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Cognitive Decline

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    Cognitive Decline Cognitive Decline Presentation Transcript

    • Cognitive Decline
      • AD (family history; usually begins as aMCI, in 70’s, 80’s)
      • Pick Complex
        • FTLD (Semantic Dementia, bvFTD, PNFA); FTLD-t; FTLD-u
        • Progressive Supranuclear Palsy
        • Corticobasal Degeneration
        • Pick’s Disease
        • ALS-FTD
      • Vascular
        • Multiple infarcts
        • Small vessel disease
        • Vasculitis (e.g. CNS Vasculitis, Wegener’s)
        • Amyloid angiopathy
        • CADASIL
      • Dementia with Lewy Bodies
      • Parkinson’s Disease, Parkinson’s Plus syndromes
      • Neoplastic (mets, primary brain tumors, carcinomatous or lymphomatous meningitis)
      • Paraneoplastic (limbic or extralimbic) encephalitis
      • Normal pressure hydrocephalus
    • Shortness of Breath
      • CHF
        • Cardiomyopathy
        • Acute MI
        • Neurogenic (e.g. SAH, stroke)
        • Atrial fibrillation
      • Pneumonia
        • Aspiration (Dysphagia)
        • Infectious
        • Interstitial
      • Idiopathic Pulmonary Fibrosis
      • Neuromuscular Disease
        • ALS
        • MG
        • Polymyositis, dermatomyositis
    • Dysphagia
      • Obstructive
      • Neurogenic
        • Brain
          • Neurodegenerative (e.g. PSP)
          • Vascular (usually brainstem when chronic)
          • Tumor
          • Infection
        • Motor Neuron (e.g. ALS)
        • NM junction (e.g. MG)
        • Lower motor neuron (e.g. GBS)
        • Muscle (e.g. Polymyositis; oculopharyngeal muscular dystrophy)
    • Renal Failure
      • Dehydration
        • Poor intake secondary to dysphagia
        • Vomiting (hyponatremia, hyperkalemia)
      • Dye
      • Medications
      • Infections
      • Amyloidosis
      • Wegener’s (affects brain, lung, as well as kidney)
    • AD
      • Progressive decline in memory & 1+ other domain of cognition
      • family history (but not especially important unless there is family history of early onset AD, in 40’s or 50’s; usually APP or presenilin I or II mutation)
      • usually begins as amnestic MCI
      • Usually begins in 70’s or 80’s
      • Histology: Amyloid plaques & neurofibrillary tangles
      • Can’t account for dysphagia, SOB, gait impairment, or renal failure. AD patients have poor p.o. intake because they forget to eat.
    • Pick Complex: Clinical Subtypes
      • FTLD (Semantic Dementia, bvFTD, PNFA)
        • Primary Progressive Aphasia &/or
        • Change in personality, comportment, behavior
      • Progressive Supranuclear Palsy syndrome
        • Dysphagia, Dysarthria (UMN, “spastic”), pseudobulbar lability
        • Falls, Gait Disorder
        • Impaired eye movements
        • Dementia
        • Usually begins in 50’s or 60’s
      • Corticobasal Syndrome (spastic hemiparesis, apraxia)
      • ALS-FTD
        • Dysphagia, Dysarthria (UMN + LMN)
        • Falls, Gait Disorder, Weakness, Spasticity
        • Usually begins in 40’s, 50’s, or 60’s
      • All can be associated with Parkinsonism, Rigidity, Tremor
    • Pathological Classification of FTLD/Pick Complex
      • Tau-opathies
        • Pick’s Disease (Pick bodies)
        • PSP
        • Corticobasal degeneration
        • ALS-Parkinsonism-Dementia Complex of Guam
        • Tangle dominant dementia
        • Diffuse neurofibrillary tangle demenia with calcifications
        • Agyrophilic grain disease
        • Sporadic multisystem tauopathy
    • Pathological Classification of FTLD/Pick Complex
      • Ubiquitinopathies
        • TDP 43: FTLD-U types 1-4 (ALS-FTD, FTD, ALS)
        • FTLD-PLS
        • FTLD-non-TDP (many have hippocampal sclerosis)
      • Other
        • DLDH: Dementia Lacking Distinctive Histology
        • Basophilic inclusion body disease
        • FTLD+ CHMP2B
        • Neurofilament inclusion body disease
    • Vascular Cognitive Decline
      • Multiple infarcts
        • Just has one lacune
      • Small vessel disease
        • Mild to moderate
      • Vasculitis
        • No large vessel strokes
        • No headaches
      • Amyloid angiopathy
        • No hemorrhage on CT (but dx requires gradient echo/susceptability/ “hemosiderin” MRI
      • CADASIL
        • Too old, no family history, no headache
    • Dementia with Lewy Bodies
      • Parkinsonism ( tremor, rigidity, gait disorder …)
