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PubMed2026

Age at menopause and subjective cognitive symptoms predict digital cognitive outcomes at the gynecological Well-Woman visit.

INTRODUCTION: Women are at increased risk for Alzheimer's Disease (AD). Growing evidence suggests that the menopausal transition may represent a vulnerable window for development of AD-related pathology. Yet, women are diagnosed with AD later than men. Conducting routine cognitive screenings and integrating information about both cognitive symptoms and age at menopause may help address sex-based disparities in detection and prevention. This study investigated whether subjective cognitive symptoms, in combination with age at menopause, were associated with performance on a digital cognitive task in postmenopausal women. METHODS: 183 postmenopausal women (mean age = 63.8, range = 45-85) were recruited after their Well-Woman visit. Participants completed the Screener for Cognitive Problems in Everyday Life (SCoPE) to assess subjective cognitive symptoms, followed by a sensitive measure of objective cognition: the Linus Health Digital Clock and Recall (DCR™). Information was also collected on age at menopause. We examined associations of subjective cognitive symptoms and age at menopause with digital cognitive performance, adjusting for age, education and depression. Model fit was evaluated using adjusted R2, AIC, and BIC. RESULTS: 48.1% of women reported one or more cognitive symptoms on the SCoPE. On objective testing, 73.2% scored in the normal range, 20.8% in the borderline range, and 6.0% in the impaired range. SCoPE total score was negatively associated with objective cognitive performance in adjusted models (B = -.12, p = .03). Age at menopause showed a significant quadratic association with cognitive performance (B = -0.006, p<.001). SCoPE total was not associated with DCR subtests, while age at menopause predicted both Delayed Recall and Clock Drawing. CONCLUSION: Subjective cognitive symptoms and age at menopause were associated with lower performance on a sensitive, objective cognitive test. Findings support routine cognitive screening and suggest that subjective cognitive symptoms as well as age at menopause are associated with cognitive function.

Humans↗

PubMed2026

Effectiveness of Wearable Digital Therapeutics in Improving Sleep Outcomes Among Individuals With Insomnia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. OBJECTIVE: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the I² statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] -4.52, 95% CI -8.38 to -0.67, PI -9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%-2.11%, PI 1.85%-2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98-35.24, PI -16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (R²=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (P=.07). Certainty of evidence ranged from moderate to high. CONCLUSIONS: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base.

Humans↗

PubMed2026

Association between pulse pressure and markers of cognitive function: a systematic review and meta-analysis.

Our aim was to systematically review and meta-analyse evidence on the association between pulse pressure (PP) and cognitive function using PubMed, PsycInfo, Embase and Scopus (inception-July 2025) publication databases. Studies were included if they reported an association between PP and cognitive function and summarized narratively and by performing fixed-effects meta-analysis. The search identified 4171 publications with 43 studies meeting inclusion criteria. Domains assessed included global cognition, memory, language, attention, executive function, processing speed and visuospatial ability. Meta-analysis suggests a positive association between PP and global cognition, and a negative association with memory in both cross-sectional and longitudinal studies with inconsistent findings from narratively summarized studies. Processing speed, executive function and language negatively associated with PP in cross-sectional studies with limited evidence provided by longitudinal studies or narratively summarized studies. There was limited evidence of an association with attention and visuospatial ability.

Humans↗

PubMed2026

Development and Validation of a Predictive Model for Identification of Cognitive Impairment Risk in Older Adults with Subjective Cognitive Decline：A Longitudinal Study.

BACKGROUND: Subjective cognitive decline (SCD) is a transitional state between objective cognitive impairment and cognitively intact mental status, providing a critical window for implementing preventive interventions to delay objective cognitive decline. AIMS: We aimed to develop a predictive model for SCD progression in older adults with mild cognitive impairment (MCI). This model will facilitate the identification of risk factors and establishment of targeted interventions for community-based SCD management. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) was utilized in this study, extracting 18 indicators. Potential predictors selected through univariate Cox regression and LASSO regression analyses were sequentially incorporated into a multivariable Cox regression model. A nomogram was constructed to establish a predictive model. Model validation encompassed Area Under Curve (AUC) metrics for discriminative capacity, complemented by quantitative assessments using calibration curve analysis for precision verification and decision curve analysis (DCA) for clinical utility evaluation. RESULTS: A total of 1099 older adults with SCD were included in the final analysis, of whom 114 (10.3%) developed MCI. Multivariable Cox regression identified residence, marital status, educational level, social participation, gait speed, and baseline cognitive function. The model demonstrated time-dependent AUC values of 0.885, 0.830, 0.839, and 0.836 in the training set when evaluating discriminative capacity at 2-, 4-, 7-, and 9-year, respectively. The predictive model showed excellent predictive ability according to AUC, calibration curve, and DCA. CONCLUSIONS: A predictive model was created to estimate the risk of developing MCI in older individuals with SCD, offering clinician-actionable intervention benchmarks for preventive care.

