Subjective Cognitive Decline: Level of Risk for Future Dementia and Mild Cognitive Impairment, a Meta-Analysis of Longitudinal Studies.

Subjective Cognitive Decline (SCD) in older adults has been identified as a risk factor for dementia, although the literature is inconsistent, and it is unclear which factors moderate progression from SCD to dementia. Through separate meta-analyses, we aimed to determine if SCD increased the risk of developing dementia or mild cognitive impairment (MCI). Furthermore, we examined several possible moderators. Longitudinal studies of participants with SCD at baseline, with data regarding incident dementia or MCI, were extracted from MEDLINE and PsycINFO. Articles were excluded if SCD occurred solely in the context of dementia, MCI, or as part of a specific disease. Pooled estimates were calculated using a random-effects model, with moderator analyses examining whether risk varied according to SCD definition, demographics, genetics, recruitment source, and follow-up duration. Risk of study bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. 46 studies with more than 74,000 unique participants were included. SCD was associated with increased risk of developing dementia (HR = 1.90, 95% CI 1.52-2.36; OR = 2.48, 95% CI 1.97-3.14) and MCI (HR = 1.73, 95% CI 1.18-2.52; OR = 1.83, 95% CI 1.56-2.16). None of the potential moderating factors examined influenced the HR or OR of developing dementia. In contrast, including worry in the definition of SCD, younger age, and recruitment source impacted the OR of developing MCI, with clinic samples demonstrating highest risk. SCD thus represents an at-risk phase, ideal for early intervention, with further research required to identify effective interventions for risk reduction, and cognitive-behavioural interventions for cognitive management. PROSPERO, protocol number: CRD42016037993.

Naturalistic prospective memory in older adults: Predictors of performance on a habitual task.

Age-related difficulties in episodic prospective memory (PM) are common. However, little is known about habitual PM, which involves remembering to carry out intended actions that are regular and repeated. This is important for many health-related tasks and for maintaining independence in daily living activities. This study investigates, in older people, the predictors of habitual PM performance in a naturalistic setting. A group of 191 community-based, older adults (aged 65-89 years) wore an actigraph over two weeks. The habitual PM task involved pressing a button twice daily (Bed-time, Rise-time) on the actigraph. Accuracy of response was calculated for Bed-time and Rise-time, determined by light, movement, and diary data. The contribution of retrospective memory and executive function to PM performance was assessed. PM was more accurate at Bed-time compared to Rise-time (p < .01), and better in the first compared to the second week (p < .01). Retrospective memory contributed small but significant unique variance (ß = .24) to PM accuracy. For older adults living in the community, both contextual factors (e.g., time of day) and retrospective memory are important for individuals' ability to remember to perform daily tasks. This is relevant when planning interventions for maintaining independent living in ageing.

Objective but not subjective sleep predicts memory in community-dwelling older adults.

Research on the relationship between habitual sleep patterns and memory performance in older adults is limited. No previous study has used objective and subjective memory measures in a large, older-aged sample to examine the association between sleep and various domains of memory. The aim of this study was to examine the association between objective and subjective measures of sleep with memory performance in older adults, controlling for the effects of potential confounds. One-hundred and seventy-three community-dwelling older adults aged 65-89 years in Victoria, Australia completed the study. Objective sleep quality and length were ascertained using the Actiwatch 2 Mini-Mitter, while subjective sleep was measured using the Pittsburgh Sleep Quality Index. Memory was indexed by tests of retrospective memory (Hopkins Verbal Learning Test - Revised), working memory (n-back, 2-back accuracy) and prospective memory (a habitual button pressing task). Compared with normative data, overall performance on retrospective memory function was within the average range. Hierarchical regression was used to determine whether objective or subjective measures of sleep predicted memory performances after controlling for demographics, health and mood. After controlling for confounds, actigraphic sleep indices (greater wake after sleep onset, longer sleep-onset latency and longer total sleep time) predicted poorer retrospective (∆R(2)  = 0.05, P = 0.016) and working memory (∆R(2)  = 0.05, P = 0.047). In contrast, subjective sleep indices did not significantly predict memory performances. In community-based older adults, objectively-measured, habitual sleep indices predict poorer memory performances. It will be important to follow the sample longitudinally to determine trajectories of change over time.

