Chang-Ho Yun

Objective: We investigated the longitudinal association between cognitive decline, amyloid‐β deposition, and perivascular diffusivity using diffusion tensor image analysis along the perivascular space (DTI‐ALPS) index. Methods: This 2‐year longitudinal study included 211 participants from the Alzheimer's Disease Neuroimaging Initiative, categorized into sustained cognitively normal, incident mild cognitive impairment, persistent mild cognitive impairment, and incident Alzheimer's disease (AD). The DTI‐ALPS index and amyloid‐β standardized uptake value ratio (SUVR) from amyloid positron emission tomography were obtained at baseline and follow‐up. Linear mixed‐effects models were used to examine longitudinal changes in the DTI‐ALPS index and their associations with cognitive decline and amyloid‐β accumulation. Multiple mediation analyses were performed to evaluate whether amyloid burden and gray matter atrophy mediated the relationship between changes in the DTI‐ALPS index and cognitive performance. Additional analyses assessed the effect of baseline amyloid‐β positivity. Results: The incident mild cognitive impairment and incident AD groups showed greater longitudinal declines in the DTI‐ALPS index than the sustained cognitively normal group. Longitudinal reductions in the DTI‐ALPS index were associated with greater cognitive decline and increased amyloid‐β accumulation. Mediation analyses showed no significant indirect effects through SUVR or gray matter volume. Although baseline amyloid‐β positivity alone was not associated with longitudinal DTI‐ALPS changes, significant interactions with clinical progression were observed. Interpretation: Longitudinal alterations in the DTI‐ALPS index are associated with cognitive decline and amyloid‐β accumulation. These findings support the DTI‐ALPS index as a non‐invasive imaging marker reflecting disease progression in AD. ANN NEUROL 2026;100:559–571

Study Objectives: Cognitive-behavioral therapy for insomnia (CBT-I) effectively targets dysfunctional sleep beliefs but remains inaccessible to most. This study examined whether a single 60-minute mass psychoeducation session, incorporating Scarcity Theory with CBT-I psychoeducation elements and Acceptance and Commitment Therapy concepts, could reduce dysfunctional beliefs and insomnia symptoms over 4 weeks. Materials and Methods: This prospective, single-arm study was conducted at Seoul National University Bundang Hospital. Of 182 lecture attendees, 81 consented, 40 completed baseline and immediate post-lecture assessments, and 29 completed all four timepoints through 4 weeks. The primary outcome was the Korean Dysfunctional Beliefs and Attitudes about Sleep-6 (K-DBAS-6). Secondary outcomes included the Insomnia Severity Index-3 (ISI-3), Bandwidth Tax Visual Analogue Scale (BT-VAS), and Patient Global Impression measures. Longitudinal effects were analyzed using repeated measures ANOVA (N = 29). Results: K-DBAS-6 decreased significantly (d z = 0.63, p = .003). ISI-3 (d z = 0.60, p = .003), BT-VAS (d z = 0.62, p = .002), and PGI-S (d z = 0.97, p < .001) also improved. BT-VAS showed immediate post-lecture reduction (d z = 0.63, p < .001; N = 40). At 4 weeks, 72.4% reported global improvement (PGI-I ≤ 3). Anchor-based minimal clinically important differences were 1.32 (K-DBAS-6), 1.58 (ISI-3), and 1.83 (BT-VAS). All effects remained significant after adjusting for age and sex. Conclusions: A single mass psychoeducation session informed by Scarcity Theory produced significant, sustained reductions in dysfunctional sleep beliefs and insomnia symptoms with medium effect sizes. This scalable approach warrants investigation as a first-step intervention for insomnia.

Sleep is a critical physiological process essential for overall brain health. Recent research shows that the glymphatic system is a key player in facilitating the metabolic waste clearance. However, the continuous real-time monitoring of brain water dynamics during sleep remains substantially challenging. Here, we introduce a soft, wearable near-infrared spectroscopy (NIRS) system to detect brain water dynamics potentially linked to glymphatic activity. The device features an integration of multi-wavelength LEDs and photodetectors. The in vivo study with multiple human subjects captures the device's overnight sleep monitoring in a natural home environment, revealing continuous changes in brain water dynamics across different sleep stages. Our results support the link between sleep stage-dependent water dynamics and glymphatic activity. Spectral analysis identifies several physiological rhythms during sleep, including respiration, heart rate, and oscillations linked to slow-wave activity. These advancements significantly enhance the NIRS system's potential for a deeper understanding of brain health.

