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

Objective: 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: ß=-0.32, p<0.001; brooding: ß=-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.

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

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 and 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 ±â€…SD: 69.0 ±â€…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 magnetic resonance imaging 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. CONCLUSIONS: Our results show that slow delta is particularly associated with preserved brain structure, and highlight the importance of analyzing 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 among sleep, amyloid pathology, and dementia risk in older populations. CLINICAL TRIAL INFORMATION: Name: Study in Cognitively Intact Seniors Aiming to Assess the Effects of Meditation Training (Age-Well). URL: https://clinicaltrials.gov/ct2/show/NCT02977819?term=Age-Well&draw=2&rank=1. See STROBE_statement_AGEWELL in supplemental materials. REGISTRATION: EudraCT: 2016-002441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819.

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.

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

BACKGROUND 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 Aß+ individuals) in baseline analyses and 111 at follow-up. The apnea-hypopnea index interacted with entorhinal (ß = -0.81, p < 0.001, pη2 = 0.19), whole hippocampal (ß = -0.61, p < 0.001, pη2 = 0.10), subiculum (ß = -0.56, p = 0.002, pη2 = 0.08), CA1 (ß = -0.55, p = 0.002, pη2 = 0.08), and DG (ß = -0.53, p = 0.003, pη2 = 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. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02977819.

Distinct Sleep Alterations in Alcohol Use Disorder Patients with and without Korsakoff's Syndrome: Relationship with Episodic Memory.

Alcohol Use Disorder (AUD) results in sleep disturbances that may have deleterious impacts on cognition, especially on memory. However, little is known about the sleep architecture in patients with Korsakoff's syndrome (KS). This study aims at characterizing sleep disturbances in KS compared to AUD without KS and at specifying the relationships with cognitive impairments. Twenty-nine AUD patients (22 without KS and 7 with KS) and 15 healthy controls underwent a neuropsychological assessment and a polysomnography. The severity of sleep-disordered breathing and sleep fragmentation was similar in AUD and KS patients compared to controls. Sleep architecture differed between both patient groups: the proportion of slow-wave sleep was reduced in AUD patients only, while a lower proportion of rapid-eye movement (REM) sleep was specifically observed in KS patients. The proportion of REM sleep correlated with the severity of episodic memory deficits when AUD and KS were examined together. These data provide evidence for both similarities and specificities regarding sleep alterations in AUD patients with and without KS. They also indicate that altered sleep architecture may contribute to the pathophysiology of alcohol-related memory disorders.

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

OBJECTIVE: 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;93:979-990.

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

Sleep 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 ±â€…SD: 69.3 ±â€…4.1 years) and 32 young-middle aged (34.5 ±â€…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 < .001). This effect was not mediated by NREM sleep fragmentation. The clustering level of fast spindles modulated their characteristics (p < .001). Finally, the mean size of spindle clusters was positively associated with memory consolidation (p = .036) and negatively with NREM sleep micro-arousal density (p = .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 aging, to understand the impact of age-related sleep changes on memory. Clinical Trial Information: Name: Study in Cognitively Intact Seniors Aiming to Assess the Effects of Meditation Training (Age-Well). URL: https://clinicaltrials.gov/ct2/show/NCT02977819?term=Age-Well&draw=2&rank=1. See STROBE_statement_AGEWELL.doc in supplementary material. Registration: EudraCT: 2016-002441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819.

Alterations in resting-state functional connectivity associated to the age-related decline in time-based prospective memory.

Time-based prospective memory (TBPM) is defined as the ability to remember to perform intended actions at a specific time in the future. TBPM is impaired in aging, and this decline has been associated with white-matter alterations within the superior fronto-occipital fasciculus. In the present study, we used resting-state functional magnetic resonance imaging from 22 healthy young (26 ± 5.2 years) and 23 older (63 ± 6.1 years) participants to investigate how age-related alterations in resting-state functional connectivity are related to TBPM performance, and whether these alterations are associated with the white-matter disruptions we have previously observed with diffusion tensor imaging. Whole-brain analyses revealed lower resting-state functional connectivity in older participants compared with younger ones, which in turn correlated with TBPM performance. These correlations were mainly located in the salience network and the parietal part of the frontoparietal network. Our findings suggest that resting-state functional connectivity alterations contribute to the age-related decline in TBPM.

