Sleep Disturbance Forecasts β-Amyloid Accumulation across Subsequent Years

Winer, Joseph R.; Mander, Bryce A.; Kumar, Samika; Reed, Mark; Baker, Suzanne L.; Jagust, William J.; Walker, Matthew P.

doi:10.1016/j.cub.2020.08.017

Cited by 139 publications

(134 citation statements)

References 73 publications

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“…The poor sleep quality and sleep deprivation associated with insomnia complaints, could accelerate these age-related changes potentiating disease-specific neuronal vulnerabilities causing neurodegenerative disorders [ 55 ]. For instance, results from a recent study suggest that that sleep disturbances could predict accumulation of beta-amyloid across subsequent years [ 11 ]. Furthermore, relevant changes within frontal regions, from cortical atrophy to protein accumulation, have been identified in many early neurodegenerative disorders [ 27 , 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Specific cortical and subcortical grey matter regions are associated with insomnia severity

et al. 2021

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Background There is an increasing awareness that sleep disturbances are a risk factor for dementia. Prior case-control studies suggested that brain grey matter (GM) changes involving cortical (i.e, prefrontal areas) and subcortical structures (i.e, putamen, thalamus) could be associated with insomnia status. However, it remains unclear whether there is a gradient association between these regions and the severity of insomnia in older adults who could be at risk for dementia. Since depressive symptoms and sleep apnea can both feature insomnia-related factors, can impact brain health and are frequently present in older populations, it is important to include them when studying insomnia. Therefore, our goal was to investigate GM changes associated with insomnia severity in a cohort of healthy older adults, taking into account the potential effect of depression and sleep apnea as well. We hypothesized that insomnia severity is correlated with 1) cortical regions responsible for regulation of sleep and emotion, such as the orbitofrontal cortex and, 2) subcortical regions, such as the putamen. Methods 120 healthy subjects (age 74.8±5.7 years old, 55.7% female) were recruited from the Hillblom Healthy Aging Network at the Memory and Aging Center, UCSF. All participants were determined to be cognitively healthy following a neurological evaluation, neuropsychological assessment and informant interview. Participants had a 3T brain MRI and completed the Insomnia Severity Index (ISI), Geriatric Depression Scale (GDS) and Berlin Sleep Questionnaire (BA) to assess sleep apnea. Cortical thickness (CTh) and subcortical volumes were obtained by the CAT12 toolbox within SPM12. We studied the correlation of CTh and subcortical volumes with ISI using multiple regressions adjusted by age, sex, handedness and MRI scan type. Additional models adjusting by GDS and BA were also performed. Results ISI and GDS were predominantly mild (4.9±4.2 and 2.5±2.9, respectively) and BA was mostly low risk (80%). Higher ISI correlated with lower CTh of the right orbitofrontal, right superior and caudal middle frontal areas, right temporo-parietal junction and left anterior cingulate cortex (p<0.001, uncorrected FWE). When adjusting by GDS, right ventral orbitofrontal and temporo-parietal junction remained significant, and left insula became significant (p<0.001, uncorrected FWE). Conversely, BA showed no effect. The results were no longer significant following FWE multiple comparisons. Regarding subcortical areas, higher putamen volumes were associated with higher ISI (p<0.01). Conclusions Our findings highlight a relationship between insomnia severity and brain health, even with relatively mild insomnia, and independent of depression and likelihood of sleep apnea. The results extend the previous literature showing the association of specific GM areas (i.e, orbitofrontal, insular and temporo-parietal junction) not just with the presence of insomnia, but across the spectrum of severity itself. Moreover, our results suggest subcortical structures (i.e., putamen) are involved as well. Longitudinal studies are needed to clarify how these insomnia-related brain changes in healthy subjects align with an increased risk of dementia.

