No abstract

No abstract

People with Alzheimer' s disease (AD) commonly complain of sleep disturbances, which are seen in a wide variety of conditions that become more common in late life. It is not known whether sleep-related symptoms are associated with AD independently of their association with other illnesses. Secondary analyses of sleep-related measures collected through the Survey of Health, Ageing and Retirement in Europe (SHARE; i.e., sleeping problems, fatigue, taking sleeping medication, and trouble sleeping or a change in pattern) were conducted on those who reported the absence of AD or dementia at baseline. A 'sleep disturbance index' (SDI) using sleep-related measures was created and compared to a frailty index reflecting overall health status. Each sleep measure independently predicted self-reported AD or dementia and mortality within ~4 years. Combined, the SDI was associated with an increased risk of developing AD or dementia (OR= 1.23, 95%CI = 1.11-1.36) and mortality (OR = 1.18, 95% CI = 1.12-1.24), and remained a strong factor for dementia when overall health status was added to the risk model (p = 0.054). These findings indicate that sleep disturbance may exist prior to the manifestation of other typical symptoms observed in AD (e.g., memory loss). Sleep-related questions may be useful for screening individuals at risk for dementia and may allow for the earlier detection of AD at the preclinical stage.

Circadian rhythms in physiological, endocrine and metabolic functioning are controlled by a neural clock located in the suprachiasmatic nucleus (SCN). This structure is endogenously rhythmic and the phase of this rhythm can be reset by light information from the eye. A key feature of the SCN is that while it is a small structure containing on the order of about 20,000 cells, it is amazingly heterogeneous. It is likely that anatomical heterogeneity reflects an underlying functional heterogeneity. In this review, we examine the physiological responses of cells in the SCN to light stimuli that reset the phase of the circadian clock, highlighting where possible the spatial pattern of such responses. Increases in intracellular calcium are an important signal in response to light, and this increase triggers many biochemical cascades that mediate responses to light. Furthermore, only some cells in the SCN are actually endogenously rhythmic, and these cells likely do not receive strong direct input from the retina. Therefore, this review also considers how light information is conveyed from the retinorecipient cells to the endogenously rhythmic cells that track circadian phase. A number of neuropeptides, including vasoactive intestinal polypeptide, gastrin-releasing peptide and substance P, may be particularly important in relaying such signals, but other neurochemicals such as GABA and nitric oxide may participate as well. A thorough understanding of the intracellular and intercellular responses to light, as well as the spatial arrangements of such responses may help identify important pharmacological targets for therapeutic interventions to treat sleep and circadian disorders.