Aug 2026· Brain Communications· Vol 8· 0 citations· 69 references
Medicine
TL;DR
Overall, white matter connectivity of the anterior thalamic radiation and superior longitudinal fasciculus was not robustly associated with sleep spindle density or slow oscillatory power in this at-risk cohort, but superior longitudinal fasciculus II connectivity may differentially relate to spindle amplitude in mild cognitive impairment, potentially reflecting altered thalamocortical network engagement in early neurodegeneration.
Abstract
Abstract While sleep disturbance increases with age and neurodegeneration, the relationship between sleep micro-architecture and changes in key white matter tracts is unknown. We aimed to determine how sleep spindles and slow oscillations relate to structural connectivity within selected white matter tracts in older adults at risk for dementia. In this cross-sectional study, 67 participants (mean age = 68.1; 47 females) with subjective cognitive decline (n = 21) or mild cognitive impairment (n = 46) underwent neuropsychological assessment, magnetic resonance imaging and polysomnography. White matter connectivity of anterior thalamic radiation and superior longitudinal fasciculus subdivisions II and III was quantified using whole-brain tractography, with left and right tracts combined. Primary sleep micro-architecture outcomes included slow (11–13 Hz) and fast (13–16 Hz) spindle density and slow oscillation (0.25–1 Hz) power. Secondary outcomes included: overall spindle density (11–16 Hz) and amplitude. Linear regressions assessed associations between sleep micro-architecture and structural connectivity, adjusting for age and sex, with cognitive classification as a moderator. Multiple comparisons were controlled for using the Benjamini–Hochberg false discovery rate procedure, with q < 0.1 considered statistically significant. The mild cognitive impairment group exhibited lower frontal and central fast spindle density compared to the subjective cognitive impairment group (P < 0.05), with no other group differences in sleep macro-architecture or slow oscillatory activity. After false discovery rate correction, there were no significant associations between slow spindle density, fast spindle density or slow oscillation power and tract connectivity. An interaction between central fast spindle density and superior longitudinal fasciculus III connectivity was observed prior to false discovery rate correction, explaining 8% of unique variance, but did not remain significant after correction (q > 0.10). Exploratory analyses reveal a significant interaction between superior longitudinal fasciculus II connectivity and cognitive classification on spindle amplitude, with greater connectivity associated with higher spindle amplitude in individuals with mild cognitive impairment (P = 0.001), but not in those with subjective cognitive decline (P > 0.05). Overall, white matter connectivity of the anterior thalamic radiation and superior longitudinal fasciculus was not robustly associated with sleep spindle density or slow oscillatory power in this at-risk cohort. However, superior longitudinal fasciculus II connectivity may differentially relate to spindle amplitude in mild cognitive impairment, potentially reflecting altered thalamocortical network engagement in early neurodegeneration.
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, and 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
Sleep electroencephalography (EEG) is linked with cognitive function and dementia risk. Integrated EEG-derived scores, such as the Brain Health Score (BHS), trained to jointly reflect cognitive function and disease risk, and the Brain Age Index (BAI), which estimates brain aging, also correlate with neuropsychological (NP) performance. Yet, it remains unclear whether these sleep scores are associated with the rate of future cognitive decline.
This study included 639 Framingham Heart Study Generation 2 and Omni 1 participants with sleep EEG in mid-to-late life and ≥2 NP tests over an average of 14.3 years. Linear mixed effects models estimated associations between BHS and annual changes in memory, executive function, or language. We also evaluated associations between BAI and cognitive decline among 509 Generation 2 participants with BAI values.
Participants were on average 58.4 years at sleep assessment, 54% female, and 86% non-Hispanic White. Each 1-SD higher BHS was associated with 0.015 SD/year slower memory decline (95% CI: 0.009-0.021), 0.009 SD/year slower executive function decline (95% CI: 0.005-0.014), and 0.011 SD/year slower language decline (95% CI: 0.005-0.017). In contrast, BAI was not associated with changes in any cognitive domain.