Humans↗

PubMed2026

Dual-Reporter Gene-Based Multimodal Imaging for Tracking Mesenchymal Stem Cells in Diabetic Skin Wound Repair.

BACKGROUND: Diabetic foot ulcer (DFU) is a clinically challenging complication characterized by poor healing outcomes, and conventional therapies provide limited benefit. Mesenchymal stem cell (MSC) transplantation offers a promising strategy for DFU repair. However, the low survival of transplanted MSCs in the hostile wound microenvironment, coupled with the lack of real-time, non-invasive methods to track these cells in vivo, severely hampers their therapeutic efficacy and clinical translation. METHODS: We engineered MSCs to co-express a dual reporter system comprising near-infrared fluorescent protein (iRFP) and ferritin heavy chain (FTH1). These modified cells were then integrated with a fibrin glue (FG) scaffold to create a unified platform that supports both multimodal imaging and therapeutic function within skin wounds. First, FTH1 overexpression enhances the antioxidant capacity of MSCs, while the FG scaffold provides structural support; this combination enhances cell survival and retention. Second, the iRFP/FTH1 dual reporter enables near-infrared fluorescence imaging and MRI-based localization, establishing a multimodal platform for real-time cell tracking. RESULTS: In a full-thickness skin defect model in diabetic mice, multimodal imaging revealed that transplanted cells persisted in the wound area for approximately seven days. Treatment with iRFP/FTH1-MSCs/FG significantly accelerated wound closure and promoted hair follicle regeneration and angiogenesis. Additionally, local iron deposition resulting from FTH1 expression enhanced fibroblast migration and collagen synthesis, further facilitating extracellular matrix remodeling. Mechanistic studies demonstrated that this therapy drives macrophage polarization toward the anti-inflammatory M2 phenotype and activates the PI3K-AKT-VEGF signaling pathway. These complementary effects synergistically enhance tissue regeneration and systematically improve diabetic wound healing. CONCLUSIONS: Collectively, this multimodal stem cell-scaffold system effectively integrates dynamic cell tracking with stem cell therapy during skin wound repair. It addresses a critical technical gap in visualizing stem cells within the wound microenvironment and provides valuable methodological and theoretical foundations for optimizing regenerative strategies for diabetic skin wounds.

Animals↗

PubMed2026

Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: A systematic review of clinical and preclinical evidence.

Psychedelic agents induce a window of heightened neuroplasticity that extends beyond acute intoxication, during which neural circuits are more amenable to change. This period may facilitate changes in cognition relevant to the treatment of psychiatric disorders. This systematic review synthesised clinical and preclinical evidence of subacute and long-term (≥1 day) effects of classic and non-classic psychedelics on cognition. MEDLINE, EMBASE, APA PsycInfo and Web of Science were searched to identify human and animal studies investigating psychedelics and cognition (executive function, attention, decision-making). Sixty-seven (47 clinical, 20 preclinical) articles met inclusion criteria. Psilocybin demonstrated the most consistent evidence of subacute and longer-term cognitive improvement, particularly in cognitive flexibility and attention. Ketamine showed enhancement across cognitive domains, although findings were heterogeneous. LSD and DMT showed no consistent subacute changes, while MDMA was associated with transient cognitive impairments that resolved within days. Risk of bias assessments revealed selective outcome reporting, poor reporting of missing data and inadequate methodological detail, limiting the confidence of findings. Current evidence provides preliminary support for subacute changes in cognition following administration of select psychedelic agents. Cognitive improvements were more frequently seen in psychiatric populations than healthy subjects, which may reflect a remediation of existing cognitive deficit rather than enhancement above normal functioning. Adequately powered, controlled studies with standardised reporting of cognitive outcomes are required to determine the magnitude, durability and clinical relevance of psychedelic-associated cognitive change.

