Cognitive%20Decline

1
Cognitive Decline

• AD (family history usually begins as aMCI, in
  70s, 80s)
• Pick Complex
• FTLD (Semantic Dementia, bvFTD, PNFA) FTLD-t
  FTLD-u
• Progressive Supranuclear Palsy
• Corticobasal Degeneration
• Picks Disease
• ALS-FTD
• Vascular
• Multiple infarcts
• Small vessel disease
• Vasculitis (e.g. CNS Vasculitis, Wegeners)
• Amyloid angiopathy
• CADASIL
• Dementia with Lewy Bodies
• Parkinsons Disease, Parkinsons Plus syndromes
• Neoplastic (mets, primary brain tumors,
  carcinomatous or lymphomatous meningitis)
• Paraneoplastic (limbic or extralimbic)
  encephalitis
• Normal pressure hydrocephalus

2
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

3
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)

4
Renal Failure

• Dehydration
• Poor intake secondary to dysphagia
• Vomiting (hyponatremia, hyperkalemia)
• Dye
• Medications
• Infections
• Amyloidosis
• Wegeners (affects brain, lung, as well as kidney)

5
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 40s or 50s usually APP or presenilin I or
  II mutation)
• usually begins as amnestic MCI
• Usually begins in 70s or 80s
• Histology Amyloid plaques neurofibrillary
  tangles
• Cant account for dysphagia, SOB, gait
  impairment, or renal failure. AD patients have
  poor p.o. intake because they forget to eat.

6
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 50s or 60s
• Corticobasal Syndrome (spastic hemiparesis,
  apraxia)
• ALS-FTD
• Dysphagia, Dysarthria (UMN LMN)
• Falls, Gait Disorder, Weakness, Spasticity
• Usually begins in 40s, 50s, or 60s
• All can be associated with Parkinsonism,
  Rigidity, Tremor

7
Pathological Classification of FTLD/Pick Complex

• Tau-opathies
• Picks 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

8
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

9
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

10
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

Cant account for dysphagia, SOB, gait
impairment, or renal failure
11
Parkinsons

• Parkinsons Disease
• Unilateral onset
• Bradykinesia, bradyphrenia
• Tremor
• Rigidity
• Gait disorder, falls
• Subcortical cognitive decline
• Can have dysphagia and dementia, but usually not
  so prominent
• Parkinsons Plus syndromes
• Multisystem Atrophy
• Shy-Drager

12
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

13
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

14
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 40s-60s, disease duration
  1-4 years

15
What can account for cognitive decline SOB
Dysphagia?

• Progressive Supranuclear Palsy
• Dysphagia dysarthria, Falls, Parkinsonism/Rigidi
  ty, 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 50s or 60s with duration of
  6-12 years.

16
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

17
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

18
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 mans obvious onset was about age 75, but
  decline might well have started in his 60s