We aimed to examine the association between sleep duration and thirst level, indicator of altered hydration status. We performed a secondary analysis of the 2018 Korean Sleep-Headache Study, a nationally representative cross-sectional survey conducted in the Republic of Korea. Of 2,501 participants who completed the survey, 2,468 were included in the final analysis (age, 47.9 ± 16.4 years; 49.8% male). Participants were categorized into the high- or low-thirst group based on self-reported thirst frequency. Sleep duration was grouped as ≤ 6, > 6-7, > 7-8, and > 8 h. Logistic regression assessed the relationship between sleep duration and high thirst, adjusting for multiple lifestyle and health variables. Short sleep duration (≤ 6 h) was significantly associated with high thirst (adjusted OR 1.69; 95% CI, 1.00-2.86; p = 0.049), compared to the reference group (> 7-8 h). Age-stratified analyses revealed that adults ≥ 50 years showed a significant association between sleep duration of > 6-7 h and high thirst (OR 2.26; 95% CI, 1.23-4.12; p = 0.01). Sensitivity analyses indicated diabetes and habitual snoring as key contributors, and depressive mood consistently predicted high thirst. These findings suggest a complex interplay between sleep, thirst perception, and hydration, potentially mediated by metabolic and sleep-related disorders.

Objectives: Sleep inertia, a transitional state of grogginess and impaired alertness upon awakening, varies in duration and influencing factors. This study examined its characteristics and associations with sociodemographic factors, sleep patterns, and comorbidities in a Korean adult population. Methods: Data from 2,355 participants (49.2% male, aged 19–92) in the Korean Sleep Headache Study (2018) was analyzed. Morning sleep inertia was assessed via self-reported duration in minutes using the question, “How long does it typically take for you to clear your grogginess in the morning after waking from overnight sleep?” While this single-item question was appropriate for a population-based study, it may not fully capture the multidimensional nature of sleep inertia. Multiple linear regression analyses were conducted using log-transformed sleep inertia as the dependent variable. Results: The mean (SD) sleep inertia was 15.8 (12.9) minutes. Females reported 1.1 minutes longer sleep inertia than males, although no significant differences were observed across age groups. Participants with anxiety reported 14.3 minutes longer inertia than those without anxiety, showing the largest effect size (Cohen’s d = 1.12). Sleep inertia was negatively associated with sleep duration (beta [95% CI]: −0.05 [−0.07, −0.02]), morning chronotype (−0.16 [−0.24, −0.08]), and habitual snoring (−0.10 [−0.17, −0.02]), but positively associated with evening chronotype (0.12 [0.04, 0.19]), insomnia (0.22 [0.13, 0.30]), excessive daytime sleepiness (0.10 [0.02, 0.19]), and anxiety (0.39 [0.14, 0.63]) ( p < 0.02 for all). Conclusions: Sleep inertia was associated with sleep duration, chronotype, sleep-related symptoms, and anxiety. These findings underscore the need for targeted interventions to alleviate the adverse impact of sleep inertia on daily functioning.

Rationale: Obstructive sleep apnea (OSA) may impair perivascular diffusivity, a proposed glymphatic biomarker, contributing to cognitive decline. Objectives: To investigate the longitudinal impact of OSA on cognitive performance and perivascular diffusivity measured by diffusion tensor imaging along the perivascular space (DTI-ALPS) and whether changes in diffusivity mediate the relationship between OSA and cognition. Methods: In a community-based cohort, 1,110 participants underwent polysomnography, brain DTI, and cognitive assessments at baseline and 4-year follow-up. Participants were categorized by apnea–hypopnea index (AHI) at baseline and further grouped longitudinally as OSA-free, improved OSA, stable OSA, or worsened OSA. DTI-ALPS index was calculated at both time points to assess perivascular diffusivity. Multivariable models were adjusted for age, sex, education, body mass index, smoking, alcohol use, hypertension, diabetes, total sleep time, and sleep efficiency. Longitudinal models (i.e., Δ-values) also included baseline outcome values. Measurements and Main Results: Higher AHI was consistently associated with lower DTI-ALPS index. Each 1–event-per-hour increase in AHI corresponded to a 0.008 decrease in DTI-ALPS index at baseline and a 0.007 decrease over 4 years (both P < 0.001), with the worsened OSA group showing the greatest reduction. Increases in DTI-ALPS index were associated with improvements in visual memory, including immediate recall (β = 0.401), delayed recall (β = 0.351), and recognition (β = 0.145; all P < 0.001). ΔDTI-ALPS mediated the relationship between ΔAHI and changes in immediate visual recall (β = −0.015), delayed recall (β = −0.021), and recognition (β = −0.016; all P < 0.001). Conclusions: OSA severity was associated with altered perivascular diffusivity and related changes in memory, suggesting a potential pathway linking OSA to cognitive impairment via perivascular fluid dynamics.

