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Background: Accumulation of critically short telomeres (CST) is implicated in decreased tissular regenerative capacity and increased susceptibility to degenerative diseases such as Alzheimer's disease (AD). Telomere shortening has also been associated with age-related brain changes. However, it remains unclear whether CST accumulation is directly associated with AD markers or instead amplifies age-related effects, potentially increasing susceptibility of developing AD in cognitively healthy older adults. Methods: This cross-sectional study used baseline data of 129 community-dwelling cognitively healthy older adults from the Age-Well trial (NCT02977819), aged 65 years and older enrolled between 2016 and 2018, in France. Using linear regressions, we analyzed the relationship between an innovative marker of telomere shortening, the percentage of CST (%CST), structural, functional and molecular neuroimaging outcomes, and multiple blood-based biomarkers related to AD pathophysiology. The effect of apolipoprotein E ε4 genotype (APOE4) was assessed on these relationships using interaction analysis. Results: A higher %CST was associated with lower global kurtosis fractional anisotropy (β = -.230; P =.010), particularly in frontal and temporal regions. A higher %CST was also related to higher plasma levels of Neurofilament light chain (β =.195; P =.020) and a lower subiculum volume (β = -.206; P =.020), although these associations did not meet the threshold for multiple comparisons. %CST was not associated with AD-related neuroimaging markers, including the AD-sensitive gray matter pattern (β = -.060; P =.441), glucose metabolism pattern (β = -.099; P =.372), brain perfusion pattern (β = -.106; P =.694) or hippocampus volume (β = -.106; P =.194). In APOE4 carriers, higher %CST was associated with lower subiculum (β = -.423; P = 0.003), DG (β = -.410; P = 0.018) and CA1 volumes (β = -.373; P = 0.024), even though associations with DG and CA1 volumes did not survive multiple comparison. Conclusions: Although an increase in %CST does not appear to be directly linked to the pathophysiology of AD in cognitively healthy older adults, it could heighten the susceptibility of APOE4 carriers to develop AD plausibly due to greater vulnerability to age-related effects. However, longitudinal studies would be necessary to determine whether %CST influences the development and progression of AD later in life. [ABSTRACT FROM AUTHOR]

Understanding the factors that predict why some individuals perceive to respond more to meditation training than others could impact the development, efficacy, adherence levels, and implementation of meditation-based interventions. We investigated individual-level variables associated with self- and teacher-perceived responsiveness to longer-term meditation training. This study presents a secondary analysis of the Age-Well trial (NCT02977819, 30/11/2016) and includes 90 healthy older adults (65–84 years) that were randomised to an 18-month meditation training or a non-native language (English) training. Responsiveness was measured post-intervention using participants' and teachers' ratings of four psychological domains (connection, positive/negative emotions, meta-awareness) in relation to two contexts (during sessions, in daily life), teachers' perception of overall benefit, and a global composite comprising all self- and teacher-perceived responsiveness measures. Linear regression modelling indicates that, when including baseline variables (sex, education, neuroticism, cognition, expectancy) and engagement (hours of formal practice during intervention), only higher levels of engagement were associated with higher global composite scores (standardised estimate = 0.50, 95% CI: 0.24–0.77, p < 0.001). Global composite scores were not correlated with pre-post changes in well-being. Findings indicate that more time spent practising meditation was related to greater perceived intervention effects. We suggest that future studies closely monitor levels of engagement and map reasons for disengagement. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Older adults experiencing subjective cognitive decline (SCD) have a higher risk of dementia. Reducing this risk through behavioral interventions, which can increase emotional well‐being (mindfulness and compassion) and physical activity, is crucial in SCD. METHODS: SCD‐Well is a multicenter, observer‐blind, randomized, controlled, superiority trial. Three hundred forty‐seven participants (mean [standard deviation] age: 72.7 [6.9] years; 64.6% women) were recruited from memory clinics in four European sites to assess the impact of an 8‐week caring mindfulness‐based approach for seniors (CMBAS) and a health self‐management program (HSMP) on mindfulness, self‐compassion, and physical activity. RESULTS: CMBAS showed a significant within‐group increase in self‐compassion from baseline to post‐intervention and both a within‐ and between‐group increase to follow‐up visit (24 weeks). HSMP showed a significant within‐ and between‐group increase in physical activity from baseline to post‐intervention and to follow‐up visit. DISCUSSION: Non‐pharmacological interventions can differentially promote modifiable factors linked to healthy aging in older adults with SCD. [ABSTRACT FROM AUTHOR]