Effect of an 18-Month Meditation Training on Regional Brain Volume and Perfusion in Older Adults: The Age-Well Randomized Clinical Trial.

Importance: No lifestyle-based randomized clinical trial directly targets psychoaffective risk factors of dementia. Meditation practices recently emerged as a promising mental training exercise to foster brain health and reduce dementia risk. Objective: To investigate the effects of meditation training on brain integrity in older adults. Design, Setting, and Participants: Age-Well was a randomized, controlled superiority trial with blinded end point assessment. Community-dwelling cognitively unimpaired adults 65 years and older were enrolled between November 24, 2016, and March 5, 2018, in France. Participants were randomly assigned (1:1:1) to (1) an 18-month meditation-based training, (2) a structurally matched non-native language (English) training, or (3) no intervention arm. Analysis took place between December 2020 and October 2021. Interventions: Meditation and non-native language training included 2-hour weekly group sessions, practice of 20 minutes or longer daily at home, and 1-day intensive practices. Main Outcomes and Measures: Primary outcomes included volume and perfusion of anterior cingulate cortex (ACC) and insula. Main secondary outcomes included a global composite score capturing metacognitive, prosocial, and self-regulatory capacities and constituent subscores. Results: Among 137 participants (mean [SD] age, 69.4 [3.8] years; 83 [60.6%] female; 54 [39.4%] male) assigned to the meditation (n = 45), non-native language training (n = 46), or no intervention (n = 46) groups, all but 1 completed the trial. There were no differences in volume changes of ACC (0.01 [98.75% CI, -0.02 to 0.05]; P = .36) or insula (0.01 [98.75% CI, -0.02 to 0.03]; P = .58) between meditation and no intervention or non-native language training groups, respectively. Differences in perfusion changes did not reach statistical significance for meditation compared with no intervention in ACC (0.02 [98.75% CI, -0.01 to 0.05]; P = .06) or compared with non-native language training in insula (0.02 [98.75% CI, -0.01 to 0.05]; P = .09). Meditation was superior to non-native language training on 18-month changes in a global composite score capturing attention regulation, socioemotional, and self-knowledge capacities (Cohen d, 0.52 [95% CI, 0.19-0.85]; P = .002). Conclusions and Relevance: The study findings confirm the feasibility of meditation and non-native language training in elderly individuals, with high adherence and very low attrition. Findings also show positive behavioral effects of meditation that were not reflected on volume, and not significantly on perfusion, of target brain areas. Trial Registration: ClinicalTrials.gov Identifier: NCT02977819.

Determinants of health-related quality of life in recently detoxified patients with severe alcohol use disorder.

BACKGROUND: Health-related quality of life (HRQoL) is an important clinical outcome in Alcohol Use Disorder (AUD) and is considered as a relevant indicator of treatment success. While a better understanding of the factors affecting HRQoL would enable to adjust patients' care to favour treatment outcome, the determinants of HRQoL in AUD remain unclear. This study aims at describing HRQoL in AUD patients and at identifying its best predictors. METHODS: 53 recently detoxified patients with severe AUD (sAUD) underwent a cognitive assessment and filled in a HRQoL questionnaire dedicated to AUD patients (Alcohol Quality of Life Scale; AQoLS), as well as questionnaires concerning socio-demographics, alcohol history, sleep quality, depression, anxiety and impulsivity. 38 healthy controls (HC) underwent the same assessment (except AQoLS) in order to identify the altered cognitive and clinical variables that could potentially be determinants of HRQoL in sAUD. RESULTS: sAUD patients reported that alcohol affects their HRQoL mainly in the "negative emotions", "control", "relationships", and "sleep" domains. Compared to HC, they were impaired on episodic memory, working memory, executive functions, and processing speed tasks. They also reported lower sleep quality, higher depression, anxiety and impulsivity. No association was found between AQoLS total score and socio-demographics, cognitive performance, or sleep quality in patients. We found a significant correlation between HRQoL and depression/anxiety as well as impulsivity. Anxiety and impulsivity were indeed the only significant predictors of HRQoL, explaining 47.7% of the variance. CONCLUSION: Anxiety and impulsivity are crucial determinants of HRQoL in recently detoxified sAUD patients. Since anxiety and impulsivity are frequent issues in addiction and especially in AUD, they should be particularly considered by clinicians to favour treatment outcomes.