Hallucinogens↗

PubMed2026

Branded packaging raises likelihood of cigarette purchasing in an experimental retail setting by increasing craving.

INTRODUCTION: Exposure to branded cigarette packaging in retail settings has been shown to be associated with purchasing behavior, but the mechanisms underlying this effect are unclear. This study tested whether cigarette craving and perceived health harms mediate the effect of branded packaging on cigarette purchasing in a simulated retail environment. METHODS: Young adults aged 21-34 who currently smoke cigarettes (n = 290) completed an experimental shopping task in the RAND StoreLab, a life-sized replica of a convenience store. Participants were randomly assigned to one of two conditions: (1) branding present, in which branded cigarette packages were displayed; and (2) branding absent condition, in which branded elements were removed and packages were standardized in a brown-green color and uniform text. Cigarette purchases were recorded, and participants completed post-shopping measures of cigarette craving and perceived health harms. Causal effect decomposition analyses were used to assess whether these variables mediated the effect of study condition on the likelihood of purchasing cigarettes. RESULTS: Craving, but not perceived health harms, partially mediated the effect of branded packaging on cigarette purchasing. Exposure to branded packs increased the likelihood of purchasing by elevating craving (average mediated effect = 2.4%, 95% CI 0.2% - 5.0%, p = .03). CONCLUSIONS: Branded cigarette packaging appears to increase cigarette purchasing at least in part by increasing cigarette craving at point of sale. Interventions that address craving management in retail settings (e.g., just-in-time interventions, prn nicotine replacement therapy) may help mitigate the impact of branding on young adults' cigarette purchasing.

Humans↗

PubMed2026

Game changer? Cognitive-motor effects of VR exergaming compared to video-based training.

BACKGROUND/OBJECTIVE: Virtual reality (VR) exergaming enhances several cognitive domains through multisensory engagement. Acute cognitive benefits of VR are established, but evidence for direct comparisons with non-immersive controls is limited. This study aimed to determine whether VR exercise provides additional cognitive and cognitive-motor benefits beyond a matched non-immersive active stick-fight video (SFV) intervention, and whether effects persist after training. METHODS: In this randomized quasi-experimental study, N = 55 healthy adults (VR: n = 30; SFV: n = 25; 25.5 ± 7.1 years; 41.8% female) completed an 8-week program (2 × 30 min/week), of VR or SFV matched in movement patterns, frequency, intensity and duration. Measurements included reaction time (RT), Stroop Test (versions 1-3), Letter Cancellation Test (LCT), Trail Making Test (TMT), Trail Walking Test (TWT) and Fitts task (difficulty level 1-4). Data were analyzed using mixed-design ANOVAs. RESULTS: Improvements were observed in Stroop reading (F(1,53) = 14.84, p < .001, η2 = 0.219), Stroop inhibition (F(1,53) = 10.99, p = .002, η2 = 0.172), and LCT (F(1,53) = 4.57, p = .037, η2 = 0.079). A time × group interaction was found for TMT (F(1,53) = 6.55, p = .031, η2 = 0.110), indicating greater changes following VR training. Both groups improved cognitive-motor performance (TWT: F(1,25) = 55.32, p < .001, η2 = 0.689; Fitts3: F(1,53) = 44.97, p < .001, η2 = 0.459), with greater gains for VR in Fitts3 (p = .006). CONCLUSION(S): Eight weeks of VR and SFV enhanced cognitive and cognitive-motor performance. VR provided domain-specific advantages in executive function, but these effects were not uniformly persistent. SFV sustained more improvements in real-world-relevant cognitive-motor tasks.

