Pathophysiology
Clinical meaning
Dementia and delirium are distinct neurocognitive disorders with different pathophysiology, onset, and management. Dementia represents chronic, progressive neurodegeneration. Alzheimer disease (AD, 60-80% of dementia) involves accumulation of extracellular amyloid-beta plaques and intracellular neurofibrillary tangles (hyperphosphorylated tau protein) that disrupt synaptic transmission, trigger neuroinflammation, and cause neuronal death. Cholinergic neurons in the nucleus basalis of Meynert are particularly vulnerable, leading to acetylcholine deficiency that correlates with memory impairment. Vascular dementia (second most common) results from cumulative cerebrovascular damage (multi-infarct or small vessel disease). Lewy body dementia involves alpha-synuclein protein aggregation in cortical neurons causing fluctuating cognition, visual hallucinations, and parkinsonism. Delirium is an acute, fluctuating disturbance of attention and awareness caused by a medical condition, medication, or substance. The pathophysiology involves widespread neurotransmitter imbalance: decreased acetylcholine, excess dopamine, cortisol-mediated neuroinflammation, and disruption of circadian regulation. Common precipitants include infection (UTI, pneumonia), medications (anticholinergics, opioids, benzodiazepines), metabolic derangements, pain, sleep deprivation, and hospital environment changes. Delirium is reversible when the underlying cause is treated.