Search Results (471)

Background/Objective: Mental fatigue (MF) significantly impairs psychomotor performance in dynamic sports; however, its specific impact on closed-skill precision-demanding tasks remains underexplored. This study investigated the acute effects of experimentally induced MF exposure on psychophysiological responses, mood states, and archery shooting performance. Methods: Fifteen well-trained male compound-bow archers participated in a randomized crossover study. Participants completed an MF condition (30 min modified Stroop task) and a control condition (CON; passive viewing of a neutral documentary), separated by a 72 h washout period. Continuous heart rate (HR), archery shooting accuracy, ratings of perceived exertion (RPE), rating scale of mental effort (RSME), state anxiety (VAS-A), mood states, and exercise enjoyment scale (EES) were assessed. Results: The Stroop task successfully induced subjective MF. Consequently, shooting accuracy significantly deteriorated in the MF condition compared to that in the CON condition (p < 0.001; g = 0.731). While HR and VAS-A remained consistent across conditions, the MF condition elicited a significant increase in RPE (p = 0.007; g = 0.836) and RSME (p = 0.010; g = 0.794). Furthermore, MF significantly increased feelings of anger and fatigue while drastically reducing PACES (p < 0.001; g = 1.530). Conclusions: Acute MF significantly degrades fine motor accuracy in precision sports. The pronounced dissociation between elevated RPE and stable peripheral physiological strain suggests that performance decline is driven by top-down cognitive burden rather than physiological limitations. Therefore, systematic monitoring of cognitive load is crucial for optimizing performance in precision sports. Full article

Dementia caregiving represents a major public health challenge, with spousal caregivers assuming the greatest burden. Spouses, themselves typically older adults, provide high intensity, long-term, and largely unpaid care across all stages of cognitive decline. Despite their central role in dementia care, the health consequences experienced by spousal caregivers remain insufficiently characterized in the literature and inadequately addressed in clinical and public health practice. This structured narrative review synthesizes current evidence on the multidimensional impact of dementia caregiving on the physical, psychological, cognitive, social, and financial health of spousal caregivers. It further contextualizes these consequences within the trajectory of dementia progression, and identifies interventions, support systems, and policy considerations necessary to mitigate caregiver burden. Spousal caregivers experience disproportionate burden due to continuous, escalating responsibilities that often mirror the progressive deterioration of their partners. Emotional burdens, including uncertainty during pre-diagnostic stages, role strain, conflict, loss of intimacy, and anticipatory grief. Physically, spouses endure musculoskeletal strain, sleep disruption, poor nutrition, and heightened frailty risk. Psychologically, spousal caregivers exhibit elevated rates of depression, anxiety, loneliness, and stress-related disorders. Socially, caregivers experience substantial isolation, stigma, and erosion of social networks. Financial hardship, including early retirement, reduced employment, and uncompensated care hours, further exacerbate stress. Evidence suggests that chronic caregiving stress contributes to biological changes such as immune dysregulation, inflammation, acceleration, aging, and potential cognitive decline in caregivers themselves. Caregiver burden influences patient outcomes as evidenced by increased emergency department use, falls, and earlier institutionalization in persons with dementia whose caregiver is subjected to a high burden. Current care models rarely include routine, caregiver assessment or structured guidance following diagnosis, resulting in substantial unmet needs. Effective mitigation requires integrated, stage-sensitive interventions, including psychosocial support, caregiver education, respite services, culturally tailored programs, and digital health tools, alongside broader policy reforms to reduce financial and structural barriers. Full article