Humans↗

PubMed2026

Impact of a multimodal prehabilitation program on postoperative cognitive dysfunction: a single-center randomized controlled trial.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a frequent complication after cardiac surgery. Exercise-based prehabilitation may enhance functional reserve and reduce vulnerability to perioperative cerebral insults. We hypothesized that multimodal prehabilitation reduces POCD 3 months after cardiac surgery. METHODS: This prespecified substudy of a single-center randomized controlled trial (NCT03466606) included patients aged ≥50 years undergoing elective coronary artery bypass grafting and/or valve surgery. Participants were randomized 1:1 to 4-6 weeks of multimodal prehabilitation (exercise training, nutritional support, and psychological support) or standard preoperative care. Cognitive function was assessed at baseline and 3 months postoperatively using an age- and education-adjusted neuropsychological battery. POCD was defined as performance ≥1.5 standard deviations below normative values in at least 2 cognitive tests, excluding the Mini-Mental State Examination. Logistic regression analyses were performed to evaluate factors associated with POCD. RESULTS: Of 160 participants screened from the parent trial, 134 met eligibility criteria for the substudy and were randomized; 116 completed 3-month follow-up (prehabilitation n = 53; control n = 63). POCD occurred in 29 patients (25%), including 15/53 (28%) in the prehabilitation group and 14/63 (22%) in controls (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.54-3.50, P = 0.52). In multivariable analysis, preoperative cognitive impairment was independently associated with POCD (OR 13.28, 95% CI 4.06-43.41, P < 0.001), whereas prehabilitation was not (OR 1.09, 95% CI 0.35-3.45, P = 0.877). Higher physical activity levels at 3 months were associated with lower odds of POCD (OR 0.97, 95% CI 0.95-1.00, P = 0.047). CONCLUSIONS: In this randomized controlled trial, a 4-6-week multimodal prehabilitation program did not reduce postoperative cognitive dysfunction 3 months after cardiac surgery. Although the intervention did not achieve measurable cognitive protection, the observed association between postoperative physical activity levels and postoperative cognitive dysfunction warrants further investigation.

Humans↗

PubMed2025

Psychological interventions for children with chronic physical conditions: a systematic review assessing the role of coping, emotional and cognitive processes.

OBJECTIVES: Coping, emotional and cognitive processes are crucial in child development, particularly in children with pediatric chronic physical conditions (CPC). No systematic review in pediatric psychology has investigated the effectiveness of interventions on these processes concurrently. This review addresses this gap by focusing on the effectiveness of psychological interventions on coping, emotional and cognitive processes in children with CPCs. METHODS: Five electronic databases were searched for studies assessing at least one of these processes. Only randomized-controlled trials with children (8-12 years) with a CPC (e.g. diabetes, asthma), which implemented a psychological intervention were included. This study is registered in (CRD42021233505). RESULTS: Ten intervention studies were identified. While cognitive interventions (Cogmed) showed some improvements in working memory, the effects varied across studies despite similar methodologies. Coping interventions (e.g. Coping Skills Training) showed little effect on coping strategies or psychological health variables and were no more beneficial than control groups. No study trained coping, emotional processes and cognitive processes together. CONCLUSION: This review shows current limitations in evaluating psychological interventions targeting coping, cognitive or emotional processes in children with CPCs, limiting a comprehensive understanding of the interventions' action mechanisms. Systematically including underlying processes in intervention studies could help to better adjust those interventions.

Humans↗

PubMed2026

Role of Polygenic Risk Scores in Predicting Cognitive Functioning after Mild Traumatic Brain Injury: A TRACK-TBI Study.

Patients with traumatic brain injury (TBI) and Glasgow Coma Scale scores of 13-15 (historically called mild TBI [mTBI]) commonly experience changes in cognitive functioning, including processing speed, memory, and executive functioning. In a prospective sample (N = 523) of individuals of European descent who had been treated in a U.S. level 1 trauma center for mTBI, we examined the prognostic value of four polygenic risk scores (PRS) for cognitive outcomes at 6-months postinjury. To estimate the impact of mTBI on cognition, primary cognitive outcomes were scaled as z-scores reflecting changes in performance relative to predicted preinjury performance. The PRS examined were previously developed and validated to predict cognition-related outcomes of educational attainment (Education-PRS), intelligence (Intelligence-PRS), and Alzheimer's disease (AD-mild traumatic brain injury (APOE)-PRS and AD + APOE-PRS). Both the Education-PRS and Intelligence-PRS displayed bivariate associations with all four cognitive outcomes (β = 0.19-0.32), whereas neither Alzheimer's disease PRS was significantly associated with any outcome. After controlling for other factors known to predict cognitive outcomes of TBI (e.g., sex, education, mTBI severity defined by a combination of Glasgow Coma Scale scores and the presence/absence of acute intracranial findings on clinical neuroimaging), the Education-PRS and Intelligence-PRS remained independently predictive of verbal episodic memory (β = 0.10-0.16), whereas their associations with processing speed and executive functioning were mostly nonsignificant and were mediated through educational attainment. Looking across primary z-score and secondary raw score outcomes, cognitive outcomes 6 months post-mTBI were good on average, and PRS made small independent contributions to outcome prediction. The mediation model findings may support theories of cognitive reserve, which propose that individuals with stronger preinjury cognitive processing abilities (often estimated by educational history) can better compensate for TBI. Moreover, findings indicate that PRS may contribute modestly to multivariable models predicting cognitive function after TBI.