Association of the Sleep Regularity Index With Incident Dementia and Brain Volume.

BACKGROUND AND OBJECTIVES: Irregular sleep may increase the risk of cardiometabolic conditions, but its association with incident dementia is unclear. The aim of this study was to assess the association between sleep regularity, that is, the day-to-day consistency in sleep-wake patterns and the risk of incident dementia and related brain MRI endophenotypes. METHODS: We used Cox proportional hazard models to investigate the relationships between sleep regularity and incident dementia in 88,094 UK Biobank participants. The sleep regularity index (SRI) was calculated as the probability of being in the same state (asleep/awake) at any 2 time points 24 hours apart, averaged over 7 days of accelerometry. RESULTS: The mean age of the sample was 62 years (SD = 8), 56% were women, and the median SRI was 60 (SD = 10). There were 480 cases of incident dementia over a median 7.2 years of follow-up. Following adjustments for demographic, clinical, and genetic confounders (APOE ε4), there was a nonlinear association between the SRI and dementia hazard (p [global test of spline term] < 0.001) with hazard ratios (HRs) following a U-shape pattern. HRs, relative to the median SRI, were 1.53 (95% CI 1.24-1.89) for participants with SRI at the 5th percentile (SRI = 41) and 1.16 (95% CI 0.89-1.50) for those with SRI at the 95th percentile (SRI = 71). In a subset with brain MRI (n = 15,263), gray matter and hippocampal volume tended to be lowest at the extremes of the SRI. DISCUSSION: Sleep regularity displayed a U-shaped association with risk of incident dementia. Irregular sleep may represent a novel dementia risk factor.

Cross-sectional associations between neighborhood characteristics, cognition and dementia risk factor burden in middle-aged and older Australians.

Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition. This was a cross-sectional analysis of 2016-2020 data from the Healthy Brain Project, a population-based cohort of community-dwelling individuals across Australia. Participants were aged 40-70 and free of dementia. Measures included greenspace (greenspace % in the local area, and distance to greenspace, n = 2,181); and intersection density (n = 1,159), and crime (rate of recorded offences; n = 1,159). Outcomes included a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score to index the burden of modifiable vascular dementia risk factors; and composite scores of both memory and attention, derived from the Cogstate Brief Battery. Linear regressions adjusted for age, sex, education, and personal socio-economic status, demonstrated distance to greenspace (b ± SE per 2-fold increase = 0.09 ± 0.03, p =.005) and crime rate (b ± SE per 2-fold increase = 0.07 ± 0.03, p =.018) were associated with higher modified CAIDE. Higher crime was associated with lower memory performance (b ± SE = -0.03 ± 0.01, p =.018). The association between distance to greenspace and modified CAIDE was only present in low-moderate socioeconomic status neighborhoods (p interaction = 0.004). Dementia prevention programs that address modifiable risk factors in midlife should consider the possible role of neighborhood characteristics.

Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology.

BACKGROUND AND OBJECTIVES: Both short and long sleep duration were previously associated with incident dementia, but underlying mechanisms remain unclear. We evaluated how self-reported sleep duration and its change over time associate with (A)myloid, (T)au, (N)eurodegeneration, and (V)ascular neuroimaging markers of Alzheimer disease. METHODS: Two Framingham Heart Study overlapping samples were studied: participants who underwent 11C-Pittsburg Compound B amyloid and 18F-flortaucipir tau PET imaging and participants who underwent an MRI. MRI metrics estimated neurodegeneration (total brain volume) and cerebrovascular injuries (white matter hyperintensities [WMHs] volume, covert brain infarcts, free-water [FW] fraction). Self-reported sleep duration was assessed and split into categories both at the time of neuroimaging testing and approximately 13 years before: short ≤6 hours. average 7-8 hours, and long ≥9 hours. Logistic and linear regression models were used to examine sleep duration and neuroimaging metrics. RESULTS: The tested cohort was composed of 271 participants (age 53.6 ± 8.0 years; 51% male) in the PET imaging sample and 2,165 participants (age 61.3 ± 11.1 years; 45% male) in the MRI sample. No fully adjusted association was observed between cross-sectional sleep duration and neuroimaging metrics. In fully adjusted models compared with consistently sleeping 7-8 hours, groups transitioning to a longer sleep duration category over time had higher FW fraction (short to average ß [SE] 0.0062 [0.0024], p = 0.009; short to long ß [SE] 0.0164 [0.0076], p = 0.031; average to long ß [SE] 0.0083 [0.0022], p = 0.002), and those specifically going from average to long sleep duration also had higher WMH burden (ß [SE] 0.29 [0.11], p = 0.007). The opposite associations (lower WMH and FW) were observed in participants consistently sleeping ≥9 hours as compared with people consistently sleeping 7-8 hours in fully adjusted models (ß [SE] -0.43 [0.20], p = 0.028; ß [SE] -0.019 [0.004], p = 0.020). Each hour of increasing sleep (continuous, ß [SE] 0.12 [0.04], p = 0.003; ß [SE] 0.002 [0.001], p = 0.021) and extensive increase in sleep duration (≥2 hours vs 0 ± 1 hour change; ß [SE] 0.24 [0.10], p = 0.019; ß [SE] 0.0081 [0.0025], p = 0.001) over time was associated with higher WMH burden and FW fraction in fully adjusted models. Sleep duration change was not associated with PET amyloid or tau outcomes. DISCUSSION: Longer self-reported sleep duration over time was associated with neuroimaging biomarkers of cerebrovascular pathology as evidenced by higher WMH burden and FW fraction. A longer sleep duration extending over time may be an early change in the neurodegenerative trajectory.

