Interacting influences of aging and Alzheimer's disease on circadian rhythms

Aging leads to changes in circadian rhythms, including decreased amplitude or robustness, altered synchrony with the environment, and reduced coordination of rhythms within body. These circadian rhythm alterations are more pronounced in age-associated neurodegenerative disorders such as Alzheimer's disease (AD), in which they often precede the onset of other symptoms by many years. As well as their early onset, the findings that fragmentation of daily rest-activity rhythms in non-demented older subjects is associated earlier cognitive decline, increased risk of incident AD, and preclinical AD neuropathology, suggest that circadian rhythm disruption may contribute to the development and progression of the neuropathological changes occurring in AD. Conversely, other studies have implicated amyloid-beta, a prominent neurotoxin that accumulates in AD, in the impairment of circadian rhythms. Thus, circadian rhythm disruption and AD-associated neurodegeneration may interact to form a deleterious cycle. This article reviews the neural and molecular mechanisms underlying the age- and AD-related changes in circadian rhythms. It also explores therapeutic strategies proposed to ameliorate circadian rhythm deficits in elderly and demented individuals.