Consommation d'alcool à risque : les séniors, grands oubliés des politiques de prévention.

With the aging of the population, it is necessary to implement prevention policies aimed at maintaining the elderly in good health and promoting their autonomy. Alcohol consumption is an avoidable risk factor in deteriorating health and loss of autonomy that can be addressed through targeted public health policies. We must consider both the long-term effects, by informing young people of the risks to their future health, and the deleterious short-term effects (accidents, falls) for older subjects. Even if there are recommendations for alcohol consumption issued by Santé Publique France, they are aimed at the general population and do not take into account the specificities of the elderly, whose vulnerability will depend both on current consumption and on the history of alcohol use during their lives. Several countries have issued recommendations specifically for this population, but the definitions of alcohol units vary from one country to another, making it very difficult to apply these recommendations in France. A public health policy specifically addressing the alcohol consumption of seniors in France is therefore absolutely crucial.

Sleep-dependent memory consolidation in breast cancer: Use of a virtual reality prospective memory task.

Background: Previous studies have revealed both sleep alterations and prospective memory (PM) impairments in breast cancer (BC) patients. PM refers to memory of intended actions and is crucial for daily living tasks and treatment compliance. As sleep is known to favor memory consolidation, one may expect that changes in sleep quality related to BC would have an impact on PM performance. This study aimed at assessing sleep-dependent consolidation of intentions using an ecological, virtual reality-based PM task in BC patients not treated with chemotherapy. Materials and methods: Thirty-seven early stages BC patients and 21 healthy controls (HC) participated in this study. PM was assessed using a virtual reality task, during which participants learnt a list of intentions and recalled them after a retention interval filled with a day awake or a night of sleep monitored by polysomnography. Sleep spindles and slow waves, brain oscillations involved in sleep-dependent memory consolidation, were quantified automatically using the Aseega software (Physip). Subjective sleep disturbances and markers of quality of life (psychological distress, fatigue, and well-being) were assessed by questionnaires. Results: Greater PM performance was observed after sleep than after an equivalent period of daytime wakefulness for both groups (HC and BC). PM performance after sleep did not differ significantly between groups. Yet, BC patients reported greater sleep disturbances than HC which were related with poorer intentions retrieval, greater psychological distress, fatigue and poorer well-being. The frequency of spindles was higher and the amplitude of slow waves lower in BC patients compared to HC. However, no significant association was observed between polysomnography parameters and PM scores in the whole sample of participants. Conclusion: Although subtle changes in brain oscillations involved in sleep-dependent memory consolidation were observed, these changes did not significantly impair overnight PM consolidation in BC patients. Nevertheless, poorer PM performance was associated with greater sleep complaints which in turn were related to poorer quality of life. Overall, these data suggest that sleep-dependent PM consolidation mechanisms are not altered in early stages BC patients not treated with chemotherapy. Further investigations are needed to understand the association between markers of quality of life and sleep-dependent memory consolidation.

Recent advances in memory consolidation and information processing during sleep.

Increasingly studied in a systematic manner since the 1970s, the cognitive processes of the brain taking place during sleeping periods remain an important object of scrutiny in the scientific community. In particular, sleep has been demonstrated to play a significant role for learning and memory consolidation processes, and sleep scientists have started unravelling its underlying neurophysiological mechanisms. However, sleep remains a multidimensional phenomenon, and many questions remain left open for future research. In this selective review article, we address recent advances in particular domains in which sleep research has further progressed in the past decade. We highlight the developmental trajectory of sleep-dependent learning and memory consolidation processes, from their development in childhood to their potential impairments in ageing, and the nature and extent of our capabilities for information processing, learning, and memory reinforcement during sleep.