The impact of elder abuse training on subacute health providers and older adults: study protocol for a randomized control trial.

BACKGROUND: Elder abuse often goes unreported and undetected. Older people may be ashamed, fearful, or otherwise reticent to disclose abuse, and many health providers are not confident in asking about it. In the No More Shame study, we will evaluate a co-designed, multi-component intervention that aims to improve health providers' recognition, response, and referral of elder abuse. METHODS: This is a single-blinded, pragmatic, cluster randomised controlled trial. Ten subacute hospital sites (i.e. clusters) across Australia will be allocated 1:1, stratified by state to a multi-component intervention comprising a training programme for health providers, implementation of a screening tool and use of site champions, or no additional training or support. Outcomes will be collected at baseline, 4 and 9 months. Our co-primary outcomes are change in health providers' knowledge of responding to elder abuse and older people's sense of safety and quality of life. We will include all inpatients at participating sites, aged 65 + (or aged 50 + if Aboriginal or Torres Strait Islander), who are able to provide informed consent and all unit staff who provide direct care to older people; a sample size of at least 92 health providers and 612 older people will provide sufficient power for primary analyses. DISCUSSION: This will be one of the first trials in the world to evaluate a multi-component elder abuse intervention. If successful, it will provide the most robust evidence base to date for health providers to draw on to create a safe environment for reporting, response, and referral. TRIAL REGISTRATION: ANZCTR, ACTRN12623000676617p . Registered 22 June 2023.

Inclusive dementia care for ethnically diverse families.

PURPOSE OF REVIEW: With population ageing and global migration, rates of dementia are set to rapidly increase in ethnically diverse populations. This narrative review examines recent evidence on what constitutes culturally appropriate models of care. RECENT FINDINGS: Barriers to inclusive care continue to prevail, amplifying dementia disparities in ethnically diverse communities. Cultural models that can address these include ensuring health and aged care staff are culturally competent, language supports are available, and cultural practices are integrated into daily care routines. Fundamentally, systems must be reformed to ensure they meet the needs of diverse end-users. More inclusive and widespread ethno-specific services are needed, and governments need to be mindful of demographic transitions in their populations and plan accordingly to meet future demand. Digital media and new technologies offer promising new ways to deliver culturally appropriate care to ethnically diverse groups, but its full potential is yet to be realised. SUMMARY: Persistent dementia disparities in ethnically diverse communities can be overcome by operationalising cultural models of care, leveraging the promise of digital media, and systems redesign.

Sleep regularity and mortality: a prospective analysis in the UK Biobank.