Background/Objectives: Longer lifetime exposure to endogenous estradiol (L_EE2) has been associated with lower risk of age-related cognitive decline and dementia. Complementary to cognitive decline, behavioral and functional decline are also predictive of dementia risk; however, the association between L_EE2 and these domains is underexplored. We investigated whether L_EE2 is correlated with later-life changes in behavior and function. Methods: Baseline data from 1156 females enrolled in the CAN-PROTECT study were analyzed. L_EE2 was estimated based on the length of the reproductive period (menopause age–menarche age) plus years pregnant and scaled in 5-year increments. Objective cognition was measured using the CAN-PROTECT neuropsychological battery, while subjective cognition, behavior, and function were measured using the Revised Everyday Cognition (ECog-II) scale, Mild Behavioral Impairment Checklist (MBI-C), and Standard Assessment of Global Everyday Activities (SAGEA) scale, respectively. Linear regressions modeled the association between L_EE2 and neuropsychological performance. Three separate negative binomial regression models examined the association between L_EE2 and ECog-II, MBI-C, and SAGEA total scores. All models adjusted for menopause hormone therapy, menopause type, age at first childbirth, body mass index, age, education, and ethnocultural background. Results: Each five-year increase in L_EE2 was associated with a lower MBI-C score (count ratio [CR] = 0.89, 95% CI [0.82, 0.97]) and lower SAGEA score (CR = 0.91, 95% CI [0.84, 0.98]). L_EE2 was not significantly associated with any objective or subjective cognitive measures. Conclusions: Longer L_EE2 may associate with lower severity of later-life behavioral and functional symptoms in older women. Full article

Background: Small-sided games (SSG) and running-based high-intensity interval training (HIIT) are commonly used in soccer conditioning to improve aerobic fitness and performance. Although both modalities induce high cardiovascular stress, their acute neuromuscular, perceptual, and cognitive responses remain incompletely understood when examined within the same cohort. This study compared the acute physical, psychophysiological, and cognitive responses to SSG and Tabata-type HIIT in amateur male soccer players. Methods: Thirty-two male amateur players (n = 32; age: 20.53 ± 1.65 years) completed a counterbalanced within-subject crossover design. Participants performed a 4v4 SSG protocol and a running-based Tabata-HIIT protocol (8 × 20 s, 10 s recovery) on separate days (48 h apart). Countermovement jump (CMJ), squat jump (SJ), 20-m sprint, agility t-test, heart rate, perceived exertion (Borg CR-10), mental effort, and cognitive performance (d2 test) were assessed pre- and post-exercise. Parametric variables were analyzed using 2 × 2 repeated-measures ANOVA (time × protocol; η²p), and non-parametric data were analyzed using Friedman and Wilcoxon tests (r) (p < 0.05). Results: Both protocols elicited similar cardiovascular responses (~90% HR_max). A significant protocol × time interaction was observed for CMJ (p < 0.001), showing a decline after Tabata-HIIT, whereas performance was maintained after SSG. No inter-protocol differences were found for SJ, sprint, or agility. Perceived exertion and mental effort during recovery were higher following Tabata-HIIT (p < 0.05). Cognitive performance improved after both protocols (p < 0.001), with no between-protocol differences. Conclusions: Despite comparable cardiovascular load, Tabata-HIIT was associated with greater acute neuromuscular and perceptual strain, whereas SSG preserved neuromuscular performance. Perceptual and mental responses may therefore differ despite similar physiological intensity, which may inform soccer training prescription. Full article

Understanding Alzheimer’s Disease (AD) progression using resting-state functional Magnetic Resonance Imaging (rs-fMRI) remains an open challenge. Variational Autoencoders (VAEs) provide compact representations of high-dimensional neuroimaging data but lack mechanisms to highlight disease-relevant features. We propose KS-VAE, a novel framework that integrates the Kolmogorov–Smirnov test into the latent space of VAEs to identify statistically significant variables discriminating healthy from pathological brain states. This integration enables measurement of latent space shifts associated with cognitive decline, offering a quantitative approach to neurodegenerative processes. By modifying the most relevant variables, KS-VAE generates synthetic samples that simulate transitions between clinical conditions while preserving anatomical plausibility. The method enhances the modeling of temporal and distributional dynamics underlying disease progression and provides interpretable analysis of class-relevant features. Applied to rs-fMRI scans of 220 subjects from the ADNI cohort, KS-VAE demonstrated robust class separation between cognitively normal and Alzheimer’s disease subjects, achieving a classification accuracy of 84.5% and an F1-score of 84.5%, and clinically consistent synthetic transitions. KS-VAE thus offers a statistically grounded and clinically interpretable framework for understanding Alzheimer’s disease progression. Full article

