Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need?

Sleep disruption appears to be a core component of Alzheimer's disease (AD) and its pathophysiology. Signature abnormalities of sleep emerge before clinical onset of AD. Moreover, insufficient sleep facilitates accumulation of amyloid-β (Aβ), potentially triggering earlier cognitive decline and conversion to AD. Building on such findings, this review has four goals, evaluating: (i) associations and plausible mechanisms linking NREM sleep disruption, Aβ, and AD, (ii) a role for NREM sleep disruption as a novel factor linking cortical Aβ to impaired hippocampus-dependent memory consolidation, (iii) the potential diagnostic utility of NREM sleep disruption as a new biomarker of AD, and (iv) the possibility of sleep as a new treatment target in aging, affording preventative and therapeutic benefits.

Recent proposals suggest that sleep may be a factor associated with accumulation of two core pathological features of Alzheimer's disease (AD): tau and ␤-amyloid (A␤). Here we combined PET measures of A␤ and tau, electroencephalogram sleep recordings, and retrospective sleep evaluations to investigate the potential utility of sleep measures in predicting in vivo AD pathology in male and female older adults. Regression analyses revealed that the severity of impaired slow oscillation-sleep spindle coupling predicted greater medial temporal lobe tau burden. A␤ burden was not associated with coupling impairment but instead predicted the diminished amplitude of Ͻ1 Hz slow-wave-activity, results that were statistically dissociable from each other. Additionally, comparisons of AD pathology and retrospective, self-reported changes in sleep duration demonstrated that changes in sleep across the lifespan can predict late-life A␤ and tau burden. Thus, quantitative and qualitative features of human sleep represent potential noninvasive, cost-effective, and scalable biomarkers (current and future forecasting) of AD pathology, and carry both therapeutic and public health implications.

Objective 18F-flortaucipir (formerly 18F-AV1451 or 18F-T807) binds to neurofibrillary tangles in Alzheimer’s disease (AD), but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo 18F-flortaucipir uptake in patients meeting clinical research criteria for PSP (N=33) to normal controls (N=46) and patients meeting criteria for Parkinson’s disease (PD, N=26). Methods Participants underwent MRI and positron emission tomography for amyloid-β (11C-PiB or 18F-florbetapir) and tau (18F-flortaucipir). 18F-flortaucipir Standardized Uptake Value Ratios were calculated (t=80–100 min, cerebellum gray matter reference). Voxelwise and region-of-interest group comparisons were performed in template space, with Receiver Operating Characteristic curve analyses to assess single-subject discrimination. Qualitative comparisons with postmortem tau are reported in one patient who died nine months after 18F-flortaucipir. Results Clinical PSP patients showed bilaterally elevated 18F-flortaucipir uptake in globus pallidus, putamen, subthalamic nucleus, midbrain and dentate nucleus relative to controls and PD patients (voxelwise p<0.05 family-wise-error-corrected). Globus pallidus binding best distinguished PSP patients from controls and PD (Area Under the Curve (AUC)=0.872 vs. controls, AUC=0.893 vs. PD). PSP clinical severity did not correlate with 18F-flortaucipir in any region. A patient with clinical PSP and pathological diagnosis of corticobasal degeneration had severe tau-pathology in PSP-related brain structures with good correspondence between in vivo 18F-flortaucipir and postmortem tau neuropathology. Interpretation 18F-flortaucipir uptake was elevated in PSP versus controls and PD patients in a pattern consistent with the expected distribution of tau pathology.

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