Background: Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort. Methods: The sleep regularity index (SRI) was calculated as the probability of an individual being in the same state (asleep or awake) at any two time points 24 hr apart, averaged over 7 days of accelerometry (range 0-100, with 100 being perfectly regular). The SRI was related to the risk of mortality in time-to-event models. Results: The mean sample age was 62 years (standard deviation [SD], 8), 56% were women, and the median SRI was 60 (SD, 10). There were 3010 deaths during a mean follow-up of 7.1 years. Following adjustments for demographic and clinical variables, we identified a non-linear relationship between the SRI and all-cause mortality hazard (p [global test of spline term]<0.001). Hazard ratios, relative to the median SRI, were 1.53 (95% confidence interval [CI]: 1.41, 1.66) for participants with SRI at the 5th percentile (SRI = 41) and 0.90 (95% CI: 0.81, 1.00) for those with SRI at the 95th percentile (SRI = 75), respectively. Findings for CVD mortality and cancer mortality followed a similar pattern. Conclusions: Irregular sleep-wake patterns are associated with higher mortality risk. Funding: National Health and Medical Research Council of Australia (GTN2009264; GTN1158384), National Institute on Aging (AG062531), Alzheimer's Association (2018-AARG-591358), and the Banting Fellowship Program (#454104).

Sleep Regularity and Mortality: A Prospective Analysis in the UK Biobank.

Background: Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort. Methods: The sleep regularity index (SRI) was calculated as the probability of an individual being in the same state (asleep or awake) at any two time points 24 hours apart, averaged over 7-days of accelerometry (range 0-100, with 100 being perfectly regular). The SRI was related to the risk of mortality in time-to-event models. Findings: The mean sample age was 62 years (SD, 8), 56% were women, and the median SRI was 60 (SD, 10). There were 3010 deaths during a mean follow-up of 7.1 years. Following adjustments for demographic and clinical variables, we identified a non-linear relationship between the SRI and all-cause mortality hazard (p [global test of spline term] < 0·001). Hazard Ratios, relative to the median SRI, were 1·53 (95% confidence interval [CI]: 1·41, 1·66) for participants with SRI at the 5th percentile (SRI = 41) and 0·90 (95% CI: 0·81, 1·00) for those with SRI at the 95th percentile (SRI = 75), respectively. Findings for CVD mortality and cancer mortality followed a similar pattern. Conclusions: Irregular sleep-wake patterns are associated with higher mortality risk. Funding: National Health and Medical Research Council of Australia (GTN2009264; GTN1158384), National Institute on Aging (AG062531), Alzheimer's Association (2018-AARG-591358), and the Banting Fellowship Program (#454104).

Multi-modal sleep intervention for community-dwelling people living with dementia and primary caregiver dyads with sleep disturbance: protocol of a single-arm feasibility trial.

Background: Disturbed sleep is common among people living with dementia and their informal caregivers, and is associated with negative health outcomes. Dyadic, multi-modal interventions targeting caregiver and care-recipient sleep have been recommended yet remain limited. This protocol details the development of a single-arm feasibility trial of a multi-modal, therapist-led, six-week intervention targeting sleep disturbance in dyads of people living with dementia and their primary caregiver. Methods: We aim to recruit 24 co-residing, community-dwelling dyads of people living with dementia and their primary informal caregiver (n = 48) with sleep concerns (Pittsburgh Sleep Quality Index ≥5 for caregivers, and caregiver-endorsed sleep concerns for the person living with dementia). People who live in residential care settings, are employed in night shift work, or are diagnosed with current, severe mental health conditions or narcolepsy, will be excluded. Participants will wear an actigraph and complete sleep diaries for two weeks prior, and during the last two weeks, of active intervention. The intervention is therapist-led and includes a mix of weekly small group video sessions and personalised, dyadic sessions (up to 90 min each) over six weeks. Sessions are supported by a 37-page workbook offering strategies and spaces for reflections/notes. Primary feasibility outcomes are caregiver: session attendance, attrition, and self-reported project satisfaction. Secondary outcomes include dyadic self-reported and objectively-assessed sleep, depression and anxiety symptoms, quality of life, and social support. Self-report outcomes will be assessed at pre- and post-intervention. Discussion: If feasible, this intervention could be tested in a larger randomised controlled trial to investigate its efficacy, and, upon further testing, may potentially represent a non-pharmacological approach to reduce sleep disturbance among people living with dementia and their caregivers. ANZCTR Trial registration: ACTRN12622000144718: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382960&showOriginal=true&isReview=true.

The MINDSET Study: Co-Designing Training for Interpreters in Dementia and Cognitive Assessments.

