Post on 30-Dec-2019
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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