Wake-active neurons across aging and neurodegeneration: a potential role for sleep disturbances in promoting disease

Abstract

Sleep/wake disturbance is a feature of almost all common age-related neurodegenerative diseases. Although the reason for this is unknown, it is likely that this inability to maintain sleep and wake states is in large part due to declines in the number and function of wake-active neurons, populations of cells that fire only during waking and are silent during sleep. Consistent with this, many of the brain regions that are most susceptible to neurodegeneration are those that are necessary for wake maintenance and alertness. In the present review, these wake-active populations are systematically assessed in terms of their observed pathology across aging and several neurodegenerative diseases, with implications for future research relating sleep and wake disturbances to aging and age-related neurodegeneration.

Objective but not subjective sleep predicts memory in community‐dwelling older adults

“…In demonstrating that longer objectively measured TST was negatively associated with memory performance, the present study extended previous research in older adults that has relied on self‐report to associate sleep quantity with poorer memory (Miller et al ., ). One possible explanation relating memory decline and age‐related changes in sleep–wake control would be if they shared a common underlying aetiology; for example, age‐related reductions in wake‐promoting neurons, such as the cholinergic neurons of the nucleus basalis of Meynert, are implicated in both memory performance and sleep–wake control (for review, see Stern and Naidoo, ). Furthermore, in older adults, self‐reported longer sleep duration has been associated with other negative health outcomes, such as higher prevalence of stroke (Fang et al ., ) and increased brain white‐matter hyperintensity volumes (Ramos et al ., ), which are associated with decreased memory performance (Silbert et al ., ).…”

Sleep and Human Aging

“…Beyond the medial temporal lobe, AD post-mortem studies have established that neurofibrillary tangles within the preoptic area of the hypothalamus correlate with the severity of prior fragmented sleep (Lim et al, 2014). Interestingly, tau deposition is also present in other sleep-regulating areas such as the locus coeruleus and basal forebrain and can be observed even in cognitively normal older adults (Braak and Del Tredici, 2016; Braak et al, 2011; Stern and Naidoo, 2015). This leads to the currently untested hypothesis that tau within these regions may trigger sleep abnormalities years before degenerative disease onset and, if such sleep disruption is specific, could serve as an early diagnostic biomarker (Holth et al, 2016).…”

Circadian Rhythms, Sleep, and Disorders of Aging

“…Pathologically, PD is characterized by loss of midbrain dopaminergic neurons and by abnormal accumulation of the protein alpha-synuclein into intraneuronal inclusions called Lewy bodies [80]. PD also involves destruction of multiple wake-active neuronal populations [81], including a decrease in the number of hypothalamic hypocretin neurons [82,83]. …”