      • Hallucinations
      • Marked fluctuations in mental state
      • Marked visuospatial deficits
      • Autonomic dysfunction
        • Orthostatic hypotention
      • Sensitivity to neuroleptics
      Can’t account for dysphagia, SOB, gait impairment, or renal failure
    • Parkinson’s
      • Parkinson’s Disease
        • Unilateral onset
        • Bradykinesia, bradyphrenia
        • Tremor
        • Rigidity
        • Gait disorder, falls
        • Subcortical cognitive decline
        • Can have dysphagia and dementia, but usually not so prominent
      • Parkinson’s Plus syndromes:
        • Multisystem Atrophy
        • Shy-Drager
    • Neoplastic
      • Brain mets
      • primary brain tumors
      • carcinomatous or lymphomatous meningitis
      • Gliomatosis cerebrii
      • Paraneoplastic encephalitis
      • CT negative for tumor
      • Too chronic for neoplastic meningitis or gliomatosis cerebrii
    • Infectious
      • HIV
        • Subcortical cognitive decline
          • Slow, poor recall, poor executive dysfunction
      • Lyme
        • Sero-positive, + CSF
        • Can cause arrhythmia
        • No fever
        • Too chronic
      • West Nile
        • No fever
        • Too chronic
    • What can account for cognitive decline + SOB + Dysphagia?
      • “ Proteinopathies” – protein misfolding disorders
      • ALS-FTD
        • Usually ubiquitin-opathy
          • usually TDP-43; transactivation response (TAR) DNA binding protein, molecular weight 43 kDa
            • Nuclear protein involved in transcription, alternative splicing
            • Cytoplasmic inclusions
          • 4 subtypes; distinct distributions cause SD, ALS-FTD or bvFTD, bvFTD
        • Many have progranulin mutation 17q21 ( PRGN);
        • Others have mutations in 9q21-12 ( VCP ) or 9p21-13 or CHMP2B
        • Family history in 7.7% (ALS) to 62.% (FTD; FTLD-U)
          • Geser et al., 2009; Archives of Neurology
        • Bulbar onset with dysphagia and respiratory difficulty in 32-38%
        • Onset is usually in 40’s-60’s, disease duration 1-4 years
    • What can account for cognitive decline + SOB + Dysphagia?
      • Progressive Supranuclear Palsy
        • Dysphagia & dysarthria, Falls, Parkinsonism/Rigidity, Vertical Eye Movement Impairment, Dementia or Aphasia
        • Tau-opathy (another protein misfolding disorder), specific isoform often causes PSP
        • Many have mutations in Chr 3 or 17q21 ( MAPT ) – associated with variable isoforms of tau
        • Same mutation can cause PSP in 1 family member, corticobasal syndrome in another, and progressive nonfluent aphasia or bvFTD (types of FTLD-t) in another
      • Usually starts in 50’s or 60’s with duration of 6-12 years.
    • Does Exam Help?
      • AD should have normal neurological exam except dementia
      • ALS-FTD should have:
        • Fasciculations (LMN)
        • Hyperreflexia (“reflexes appeared symmetric”)
        • Babinski &/or Hoffman signs (UMN)
        • Weakness (limb or bulbar); 3+ limbs but “poor effort”
        • Dysarthria (usually present if neurogenic dysphagia is present)
        • Dementia
      • PSP should have:
        • Impaired eye movements , dysphagia/ dysarthria , rigidity or tremor, gait impairment, dementia
    • Does Imaging Help?
      • AD:
        • Bilateral temporoparietal atrophy on CT, MRI
        • Bilateral temporoparietal hypoperfusion on SPECT
        • Bilateral temporoparietal hypometabolism on PET
        • (+PIB in amyloid PET)
      • ALS-FTD
        • Asymmetric fronto/temporal atrophy on CT, MRI
        • Asymmetric fronto/temporal abnormalities on PET or SPECT or MRS
      • PSP (and other tau-opathies)
        • May see frontal &/or parietal atrophy on CT, MRI
        • + midbrain & superior cerebellar peduncle atrophy for PSP
      • Vascular Dementia
        • Strokes and/or white matter disease on CT, MRI
        • Microhemorrhages on GRE/SWI MRI for amyloid angiopathy
    • Clinical Diagnosis
      • Mixed dementia
        • Protein-opathy (with some evidence of vascular disease +/- AD)
          • Most likely tau-opathy unless fasciculations or hyperreflexia were missed on exam
        • May have presented late due to his “cognitive reserve”
          • Physicists and other highly educated people often compensate well for substantial cognitive decline
          • This man’s obvious onset was about age 75, but decline might well have started in his 60’s