Background/Objective: Cognitive frailty, the coexistence of physical frailty and cognitive impairment, is a potentially reversible and high-risk state for dementia. This study examined the association between Color Kanji Pick-out Test (CKPT) app performance and cognitive frailty independent of Mini-Mental State Examination (MMSE) scores in community-dwelling older women. Methods: In this cross-sectional study, the participants were 102 community-dwelling older women without dementia and with MMSE scores ≥ 27 (73.6 ± 6.0 years). Reversible cognitive frailty was defined as subjective cognitive decline (≥1 point in the cognitive domain of the Kihon Checklist) plus physical frailty or prefrailty, according to the Japanese Cardiovascular Health Study (J-CHS) criteria. Firth’s penalized logistic regression using three prespecified models, adjusted for age and education, was used to examine the independent associations between CKPT app performance and MMSE scores with reversible cognitive frailty. Results: Fourteen participants (13.7%) met the criteria for cognitive frailty. In separate models, higher CKPT app and MMSE scores were significantly associated with lower odds of cognitive frailty (CKPT: odds ratio [OR] 0.470, p = 0.019; MMSE: OR 0.548, p = 0.020). In a multivariable model including both measures, the CKPT app (OR 0.499, p = 0.031) and MMSE scores (OR 0.553, p = 0.031) remained independently associated with cognitive frailty, and this model had the lowest Akaike information criterion. Conclusions: The CKPT app performance was independently associated with cognitive frailty beyond global cognition. The CKPT app may detect subtle executive and attentional vulnerabilities not captured by the MMSE, supporting practical, objective, early screening and risk stratification of cognitive frailty. Full article

Background and Objectives: During the past 25 years, a significant body of research has been conducted reporting on the salutary effects of the Mediterranean diet and extra-virgin olive oil, one of its main components. The initial studies were epidemiological observations on populations with very low mortality rates due to significant reductions in myocardial infarction fatalities. Population-based studies demonstrated that the Mediterranean diet with olive oil consumption is associated with a lower prevalence of cardiovascular and cerebrovascular disease, obesity, arthritis, and cancer. Materials and Methods: In this narrative review, we present recent studies on the effects of extra-virgin olive oil and the Mediterranean diet—compared with various other diets—on several vascular risk factors, including hypertension, hyperlipidemia, type 2 diabetes mellitus, and obesity, as well as their impact on cognitive decline and dementia. Results: This diet has been shown to improve cognitive function in patients with mild cognitive impairment, Alzheimer’s disease, vascular cognitive impairment, and vascular dementia. The main mechanisms responsible for cognitive improvement include control of arterial hypertension by reducing systolic and diastolic blood pressure, lowering triglycerides and low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol, along with improvement in fasting glucose, insulin levels, and hemoglobin A1c in subjects with type 2 diabetes mellitus, as well as lowering body mass index and obesity. Conclusions: The Mediterranean diet and olive oil induce—along with prevention of cardiovascular disease and stroke—a significant improvement of vascular risk factors, slowing the progression of both vascular dementia and Alzheimer’s disease. There is a need for additional placebo-controlled clinical trials to confirm the supportive nutritional role of extra-virgin olive oil in age-associated cognitive decline in the elderly. Full article

