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Dementia And Memory Disturbances

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  • 1. DEMENTIA AND MEMORY DISTURBANCES Alina Valdes, M.D.
  • 2. Dementia
    • Progressive loss of intellectual function
    • Key – memory loss
    • Abnormalities of cognition :
      • Language
      • Spatial processing
      • Praxis (learned motor behavior)
      • Executive function (ability to plan and sequence)
  • 3.
    • Tests
      • Serum electrolytes, liver, renal, and thyroid function, vitamin B12 level, and serologic studies for syphilis
      • MRI of brain if focal signs on neuro exam and in patients <65 years old at onset
      • Neuropsychological testing
        • Mini-Mental Status Exam – better for cortical
        • Visuospatial processing – clock drawing
        • Praxis – “show how you would …”
        • Planning and sequencing – connect letters and numbers randomly drawn on a page
  • 4. Cortical Vs. Subcortical Dementia
    • Cortical
      • Symptoms : major changes in memory, language deficits, perceptual deficits, praxis disturbances
      • Affected brain regions : temporal cortex (medial), parietal cortex, and frontal lobe cortex
      • Examples : Alzheimer’s disease, diffuse Lewy body disease, vascular dementia, frontotemporal dementias
  • 5.
    • Subcortical
      • Symptoms : behavioral changes, impaired affect and mood, motor slowing, executive dysfunction, less severe changes in memory
      • Affected brain regions : thalamus, striatum, midbrain, striatofrontal projections
      • Examples : Parkinson’s disease, progressive supranuclear palsy, normal pressure hydrocephalus, Huntington’s disease, Creutzfeldt-Jakob disease, chronic meningitis
  • 6. Etiologic Diagnosis of Progressive Dementias in Adults
    • Neurodegenerative Diseases
      • Alzheimer’s disease
      • Parkinson’s disease
      • Diffuse Lewy body disease
      • Progressive supranuclear palsy
      • Multisystem atrophy
      • Huntington’s disease
      • Frontotemporal dementias – e.g. Pick’s disease
  • 7.
    • Structural Disease or Trauma
      • Normal pressure hydrocephalus
      • Neoplasms
      • Dementia pugilistica
    • Vascular Disease
      • Vascular dementia
      • Vasculitis
    • Heredometabolic Disease
      • Wilson’s disease
      • Other late-onset lysosomal storage diseases
  • 8.
    • Demyelinating or Dysmyelinating Disease
      • Multiple sclerosis
    • Infectious Disease
      • Human immunodeficiency virus, type 1
      • Tertiary syphilis
      • Creutzfeldt-Jakob disease
      • Progressive multifocal leukoencephalopathy
      • Whipple’s disease
      • Chronic meningitis – e.g. Cryptococcal
  • 9.
    • Metabolic or Nutritional Disease
      • Vitamin B12 deficiency
      • Thyroid hormone deficiency or excess
      • Thiamine deficiency (Wernicke-Korsakoff syndrome)
      • Alcoholism
    • Psychiatric Diseases
      • Pseudodementia from depression
  • 10. Alzheimer’s Disease (AD)
    • About 70% of all cases of dementia in elderly
    • Incidence increases with age
    • Occurs in up to 30% of persons >85 years old
    • Characterized by :
      • Progressive loss of cortical neurons
      • Formation of amyloid plaques (beta-amyloid is major component) and intraneuronal neurofibrillary tangles (hyperphosphorylated tau proteins is major constituent)
  • 11.
    • Starts in hippocampus and entorhinal cortex and spreads to involve diffuse areas of association cortex in temporal, parietal, and frontal lobes
    • Relative deficiency of cortical acetylcholine from loss of neurons in nucleus basalis – treat symptomatic disease with centrally acting acetylcholinesterase inhibitors
  • 12.
    • Two forms :
        • Young-onset hereditary or familial form
          • Uncommon
          • Autosomal dominant
          • Three specific genetic abnormalities determined
        • More common, sporadic form
          • Occurs in persons >65 years old
  • 13.
    • Clinical Features
      • Begins gradually
      • Affects multiple cognitive functions:
        • Memory
        • Orientation
        • Language
        • Visuospatial processing
        • Praxis
        • Judgment
        • Insight
  • 14.
      • Depression frequent early
      • Frank psychosis with agitation and behavioral disinhibition occur in advanced stages
      • Patients become dependent for all activities of daily living
      • Rate of progression from 5 to 15 years
      • Definitive diagnosis requires biopsy (rarely done) or autopsy confirmation
  • 15.
    • Diagnostic Criteria for Probable AD
      • Progressive functional decline and dementia established by clinical exam and mental status testing and confirmed by neuropsychological assessment
      • Cognitive deficits in two or more domains (including memory impairment)
      • Normal level of consciousness at presentation
      • Not developmentally acquired ; onset between 40 and 90 yr
      • Absence of other illnesses capable of causing dementia
  • 16.
    • Treatment
      • Cholinesterase-inhibiting drugs : benefit <50% of patients
        • Tacrine (Cognex): can be hepatotoxic; must be given QID
        • Donepezil (Aricept): given once daily; fewer side effects
        • Rivastigmine (Exelon)
      • Nursing services
      • Antipsychotics, antidepressants, and anxiolytics
        • Useful for behavioral disturbances: most common cause of nursing home placement
  • 17. CT scan in Alzheimer’s disease . Note the marked dilatation of the sulci and fissures, especially frontally, the poor visual distinction between grey matter and white matter, the ventricular enlargement – greater on the patient’s left (right of picture) and the general reduction in brain size. The picture is not diagnostic of Alzheimer’s disease: similar abnormalities occur in Huntington’s disease and Niemann-Pick’s disease.
