Aug 2026· Journal of Affective Disorders· Vol 414, pp.
122346
· 0 citations· 50 references
Medicine
TL;DR
CircS is associated with SCD severity, while exploratory analyses suggest possible nonlinear associations between CircS score and selected plasma biomarkers and male participants showed a stronger association with SCD-domain scores.
Abstract
Background
Established evidence linking circadian syndrome (CircS) to cognitive impairment. However, the association with subjective cognitive decline (SCD) and its sex-specific patterns remains unclear.
Methods
This cross-sectional study included 2008 cognitively normal adults from the Hubei Memory and Aging Cohort Study (HMACS). CircS was evaluated by metabolism, sleep, and depression. SCD was assessed based on the SCD-I framework. Regression, restricted cubic spline, subgroup analyses, and indirect-effect analysis were performed.
Results
CircS was associated with various SCD outcomes, with a dose-response relationship. CircS was dose-responsively linked to GFAP and nonlinearly to Aβ42/40 (Pₙₒₙₗᵢₙₑₐᵣ = 0.029) and NfL (Pₙₒₙₗᵢₙₑₐᵣ = 0.030). Subgroup analysis revealed that CircS was associated with higher SCD-domain in males (β = 0.32, 95% CI: 0.14-0.49; P for interaction = 0.003), and lower GFAP levels in females (β = -0.25, 95% CI: -0.38 to -0.11; P for interaction = 0.021). Indirect-effect models did not show evidence of the inflammatory markers examined statistically accounted for the observed association between CircS and SCD.
Conclusions
CircS is associated with SCD severity, while exploratory analyses suggest possible nonlinear associations between CircS score and selected plasma biomarkers. Male participants showed a stronger association with SCD-domain scores. The clinical implications of these findings require validation in longitudinal studies.
Cardiometabolic index (CMI) reflects visceral fat accumulation and lipid metabolism and has been linked to metabolic and cardiovascular diseases. Its association with cognitive function in older adults remains unclear. This study aimed to assess the relationship between CMI and global cognitive performance in a nationally representative sample of United States adults aged 60 years and older. We conducted a cross-sectional analysis of National Health and Nutrition Examination Survey 2011 to 2014 data (n = 1326). CMI was analyzed both as a continuous variable and by quartiles (Q1–Q4). Survey-weighted linear regression models examined associations with global cognitive function (GCF), adjusting sequentially for demographics (ModelI) and full covariates (ModelII). Threshold effects and smoothing curves explored nonlinear links. Interaction tests and subgroup analyses evaluated effect modification by diabetes status. In the minimally adjusted model, higher continuous CMI was associated with lower GCF (β = −2.46, 95% confidence interval [CI]: 4.58–−0.35; P = .0318), but this association was not significant after full adjustment (β = −0.56, 95% CI: 2.49–1.36; P = .5807). When using quartiles, a negative trend was observed in the crude (P for trend = .0392) and minimally adjusted models (P for trend = .0166) but not in the fully adjusted model (P for trend = .4825). Nonlinear analysis identified an inflection at CMI = 0.16 for digit symbol substitution test (β = 142.74, 95% CI: 70.18–215.30; P < .001) and GCF (β = 173.67, 95% CI: 77.01–270.32; P < .001). Diabetes status significantly modified the CMI–GCF relationship (P for interaction = .035). CMI is negatively associated with cognitive function in older adults. These findings suggest that higher CMI may indicate a greater risk of cognitive decline.
Ying Liu, Qian Hu, Qin Li et al.· Medicine· 0 citations
BACKGROUND
Age-related changes in sleep microstructure may contribute to cognitive decline, but their value as markers of cognitive trajectories in healthy aging is unclear. We examined associations between baseline sleep microstructure and both concurrent cognition and ten-year cognitive change in older men.
METHODS
Men from the Metropolit 1953 Danish Male Birth Cohort completed cognitive assessment at two time points a decade apart (2010-2013 and 2020-2022; n = 206 at baseline, n = 106 at follow-up). Polysomnography was performed at baseline only (n = 176); microstructure analyses (spindles, slow waves, EEG coherence) were restricted to participants with adequate NREM sleep (n = 82). Cross-sectional and longitudinal associations were assessed using Spearman and partial Spearman correlations with Benjamini-Hochberg correction.