Background/Objectives: The glymphatic system plays a crucial role in clearing brain metabolic waste, and its dysfunction has been correlated to various neurological disorders. The Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index has been proposed as a non-invasive marker of glymphatic function by measuring diffusivity along perivascular spaces; however, its sensitivity to sleep-related changes in glymphatic activity has not yet been validated. This study aimed to evaluate the feasibility of using the DTI-ALPS index as a quantitative marker of dynamic glymphatic activity during sleep. Methods: Diffusion tensor imaging (DTI) data were obtained from 12 healthy male participants (age = 24.44 ± 2.5 years; Pittsburgh Sleep Quality Index (PSQI) < 5), once while awake and 16 times during sleep, following 24 h sleep deprivation and administration of 10 mg zolpidem. Simultaneous MR-compatible electroencephalography was used to determine whether the subject was asleep or awake. DTI preprocessing included eddy current correction and tensor fitting. The DTI-ALPS index was calculated from nine regions of interest in projection and association areas aligned to standard space. The final analysis included nine participants (age = 24.56 ± 2.74 years; PSQI < 5) who maintained a continuous sleep state for 1 h without awakening. Results: Among nine ROI pairs, three showed significant increases in the DTI-ALPS index during sleep compared to wakefulness (Friedman test; p = 0.027, 0.029, 0.034). These ROIs showed changes at 14, 19, and 25 min after sleep induction, with FDR-corrected p-values of 0.024, 0.018, and 0.018, respectively. Conclusions: This study demonstrated a statistically significant increase in the DTI-ALPS index within 30 min after sleep induction through time-series DTI analysis during wakefulness and sleep, supporting its potential as a biomarker reflecting glymphatic activity.

Purpose Excessive daytime sleepiness (EDS) is a common condition with implications for individual health and public safety. While factors such as snoring and depression are known contributors to EDS, the role of grit in EDS remains unexplored. This study aimed to investigate the association between and EDS in a representative sample of Korean adults, with a specific focus on the two components of grit: perseverance of effort (PE) and consistency of interest (CI). Methods A nationwide cross-sectional survey was conducted through door-to-door interviews using structured questionnaires between September and December 2018 in Korea. EDS was assessed using the Epworth Sleepiness Scale, while grit was measured using the Short Grit Scale, comprising PE and CI subscales. Multivariable logistic regression analyses were performed to explore the association between grit and EDS, adjusting for covariates. Results A total of 2,356 participants (49.3% male; aged 19–92 years) were enrolled in the study. The prevalence of EDS was 15.2%. Participants with EDS had significantly lower overall grit scores, driven by lower CI subscale scores. After adjusting for confounders, higher grit scores were significantly associated with EDS (OR 0.35, 95% CIs 0.26–0.45, p < 0.001). This association persisted in subgroup analyses, including those with depression and habitual snoring. In contrast, no significant association was observed between the PE subscales and EDS. Conclusion Our findings suggest that intrinsic motivation, as reflected by the CI subscale of grit, is inversely associated with EDS. Therefore, exploring interventions that include nurturing grit could be a potential approach to addressing EDS.

This study investigates brain water dynamics across the sleep-wake cycle using near-infrared spectroscopy (NIRS) and linear mixed-effects modeling, motivated by prior observations that glymphatic activity increases during non-rapid eye movement (NREM) and decreases during REM sleep. Forty-one healthy volunteers underwent polysomnography with concurrent cerebral NIRS, with measurements taken 30 minutes before sleep, throughout the night, and for 60 minutes after waking. Brain water content (arbitrary unit, A.U.) was block-averaged for 5-minute epochs and analyzed across WAKE→NREM, NREM→WAKE, NREM→REM, and REM→NREM transitions. Water content significantly increased during WAKE→NREM (0.57 A.U., d =  0.77, p < 0.001) and decreased during NREM→WAKE (−0.93 A.U., d = −1.25, p < 0.001). Decreases during NREM→REM (−0.40 A.U., d =  −0.53, p < 0.05) were followed by increases during REM→NREM (0.62 A.U., d =  1.10, p < 0.001). Brain water accumulation was significantly greater during the first compared to the last NREM cycle (0.70 A.U., d =  0.86, p < 0.01). These findings reveal robust, state-dependent fluctuations in brain water content that parallel established glymphatic physiology. Water-sensitive NIRS may offer a promising non-invasive approach to monitoring sleep-related brain fluid dynamics in humans, though further multimodal studies are needed to determine its specificity for glymphatic activity.

Lee G, et al. J Nutr Health. 2025 Dec;58(6):541-556. https://doi.org/10.4163/jnh.2025.58.6.541