Humans↗

PubMed2026

Ultra-high-field 7T MRI reveals neural abnormalities of attention networks in relation to cognitive impairment in hypertension.

Hypertension is a significant risk factor for cognitive impairment (CI), yet the corresponding neural network abnormalities remain underexplored. In this study, we examined the associations among global and domain-specific cognitive dysfunction, neuroimaging measures, and blood pressure in a subgroup of hypertensive patients with CI (N = 41) from a randomized controlled trial who underwent ultra-high-field 7 T MRI. Structural atrophy related to CI was localized to regions overlapping the attention networks. Both whole-brain and within-network dysfunction of the attention networks were associated with worse global cognitive performance. Notably, hyperconnectivity within key attention network hubs, including the right anterior insula and posterior intraparietal sulcus, was associated with declined processing speed in hypertensive patients, mediating the association between pulse pressure and processing speed. These findings provide new insights into the neural pathophysiology of hypertension-related CI and suggest potential network-based targets for intervention.

Magnetic Resonance Imaging↗

PubMed2026

Effects of permissive hypercapnia on intraoperative cerebral oxygenation and early postoperative cognitive function in older patients with fragile brain function during the non-acute phase undergoing laparoscopic colorectal surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Older adults with non-acute fragile brain function (NFBF) may be particularly susceptible to perioperative disturbances in cerebral oxygenation and postoperative neurocognitive decline. Permissive hypercapnia (PHC) may enhance cerebral oxygenation, but its effects in this population remain unclear. We examined whether PHC-based ventilation improves intraoperative regional cerebral oxygen saturation (rSO2) and early postoperative cognitive outcomes in older patients with NFBF undergoing elective laparoscopic colorectal surgery. METHODS: In this single-center, single-blind randomized trial, 76 patients were assigned in a 1:1 ratio to PHC-based or conventional ventilation. The primary outcome was the absolute change in rSO2 from baseline (T0) to the end of surgery (T4). Analyses followed the intention-to-treat principle, with prespecified per-protocol sensitivity analysis. Secondary outcomes included intraoperative rSO2 trajectories, cerebral oxygen extraction-related indices, early postoperative cognitive screening, serum neuron-specific enolase and interleukin-6, and safety outcomes. RESULTS: PHC significantly increased rSO2 relative to conventional ventilation (left: adjusted mean difference [aMD] 10.64, 95% CI 8.96-12.33; right: aMD 10.16, 95% CI 8.22-12.11; both P < 0.001), with consistent sensitivity results. Repeated-measures analyses showed persistently higher intraoperative rSO2 in the PHC group. Cerebral oxygen extraction-related indices were generally lower with PHC. However, early postoperative cognitive outcomes and serum biomarkers did not differ between groups. Emergence time was modestly longer with PHC, whereas adverse events were comparable. CONCLUSIONS: PHC-based ventilation favorably modified intraoperative cerebral oxygenation and oxygen-extraction profiles but did not translate into detectable early postoperative cognitive or biomarker benefits in older adults with NFBF.

Humans↗

PubMed2026

Effect of a PROtein-enriched MEDiterranean diet and EXercise (PROMED-EX) on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline: the PROMED-EX randomized controlled trial.

