Effect of cognitive reserve on the association between slow wave sleep and cognition in community-dwelling older adults

Sleep, especially slow wave sleep (SWS), is essential for cognitive functioning and is reduced in aging. The impact of sleep quality on cognition is variable, especially in aging. Cognitive reserve (CR) may be an important modulator of these effects. We aimed at investigating this question to better identify individuals in whom sleep disturbances might have greater behavioral consequences. Polysomnography and neuropsychological assessments were performed in 135 cognitively intact older adults (mean age ± SD: 69.4 ± 3.8y) from the Age-Well randomized controlled trial (baseline data). Two measures of cognitive engagement throughout life were used as CR proxies. Linear regression analyses were performed between the proportion of SWS, and executive function and episodic memory composite scores. Then, interaction analyses between SWS and CR proxies on cognition were conducted to assess the possible impact of CR on these links. SWS was positively associated with episodic memory, but not with executive function. CR proxies modulated the associations between SWS and both executive and episodic memory performance. Specifically, individuals with higher CR were able to maintain cognitive performance despite low amounts of SWS. This study provides the first evidence that CR may protect against the deleterious effects of age-related sleep changes on cognition

Exposure to negative socio-emotional events induces sustained alteration of resting-state brain networks in older adults

Basic emotional functions seem well preserved in older adults. However, their reactivity to and recovery from socially negative events remain poorly characterized. To address this, we designed a ‘task–rest’ paradigm in which 182 participants from two independent experiments underwent functional magnetic resonance imaging while exposed to socio-emotional videos. Experiment 1 (N = 55) validated the task in young and older participants and unveiled age-dependent effects on brain activity and connectivity that predominated in resting periods after (rather than during) negative social scenes. Crucially, emotional elicitation potentiated subsequent resting-state connectivity between default mode network and amygdala exclusively in older adults. Experiment 2 replicated these results in a large older adult cohort (N = 127) and additionally showed that emotion-driven changes in posterior default mode network–amygdala connectivity were associated with anxiety, rumination and negative thoughts. These findings uncover the neural dynamics of empathy-related functions in older adults and help understand its relationship to poor social stress recovery

Multimodal neuroimaging correlates of spectral power in NREM sleep delta sub-bands in cognitively unimpaired older adults

International audienceAbstract Study Objectives In aging, reduced delta power (0.5-4 Hz) during N2 and N3 sleep has been associated with gray matter (GM) atrophy and hypometabolism within frontal regions. Some studies have also reported associations between N2-N3 sleep delta power in specific sub-bands and amyloid pathology. Our objective was to better understand the relationships between spectral power in delta sub-bands during N2-N3 sleep and brain integrity using multimodal neuroimaging. Methods In-home polysomnography was performed in 127 cognitively unimpaired older adults (mean age ± SD: 69.0 ± 3.8 years). N2-N3 sleep EEG power was calculated in delta (0.5-4 Hz), slow delta (0.5-1 Hz) and fast delta (1-4 Hz) frequency bands. Participants also underwent MRI and Florbetapir-PET (early and late acquisitions) scans to assess GM volume, brain perfusion and amyloid burden. Amyloid accumulation over ~21 months was also quantified. Results Higher delta power was associated with higher GM volume mainly in fronto-cingular regions. Specifically, slow delta power was positively correlated with GM volume and perfusion in these regions, while the inverse association was observed with fast delta power. Delta power was neither associated with amyloid burden at baseline, nor its accumulation over time, whatever the frequency band considered. Conclusion Our results show that slow delta is particularly associated with preserved brain structure, and highlight the importance of analysing delta power sub-bands to better understand the associations between delta power and brain integrity. Further longitudinal investigations with long follow-ups are needed to disentangle the associations between sleep, amyloid pathology and dementia risk in older populations

Associations Between Repetitive Negative Thinking and Objective and Subjective Sleep Health in Cognitively Healthy Older Adults