RESULTS
Over ten years, processing speed (TMT-B: +6.1 s) and symbol conversion (SDMT: -2.3) declined significantly. Higher sleep efficiency was associated with better cognitive maintenance, whereas increased wake after sleep onset and an increased arousal index correlated with poorer memory and learning. A higher proportion of N1 sleep was linked to poorer executive function, whereas N2 and N3 were positively associated with cognitive outcomes. Fast spindle amplitude and frequency, slow-wave characteristics, and N2 and REM coherence correlated with processing speed, attention, and global cognition.
CONCLUSIONS
Baseline sleep microstructure, including spindle, slow-wave dynamics and EEG coherence, was associated with cognitive aging and may provide candidate markers of cognitive resilience or decline. These exploratory findings support further longitudinal studies to determine their predictive value for neurodegenerative disease.
Olalla Urdanibia-Centelles, Sine Arvedsen, A. Brink-Kjær et al.· Sleep Medicine· 0 citations
Background: Cardiometabolic risk factors are increasingly recognised as contributors to cognitive decline, yet their associations with domain-specific cognitive performance in adults with prediabetes or well-controlled type 2 diabetes (T2DM) remain poorly characterised. Methods: This cross-sectional study included 49 adults with prediabetes or well-controlled T2DM (managed by diet or metformin alone; HbA1c < 8%). Cognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Trail Making Tests (TMTs) parts A and B, Stroop, and Digit Symbol Substitution Test (DSST). Multivariable linear regression examined associations between cardiometabolic predictors (adiposity [DXA], glycaemic indices [OGTT], and serum lipids) and cognitive outcomes, adjusting for age, BMI, and education. Results: Higher HbA1c was independently associated with increased false alarms on the rapid visual processing task (RVPPFA; β = 0.04 [95% CI 0.01, 0.07]; p = 0.015); fasting and 2 h glucose were not associated with any cognitive measure. Higher triglycerides were associated with lower sustained attention accuracy (RVPA; β = −0.02 [95% CI −0.04, −0.004]; p = 0.016) and lower DSST scores (β = −4.61 [95% CI −8.81, −0.40]; p = 0.033). Higher HDL cholesterol was independently associated with better sustained attention (RVPA; β = 0.08 [95% CI 0.02, 0.15]; p = 0.017). No consistent associations were found between adiposity measures and any cognitive outcome, with no effect modification by sex or diabetes status (all Pinteraction > 0.05). Conclusions: In cognitively healthy adults with prediabetes or well-controlled T2DM, higher HbA1c and triglycerides and lower HDL were associated with poorer domain-specific cognitive performance in the absence of overt cognitive impairment. Larger longitudinal studies are needed to establish whether these associations represent early cognitive changes and to determine whether reducing cardiometabolic risk can preserve cognitive function.
R. Hariharan, Simon M Bell, Arshad Majid et al.· Medical Science· 0 citations
INTRODUCTION
Vascular risk factors (VRFs) are established contributors to cognitive decline, yet they often co-occur in distinct patterns. Whether VRF pattern-cognition associations are modified by age or apolipoprotein E (APOE) genotype remains unclear.
METHODS
We analyzed 44,879 participants aged 60 to 90 years from the National Alzheimer's Coordinating Center (NACC) with normal cognition or mild cognitive impairment (MCI). Latent class analysis (LCA) identified VRF patterns from 7 indicators: hypertension, diabetes, hypercholesterolemia, myocardial infarction, atrial fibrillation, heart failure, and stroke. Multivariable linear regression examined associations between VRF patterns and Mini-Mental State Examination (MMSE) scores, with stratification by age and APOE ε4 status.
RESULTS
Five VRF patterns were identified: Low Risk (38.4%), Metabolic Predominant (40.5%), Hypertension Predominant (16.0%), Arrhythmia-Cardiac (2.7%), and High Multimorbidity (2.4%). Each additional VRF was associated with 0.056-point lower MMSE (β=-0.056, 95% CI: -0.072 to -0.039, P<0.001). Significant age × pattern (P=0.0015) and APOE × pattern (P=0.0016) interactions emerged. In younger-old adults (60 to 74 y), Metabolic Predominant was associated with lower MMSE (β=-0.171, P<0.001), but not in older-old adults (75 to 90 y; β=0.020, P=0.53). Among APOE ε4 carriers, the Metabolic Predominant association was substantially stronger (β=-0.228, P<0.001) compared with noncarriers (β=-0.053, P=0.025), a 4.3-fold difference in magnitude.