There is a growing demand for interpreter-mediated cognitive assessments for dementia. However, most interpreters lack specialist knowledge of dementia and cognitive assessment tools. This can negatively affect the way instructions and responses are conveyed between clinicians and patients, undermining clinicians' ability to accurately assess for cognitive impairment. This article reports on the co-design of an online dementia training package, MINDSET, which aims to address this gap. Two iterative online co-design workshops were conducted in October and November 2021, using a World Café approach. Sixteen clinicians, interpreters, and multilingual family carers of a person with dementia participated. Based on these workshops, training and assessment materials were developed and tested with 12 interpreters from April to June 2022. The training package comprises online modules: 1) Knowledge of Dementia and Australia's Aged Care System, 2) Briefings and Introductions, 3) Interpreting Skills, 4) Interpreting Ethics, and 5) Cross-cultural Communication. The codesign process highlighted divergent perspectives between clinicians and interpreters on an interpreter's role during a cognitive assessment, but it also facilitated negotiation and consensus building, which enriched the training content. The training is now developed and will be evaluated in a randomized control trial and subsequent implementation study.

The treatment of sleep dysfunction to improve cognitive function: A meta-analysis of randomized controlled trials.

OBJECTIVE: This meta-analysis of randomized controlled trials (RCTs) evaluates if treating sleep disturbances improves cognitive function over at least 12 weeks. METHODS: Multiple data sources were searched until November 1, 2021. RCTs were included if they examined the effect of an intervention (behavioral or medical) on sleep and cognition in an adult sample with sleep disturbances and had an intervention duration and follow-up of at least 12 weeks. Two independent reviewers located 3784 studies; 16 satisfied the inclusion criteria. Primary outcomes included the broad cognitive domains of visual processing, short-term memory, long-term storage and retrieval, processing speed, and reaction time. RESULTS: Most trials were conducted in participants with obstructive sleep apnea (OSA; N = 13); the most studied intervention was continuous positive airway pressure (CPAP; N = 10). All RCTs were 12 months in duration or less. The estimates of mean pooled effects were not indicative of significant treatment effect for any primary outcome. Although the interventions reduced daytime sleepiness (Hedge's g, 0.51; 95% confidence interval, 0.29-0.74; p < 0.01), this did not lead to cognitive enhancement. CONCLUSIONS: Overall, there was insufficient evidence to suggest that treating sleep dysfunction can improve cognition. Further studies with longer follow-up duration and supporting biomarkers are needed.

Associations Between Amyloid Burden, Hypoxemia, Sleep Architecture, and Cognition in Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased risk of amyloid-ß (Aß) burden, the hallmark of Alzheimer's disease, and cognitive decline. OBJECTIVE: To determine the differential impacts of hypoxemia and slow-wave sleep disruption on brain amyloid burden, and to explore the effects of hypoxemia, slow-wave sleep disruption, and amyloid burden on cognition in individuals with and without OSA. METHODS: Thirty-four individuals with confirmed OSA (mean±SD age 57.5±4.1 years; 19 males) and 12 healthy controls (58.5±4.2 years; 6 males) underwent a clinical polysomnogram, a NAV4694 positron emission tomography (PET) scan for Aß burden, assessment of APOEɛ status and cognitive assessments. Linear hierarchical regressions were conducted to determine the contributions of demographic and sleep variables on amyloid burden and cognition. RESULTS: Aß burden was associated with nocturnal hypoxemia, and impaired verbal episodic memory, autobiographical memory and set shifting. Hypoxemia was correlated with impaired autobiographical memory, and only set shifting performance remained significantly associated with Aß burden when controlling for sleep variables. CONCLUSIONS: Nocturnal hypoxemia was related to brain Aß burden in this sample of OSA participants. Aß burden and hypoxemia had differential impacts on cognition. This study reveals aspects of sleep disturbance in OSA that are most strongly associated with brain Aß burden and poor cognition, which are markers of early Alzheimer's disease. These findings add weight to the possibility that hypoxemia may be causally related to the development of dementia; however, whether it may be a therapeutic target for dementia prevention in OSA is yet to be determined.

Association Between Slow-Wave Sleep Loss and Incident Dementia.