International audienceObjective: Poor sleep and high levels of repetitive negative thinking (RNT), including future-directed (ie, worry) and past-directed (ie, brooding) negative thoughts, have been associated with markers of dementia risk. The relationship between RNT and sleep health in older adults is unknown. This study aimed to investigate this association and its specificities including multiple dimensions of objective and subjective sleep.Methods: This study used a cross sectional quantitative design with baseline data from 127 cognitively healthy older adults (mean age 69.4 ± 3.8 years; 63% female) who took part in the Age-Well clinical trial, France. RNT (ie, worry and brooding) levels were measured using the Penn State Worry Questionnaire and the Rumination Response Scale (brooding subscale). Polysomnography was used to assess sleep objectively, and the Pittsburgh Sleep Quality Index and the St. Mary's Hospital Sleep Questionnaire were used to measure sleep subjectively. In primary analyses the associations between RNT and sleep (ie, objective sleep duration, fragmentation and efficiency and subjective sleep disturbance) were assessed via adjusted regressions.Results: Higher levels of RNT were associated with poorer objective sleep efficiency (worry: β=-0.32, p<0.001; brooding: β=-0.26, p=0.002), but not objective sleep duration, fragmentation, or subjective sleep disturbance. Additional analyses, however, revealed differences in levels of worry between those with short, compared with typical and long objective sleep durations (p < 0.05).Conclusion: In cognitively healthy older adults, RNT was associated with sleep characteristics that have been implicated in increased dementia risk. It will take additional research to ascertain the causal link between RNT and sleep characteristics and how they ultimately relate to the risk of developing dementia

Rapid Eye Movement Sleep, Neurodegeneration, and Amyloid Deposition in Aging

International audienceObjective: Rapid eye movement (REM) sleep is markedly altered in Alzheimer's disease (AD), and its reduction in older populations is associated with AD risk. However, little is known about the underlying brain mechanisms. Our objective was to investigate the relationships between REM sleep integrity and amyloid deposition, gray matter volume, and perfusion in aging.Methods: We included 121 cognitively unimpaired older adults (76 women, mean age 68.96 ± 3.82 years), who underwent a polysomnography, T1-weighted magnetic resonance imaging, early and late Florbetapir positron emission tomography scans to evaluate gray matter volume, perfusion, and amyloid deposition. We computed indices reflecting REM sleep macro- and microstructural integrity (ie, normalized electroencephalographic spectral power values). Voxel-wise multiple regression analyses were conducted between REM sleep indices and neuroimaging data, controlling for age, sex, education, the apnea-hypopnea index, and the apolipoprotein E ε4 status.Results: Lower perfusion in frontal, anterior and posterior cingulate, and precuneus areas was associated with decreased delta power and electroencephalographic slowing (slow/fast frequencies ratio), and increased alpha and beta power. To a lower extent, similar results were obtained between gray matter volume and delta, alpha, and beta power. In addition, lower REM sleep theta power was more marginally associated with greater diffuse amyloid deposition and lower gray matter volume in fronto-temporal and parieto-occipital areas.Interpretation: These results suggest that alterations of REM sleep microstructure are associated with greater neurodegeneration and neocortical amyloid deposition in older adults. Further studies are warranted to replicate these findings, and determine whether older adults exhibiting REM sleep alterations are more at risk of cognitive decline and belonging to the Alzheimer's continuum. ANN NEUROL 2023

