DEMENTIA n Acquired generalized and often progressive impairment of - - PDF document

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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

5 10 15 20 25 30

• 10
• 8
• 6
• 4
• 2

2 4 6 8 10 Estimated years into illness MMSE score

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

The bee poin

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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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The may Veri loca

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