Sleep Disturbances in MCI and AD: Neuroinflammation as a Possible Mediating Pathway

Pak, Victoria M.; Onen, S. Hakki; Bliwise, Donald L.; Kutner, Nancy G.; Russell, Katherine L.; Onen, Fannie

doi:10.3389/fnagi.2020.00069

Cited by 30 publications

(23 citation statements)

References 140 publications

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“…Interestingly, the prefrontal cortex is especially susceptible to oxidative stress and furthermore, sleep deprivation especially affects neuropsychological performance on tasks related to the prefrontal cortex (executive domains) [ 36 ]. Thus, it is possible that grey matter health in dorsal-orbitofrontal areas is vulnerable to insufficient sleep [ 37 , 38 ].…”

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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“…51 Notably, except for specific effects of surgery and anesthesia on perioperative sleep, there are many similarities between perioperative sleep disturbance and sleep disruption at home. [52][53][54] Based on the common characteristics of sleep disruption at home and perioperative sleep disturbance, we could provide more directions and choices for future studies investigating postoperative neurocognitive disorders.…”

Section: Role Of Sleep Disruption In Cognitive Impairmentsmentioning

confidence: 99%

The Role of Perioperative Sleep Disturbance in Postoperative Neurocognitive Disorders

Wang¹,

Duan²,

Tang³

et al. 2021

NSS

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Postoperative neurocognitive disorder (PND) increases the length of hospital stay, mortality, and risk of long-term cognitive impairment. Perioperative sleep disturbance is prevalent and commonly ignored and may increase the risk of PND. However, the role of perioperative sleep disturbances in PND remains unclear. Nocturnal sleep plays an indispensable role in learning, memory, and maintenance of cerebral microenvironmental homeostasis. Hospitalized sleep disturbances also increase the incidence of postoperative delirium and cognitive dysfunction. This review summarizes the role of perioperative sleep disturbances in PND and elucidates the potential mechanisms underlying sleep-deprivation-mediated PND. Activated neuroinflammation and oxidative stress; impaired function of the blood-brain barrier and glymphatic pathway; decreased hippocampal brain-derived neurotrophic factor, adult neurogenesis, and sirtuin1 expression; and accumulated amyloid-beta proteins are associated with PND in individuals with perioperative sleep disorders. These findings suggest that the improvement of perioperative sleep might reduce the incidence of postoperative delirium and postoperative cognitive dysfunction. Future studies should further investigate the role of perioperative sleep disturbance in PND.

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“…One potential factor that could explain the link between poor sleep and neurodegenerative processes is neuroinflammation [ 33 ]. An interesting new hypothesis is that glymphatic flow, most active during NREM sleep, clears the brain of proinflammatory waste products during sleep.…”

Section: Perioperative Sleep Disturbancesmentioning

confidence: 99%

Sleep Well and Recover Faster with Less Pain—A Narrative Review on Sleep in the Perioperative Period

Sipilä

Kalso

2021

JCM

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Sleep disturbance, pain, and having a surgical procedure of some kind are all very likely to occur during the average lifespan. Postoperative pain continues to be a prevalent problem and growing evidence supports the association between pain and sleep disturbances. The bidirectional nature of sleep and pain is widely acknowledged. A decline in sleep quality adds a risk for the onset of pain and also exacerbates existing pain. The risk factors for developing insomnia and experiencing severe pain after surgery are quite similar. The main aim of this narrative review is to discuss why it is important to be aware of sleep disturbances both before and after surgery, to know how sleep disturbances should be assessed and monitored, and to understand how better sleep can be supported by both pharmacological and non-pharmacological interventions.

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Sleep Disturbances in MCI and AD: Neuroinflammation as a Possible Mediating Pathway

Cited by 30 publications

References 140 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

The Role of Perioperative Sleep Disturbance in Postoperative Neurocognitive Disorders

Sleep Well and Recover Faster with Less Pain—A Narrative Review on Sleep in the Perioperative Period

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