Harmonisation and Between-Country Differences of the Lifetime of Experiences Questionnaire in Older Adults.

Background: The Lifetime of Experiences Questionnaire (LEQ) assesses complex mental activity across the life-course and has been associated with brain and cognitive health. The different education systems and occupation classifications across countries represent a challenge for international comparisons. The objectives of this study were four-fold: to adapt and harmonise the LEQ across four European countries, assess its validity across countries, explore its association with brain and cognition and begin to investigate between-country differences in life-course mental activities. Method: The LEQ was administered to 359 cognitively unimpaired older adults (mean age and education: 71.2, 13.2 years) from IMAP and EU-funded Medit-Ageing projects. Education systems, classification of occupations and scoring guidelines were adapted to allow comparisons between France, Germany, Spain and United Kingdom. We assessed the LEQ's (i) concurrent validity with a similar instrument (cognitive activities questionnaire - CAQ) and its structural validity by testing the factors' structure across countries, (ii) we investigated its association with cognition and neuroimaging, and (iii) compared its scores between countries. Results: The LEQ showed moderate to strong positive associations with the CAQ and revealed a stable multidimensional structure across countries that was similar to the original LEQ. The LEQ was positively associated with global cognition. Between-country differences were observed in leisure activities across the life-course. Conclusions: The LEQ is a promising tool for assessing the multidimensional construct of cognitive reserve and can be used to measure socio-behavioural determinants of cognitive reserve in older adults across countries. Longitudinal studies are warranted to test further its clinical utility.

Contribution of sleep disturbances to the heterogeneity of cognitive and brain alterations in alcohol use disorder.

Cognitive and brain alterations are common in alcohol use disorder and vary importantly from one patient to another. Sleep disturbances are also very frequent in these patients and remain largely neglected even though they can persist after drinking cessation. Sleep disturbances may be the consequence of specific brain alterations, resulting in cognitive impairments. But sleep disruption may also exacerbate alcohol-related brain abnormalities and cognitive deficits through common pathophysiological mechanisms. Besides, sleep disturbances seem a vulnerability factor for the development of alcohol use disorder. From a clinical perspective, sleep disturbances are known to affect treatment outcome and to increase the risk of relapse. In this article, we conducted a narrative review to provide a better understanding of the relationships between sleep disturbances, brain and cognition in alcohol use disorder. We suggest that the heterogeneity of brain and cognitive alterations observed in patients with alcohol use disorder could at least partially be explained by associated sleep disturbances. We also believe that sleep disruption could indirectly favor relapse by exacerbating neuropsychological impairments required in psychosocial treatment and for the maintenance of abstinence. Implications for clinical practice as well as perspectives for future research are proposed.

Association of quality of life with structural, functional and molecular brain imaging in community-dwelling older adults.