CONCLUSIONS
VRF-cognition associations show significant heterogeneity by age and APOE genotype. Attenuated associations in older-old adults may reflect survivor bias, while stronger associations in APOE ε4 carriers are consistent with gene-environment interactions.
Yang Kong, Xian Li, Rui-Qian Guan et al.· Alzheimer Disease and Associ...· 0 citations
Sleep disturbances can trigger peripheral inflammatory responses, and both poor sleep and inflammation have been linked to cognitive impairment. However, whether peripheral inflammation mediates the association between sleep quality and cognitive health remains insufficiently tested. We analyzed data from two independent cohorts: 259,817 non-demented participants (mean age 58 years, 55.39% female, mean follow-up 10.29 years) from the UK Biobank (UKB) and 1,107 participants (mean age 74 years, 56.82% female, mean follow-up 4.17 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). At baseline, sleep quality was assessed using self-reported or caregiver-reported information. Peripheral blood lymphocyte count (LYM), neutrophil count (NEU), neutrophil-to-lymphocyte ratio (NLR), and serum C-reactive protein (CRP) were used as pragmatic peripheral inflammatory markers. Causal mediation analyses tested whether peripheral inflammation mediated the associations of sleep quality with cognitive performance and risk of incident dementia. In both cohorts, poor sleep quality was associated with higher levels of LYM, NEU, NLR and CRP (p < 0.001), and with lower cognitive function (p < 0.001). Poor sleep quality was also associated with an increased risk of incident dementia in UKB (p < 0.001), whereas this association was not significant in ADNI (p = 0.33). Higher NEU, NLR, and CRP levels were associated with lower cognitive function (UKB, p < 0.001; ADNI, p < 0.05) and increased risk of dementia (p < 0.001). In UKB, selected markers mediated the associations of sleep quality with fluid intelligence (p < 0.001), numeric memory score (p < 0.05), and risk of incident all-cause dementia and Alzheimer's disease (p < 0.001). However, the mediation proportions were limited (< 10%). In ADNI, no significant mediation was observed. These findings suggest that peripheral inflammation provides a statistically significant but quantitatively limited explanation for the association between sleep and cognitive health. Future studies should investigate additional mechanisms and potential intervention targets in more diverse cohorts.
Liang-Jie Xu, Liang-Yu Huang, Shi Tang et al.· Brain, behavior, and immunit...· 0 citations
Long COVID is clinically heterogeneous, and reproducible biomarker patterns remain limited. This cross-sectional study aimed to identify clinical-cognitive profiles in 304 patients with long COVID and examine their associations with inflammatory-endothelial biomarkers and intermediate vascular measures. Latent profile analysis was performed using cognitive, subjective memory, fatigue, sleep, pain, affective, frailty, dyspnea, functional and health-related quality-of-life indicators. Associations between retained profiles and biomarkers or vascular variables were examined using linear models adjusted for age, sex, educational level and body mass index. A four-profile solution was retained, comprising a low global burden profile (42.1%), an intermediate affective-mental profile (22.1%), a high multisystem burden profile (17.9%) and an intermediate physical-functional profile (17.9%), with mean posterior probabilities from 0.924 to 0.965. The two intermediate profiles showed a cross-over SF-36 pattern, with lower MCS and relatively preserved PCS in the affective-mental profile and the reverse pattern in the physical-functional profile. Profiles were associated with ICAM-1, F(3,267) = 5.84, BH-adjusted
p
= .008, partial
ηp
2
= .065, but not with vascular measures. ICAM-1 remained significant across analyses accounting for classification uncertainty, whereas the endothelin-1 finding was not consistently reproduced. These findings support latent phenotyping as a descriptive strategy for organising long COVID heterogeneity and identify ICAM-1 as the principal hypothesis-generating inflammatory-endothelial correlate of the clinical profiles.
David Arjol, L. Gómez-Sánchez, Silvia Arroyo-Romero et al.· Scientific Reports· 0 citations