Pathophysiology
Clinical meaning
Dementia and delirium are the two most common causes of cognitive impairment in older adults, but they arise from fundamentally different pathological processes and require distinct clinical approaches. Dementia represents chronic, progressive neurodegeneration. Alzheimer disease (60-70% of cases) is driven by accumulation of extracellular amyloid-beta plaques (from abnormal cleavage of amyloid precursor protein by beta and gamma secretases) and intracellular neurofibrillary tangles of hyperphosphorylated tau protein. These deposits disrupt synaptic transmission, trigger neuroinflammation via microglial activation, and cause progressive neuronal death beginning in the entorhinal cortex and hippocampus (explaining early memory deficits) and spreading to the neocortex. The cholinergic hypothesis identifies degeneration of the nucleus basalis of Meynert as critical โ this structure provides the primary cholinergic input to the cerebral cortex, and its loss correlates with severity of cognitive decline. Delirium is an acute syndrome caused by widespread disruption of cortical function from a metabolic, infectious, toxic, or structural insult. The neuroinflammatory model proposes that systemic inflammation generates cytokines that cross the blood-brain barrier (BBB), activate microglia, and cause direct neurotoxicity. The neurotransmitter hypothesis identifies cholinergic deficiency and dopaminergic...