Dementia and Degenerative Disorders Overview

Dementia and Degenerative Disorders

• Characterized by neuron loss in gray matter, often due to protein accumulation damaging neurons.

Alzheimer Disease (AD)

• Degenerative cortical disease, most common dementia type.
• Clinical features include: slow-onset memory loss (short-term to long-term), disorientation, loss of learned motor skills, language, behavioral/personality changes, and death from infection.
• Usually sporadic in elderly with risk increasing with age.
• ApoE alleles (particularly ε4) increase risk.
• Early-onset AD occurs in familial cases with presenilin 1 and 2 mutations or Down syndrome.
• Morphological features:
  • Cerebral atrophy with broadened sulci and widened ventricles.
  • Neuritic plaques: extracellular amyloid-beta (Aβ) aggregates from APP.
  • Neurofibrillary tangles: intracellular hyperphosphorylated tau protein aggregates.
• Diagnosis: clinical and pathological correlations; confirmed by autopsy.

Vascular Dementia

• Multifocal infarction and injury due to hypertension, atherosclerosis, or vasculitis.
• Second most common dementia cause.

Pick Disease

• Degenerative frontal and temporal cortex disease.
• Characterized by Pick bodies (tau protein aggregates).
• Early behavioral and language symptoms, progressing to dementia.

Parkinson Disease

• Degenerative loss of dopaminergic neurons in substantia nigra.
• Clinical features ('TRAP'): tremor, rigidity, akinesia/bradykinesia, and postural instability.
• Histological: loss of pigmented neurons and Lewy bodies.
• Dementia is a late-stage common feature.

Huntington Disease

• Degeneration of GABAergic neurons in caudate nucleus.
• Autosomal dominant disorder with expanded trinucleotide repeats (CAG).
• Progressive chorea (involuntary movements), dementia, and depression.

Normal Pressure Hydrocephalus

• Increased CSF causing dilated ventricles.
• Can cause dementia in adults, often idiopathic.
• Wet, wobbly, and wacky symptoms (urinary incontinence, gait instability, and dementia).

Spongiform Encephalopathy

• Degenerative disease caused by prion protein.
• Conversion of normal prion protein (PrP^c) to misfolded prion protein (PrP^Sc).
• Pathologic protein is not degradable leading to neuron and glial damage and vacuole formation.
• Creutzfeldt-Jakob Disease (CJD) is most common, potentially sporadic or transmitted from infected human tissue.
• Variant CJD is linked to bovine spongiform encephalopathy (BSE).