Higher sleep EEG–derived brain health in mid-to-late life was associated with slower decline in multiple cognitive domains over more than a decade of follow-up, whereas an EEG-based measure of brain aging was not. These findings suggest that sleep EEG-derived, data-driven brain health metrics may have value as novel biomarkers for risk of cognitive decline.
Francesca R Marino, W. Ganglberger, Haoqi Sun et al.· SLEEP Advances· 0 citations
INTRODUCTION
Alzheimer's disease (AD) is characterized by progressive cognitive decline and brain network dysfunction. EEG microstates offer a sight into rapid network dynamics. However, microstate alterations in AD during waking and different sleep stages remain unexplored.
METHODS
Overnight EEG was recorded from 15 AD patients and 15 healthy controls. Sleep stages (Wake, N1, N2, N3, REM) were manually scored. Microstate analysis extracted temporal parameters and transition probabilities separately for each sleep stage using a common set of grand-mean template maps derived from all stages. Linear mixed models assessed group differences, and correlations examined associations with MMSE.
RESULTS
AD patients showed significantly longer durations compared to HC (Group main effect: F(1,28) = 6.78, p_FDR = 0.042) in mean duration of class A, with the largest difference during wakefulness (p = 0.018, q = 0.046). Mean occurrence of class D was significantly lower in AD (F(1,28) = 5.44, p_FDR = 0.049), with significant reductions during wakefulness and N1. Mean Occurrence of class C showed both a significant Group main effect (F(1,28) = 5.28, p_FDR = 0.049) and a Group × Sleep Stage interaction (F(4,112) = 3.31, p_FDR = 0.047) were observed, with AD patients showing lower occurrence during wakefulness and N1. For transition probabilities, AD patients showed significantly increased corrected Class B→A transition (DeltaTM_B→A), but reduced corrected Class D→B transition (DeltaTM_D→B) and raw Class C→D transition (OrgTM_C→D) (all p_FDR < 0.05). Critically, the Group × Sleep Stage interaction for the corrected Class A→D transition (DeltaTM_A→D) reached significance (F(4,112) = 6.12, p_FDR = 0.015), with the group difference largest during wakefulness (p = 0.004, q = 0.029). Partial correlations revealed that corrected B→A transition probability negatively correlated with MMSE (r = -0.642, p < 0.001); MeanOccurrence_C (r = 0.487, p = 0.003) and MeanOccurrence_D (r = 0.532, p = 0.001) also showed significant correlations with MMSE.
CONCLUSIONS
This is the first study to report that AD patients exhibit altered microstate parameters and transition probabilities across sleep stages. Present findings suggest that sleep-stage-resolved microstate analysis may offer a new tool for assessing AD.
Guanqun Hu, Yu-Jiao Tong, Ling-Feng Liu et al.· Brain Research Bulletin· 0 citations
Many people with bipolar disorder (BD) experience persistent cognitive deficits. Sleep spindles have been linked to cognitive ability in healthy populations and psychotic disorders. While there is preliminary evidence for altered spindle activity in BD, research directly examining the association between sleep spindle parameters and cognitive performance in this population is lacking. Therefore, our primary objective was to examine the association between fast spindle density and episodic memory performance in euthymic individuals with BD. As exploratory analyses, we looked at associations between fast and slow spindle density and subjective sleep quality with other cognitive domains. We also conducted a sensitivity analysis, separating all analyses by lithium intake. Thirty-four euthymic participants with BD underwent comprehensive cognitive assessments and were assessed for three consecutive nights using mobile sleep-EEG headbands. Sleep spindles were detected using validated, adapted algorithms and characterised by fast and slow spindle density. Fast spindle density was not associated with episodic memory performance (r = −0.004, p = 0.491, 95% CI [−0.353, 0.499]) but did show a significant positive association with working memory (r = 0.423, p = 0.014, 95% CI (bootstrapped) [−0.167, 0.722]). When removing participants taking lithium, several positive associations emerged between fast spindle density and cognitive performance. These findings suggest domain-specific relationships between sleep spindle activity and cognition in BD, with fast spindles potentially being associated with working memory. Preliminary evidence for lithium-related modulation highlights the importance of considering pharmacological factors. However, the analyses were underpowered, and large-scale studies are needed to deepen our understanding of sleep spindle-cognition relationships in BD.
