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Dementia

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Dementia

  1. 1. Dementia  Syndrome characterized by deterioration of ◦ Memory + 2 other cognitive domains:  Language  Visuospatial ability  Calculation  Judgment  Problem solving  Praxis  Deterioration must be severe enough to interfere with usual social functioning and activities of daily life Etiology of Dementia  Most Common Causes: ◦ Alzheimer's disease ◦ Vascular dementia  Multi-infarct  Diffuse white matter disease (Binswanger's) ◦ Alcoholism ◦ Parkinson's disease ◦ Drug/medication intoxication  Other Causes: ◦ Vitamin deficiencies  Thiamine (B1): Wernicke's encephalopathy  B12 (pernicious anemia)  Nicotinic acid (pellagra) ◦ Endocrine and other organ failure  Hypothyroidism  Adrenal insufficiency and Cushing's syndrome  Hypo- and hyperparathyroidism  Renal failure  Liver failure  Pulmonary failure ◦ Chronic infections  HIV  Neurosyphilis  Papovavirus (progressive multifocal leukoencephalopathy)  Prion (Creutzfeldt-Jakob and Gerstmann-Sträussler- Scheinker diseases)  Tuberculosis, fungal, and protozoal  Whipple's disease ◦ Head trauma and diffuse brain damage  Dementia pugilistica  Chronic subdural hematoma  Postanoxia Postencephalitis  Normal-pressure hydrocephalus ◦ Neoplastic  Primary brain tumor  Metastatic brain tumor  Paraneoplastic limbic encephalitis ◦ Toxic disorders  Drug, medication, and narcotic poisoning  Heavy metal intoxication  Dialysis dementia (aluminum)  Organic toxins ◦ Psychiatric  Depression (pseudodementia)  Schizophrenia  Conversion reaction ◦ Degenerative disorders  Huntington's disease  Pick's disease  Dementia with Lewy bodies  Progressive supranuclear palsy (Steel-Richardson syndrome)  Hereditary ataxias (some forms)  Etiology of Dementia  Motor neuron disease [amyotrophic lateral sclerosis (ALS); some forms]  Frontotemporal dementia  Cortical basal degeneration  Multiple sclerosis  Adult Down's syndrome with Alzheimer's  ALS–Parkinson's–Dementia complex of Guam ◦ Miscellaneous  Sarcoidosisa Vasculitis  CADASIL  Acute intermittent porphyria  Recurrent nonconvulsive seizures ◦ Additional conditions in children or adolescents  Hallervorden-Spatz disease  Subacute sclerosing panencephalitis  Metabolic disorders (e.g., Wilson's and Leigh's diseases, leukodystrophies, lipid storage diseases, mitochondrial mutations)  Approach to patient with dementia Important questions to answer: 1. What is the most accurate diagnosis? 2. Is there a treatable or reversible component to the dementia?  Differential Diagnosis: Treatable forms of dementia  Neurosyphilis  Chronic meningitidis  Normal Pressure Hydrocephalus  Chronic Subdural Hematoma  Nutritional deficiencies ◦ Wernicke-Korsakoff syndrome ◦ Marchiafava-Bignami disease ◦ Pellagra ◦ Vitamin B12 deficiency  Endocrine-Metabolic Disorders ◦ Myxedema ◦ Hashimoto thyroiditis encephalopathy ◦ Cushing Disease ◦ Chronic Hepatic Encephalopathy  Frontal and temporal lobe tumors  Cerebral vasculitis  Pseudodementia of depression  History  Onset, duration, tempo of progression of dementia ◦ Acute or subacute confusion  Infectious, metabolic derangement ◦ Slowly progressive memory loss in an elderly px  Alzheimer’s Disease ◦ Stepwise progression of dementia  Multi-infarct Dementia  Associated symptoms ◦ Early visual hallucination, parkinsonism, delirium  Dementia with Lewy Body ◦ History of Hypertension, Atrial Fibrillation, Diabetes  Multi-infarct Dementia ◦ Rapid progression of the dementia in association with motor rigidity and myoclonus  Creutzfeldt-Jakob Disease (CJD) ◦ Change in personality, disinhibition, apathy, progressive abnormalities in speech, relative sparing of memory  Frontotemporal Dementia  History  Recurrent head trauma ◦ Dementia pugilistica ◦ Chronic subdural hematoma ◦ Normal pressure hydrocephalus  Seizures ◦ Strokes or Neoplasm  Gait disturbance
