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Among the most important dementing disorders are Alzheimer disease (AD), which affects about 6 million people in the United States, and dementia with Lewy bodies, the second most common dementia, which includes dementia associated with Parkinson disease and dementia with Lewy bodies. Other important dementia disorders include the frontotemporal dementias (FTDs) encompassing corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), vascular cognitive impairment, and normal pressure hydrocephalus (NPH). Mild cognitive impairment is a term used for persons with cognitive impairment who do not meet dementia criteria because of lack of sufficient impairment in function. Transient global amnesia, a temporary condition, is also discussed in this chapter.

Dementias have traditionally been divided into cortical and subcortical dementias, with AD being the prototypical cortical dementia and PSP the prototypical subcortical dementia. In reality, features of both cortical and subcortical dementia often coexist, although cortical or subcortical features may be more prominent (Table 9–1).

Table 9–1.Features of cortical and subcortical dementias.


Lawrence S. Honig, MD, PhD, & William C. Kreisl, MD


  • Insidious onset, with gradual progression of memory loss

  • Impairment of one or more other cognitive domains, including language, praxis, visuospatial abilities, or executive functions

General Considerations

Alzheimer disease (AD) is the most common form of dementia in the elderly and is typically marked most prominently by memory impairment. The incidence increases with age. About 5% of individuals older than 65 years have AD, but about 50% of those older than 85 years have AD. The pathologic hallmarks of AD include neuritic amyloid plaques, neurofibrillary tangles, and synaptic and neuronal losses. The cause of the disease is unknown, but the molecular abnormalities in the brain include accumulation of a peptide, β-amyloid, in extracellular plaques and an abnormally phosphorylated protein, tau, in intracellular deposits in neurons called tangles.


A. Genetic Influences

AD occurs in “sporadic” and autosomal dominant forms. Predominantly, AD does not involve single-gene inheritance (>99.9% of cases), and most cases are thus considered sporadic. However, even in these sporadic cases, a large fraction of the risk of AD is still genetic. ...

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