Background: Sleep‐dependent memory consolidation, which is thought to rely on the dialogue between the hippocampus and the medial prefrontal cortex (mPFC) during NREM sleep, is mediated by slow waves (SW) and sleep spindles. Some studies indicate that this process is impaired in ageing but also in sleep‐disordered breathing (SDB), a very common sleep disorder in ageing. In this study, we investigated sleep‐dependent memory consolidation in older adults with or without SDB and explored the underlying mechanisms. Method: Baseline data of 57 cognitively unimpaired older adults (mean age ± SD: 68.6 ± 3.3 years) from the Age‐Well cohort were analysed. Participants underwent a structural MRI scan to obtain mPFC and hippocampal grey matter volumes, and performed a visuospatial memory task until reaching a learning criterion of 66.6% of correct answers. Post‐learning sleep was monitored using polysomnography, and delayed recall was probed the next morning. An overnight change in memory performance (OCMP) was computed as follows: (recall performance – learning performance) / learning performance. SW, slow and fast spindles during N2 and N3 sleep were automatically detected using the SleepTrip toolbox. Based on the standard apnea‐hypopnea index (AHI) cutoff of 15 events/h, participants were classified as having SDB (SDB+, n=47) or not (SDB‐, n=10). Result: There was no between‐group difference in OCMP, as well as in amplitude, duration and frequency of SW, slow and fast spindles (p>0.05). However, we found a significant group by SW density interaction after controlling for age, sex, education, total sleep time and trait‐anxiety (p=0.03). Thus, a positive association was only found between SW density and OCMP in the SDB‐ group (p=0.02; Fig 1). No correlation was found between slow or fast spindle density and OCMP in either group. Finally, mPFC and hippocampal volumes did not differ between SDB+ and SDB‐ participants (p>0.05), but SW density positively correlated with the volume of the mPFC (p=0.01; Fig 2). Conclusion: Our findings suggest that the contribution of SW to sleep‐dependent memory consolidation is impaired in participants with SDB and incriminate the mPFC. We plan to conduct connectivity and SW‐spindle coupling analyses to unravel the functional substrates of this deficit. [ABSTRACT FROM AUTHOR]

Background: Subclinical depressive symptoms increase the risk of developing Alzheimer's disease (AD). The neurobiological mechanisms underlying this link may involve stress system dysfunction, notably related to the hippocampus which is particularly sensitive to AD. We aimed to investigate the links between blood stress markers and changes in brain regions involved in the stress response in older adults with or without subclinical depressive symptoms. Methods: This cross-sectional study was conducted using baseline data from the Age-Well trial. Cognitively unimpaired (CU) older adults with (DepS; n = 73) or without (NoDepS; n = 58) subclinical depressive symptoms (defined using the 15-item Geriatric Depression Scale) were included in the analyses. Blood cortisol, epinephrine and norepinephrine were measured; as well as the resting-state functional connectivity (rs-FC) between, and gray matter (GM) volume of, the hypothalamus, hippocampus and hippocampal subfields. Blood stress markers levels and neuroimaging measures were compared between groups; then regression analyses were conducted between these measures. Results: DepS participants showed higher plasma epinephrine levels, which was associated with greater rs-FC between the CA1 and Subiculum hippocampal subfields and the hypothalamus. Lower GM volume in the CA1 and DG/CA2-3–4 subfields was also found in DepS. No between-group differences were observed for blood cortisol and norepinephrine. Conclusions: Our findings show that subclinical depressive symptoms are associated with increased sympatho-adrenomedullary axis activity, together with lower GM volume in a hippocampal subfield (i.e., CA1) particularly sensitive to AD. While causation cannot be inferred, these results suggest that screening and treating subclinical depressive symptoms in CU older adults could reduce AD risk. Trial registration: ClinicalTrials.gov Identifier: NCT02977819, Registration Date: 2016–11-25. [ABSTRACT FROM AUTHOR]

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., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)