  2. 2. ◦ Multi-infarct dementia, Parkinson’s Disease Dementia, Normal Pressure Hydrocephalus  Family history of dementia ◦ Huntington Disease ◦ Familial Alzheimer Disease  Occupation ◦ Working in a battery or chemical factory  Heavy Metal Intoxication  Review of medications ◦ Chronic sedative or tranquilizer intoxication  Recent death of a loved one, depressive signs ◦ Pseudodementia secondary to depression PE and Neurologic Examination  Corticobasal degeneration (CBD) ◦ Dystonia, alien hand, and asymmetric extrapyramidal, pyramidal, or sensory deficits or myoclonus  Progressive supranuclear palsy (PSP) ◦ Unexplained falls, axial rigidity, dysphagia, and vertical gaze deficits  Vitamin B12 deficiency ◦ Dementia with a myelopathy and peripheral neuropathy  Alzheimer’s Disease (AD) ◦ Earliest deficits involve verbal or visual episodic memory  FTD ◦ Earliest deficits often involve frontal executive or language (speech or naming) function  DLB ◦ More severe deficits in visuospatial function but do better on episodic memory tasks than patients with AD  Hearing impairment and visual loss ◦ Produce confusion and disorientation mistaken for dementia Laboratory Work-up  Routine ◦ Thyroid Function Test ◦ Vitamin B12 determination ◦ CBC ◦ Electrolytes ◦ Cranial CT or MRI  Optional ◦ CXR ◦ Lumbar Puncture ◦ Liver Function ◦ Renal Function ◦ Urine Toxin screen ◦ HIV, RPR, VDRL ◦ EEG ◦ Parathyroid Function ◦ Adrenal Function ◦ Angiogram ◦ Brain Biopsy ◦ PET ◦ SPECT Alzheimer’s Disease  Most common cause of dementia Alzheimer’s Disease  Prevalence ◦ Age: > 60 years ◦ Sex: slightly more in females  Most important risk factors: ◦ Old age ◦ Positive family history of dementia Clinical Features  Gradual development of forgetfulness ◦ Ribot’s Law of memory  Remote memories are preserved while recent memories are lost  Dysnomia ◦ Forgetting of words, especially proper names ◦ Progresses to common names à impaired speech fluency  Tendency to repeat questions before answering à later progresses to Echolalia  Acalculia or dyscalculia ◦ Impaired calculation  Visuospatial disorientation ◦ e.g. Getting lost in familiar surroundings, right to left confusion, inability to park car, etc.  Ideational and ideomotor apraxia ◦ e.g. Forgets how to use common objects  Paranoia and personality changes ◦ e.g. Conviction that others are stealing from them, imprudent financial ventures  Unsteady gait with short steps despite intact motor strength NINCDS-ADRDA Diagnostic Criteria for Alzheimer Disease 1. Dementia defined by clinical examination, MMSE or Blessed Dementia Scale 2. Age of patient (> 40 years) 3. Deficits in 2 or more areas of cognition and progressive worsening of memory and other cognitive functions (language, perception, motor skills) 4. Absence of disturbed consciousness 5. Exclusion of other brain diseases Pathology  Diffuse brain atrophy ◦ < 20% of normal brain weight ◦ Usually involves the frontal, temporal and parietal lobes  Symmetrical 3rd and lateral ventricle enlargement  Extreme atrophy of the hippocampus  Widespread loss of nerve cells Pathology  Neurofibrillary tangles ◦ Composed of hyperphosphory-lated Tau protein  Neuritic plaques ◦ Protein amyloid core surrounded by degenerating nerve terminal Pathology  Granulovacuolar degeneration of the neuron
  3. 3. ◦ Most evident in the pyramidal layer of the hippocampus Pathogenesis  Tau ◦ Cytoskeletal protein for the assembly of microtubules  In Alzheimer Disease, PSP, and Frontotemporal Dementia ◦ Hyperphosphorylation of Tau à aggregates à Neurofibrillary tangles in the neuronal cytoplasm à Neuronal death Pathogenesis Pathogenesis Pathogenesis Pathogenesis  Neurotransmitter abnormalities ◦ Acetylcholine  Marked decrease in Choline acetyltransferase (ChAT) and acetylcholine in the hippocampus and neocortex  Probably due to loss of the cells in the Nucleus basalis of Meynert ◦ Norepinephrine, GABA, Serotonin, Glutamate, Substance P, Somatostatin, Cholecystokinin  Also reduced  Still not sure if primary or secondary to hetenogeneous neuronal loss Genetic aspect of Alzheimer Disease Diagnostic Studies  MRI or CT scan of the brain ◦ Most useful but not definitive test ◦ Show disproportionate atrophy of the hippocampi with enlargement of the temporal horns of the lateral ventricles ◦ Most important for ruling out:  Brain tumor  Subdural hematoma  Cerebral infarction  Hydrocephalus  Hippocampal Atrophy  EEG ◦ Diffuse slowing (late stage)  Neuropsychologic tests ◦ Deterioration in memory and verbal access skills  E4 apolipoprotein allele ◦ A biomarker occasionally associated Alzheimer Disease  Aβ to tau ratio in the CSF ◦ Not yet validated for use  Amyloid imaging ◦ Still under study Treatment 1. Anticholinesterases ◦ Donepezil, Rivastigmine, Galantamine ◦ Indicated for the treatment of Alzheimer Disease 2. NMDA antagonist ◦ Memantine ◦ Indicated for severe stage of Alzheimer Disease in conjunction with anticholinesterases 3. Benzodiazepines ◦ Clonazepam, Lorazepam ◦ In severe sleep disturbances
  4. 4. 4. Antipsychotics ◦ Haloperidol, Risperidone, Quetiapine, etc. ◦ To suppress aberrant behaviors and hallucinations

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