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Section: Discussionmentioning

confidence: 99%

Specific cortical and subcortical grey matter regions are associated with insomnia severity

et al. 2021

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“…Sleep deprivation and selective SWS disruption enhance levels of β-amyloid ( Ju et al., 2017 ; Lucey et al., 2018 ; Ooms et al., 2014 ), tau and tau spreading ( Holth et al., 2019 ). Finally, longitudinal studies suggest that sleep disruption is associated with AD-related outcomes ( Lim et al., 2013 ; Winer et al., 2020 ). Therefore, sleep disturbances, increasing the time spent in wakefulness, might negatively contribute to the AD condition.…”

Section: Introductionmentioning

confidence: 99%

EEG alterations during wake and sleep in mild cognitive impairment and Alzheimer's disease

et al. 2021

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Summary Patients with Alzheimer's disease (AD) undergo a slowing of waking electroencephalographic (EEG) rhythms since prodromal stages, which could be ascribed to poor sleep quality. We examined the relationship between wake and sleep alterations by assessing EEG activity during sleep and (pre-sleep/post-sleep) wakefulness in AD, mild cognitive impairment (MCI) and healthy controls. AD and MCI show high sleep latency and less slow-wave sleep. Reduced sigma activity characterizes non-rapid eye movement (NREM) sleep, reflecting sleep spindles loss. The EEG slowing characterizes REM sleep and wakefulness of AD and MCI, with strong correlations among the two phenomena suggesting common neuropathological mechanisms. Evening-to-morning variations in waking EEG revealed the gradual disappearance in MCI and AD of overnight changes in delta activity, indicating a progressive decay of sleep restorative functions on diurnal activity that correlates with the impairment of sleep high-frequency activity in AD. Our findings support a linkage between wake and sleep alterations, and the importance of sleep-related processes in Alzheimer's disease progression.

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“…This effect was specific for SWA (and not for sleep efficiency and duration) and Aβ (and not total protein, tau, YKL-40, or hypocretin) [69]. Finally, longitudinal evaluation confirmed that sleep disruption is associated with future AD-related outcomes [22,[165][166][167][168][169], and the proportion of NREM SWA <1 Hz and sleep efficiency in older adults can selectively predict the speed of subsequent deposition of Aβ over time [170].…”

Section: A Mechanistic Link Between Nrem Sleep Alterations and Ad Progressionmentioning

confidence: 68%

Sleep-Based Interventions in Alzheimer’s Disease: Promising Approaches from Prevention to Treatment along the Disease Trajectory

et al. 2021

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The multifactorial nature of Alzheimer’s disease (AD) has led scientific researchers to focus on the modifiable and treatable risk factors of AD. Sleep fits into this context, given the bidirectional relationship with AD confirmed by several studies over the last years. Sleep disorders appear at an early stage of AD and continue throughout the entire course of the pathology. Specifically, sleep abnormalities, such as more fragmented sleep, increase in time of awakenings, worsening of sleep quality and primary sleep disorders raise with the severity and progression of AD. Intervening on sleep, therefore, means acting both with prevention strategies in the pre-clinical phase and with treatments during the course of the disease. This review explores sleep disturbances in the different stages of AD, starting from the pre-clinical stage. Particular attention is given to the empirical evidence investigating obstructive sleep apnea (OSA) disorder and the mechanisms overlapping and sharing with AD. Next, we discuss sleep-based intervention strategies in the healthy elderly population, mild cognitive impairment (MCI) and AD patients. We mention interventions related to behavioral strategies, combination therapies, and bright light therapy, leaving extensive space for new and raising evidence on continuous positive air pressure (CPAP) treatment effectiveness. Finally, we clarify the role of NREM sleep across the AD trajectory and consider the most recent studies based on the promising results of NREM sleep enhancement, which use innovative experimental designs and techniques.

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Sleep Disturbance Forecasts β-Amyloid Accumulation across Subsequent Years

Cited by 139 publications

References 73 publications

Specific cortical and subcortical grey matter regions are associated with insomnia severity

Specific cortical and subcortical grey matter regions are associated with insomnia severity

EEG alterations during wake and sleep in mild cognitive impairment and Alzheimer's disease

Sleep-Based Interventions in Alzheimer’s Disease: Promising Approaches from Prevention to Treatment along the Disease Trajectory

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