Independent evidence associates β-amyloid pathology with both NREM sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here, we show that β-amyloid burden within medial prefrontal cortex (mPFC) is significantly correlated with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation is not direct, but instead, statistically depends on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a novel mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly.

Aging has independently been associated with regional brain atrophy, reduced non-rapid eye movement (NREM) slow-wave activity (SWA), and impaired long-term retention of episodic memories. However, that the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. Here, we show that age-related medial prefrontal cortex (mPFC) grey-matter atrophy is associated with reduced NREM SWA activity in older adults, the extent to which statistically mediates the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represent a novel contributing factor to age-related cognitive decline in later life.

Objective To assess the efficacy of moderate aerobic physical activity with sleep hygiene education to improve sleep, mood and quality of life in older adults with chronic insomnia. Methods Seventeen sedentary adults aged ≥55 years with insomnia (mean age 61.6 (SD±4.3) years; 16 female) participated in a randomized controlled trial comparing 16 weeks of aerobic physical activity plus sleep hygiene to non-physical activity plus sleep hygiene. Eligibility included primary insomnia for at least 3 months, habitual sleep duration < 6.5 hours and a Pittsburgh Sleep Quality Index (PSQI) score > 5. Outcomes included sleep quality, mood and quality of life questionnaires (PSQI, Epworth Sleepiness Scale [ESS], Short-form 36 [SF-36], Center for Epidemiological Studies Depression Scale [CES-D]). Results The physical activity group improved in sleep quality on the global PSQI (p<0.0001), sleep latency (p=0.049), sleep duration (p=0.04), daytime dysfunction (p=0.027), and sleep efficiency (p=0.036) PSQI sub-scores compared to the control group. The physical activity group also had reductions in depressive symptoms (p=0.044), daytime sleepiness (p=0.02) and improvements in vitality (p=0.017) compared to baseline scores. Conclusion Aerobic physical activity with sleep hygiene education is an effective treatment approach to improve sleep quality, mood and quality of life in older adults with chronic insomnia.

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A hallmark feature of cognitive aging is a decline in the ability to form new memories. Parallel to these cognitive impairments are marked disruptions in sleep physiology. Despite recent evidence in young adults establishing a role for sleep spindles in restoring hippocampal-dependent memory formation, the possibility that disrupted sleep physiology contributes to age-related decline in hippocampal-dependent learning remains unknown. Here, we demonstrate that reduced prefrontal sleep spindles by over 40% in older adults statistically mediates the effects of old age on next day episodic learning, such that the degree of impaired episodic learning is explained by the extent of impoverished prefrontal sleep spindles. In addition, prefrontal spindles significantly predicted the magnitude of impaired next day hippocampal activation, thereby determining the influence of spindles on post-sleep learning capacity. These data support the hypothesis that disrupted sleep physiology contributes to age-related cognitive decline in later life, the consequence of which has significant treatment intervention potential.