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DEMENTIA

HIHIM 409

Definition

n  Acquired generalized and often progressive impairment of cognitive function that affects the content, but not the level, of consciousness.

DSM-IV Criteria for Dementia:

1.  The gradual onset and continuing decline of cognitive function from a previously higher level, resulting in impairment in social or occupational function

2.  Impairment of recent memory (the inability to learn new information), and at least one of the following:

a)  Language (word-finding difficulties) b)  Disturbances of praxis (inability to execute

skilled motor activities in the absence of weakness)

DSM-IV Criteria for Dementia: (cont.)

c)  Disturbances of visual processing (visual agnosia and constructional disturbances)

d)  Disturbances of executive function (including abstract reasoning and concentration)

3.  The cognitive deficits are not due to other psychiatric disease, neurologic diseases, or systemic diseases, and the deficits do not exclusively occur in the setting of delirium

Mild Cognitive Impairment

§ MMSE 24-28 Problem with recollection Does not meet dementia criteria

Differential Diagnosis: 1. Alzheimer Disease (pure ~40%, + mixed~70%) 2. Vascular Disease, MID (5-20%) 3. Drugs, Depression, Delirium 4. Ethanol 5. Medical / Metabolic Systems 6. Endocrine (thyroid, diabetes) 7. Neurologic, Nutritional (other primary

degenerations, etc.) 8. Tumor, Toxin, Trauma 9. Infection, Idiopathic, 10. Amnesia, Autoimmune,

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Treatable causes n  ~ 15% of causes n  NPH n  IC mass lesion (tumor, SDH) n  B12 def. n  Hypothyroidism n  Syphilis n  Depression

Estimate MMSE as a function of time

051015202530

-10 -8 -6 -4 -2 0 2 4 6 8 10

Estimated years into illness

MM

SE

sco

re

AAMI / MCI DEMENTIA

Evaluation n  Good history and physical

n  Time course, associated symptoms, PMH, Drugs n  Family Hx and good mental status examination

n  CBC, chem. 18 (with electrolytes and LFTs), TFTs, B12, RPR/VDRL, ESR, ANA, RF n  Young pts: Wilson's work-up, porphyria work-up, 24-hour

urine for heavy metals, HIV, PPD, ACE level, vitamin E n  CT &/or MRI n  EEG n  EKG

Evaluation (cont.) n  Urinalysis n  LP (with cytology, AFB and fungal stains,

ACE level, MS profile, etc.) n  Neuropsychological testing if trouble with

diagnosis n  Arteriogram/Brain biopsy as indicated

Dementia Vs acute confusional state

Alzheimer’s Disease

(AD)

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Alzheimer’s Disease (AD) Alzheimer’s Disease (AD)

n  Epidemiology n  Most common degenerative disease of the brain n  10% of people over age 65 years have AD n  20% of persons > 80 years n  30% of > 90 years old n  Male = Female

Histopathology: n  Macroscopic:

n  Atrophy, mostly temporoparietal and frontal n  Microscopic

n  Loss of neurones and synapses n  Neurofibrillary tangles (NFTs) n  amyloid plaques ( Neurotic plaques) n  Granulovsacular degeneration

n  Chemistry n  loss of neurotransmitters, especially acetylcholine

(ACh)

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Tangles

AD: a progressive CNS disorder with a characteristic pathology

Brain atrophy

Senile plaques

Neurofibrillary tangles

Katzman, 1986; Cummings and Khachaturian, 1996

Numerous tangles in hippocampus Amyloid plaque

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Risk factors for AD:

Down’s syndrome

Strong risk factors for AD* n  Age n  Down’s syndrome n  Family history n  Certain genes associated with increased risk

but do not cause AD e.g. ApoE4

Genetics

Clinical features of AD n  Gradual decline of intellectual function n  Poor short-term memory n  Visuospatial disorientation n  Language/speech problems—aphasia, anomia, and later

echolalia, mutism n  Apraxias—dressing, ideomotor n  Personality changes: indifference, apathy n  Psychiatric: Hallucination, delusions, behavioural

disturbances n  limb rigidity, flexion posture n  Urinary and faecal incontinence

