptoms

• More frontal lobe features

• Earlier onset, more rapid course

• Frontal lobe features

• Poor response to levodopa

• Rapidly accelerates

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Multisystem AtrophyMultisystem Atrophy

• Onset 55; survival 6-7 years

• Autonomic dysfunction (incontinence, impotence, orthostasis)

• Ataxia, dysarthria, contractures, dystonia• Mild to moderate dementia• Less tremor

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Progressive Supranuclear Palsy: Progressive Supranuclear Palsy: Dudley Moore (1935-2002Dudley Moore (1935-2002))

• Initially presents similar to Parkinsons (earlier age)

• Difficulty with vision• Falls• Unable to look down• Dysarthria/dysphagia• Lifespan 6 years

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Progressive Supranuclear PalsyProgressive Supranuclear Palsy

• Onset: late 50 to mid 60, survival 10 years• Mental slowness, frontal lobe dysfunction,

pseudobulbar symptoms• “surprised look”• Dysarthria, dysphagia• Often misdiagnosed:late onset of eye sx, missed

gait and posture instability

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AIDS dementia complexAIDS dementia complex• Approximately two-thirds of persons with AIDS

develop dementia, mostly due to AIDS dementia complex.

• In some patients HIV is found in the CNS at postmortem. In others an immune mechanism or an unidentified pathogen is blamed.

• Dementia is initially of a "subcortical " type.• CT - atrophy; MRI - increased T2 signal from

white matter.• Treatment with Zidovudine (AZT) halts and

partially revers neuropsychological deficit.

Dementia – diagnostic approachDementia – diagnostic approach

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MANAGEMENT……….MANAGEMENT……….

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SYMPTOM MANAGEMENTSYMPTOM MANAGEMENT

• Sundowning

• Psychoses (delusions, hallucinations)

• Sleep disturbances

• Aggression, agitation

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NONPHARMACOLOGICNONPHARMACOLOGIC

• Cognitive enhancement

• Individual and group therapy

• Regular appointments

• Communication with family, caregivers

• Environmental modification

• Attention to safety

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PHARMACOLOGICPHARMACOLOGIC• Cholinesterase inhibitors: Inhibit cholinesterase at the

synaptic cleft

• Offer a small improvement : cognition and activities of daily

living

• Examples: • donepezil, rivastigmine,

galantamine

• Memantine: (Namenda): N-Methyl-D-Aspartate

• Antagonist: A receptor activated by glutamate: decr nmda

• excessive nmda: • excitotoxicity and neurotransmittter

damage

• Memantine is neuroprotective & disease modifying;

• for moderate to severe dementia

• alone or in combination

• Other cognitive enhancers: estrogen, NSAIDs, ginkgo, vit. E

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IMPROVEMENT w/ NAMENDAIMPROVEMENT w/ NAMENDA

                                                                                                                                                

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TREATING PSYCHOSIS IN TREATING PSYCHOSIS IN DEMENTIADEMENTIA

Antipsychotic medications (side effects):• Higher potency: haloperidol (extrapyramidal symptoms)• Lower potency: thioridazine (anticholinergic effects,

sedation, hypotension, constipation, urine retention)• Atypical antipsychotics: clozapine, risperidone, olanzapine Beware new prescribing information on some of the atypical

antipsychotics!

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ANTIPSYCHOTICS USED IN ANTIPSYCHOTICS USED IN DEMENTIADEMENTIA

Drug Starting Dose Peak Effective Dose

Clozapine 12.5-25 mg twice daily 100 mg daily

Haloperidol 0.25 at bedtime 3-5 mg daily

Olanzapine 1.25-2.5 mg at bedtime 5 mg daily

Risperidone 0.25-0.5 mg at bedtime 1-1.5 mg daily

Note: Start low, go slow.

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MANAGING SLEEP MANAGING SLEEP DISTURBANCESDISTURBANCES

• Improve sleep hygiene (e.g, consistent bedtime, comfortable setting)

• Provide daytime activity, prevent daytime sleeping

• Use bright-light therapy

• Treat associated depression, delusions

• If the above do not succeed, consider:• trazodone 25-150 mg• nefazodone 100-500 mg• zolpidem 5-10 mg

• Avoid benzodiazepines or antihistamines

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MANAGING AGITATIONMANAGING AGITATION• Behavioral interventions: distraction,

supervision, routine, structure

• Behavior modification using rewards

• Pharmacologic interventions: antipsychotics, antidepressants, mood stabilizers, buspirone, -blockers

• Avoid physical restraints

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RESOURCES RESOURCES FOR MANAGEMENTFOR MANAGEMENT

• Specialist referral to:

• geriatric psychiatrist

• Neuropsychologist

• Social worker

• Physical therapist

• Attorney• Day Care, Respite

Care• Alzheimer’s

Association• Meals on Wheels