  • 18. Diffuse Lewy Body Disease
    • Lewy bodies
      • pathologic inclusions hallmark of Parkinson’s disease when restricted to brain stem
    • Patients have clinical parkinsonism with early and prominent dementia
    • Lewy bodies found in brain stem, limbic system, and cortex
    • Visual hallucinations and cognitive fluctuations common
    • Patients sensitive to adverse effects of neuroleptics
    • May be second most common cause of dementia after AD
  • 19. Vascular Dementia
    • 10% to 20% of elderly patients with dementia have MRI or CT evidence of focal stroke with focal signs on neuro exam
    • Dementia begins with stroke and progression step-wise , suggesting recurrent vascular events
    • Develop : early incontinence, gait disturbance, and flattening of affect
    • Treat risk factors for vascular disease : BP control, smoking cessation, diet modification, and anticoagulation (if needed)
  • 20. CT scan in multi-infarct dementia . The ventricles are normal in size, but there are patchy radiolucencies throughout the white matter. These indicate the presence of demyelinated patches, which result from multiple small infarcts in the brain.
  • 21. Frontotemporal Dementias
    • Often begins with marked behavioral disturbances , unlike AD
    • Classic form – Pick’s disease
    • Patients frequently hot-tempered and socially disinhibited
    • Illness progresses for years , like AD
    • No treatment
    • Inevitable decline
    • About 50% of patients have family history
  • 22. Parkinson’s Disease
    • About 50% of patients have dementia by 85 years old
    • Affects executive function disproportionately
    • Bradyphrenia – slowed thought processes
    • Bradykinesia – slowed movement
    • Dementia occurs late in disease so most patients taking drugs to improve movement by enhancing dopaminergic neurotransmission – drugs can cause psychosis so decrease before diagnose dementia
  • 23. Normal Pressure Hydrocephalus
    • Triad
        • Dementia : typically subcortical
        • Gait instability
        • Urinary incontinence
    • Walk with “ feet stuck to floor ”
    • Symptoms progress over weeks to months
    • CT shows ventricular enlargement out of proportion to cortical atrophy
  • 24.
    • Most important test – therapeutic LP
      • Remove large amount of CSF
      • Examine gait and cognitive function
    • Ventriculoperitoneal shunt may correct if:
      • Patients improve within minutes to hours of removal of 30 to 40 mL of spinal fluid
      • Trauma or subarachnoid hemorrhage
    • Cause is derangement of CSF hydrodynamics
  • 25. Hydrocephalus in an active 69-year-old man . This axial MRI at the level of the ventricular bodies shows severe ventricular enlargement, but the sulci of the brain are normal. The patient had communicating (normal pressure) hydrocephalus, associated with minimal memory impairment but no other significant abnormality. Many patients develop the clinical triad of dementia, ataxia, and incontinence.
  • 26. Slow Virus Infection / Chronic Meningitis / Dementia Related to AIDS
    • Human Immunodeficiency Virus
    • Enters CNS through monocytes and microglial system
      • Causes neuronal cell loss, vacuolization, and lymphocytic infiltration
      • Dementia : bradyphrenia and bradykinesia
      • Executive dysfunction, impaired memory, poor concentration, and apathy
      • Treat with antiretrovirals – may slow dementia
  • 27.
    • Creutzfeldt-Jakob disease
      • Subacute, dementing, transmissible: prion protein
      • Onset between 40 and 75 years
      • Spongiform degeneration and gliosis in cortex
      • 90% of patients have myoclonus vs. 10% in AD
      • Progressive dementia and change in personality over weeks to months
      • EEG – diffuse slowing and periodic sharp waves or spikes
      • CSF – test for characteristic amino acid sequence
  • 28. Memory Disturbance
    • Memory function :
      • Introspective processes
        • Declarative, explicit, aware memories
      • Not accessible to introspection
        • Nondeclarative, implicit, procedural memories
  • 29.
    • Declarative memory – consciously “knowing that …”
    • Nondeclarative memory – unconsciously “knowing how …”
    • Anterograde amnesia
      • Inability to learn new information
    • Retrograde amnesia
      • Inability to recollect prior information
  • 30. Disorders of Memory Function
    • Head injury
      • Retrograde amnesia > antegrade amnesia
      • With time, memories usually return but rarely to recall events surrounding trauma
    • Korsakoff’s syndrome
      • Near-total inability to establish new memory
      • Patients confabulate about recent events
      • Most common cause: thiamine and other nutritional deficiencies with chronic alcoholism
  • 31.
    • Aging
      • Mild loss of memory: names and dates
      • Most sensitive indicator of cognitive change: poor performance on delayed-recall tasks
      • Verbal fluency remain intact and vocabulary may increase
  • 32.
    • Transient global amnesia
      • Dramatic memory disturbance
      • Affects patients >50 years
      • Usually have only one episode , lasting 6 to 12 hrs.
      • Complete temporal and spatial disorientation
      • Orientation for person preserved
      • May be confused with psychogenic amnesia, fugue state, or partial complex status epilepticus
      • May be due to vascular insufficiency to hippocampus or midline thalamic projections
  • 33.
    • Psychogenic amnesia
      • Inconsistent loss of recent and remote memory
      • More loss of emotionally charged memory
      • Indifference to situation
      • “ Who am I ?” – seldom seen in organic disease
    • Severe depression
      • Pseudodementia – improve with antidepressants
      • Vegetative signs common
      • Signs of cortical impairment rare