Rapid Eye Movement Sleep, Neurodegeneration, and Amyloid Deposition in Aging

International audienceObjective: Rapid eye movement (REM) sleep is markedly altered in Alzheimer's disease (AD), and its reduction in older populations is associated with AD risk. However, little is known about the underlying brain mechanisms. Our objective was to investigate the relationships between REM sleep integrity and amyloid deposition, gray matter volume, and perfusion in aging.Methods: We included 121 cognitively unimpaired older adults (76 women, mean age 68.96 ± 3.82 years), who underwent a polysomnography, T1-weighted magnetic resonance imaging, early and late Florbetapir positron emission tomography scans to evaluate gray matter volume, perfusion, and amyloid deposition. We computed indices reflecting REM sleep macro- and microstructural integrity (ie, normalized electroencephalographic spectral power values). Voxel-wise multiple regression analyses were conducted between REM sleep indices and neuroimaging data, controlling for age, sex, education, the apnea-hypopnea index, and the apolipoprotein E ε4 status.Results: Lower perfusion in frontal, anterior and posterior cingulate, and precuneus areas was associated with decreased delta power and electroencephalographic slowing (slow/fast frequencies ratio), and increased alpha and beta power. To a lower extent, similar results were obtained between gray matter volume and delta, alpha, and beta power. In addition, lower REM sleep theta power was more marginally associated with greater diffuse amyloid deposition and lower gray matter volume in fronto-temporal and parieto-occipital areas.Interpretation: These results suggest that alterations of REM sleep microstructure are associated with greater neurodegeneration and neocortical amyloid deposition in older adults. Further studies are warranted to replicate these findings, and determine whether older adults exhibiting REM sleep alterations are more at risk of cognitive decline and belonging to the Alzheimer's continuum. ANN NEUROL 2023

Age-related changes in fast spindle clustering during non-rapid eye movement sleep and their relevance for memory consolidation

International audienceSleep plays a crucial role in memory consolidation. Recent data in rodents and young adults revealed that fast spindle band power fluctuates at a 0.02-Hz infraslow scale during non-rapid eye movement (NREM) sleep. These fluctuations result from a periodic temporal clustering of spindles and may modulate sleep maintenance and memory consolidation. With age, sleep undergoes substantial changes but age-related changes in spindle clustering have never been investigated. Polysomnography data were collected in 147 older (mean age ± SD: 69.3 ± 4.1 years) and 32 young-middle aged (34.5 ± 10.9 years) adults. Sleep-dependent memory consolidation was assessed in a subsample of 57 older adults using a visuospatial memory task. We analyzed power fluctuations in fast spindle frequency band, detected fast spindles and quantified their clustering during the night separating encoding and retrieval. Fast spindle band power fluctuated at a 0.02-Hz infraslow scale in young-middle aged and older adults. However, the proportion of clustered fast spindles decreased non-linearly with age (p < 0.001). This effect was not mediated by NREM sleep fragmentation. The clustering level of fast spindles modulated their characteristics (p < 0.001). Finally, the mean size of spindle clusters was positively associated with memory consolidation (p = 0.036) and negatively with NREM sleep micro-arousals density (p = 0.033). These results suggest that clusters of fast spindles may constitute stable sleep periods promoting off-line processes such as memory consolidation. We emphasize the relevance of considering spindle dynamics, obviously impaired during ageing, to understand the impact of age-related sleep changes on memory

Age-related changes in fast spindle clustering during non-rapid eye movement sleep and their relevance for memory consolidation

International audienceSleep plays a crucial role in memory consolidation. Recent data in rodents and young adults revealed that fast spindle band power fluctuates at a 0.02-Hz infraslow scale during non-rapid eye movement (NREM) sleep. These fluctuations result from a periodic temporal clustering of spindles and may modulate sleep maintenance and memory consolidation. With age, sleep undergoes substantial changes but age-related changes in spindle clustering have never been investigated. Polysomnography data were collected in 147 older (mean age ± SD: 69.3 ± 4.1 years) and 32 young-middle aged (34.5 ± 10.9 years) adults. Sleep-dependent memory consolidation was assessed in a subsample of 57 older adults using a visuospatial memory task. We analyzed power fluctuations in fast spindle frequency band, detected fast spindles and quantified their clustering during the night separating encoding and retrieval. Fast spindle band power fluctuated at a 0.02-Hz infraslow scale in young-middle aged and older adults. However, the proportion of clustered fast spindles decreased non-linearly with age (p < 0.001). This effect was not mediated by NREM sleep fragmentation. The clustering level of fast spindles modulated their characteristics (p < 0.001). Finally, the mean size of spindle clusters was positively associated with memory consolidation (p = 0.036) and negatively with NREM sleep micro-arousals density (p = 0.033). These results suggest that clusters of fast spindles may constitute stable sleep periods promoting off-line processes such as memory consolidation. We emphasize the relevance of considering spindle dynamics, obviously impaired during ageing, to understand the impact of age-related sleep changes on memory