BACKGROUND: Undernutrition in older adults is associated with adverse health outcomes including cognitive decline, yet evidence for effective preventive strategies is limited. OBJECTIVES: The objective of this study was to investigate effects of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in "at risk" community-dwelling older adults. METHODS: A total of 105 participants (69% female; aged 67.7 ± 6.1 y) at risk of undernutrition and cognitive decline were randomized to 1 of 3 groups: 1) PROMED-EX (personalized dietary counseling plus home-based exercise); 2) PROMED (personalized dietary counseling only); or 3) CON (healthy eating leaflet). The primary outcome was change in nutritional status at 6 mo, measured by the Mini Nutritional Assessment (MNA; 0-30 points). Secondary outcomes included neurocognitive test battery (NTB) z-score, PROMED diet quality score (0-14), physical performance, and health-related quality of life. Analyses followed an intention-to-treat approach using linear regression to assess between-group differences in 6-mo outcomes. RESULTS: At baseline, the mean MNA score was 22.5 ± 2.3. After 6 mo, nutritional status improved significantly in both intervention groups compared with CON: mean differences in MNA were 2.7 [95% confidence interval (CI): 1.3, 4.2] for PROMED and 2.9 (95% CI: 1.5, 4.3) for PROMED-EX (both P < 0.001). Cognitive function also improved, with NTB z-score differences of 0.3 (95% CI: 0.1, 0.5; P = 0.01) in PROMED and 0.2 (95% CI: 0.0, 0.4; P = 0.02) in PROMED-EX compared with CON. Diet quality scores significantly increased with mean differences of 4.0 (95% CI: 2.9, 5.0) for PROMED and 3.9 (95% CI: 2.8, 4.9) for PROMED-EX compared with CON (both P < 0.001). Despite low adherence to exercise, additional benefits were observed for physical performance and quality of life. CONCLUSIONS: Dietary intervention improved nutritional status in community-dwelling older adults at risk of undernutrition. Correcting undernutrition could help to slow cognitive decline and promote physical health and quality of life during aging. This study was registered at clinicaltrials.gov as NCT05166564.

Humans↗

PubMed2026

The interplay between circadian misalignment or sleep disturbances and cognition and brain function in individuals with different degrees of insulin resistance - a systematic review.

Disruption of sleep increases the risk of type 2 diabetes and worsens cognitive outcomes, yet few studies have evaluated the interaction between insulin resistance and sleep parameters in relation to cognitive outcomes or the risk of dementia. This systematic review examines how circadian misalignment and sleep disturbances affect cognition and neuroimaging findings in individuals with varying degrees of insulin resistance. Across 27 studies, disrupted circadian rhythmicity and sleep disturbances were negatively associated with brain health, possibly through its effects on insulin sensitivity, whereas the impact of sleep duration and quality were inconclusive. Methodological heterogeneity, reliance on cross-sectional designs, and limited control for confounders restricted definitive conclusions and highlighted the need for longitudinal and interventional studies with objective measurements. Nonetheless, the findings support circadian rhythmicity as a potentially modifiable risk factor for preserving cognition in insulin-resistant populations. Future research should prioritise prospective and interventional studies and focus on biological markers rather than self-reported outcomes.

Humans↗

PubMed2026

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans↗

PubMed2026

Virtual Reality Mastoidectomy as Precadaver Training for Novices: A Randomized Crossover Study.

OBJECTIVES: To compare cognitive load during virtual reality (VR) simulation and cadaveric dissection (CD) mastoidectomy training in novice learners. To determine whether training order influences cognitive load, characterize cognitive load progression during the procedure, and assess whether VR training improves subsequent cadaveric performance. METHODS: In this randomized crossover study, 24 core surgical trainees with no prior mastoidectomy experience performed a cortical mastoidectomy in both VR and CD settings. Participants were randomized to either VR-first or CD-first training sequences. Cognitive load was measured using a bespoke auditory reaction-time device at baseline and 10, 30, and 50 min. Relative reaction time (RRT) served as an objective index of cognitive load. Cadaveric performance was assessed using the Modified Welling Scale by two blinded otologists. RESULTS: Cognitive load was significantly lower during VR than CD, with mean RRT rising 26% from baseline in VR versus 60% in CD (p < 0.001). Training order did not affect cognitive load in either modality, and RRT increased progressively throughout mastoidectomy in both VR and CD. Participants who began with VR achieved significantly higher cadaveric performance scores than those who began with CD (mean 9.50 vs. 4.96; p < 0.001), and inter-rater reliability for performance scoring was high. CONCLUSION: VR mastoidectomy reduces cognitive load and enhances subsequent cadaveric performance in novice trainees, supporting its role as a cognitively optimized precadaver training modality that complements, rather than replaces, cadaveric dissection. These findings suggest VR enhances early learning efficiency and resource utilization in novice otolaryngology training. LEVEL OF EVIDENCE: N/A.

Humans↗

PubMed2026

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n = 15,765) consisted of UK Biobank participants (MDD only n = 1230; T2DM only n = 3644; comorbid T2DM + MDD n = 721). Individuals with T2DM + MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR = 4.44, 95% CI = [3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM + MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM + MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM + MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans↗