Importance: Slow-wave sleep (SWS) supports the aging brain in many ways, including facilitating the glymphatic clearance of proteins that aggregate in Alzheimer disease. However, the role of SWS in the development of dementia remains equivocal. Objective: To determine whether SWS loss with aging is associated with the risk of incident dementia and examine whether Alzheimer disease genetic risk or hippocampal volumes suggestive of early neurodegeneration were associated with SWS loss. Design, Setting, and Participants: This prospective cohort study included participants in the Framingham Heart Study who completed 2 overnight polysomnography (PSG) studies in the time periods 1995 to 1998 and 2001 to 2003. Additional criteria for individuals in this study sample were an age of 60 years or older and no dementia at the time of the second overnight PSG. Data analysis was performed from January 2020 to August 2023. Exposure: Changes in SWS percentage measured across repeated overnight sleep studies over a mean of 5.2 years apart (range, 4.8-7.1 years). Main Outcome: Risk of incident all-cause dementia adjudicated over 17 years of follow-up from the second PSG. Results: From the 868 Framingham Heart Study participants who returned for a second PSG, this cohort included 346 participants with a mean age of 69 years (range, 60-87 years); 179 (52%) were female. Aging was associated with SWS loss across repeated overnight sleep studies (mean [SD] change, -0.6 [1.5%] per year; P < .001). Over the next 17 years of follow-up, there were 52 cases of incident dementia. In Cox regression models adjusted for age, sex, cohort, positivity for at least 1 APOE ε4 allele, smoking status, sleeping medication use, antidepressant use, and anxiolytic use, each percentage decrease in SWS per year was associated with a 27% increase in the risk of dementia (hazard ratio, 1.27; 95% CI, 1.06-1.54; P = .01). SWS loss with aging was accelerated in the presence of Alzheimer disease genetic risk (ie, APOE ε4 allele) but not hippocampal volumes measured proximal to the first PSG. Conclusions and Relevance: This cohort study found that slow-wave sleep percentage declined with aging and Alzheimer disease genetic risk, with greater reductions associated with the risk of incident dementia. These findings suggest that SWS loss may be a modifiable dementia risk factor.

Insomnia Symptoms and Biomarkers of Alzheimer's Disease in the Community.

BACKGROUND: Insomnia is one of the most common sleep disorders yet its relationship to the biology of Alzheimer's disease remains equivocal. OBJECTIVE: We investigated the cross-sectional relationship between insomnia symptom severity and cerebrospinal fluid (CSF) concentrations of Alzheimer's disease biomarkers in a cognitively unimpaired middle-aged community sample. METHODS: A total of 63 participants from the Healthy Brain Project (age = 59±7 years; 67% women) completed a lumbar puncture and two weeks of actigraphy to measure two of insomnia's core features: difficulty initiating sleep (prolonged sleep onset latency) and difficulty maintaining sleep (wake after sleep onset [WASO] and number of awakenings). Additionally, the Insomnia Severity Index (ISI) was completed by 58 participants. Linear and Tobit regression were used to estimate the associations between each insomnia variable and CSF Aß42, phosphorylated tau 181 (p-tau181), total-tau, and neurofilament light chain protein (NfL), adjusting for age, sex, and APOEɛ4 genotype. RESULTS: Higher ISI score was associated with greater average levels of CSF Aß42 (per point: 30.7 pg/mL, 95% CI: 4.17-57.3, p = 0.023), as was higher WASO (per 10 min: 136 pg/mL, 95% CI: 48-223, p = 0.002) and more awakenings (per 5:123 pg/mL, 95% CI = 55-192, p < 0.001). Difficulty initiating sleep was not associated with CSF Aß42, nor were insomnia features associated with p-tau181, total-tau, or NfL levels. CONCLUSION: Insomnia symptoms were associated with higher CSF Aß42 levels in this relatively young, cognitively unimpaired sample. These findings may reflect increased amyloid production due to acute sleep disruption.

Sleep Architecture, Obstructive Sleep Apnea, and Cognitive Function in Adults.

