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

8/7/11 Definition DEMENTIA n Acquired generalized and often progressive impairment of cognitive function that affects HIHIM 409 the content, but not the level, of consciousness. DSM-IV Criteria for Dementia: DSM-IV Criteria for Dementia: (cont.) 1. The gradual onset and continuing decline of c) Disturbances of visual processing (visual agnosia cognitive function from a previously higher level, and constructional disturbances) resulting in impairment in social or occupational function d) Disturbances of executive function (including 2. Impairment of recent memory (the inability to abstract reasoning and concentration) learn new information), and at least one of the 3. The cognitive deficits are not due to other following: psychiatric disease, neurologic diseases, or a) Language (word-finding difficulties) systemic diseases, and the deficits do not b) Disturbances of praxis (inability to execute exclusively occur in the setting of delirium skilled motor activities in the absence of weakness) Differential Diagnosis: Mild Cognitive Impairment 1. A lzheimer Disease (pure ~40%, + mixed~70%) § MMSE 24-28 2. V ascular Disease, MID (5-20%) Problem with recollection 3. D rugs, D epression, D elirium Does not meet dementia criteria 4. E thanol 5. M edical / M etabolic Systems 6. E ndocrine (thyroid, diabetes) 7. N eurologic, Nutritional (other primary degenerations, etc.) 8. T umor, T oxin, T rauma 9. I nfection, I diopathic, 10. A mnesia, A utoimmune, 1

8/7/11 Treatable causes Estimate MMSE as a function of time n ~ 15% of causes 30 n NPH 25 MMSE score n IC mass lesion (tumor, SDH) 20 15 n B12 def. 10 n Hypothyroidism 5 n Syphilis 0 -10 -8 -6 -4 -2 0 2 4 6 8 10 n Depression Estimated years into illness AAMI / MCI DEMENTIA Evaluation Evaluation (cont.) n Good history and physical n Urinalysis n Time course, associated symptoms, PMH, Drugs n LP (with cytology, AFB and fungal stains, n Family Hx and good mental status examination ACE level, MS profile, etc.) n CBC, chem. 18 (with electrolytes and LFTs), TFTs, B12, RPR/VDRL, ESR, ANA, RF n Neuropsychological testing if trouble with n Young pts: Wilson's work-up, porphyria work-up, 24-hour diagnosis urine for heavy metals, HIV, PPD, ACE level, vitamin E n Arteriogram/Brain biopsy as indicated n CT &/or MRI n EEG n EKG Dementia Vs acute confusional state Alzheimer’s Disease (AD) 2

8/7/11 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 L oss 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) 3

8/7/11 Tangles AD: a progressive CNS disorder with a characteristic pathology Brain atrophy Senile plaques Neurofibrillary tangles Katzman, 1986; Cummings and Khachaturian, 1996 Amyloid plaque Numerous tangles in hippocampus 4

8/7/11 Risk factors Strong risk factors for AD* for AD: Down’s n Age syndrome 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 The n Gradual decline of intellectual function bee poin 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 5

8/7/11 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) Dementia with Lewy n Lewy bodies diffusely through cortex n Markedly fluctuating cognitive impairment bodies n Visual and/or auditory hallucinations n Paranoid delusions n Falls n Extrapyramidal features: rigidity & bradykinesia n Neuroleptic sensitivity: extrapyramidal S/Es Vascular dementia n Also called multi-infarct dementia (MID) n About 15-20% Vascular dementia n Decline can be linear or step-wise 6

8/7/11 VaD -vs.- AD Vascular dementia 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 n Step-wise decline - uneven steps, varying plateau Fronto-temporal dementia Pick’s disease Fronto-temporal dementia n Macroscopic and brain scan - atrophy only in frontal and temporal areas (until late in Pick’s disease disease) n Diagnosis easily missed initially n Histopathology: n Pick cells n Pick inclusion bodies n No amyloid plaques nor NFT n No Rx 7

8/7/11 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 Creutzfeldt-Jakob n Early symptoms behavioural or psychiatric n Apathy, irritability disease n Loss of concern n Impaired judgement and insight n Language affected Creutzfeldt-Jakob disease Creutzfeldt-Jakob disease (cont.) n Transmissible: cornea transplants, intracerebral n Dementia recording electrode implants, growth hormone n Psychiatric symptoms n Rapidly progressive dementia n Myoclonus n Focal involvement of the cerebral cortex, basal ganglia, n Extrapyramidal signs cerebellum, brainstem, and spinal cord n Cranial nerve palsies n Etiologic agent: proteinaceous infectious particle n New Variant: bovine spongiform encephalopathy ( prion ) n Earlier onset (mean age, about 30 years) n PrP c n More prolonged course (median duration over 1 year) n Cellular isoform n Prominent early psychiatric abnormalities, including n Mutation leads to accumulation of PrP Sc depression and personality changes. n Familial cases n PrP Sc n Sporadic cases 8

8/7/11 Creutzfeldt-Jakob disease (cont.) n Investigation: n EEG: periodic sharp waves and spikes n Detection of PrP Sc in brain tissue n Prognosis: n Invariably fatal n Death w/n 1 yr NORMAL-PRESSURE HYDROCEPHALUS n Sometimes called communicating (lateral, 3 rd , NORMAL-PRESSURE 4 th ventricles remain in communication) or nonobstructive hydrocephalus 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 THE END 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 9