Anna Tröger, Jules Schneider, D. Tsapekos et al.· Translational Psychiatry· 0 citations
INTRODUCTION
White matter (WM) tract function has only recently been investigated. However, whether WM function is altered in individuals with subthreshold depression (StD) remains largely unknown.
OBJECTIVES
To examine WM functional alterations in StD and their associations with cognitive performance, neurotransmitter systems, and gene expression patterns.
METHODS
A total of 188 individuals with StD and 136 healthy controls (HCs) were recruited from XXX University in the study. Participants underwent mood and cognitive assessments, as well as resting-state functional MRI.WM function was evaluated using the amplitude of low-frequency fluctuations (ALFF) in conjunction with the automated fiber quantification (AFQ) method. Correlation and linear regression analyses were performed. Subsequently, spatial associations between postmortem gene expression/neurotransmitters and WM functional alterations were investigated to uncover neural mechanisms underlaying StD from a multidimensional perspective.
RESULTS
Individuals with StD showed decreased social cognition and composite cognition compared to HCs. Individuals with StD displayed ALFF decrease in the right anterior thalamic radiation (ATR), inferior fronto-occipital fasciculus, inferior longitudinal fasciculus (ILF), and uncinate fasciculus. Rumination and depressive symptoms were associated with ALFF decrease in the right ATR; anxiety symptom was associated with ALFF decrease in the right ILF. Moreover, the abnormal pattern of WM function in StD was spatially associated with modulation of chemical synaptic transmission, regulation of synaptic plasticity, cation channel activity, and neuron projection, as well as dopaminergic and serotonergic neurotransmission.
CONCLUSION
To conclude, these findings reveal WM functional alterations in StD that are associated with mood and cognitive disturbances, and suggest that these alterations may be linked to underlying transcriptomic and neurotransmitter correlates. This study provides new clues to understand the neuro-pathophysiology of StD.
Zixuan Guo, Pan Chen, Guanmao Chen et al.· Journal of Advanced Research· 0 citations
Abstract Cognitive impairment is a common complaint in older adults, yet its evaluation relies largely on subjective reports and cognitive tests with variable sensitivity. Identifying objective neurophysiological markers of brain function may enable earlier detection and more individualized intervention strategies. A total of 454 participants (mean age 61.4 ± 7.5 years; 45.3% females) underwent bilateral dorsolateral prefrontal cortex (DLPFC) transcranial magnetic stimulation (TMS)-EEG with the Delphi-MD system, alongside cognitive testing (Monreal Cognitive Assessment [MoCA] and NeuroTrax domains: memory, attention and executive function) and emotional inventories. Linear regression tested demographic and clinical predictors of cognition. K-means clustering identified cognitive subgroups, with between-cluster interhemispheric connectivity (IHC) differences assessed by Mann–Whitney U-tests. Binary logistic regression with 5000 bootstrap resamples evaluated IHC as a predictor of cognitive cluster membership. Older age was associated with lower MoCA (worse) (P < 0.001), while male sex associated with worse verbal memory (P < 0.001); no factors were associated with attention or executive function. K-means clustering yielded two groups based on MoCA and domain scores: cognitively normal (CN, n = 367) and cognitively impaired (CI, n = 68), differing across all domains (all P < 0.001). CI participants displayed reduced DLPFC IHC (P < 0.001). Logistic regression confirmed that reduced IHC strongly predicted impairment: one-unit decrease in right DLPFC IHC corresponded to approximately 4.35-fold higher odds of impairment (reciprocal OR = 4.35, 95% CIboot = 1.82–10.00), while a one-unit decrease in left DLPFC IHC corresponded to 3.03-fold higher odds of impairment (reciprocal OR = 3.03, 95% CIboot = 1.30–6.67). These effects were independent of age and sex. Reduced DLPFC IHC measured by TMS-EEG is robustly associated with increased risk of cognitive impairment, supporting its potential as an objective, early neurophysiological biomarker quantifying cognitive decline.
N. Zifman, H. Fogel, Riki Rosenberg et al.· Brain Communications· 0 citations
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