Importance: Good sleep is essential for health, yet associations between sleep and dementia risk remain incompletely understood. The Sleep and Dementia Consortium was established to study associations between polysomnography (PSG)-derived sleep and the risk of dementia and related cognitive and brain magnetic resonance imaging endophenotypes. Objective: To investigate association of sleep architecture and obstructive sleep apnea (OSA) with cognitive function in the Sleep and Dementia Consortium. Design, Setting, and Participants: The Sleep and Dementia Consortium curated data from 5 population-based cohorts across the US with methodologically consistent, overnight, home-based type II PSG and neuropsychological assessments over 5 years of follow-up: the Atherosclerosis Risk in Communities study, Cardiovascular Health Study, Framingham Heart Study (FHS), Osteoporotic Fractures in Men Study, and Study of Osteoporotic Fractures. Sleep metrics were harmonized centrally and then distributed to participating cohorts for cohort-specific analysis using linear regression; study-level estimates were pooled in random effects meta-analyses. Results were adjusted for demographic variables, the time between PSG and neuropsychological assessment (0-5 years), body mass index, antidepressant use, and sedative use. There were 5946 participants included in the pooled analyses without stroke or dementia. Data were analyzed from March 2020 to June 2023. Exposures: Measures of sleep architecture and OSA derived from in-home PSG. Main Outcomes and Measures: The main outcomes were global cognitive composite z scores derived from principal component analysis, with cognitive domains investigated as secondary outcomes. Higher scores indicated better performance. Results: Across cohorts, 5946 adults (1875 females [31.5%]; mean age range, 58-89 years) were included. The median (IQR) wake after sleep onset time ranged from 44 (27-73) to 101 (66-147) minutes, and the prevalence of moderate to severe OSA ranged from 16.9% to 28.9%. Across cohorts, higher sleep maintenance efficiency (pooled ß per 1% increase, 0.08; 95% CI, 0.03 to 0.14; P < .01) and lower wake after sleep onset (pooled ß per 1-min increase, -0.07; 95% CI, -0.13 to -0.01 per 1-min increase; P = .02) were associated with better global cognition. Mild to severe OSA (apnea-hypopnea index [AHI] ≥5) was associated with poorer global cognition (pooled ß, -0.06; 95% CI, -0.11 to -0.01; P = .01) vs AHI less than 5; comparable results were found for moderate to severe OSA (pooled ß, -0.06; 95% CI, -0.11 to -0.01; P = .02) vs AHI less than 5. Differences in sleep stages were not associated with cognition. Conclusions and Relevance: This study found that better sleep consolidation and the absence of OSA were associated with better global cognition over 5 years of follow-up. These findings suggest that the role of interventions to improve sleep for maintaining cognitive function requires investigation.

Association of Neighborhood-Level Socioeconomic Measures With Cognition and Dementia Risk in Australian Adults.

Importance: Up to 40% of dementia cases are potentially preventable; therefore, it is important to identify high-risk groups to whom resources could be targeted for maximal impact in preventing late-life dementia. The association of neighborhood-level socioeconomic status (SES) with cognition and dementia risk is not well known, particularly in midlife when late-life dementia may still be preventable through established interventions, such as blood pressure management. Objective: To examine whether neighborhood-level SES is associated with differences in cognitive performance and dementia risk scores. Design, Setting, and Participants: This cross-sectional study analyzed data collected between November 17, 2016, and April 14, 2020, from 4656 participants in the longitudinal population-based Healthy Brain Project cohort. This large online cohort comprised community-dwelling individuals geographically dispersed across Australia. Participants were aged 40 to 70 years without dementia or other major neurological conditions. Exposures: Neighborhood-level SES was computed by matching participants' residential addresses to the Australian Bureau of Statistics Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). Postcodes provided by each participant were used to derive an IRSAD score that ranked participants according to deciles of neighborhood-level SES (range, 1-10, with higher deciles indicating greater socioeconomic advantage); neighborhoods in deciles 1 to 7 were considered to have low or intermediate SES, and neighborhoods in deciles 8 to 10 were considered to have high SES. Main Outcomes and Measures: Dementia risk estimated using the dementia risk score from the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) tool (n = 4656) and cognitive composite scores for memory and attention measured by the Cogstate Brief Battery (n = 2181). Results: Of 4656 participants (mean [SD] age, 56.1 [7.2] years; 3445 women [74.0%]), 2688 individuals (57.7%) lived in areas with high neighborhood-level SES (IRSAD decile ≥8), and 1968 (42.3%) lived in areas with low or intermediate neighborhood-level SES (IRSAD decile <8), with 1263 individuals (27.1%) residing in rural or regional areas. A total of 6 participants (0.1%) identified as African, 121 (2.6%) as Asian, 57 (1.2%) as Indigenous Australian, 24 (0.5%) as Latin American, 9 (0.2%) as Pacific Islander, 3671 (78.8%) as White or European, and 768 (16.5%) indicated other race (not specified). Each decile unit increase in neighborhood-level SES was associated with a lower CAIDE dementia risk score after adjustment for race and rurality (ß [SE] = -0.070 [0.019]; P = .004). Each decile unit increase was also associated with better memory (ß [SE] = 0.022 [0.006]; P = .006) but not with better attention (ß [SE] = 0.009 [0.007]; P = .34), as measured by Cogstate Brief Battery composite z scores after adjustment for age, sex, race, years of education, and rurality. When comparing memory performance between individuals with IRSAD scores higher and lower than decile 8, neighborhood-level SES interacted with age (F1-2171 = 6.33; P = .02) and CAIDE dementia risk scores (F1-2173 = 4.02; P = .08). Differences in memory between neighborhood-level SES categories were larger among participants who were older and had a higher risk of dementia. Conclusions and Relevance: In this study, higher neighborhood-level SES was associated with better memory and lower dementia risk scores. These results suggest that efforts to lower dementia risk factors in disadvantaged areas are needed to curtail the increasing burden of dementia and that inclusion of individuals living in areas with lower SES in research on dementia is warranted to improve understanding and potential interventions.

