Sleep/wake patterns In Alzheimer's disease: relationships with cognition and function

Abstract

Alzheimer's disease (AD), the most common dementing disorder of aging, is a progressive neurodegenerative disease of unknown etiology. Two of the common clinical features of AD are progressive cognitive and functional impairment, and disturbed sleep/wake patterns. We examined sleep/wake patterns and cognitive and functional status measures in a large sample of AD subjects ranging from mild to moderate-severe in impairment. All subjects survived at least 2 years after initial diagnosis. Regression analyses revealed that sleep/wake variables were highly correlated with and explained significant variance in cognitive and functional measures. More wakefulness during the night and longer REM latencies were associated with impaired cognition and function while more REM and slow-wave sleep were associated with preserved cognition and function. These results indicate that with advancing severity of the disease, sleep/wake patterns are disrupted in parallel with the disturbances in cognition and function that are the hallmarks of AD. Further, they suggest that the neural substrates underlying each process degenerate at somewhat comparable rates.

Melanopsin retinal ganglion cell loss in Alzheimer disease

“…By contrast, most of the previous studies, documenting a more severe circadian dysfunction in AD, included moderate or severe patients,63, 64, 65 and did not correct the results for multiple comparisons, whereas actigraphic studies investigating mild–moderate AD patients failed to reveal significant abnormalities 3, 64. Differently, laboratory‐based polysomnography studies showed significantly reduced sleep efficiency and slow wave sleep amount, even in the mild cases, as in our case series 66, 67. Selection of mild–moderate cases was constrained by the need to have the necessary compliance for reliable OCT studies.…”

Cognitive deficit is associated with phase advance of sleep–wake rhythm, daily napping, and prolonged sleep duration—a cross-sectional study in 2,947 community-dwelling older adults

“…Disturbed sleep-wake rhythm has consistently been recognized in dementia (Vitiello et al 1990(Vitiello et al , 2002aBliwise 1993;Bootzin et al 2001;Vitiello and Borson 2001;Moe et al 1995;Ancoli-Israel et al 1997;Pat-Horenczyk et al 1998;Gehrman et al 2005) while phase advance of sleep-wake cycle is regarded an age-associated variation. (Miles and Dement 1980).…”

P4–021: A hypnic hypothesis of Alzheimer's disease

“…Sleep disturbance is more frequent in patients with AD than the general population [36] , occurring in some 25-54% of patients overall [54,58] ; as this is based largely on caregiver reports, it may be an underestimate. Sleep disturbance occurs early in the course of disease [61] and worsens as disease evolves [27,69] , though not necessarily in a simple monotonic relation [39,63] . Sleep disruption is an important determinant of institutionalisation in later-stage disease [42] .…”

“…Sleep disruption is an important determinant of institutionalisation in later-stage disease [42] . Normal ageing is associated with increased sleep latency and frequent night time awakenings [24] leading to increased daytime sleepiness [36,37] , features which are exaggerated in AD [39] . AD is associated with decreased slow-wave sleep and REM sleep, prolonged REM latency, increased proportions of stages I and II sleep, and increased fragmentation of sleep, leading to an overall decrease in sleep duration [36,39] .…”

“…However, converging evidence drawn from molecular biology, sleep neuroscience [21][22][23][24][25][26][27][28][29][30][31][32][33][34] and clinical neurology [35][36][37][38][39][40][41][42] suggests that sleep may interact in diverse and important ways with the pathophysiology of AD. Ramifications of long-term disruption in the sleep-wake cycle could include synaptic overactivity and excitotoxicity [10,21,[43][44][45] , impaired synaptic pruning [46] , failure of synaptic scaling and homeostatic responses [19,20,27,[47][48][49][50][51] , transmission of pathogenic proteins (β-amyloid and tau) [9,15,16] , and disruption of neural circuitry in the vulnerable DMN [6,8,12,21,52,53] .…”