Age-related changes in fast spindle clustering during non-rapid eye movement sleep and their relevance for memory consolidation

International audienceSleep plays a crucial role in memory consolidation. Recent data in rodents and young adults revealed that fast spindle band power fluctuates at a 0.02-Hz infraslow scale during non-rapid eye movement (NREM) sleep. These fluctuations result from a periodic temporal clustering of spindles and may modulate sleep maintenance and memory consolidation. With age, sleep undergoes substantial changes but age-related changes in spindle clustering have never been investigated. Polysomnography data were collected in 147 older (mean age ± SD: 69.3 ± 4.1 years) and 32 young-middle aged (34.5 ± 10.9 years) adults. Sleep-dependent memory consolidation was assessed in a subsample of 57 older adults using a visuospatial memory task. We analyzed power fluctuations in fast spindle frequency band, detected fast spindles and quantified their clustering during the night separating encoding and retrieval. Fast spindle band power fluctuated at a 0.02-Hz infraslow scale in young-middle aged and older adults. However, the proportion of clustered fast spindles decreased non-linearly with age (p < 0.001). This effect was not mediated by NREM sleep fragmentation. The clustering level of fast spindles modulated their characteristics (p < 0.001). Finally, the mean size of spindle clusters was positively associated with memory consolidation (p = 0.036) and negatively with NREM sleep micro-arousals density (p = 0.033). These results suggest that clusters of fast spindles may constitute stable sleep periods promoting off-line processes such as memory consolidation. We emphasize the relevance of considering spindle dynamics, obviously impaired during ageing, to understand the impact of age-related sleep changes on memory

Association of Sleep-Disordered Breathing and Medial Temporal Lobe Atrophy in Cognitively Unimpaired Amyloid-Positive Older Adults

International audienceBackground and Objectives Sleep disordered breathing (SDB) has been related to amyloid deposition and an increased dementia risk. However, how SDB relates to medial temporal lobe neurodegeneration and subsequent episodic memory impairment is unclear. Our objective was to investigate the impact of amyloid positivity on the associations between SDB severity, medial temporal lobe subregions, and episodic memory performance in cognitively unimpaired older adults. Methods Data were acquired between 2016 and 2020 in the context of the Age-Well randomized controlled trial of the Medit-Aging European project. Participants older than 65 years who were free of neurologic, psychiatric, or chronic medical diseases were recruited from the community. They completed a neuropsychological evaluation, in-home polysomnography, a Florbetapir PET, and an MRI, including a specific high-resolution assessment of the medial temporal lobe and hippocampal subfields. Multiple linear regressions were conducted to test interactions between amyloid status and SDB severity on the volume of MTL subregions, controlling for age, sex, education, and the ApoE4 status. Secondary analyses aimed at investigating the links between SDB, MTL subregional atrophy, and episodic memory performance at baseline and at a mean follow-up of 20.66 months in the whole cohort and in subgroups stratified according to amyloid status. Results We included 122 cognitively intact community-dwelling older adults (mean age ± SD: 69.40 ± 3.85 years, 77 women, 26 Aβ+ individuals) in baseline analyses and 111 at follow-up. The apnea-hypopnea index interacted with entorhinal (β = −0.81, p < 0.001, pη 2 = 0.19), whole hippocampal (β = −0.61, p < 0.001, pη 2 = 0.10), subiculum (β = −0.56, p = 0.002, pη 2 = 0.08), CA1 (β = −0.55, p = 0.002, pη 2 = 0.08), and DG (β = −0.53, p = 0.003, pη 2 = 0.08) volumes such that a higher sleep apnea severity was related to lower MTL subregion volumes in amyloid-positive individuals, but not in those who were amyloid negative. In the whole cohort, lower whole hippocampal ( r = 0.27, p = 0.005) and CA1 ( r = 0.28, p = 0.003) volumes at baseline were associated with worse episodic memory performance at follow-up. Discussion Overall, we showed that SDB was associated with MTL atrophy in cognitively asymptomatic older adults engaged in the Alzheimer continuum, which may increase the risk of developing memory impairment over time