Is early-onset Alzheimer disease a distinct subgroup within the Alzheimer disease population?

Although patients with Alzheimer disease (AD) share major clinical and neurohistologic features regardless of age of onset, the hypothesis that early-onset AD comprises a distinct subgroup remains viable. Most studies addressing this hypothesis find quantitative differences between early- and late-onset AD patients. Early-onset AD is characterized by shorter survival, more rapid cognitive deterioration, greater frequency of language disturbance, more severe and widespread neurochemical abnormalities, and a greater density of neurohistologic lesions. In addition, both the chromosome 14 genetic abnormality and chromosome 21 amyloid precursor protein mutations appear restricted to early-onset familial AD. Age of onset of AD subjects may be relevant to the design of clinical trials. For example, the efficacy of a drug that slows disease progression may be more easily demonstrated in subjects with early-onset disease.