BACKGROUND: As the population ages, maintaining mental health and well-being of older adults is a public health priority. Beyond objective measures of health, self-perceived quality of life (QoL) is a good indicator of successful aging. In older adults, it has been shown that QoL is related to structural brain changes. However, QoL is a multi-faceted concept and little is known about the specific relationship of each QoL domain to brain structure, nor about the links with other aspects of brain integrity, including white matter microstructure, brain perfusion and amyloid deposition, which are particularly relevant in aging. Therefore, we aimed to better characterize the brain biomarkers associated with each QoL domain using a comprehensive multimodal neuroimaging approach in older adults. METHODS: One hundred and thirty-five cognitively unimpaired older adults (mean age ± SD: 69.4 ± 3.8 y) underwent structural and diffusion magnetic resonance imaging, together with early and late florbetapir positron emission tomography scans. QoL was assessed using the brief version of the World Health Organization's QoL instrument, which allows measuring four distinct domains of QoL: self-perceived physical health, psychological health, social relationships and environment. Multiple regression analyses were carried out to identify the independent global neuroimaging predictor(s) of each QoL domain, and voxel-wise analyses were then conducted with the significant predictor(s) to highlight the brain regions involved. Age, sex, education and the other QoL domains were entered as covariates in these analyses. Finally, forward stepwise multiple regressions were conducted to determine the specific items of the relevant QoL domain(s) that contributed the most to these brain associations. RESULTS: Only physical health QoL was associated with global neuroimaging values, specifically gray matter volume and white matter mean kurtosis, with higher physical health QoL being associated with greater brain integrity. These relationships were still significant after correction for objective physical health and physical activity measures. No association was found with global brain perfusion or global amyloid deposition. Voxel-wise analyses revealed that the relationships with physical health QoL concerned the anterior insula and ventrolateral prefrontal cortex, and the corpus callosum, corona radiata, inferior frontal white matter and cingulum. Self-perceived daily living activities and self-perceived pain and discomfort were the items that contributed the most to these associations with gray matter volume and white matter mean kurtosis, respectively. CONCLUSIONS: Better self-perceived physical health, encompassing daily living activities and pain and discomfort, was the only QoL domain related to brain structural integrity including higher global gray matter volume and global white matter microstructural integrity in cognitively unimpaired older adults. The relationships involved brain structures belonging to the salience network, the pain pathway and the empathy network. While previous studies showed a link between objective measures of physical health, our findings specifically highlight the relevance of monitoring and promoting self-perceived physical health in the older population. Longitudinal studies are needed to assess the direction and causality of the relationships between QoL and brain integrity.

Brain changes associated with sleep disruption in cognitively unimpaired older adults: A short review of neuroimaging studies.

Ageing is characterized by a progressive decline of sleep quality. Sleep difficulties are increasingly recognized as a risk factor for Alzheimer's disease (AD), and have been associated with cognitive decline. However, the brain substrates underlying this association remain unclear. In this review, our objective was to provide a comprehensive overview of the relationships between sleep changes and brain structural, functional and molecular integrity, including amyloid and tau pathologies in cognitively unimpaired older adults. We especially discuss the topography and causality of these associations, as well as the potential underlying mechanisms. Taken together, current findings converge to a link between several sleep parameters, amyloid and tau levels in the CSF, and neurodegeneration in diffuse frontal, temporal and parietal areas. However, the existing literature remains heterogeneous, and the specific sleep changes associated with early AD pathological changes, in terms of topography and neuroimaging modality, is not clearly established yet. Notably, if slow wave sleep disruption seems to be related to frontal amyloid deposition, the brain correlates of sleep-disordered breathing and REM sleep disruption remain unclear. Moreover, sleep parameters associated with tau- and FDG-PET imaging are largely unexplored. Lastly, whether sleep disruption is a cause or a consequence of brain alterations remains an open question.

Brain Substrates of Time-Based Prospective Memory Decline in Aging: A Voxel-Based Morphometry and Diffusion Tensor Imaging Study.

Time-based prospective memory (TBPM) allows us to remember to perform intended actions at a specific time in the future. TBPM is sensitive to the effects of age, but the neural substrates of this decline are still poorly understood. The aim of the present study was thus to better characterize the brain substrates of the age-related decline in TBPM, focusing on macrostructural gray matter and microstructural white matter integrity. We administered a TBPM task to 22 healthy young (26 ± 5.2 years) and 23 older (63 ± 5.9 years) participants, who also underwent volumetric magnetic resonance imaging and diffusion tensor imaging scans. Neuroimaging analyses revealed lower gray matter volumes in several brain areas in older participants, but these did not correlate with TBPM performance. By contrast, an age-related decline in fractional anisotropy in several white-matter tracts connecting frontal and occipital regions did correlate with TBPM performance, whereas there was no significant correlation in healthy young subjects. According to the literature, these tracts are connected to the anterior prefrontal cortex and the thalamus, 2 structures involved in TBPM. These results confirm the view that a disconnection process occurs in aging and contributes to cognitive decline.