Dementia, a syndrome with many causes, affects >5 million people in the United States and results in a total annual health care cost in excess of $250 billion. In adults living in the United States older than 70 years, nearly 15 percent of deaths are attributable to dementia. Dementia is defined as an acquired deterioration in cognitive abilities that impairs the successful performance of activities of daily living. Episodic memory, the ability to recall events specific in time and place, is the cognitive function most commonly lost; 10% of persons aged >70 years and 20–40% of individuals aged >85 years have clinically identifiable memory loss. In addition to memory, dementia may erode other mental faculties, including language, visuospatial, praxis, calculation, judgment, and problem-solving abilities. Neuropsychiatric and social deficits also arise in many dementia syndromes, manifesting as depression, apathy, anxiety, hallucinations, delusions, agitation, insomnia, sleep disturbances, compulsions, or disinhibition. The clinical course may be slowly progressive, as in Alzheimer’s disease (AD); static, as in anoxic encephalopathy; or may fluctuate from day to day or minute to minute, as in dementia with Lewy bodies (DLB). Most patients with AD, the most prevalent form of dementia, begin with episodic memory impairment, although in other dementias, such as frontotemporal dementia (FTD), memory loss is not typically a presenting feature. There remains insufficient evidence to recommend screening for cognitive impairment in all older adults. Focal cerebral disorders are discussed in Chap. 26 and illustrated in a video library in Chap. V2; detailed discussions of AD can be found in Chap. 423; FTD and related disorders in Chap. 424; vascular dementia in Chap. 425; DLB in Chap. 426; Huntington’s disease (HD) in Chap. 428; and prion diseases in Chap. 430.
FUNCTIONAL ANATOMY OF THE DEMENTIAS
Dementia syndromes result from the disruption of specific large-scale neuronal networks; the location and severity of synaptic and neuronal loss combine to produce the clinical features (Chap. 26). Behavior, mood, and attention are modulated by ascending noradrenergic, serotonergic, and dopaminergic pathways, whereas cholinergic signaling is critical for attention and memory functions. The dementias differ in the relative neurotransmitter deficit profiles; accordingly, accurate diagnosis guides effective pharmacologic therapy.
AD begins in the entorhinal region of the medial temporal lobe, spreads to the hippocampus, and then moves to lateral and posterior temporal and parietal neocortex, eventually causing a more widespread degeneration. Vascular dementia is associated with focal damage in a variable patchwork of cortical and subcortical regions or white matter tracts that disconnect nodes within distributed networks. In keeping with its ...