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MRI: profound atrophy Treatment

n  No cure n  Anticholinesterases

n  Tacrine, Donepezil, Rivastigmine n  Alpha tocopherol (vitamin E) n  Selegiline n  Psychotropic drugs: agitation, delusions n  Antidepressants n  Nursing home

Dementia with Lewy bodies

n  Up to 20% of dementias n  Dementia (as previously defined) n  Lewy bodies diffusely through cortex n  Markedly fluctuating cognitive impairment n  Visual and/or auditory hallucinations n  Paranoid delusions n  Falls n  Extrapyramidal features: rigidity & bradykinesia n  Neuroleptic sensitivity: extrapyramidal S/Es

Dementia with Lewy bodies

Vascular dementia

Vascular dementia n  Also called multi-infarct dementia (MID) n  About 15-20% n  Decline can be linear or step-wise

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Vascular dementia

n  Step-wise decline - uneven steps, varying plateau

n  Earlier onset than AD and M > F n  Sudden onset, stepwise deterioration n  h/o high bp, strokes n  Evidence associated arteriosclerosis, eg

coronary artery disease n  Focal neurological symptoms and signs n  Focal pathology on brain imaging

VaD -vs.- AD

Fronto-temporal dementia Pick’s disease

n  Macroscopic and brain scan - atrophy only in frontal and temporal areas (until late in disease)

n  Diagnosis easily missed initially n  Histopathology:

n  Pick cells n  Pick inclusion bodies

n  No amyloid plaques nor NFT n  No Rx

Fronto-temporal dementia Pick’s disease

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Fronto-temporal dementia Pick’s disease (cont.)

n  Onset 40-60 y.o. (20-80 y. range) n  Preservation of memory until late n  Early symptoms behavioural or psychiatric n  Apathy, irritability n  Loss of concern n  Impaired judgement and insight n  Language affected

Creutzfeldt-Jakob

disease

Creutzfeldt-Jakob disease

n  Transmissible: cornea transplants, intracerebral recording electrode implants, growth hormone

n  Rapidly progressive dementia n  Focal involvement of the cerebral cortex, basal ganglia,

cerebellum, brainstem, and spinal cord n  Etiologic agent: proteinaceous infectious particle

(prion) n  PrPc

n  Cellular isoform n  Mutation leads to accumulation of PrPSc n  Familial cases

n  PrPSc n  Sporadic cases

Creutzfeldt-Jakob disease (cont.)

n  Dementia n  Psychiatric symptoms n  Myoclonus n  Extrapyramidal signs n  Cranial nerve palsies n  New Variant: bovine spongiform encephalopathy

n  Earlier onset (mean age, about 30 years) n  More prolonged course (median duration over 1 year) n  Prominent early psychiatric abnormalities, including

depression and personality changes.

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Creutzfeldt-Jakob disease (cont.)

n  Investigation: n  EEG: periodic sharp waves and spikes n  Detection of PrPSc in brain tissue

n  Prognosis: n  Invariably fatal n  Death w/n 1 yr

NORMAL-PRESSURE HYDROCEPHALUS

NORMAL-PRESSURE HYDROCEPHALUS

n  Sometimes called communicating (lateral, 3rd, 4th ventricles remain in communication) or nonobstructive hydrocephalus

n  Triad n  Dementia n  Gait apraxia n  Incontinence

n  Idiopathic or secondary (meningitis, SAH) n  Memory defects, but rarely aphasia and agnosia

NORMAL-PRESSURE HYDROCEPHALUS (cont.)

n  Weeks-months n  Gait apraxia early, with weight bearing n  Pyramidal signs n  Urinary incontinence n  Lp: normal or low opening pressure

n  Remove 30-50 cc; prognostication n  CT scan or MRI: enlarged lateral ventricles without

increased prominence of cortical sulci n  Cisternography: delayed clearance n  Rx: CSF shunting; VA,VP,LP

THE END