Self-reported sleepiness associates with greater brain and cortical volume and lower prevalence of ischemic covert brain infarcts in a community sample.

STUDY OBJECTIVES: We evaluated if self-reported sleepiness was associated with neuroimaging markers of brain aging and ischemic damage in a large community-based sample. METHODS: Participants from the Framingham Heart Study Offspring cohort (n = 468, 62.5 ± 8.7 years old, 49.6%M) free of dementia, stroke, and neurological diseases, completed sleep questionnaires and polysomnography followed by magnetic resonance imaging (MRI), 3 years later on average. We used linear and logistic regression models to evaluate the associations between Epworth Sleepiness Scale (ESS) scores and total brain, cortical and subcortical gray matter, and white matter hyperintensities volumes, and the presence of covert brain infarcts. RESULTS: Higher sleepiness scores were associated with larger total brain volume, greater cortical gray matter volume, and a lower prevalence of covert brain infarcts, even when adjusting for a large array of potential confounders, including demographics, sleep profiles and disorders, organic health diseases, and proxies for daytime cognitive and physical activities. Interactions indicated that more sleepiness was associated with larger cortical gray matter volume in men only and in APOE ε4 noncarriers, whereas a trend for smaller cortical gray matter volume was observed in carriers. In longitudinal analyses, those with stable excessive daytime sleepiness over time had greater total brain and cortical gray matter volumes, whereas baseline sleepiness scores were not associated with subsequent atrophy or cognitive decline. CONCLUSION: Our findings suggest that sleepiness is not necessarily a marker of poor brain health when not explained by diseases or sleep debt and sleep disorders. Rather, sleepiness could be a marker of preserved sleep-regulatory processes and brain health in some cases.

The influence of subjective cognitive decline on prospective memory over 5 years.

OBJECTIVE: Subjective cognitive decline (SCD) is an important area of research within older populations, for whom prospective memory (PM) functions as a crucial part of daily life. Little is known about change in PM, following reports of SCD. This study examines longitudinal naturalistic PM in older adults with high and low levels of SCD. METHOD: Ninety-nine community-dwelling older adults were revisited after 5 to 6 years, to examine the role of baseline SCD (measured as reported memory decline from young adulthood) on episodic and habitual PM change. Episodic PM was measured by the message task and habitual PM by a time-stamped button-pressing task across 2 weeks. RESULTS: SCD status was not associated with episodic PM, with performance declining over time across both groups, η2 = .03, 95% CI [.11, .61]. Conversely, for habitual PM, there was a significant Group × Time interaction, η2 = .07, 95% CI [-.95, -.06], with people reporting high SCD demonstrating better baseline performance and declining over time, whereas low SCD remained stable. CONCLUSIONS: Older adults with SCD demonstrated greater decline in habitual PM, suggesting these tasks may be more sensitive to the effects of SCD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).