Background: Physical activity requiring self-control may yield greater post-activity cognitive improvements. Implementing such tasks within The Daily Mile could enhance cognition further while adding variety to the initiative. This study examined whether the inclusion of self-control tasks within The Daily Mile influences subsequent cognition and enjoyment. Methods: Participants, numbering 99 (10.2 ± 1.1 y), completed three trials (Daily Mile Normal, Daily Mile Self-Control, and resting), using a within-subject, order-balanced, crossover design. The Daily Mile Self-Control involved students completing tasks requiring self-control for 30 s every 2 min within The Daily Mile. Cognitive tests (Stroop test, Sternberg Paradigm, Visual Search test) were administered prior to, immediately following and 45 min following The Daily Mile and resting trials. During the trials, distance covered (m), average heart rate (beats·min⁻¹) and physical activity enjoyment (PACES) were measured. Focus groups explored factors affecting enjoyment during The Daily Mile trials. The effects of physical activity vs. rest on cognitive function were examined first, followed by the effect of adding self-control tasks to The Daily Mile. Results: There were no statistically significant differences between the Daily Mile trials on distance covered or physical activity enjoyment. However, average heart rate was significantly higher in The Daily Mile Self-Control compared to The Daily Mile Normal. Compared to rest, The Daily Mile had a positive effect on inhibitory control. Working-memory accuracy maintained following activity, but perceptual accuracy was briefly impaired. Following the addition of self-control tasks, working memory response times improved. However, accuracy on inhibitory control and perception declined immediately after activity, compared to The Daily Mile Normal. Thematic analysis indicated varied perceptions among participants, with some valuing the simplicity and control of The Daily Mile Normal, and others favoring The Daily Mile Self-Control due to the variety and cognitive challenge. Conclusions: Incorporating self-control tasks into The Daily Mile produced mixed cognitive and qualitative responses, compared to The Daily Mile Normal. This suggests that tailoring physical activity to individual preferences may optimize engagement and cognitive outcomes. Full article

Background: As accelerating population aging increases the burden of neurological disorders, assessing cognitive reserve has become crucial for identifying resilience to decline. However, its evaluation is often hindered by instruments lacking the cultural sensitivity and psychometric rigor necessary for different populations. Objective: This study aimed to examine the psychometric properties and factorial structure of the Italian version of the Subjective Cognitive Reserve Questionnaire (SCR-Q) in a general adult population. Methods: A total of 225 adults (mean age = 51.84 years, SD = 14.08; 69.8% women) completed an online assessment including the SCR-Q and resilience, life satisfaction, and anxiety measures in an incidental sample selection. The sample was randomly divided for exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Internal consistency, factorial validity, and convergent/divergent validity were evaluated. Results: EFA and CFA supported a two-factor structure reflecting a physical health dimension and a cognitive–social dimension, with the two-factor model showing acceptable fit and outperforming a unidimensional solution. Internal consistency was adequate for the total scale (α = 0.795; ω = 0.850) and for both subfactors. SCR-Q scores were positively associated with resilience and life satisfaction and negatively associated with anxiety, with stronger associations observed for the cognitive–social factor. Conclusions: The Italian SCR-Q demonstrates satisfactory psychometric properties and supports a multidimensional conceptualization of subjective cognitive reserve integrating physical, cognitive, and psychosocial domains. The instrument represents a brief and ecologically valid tool for population-level screening and prevention research. Full article

Background: Alzheimer’s disease (AD) remains an incurable disorder with severe clinical consequences. The type 3 diabetes hypothesis posits that AD may constitute a neuroendocrine disorder driven by disrupted insulin and insulin-like growth factor signaling. Amyloid pathogenesis in AD is characterized by the accumulation of beta-amyloid (Aβ) monomers, their subsequent oligomerization, and amyloid deposition. One of the causes of Aβ accumulation is disruption of amyloid precursor protein (APP) processing due to imbalance in ADAM10 and BACE1 expression. In recent years, increasing attention has been devoted to investigating the role of environmental factors in AD pathogenesis. The receptor for advanced glycation end products (RAGE) serves as a key molecular link between environmental exposure and neuroinflammatory pathology. Formaldehyde (FA) is one of the most widespread environmental pollutants. Its involvement in amyloid plaque formation has been previously reported; however, the molecular mechanisms underlying this process remain insufficiently understood. Moreover, most available data are based on prolonged FA exposure, whereas industrial FA emissions are often short-term. The objective of this study was to determine whether brief intranasal administration of FA, modeling episodic industrial pollution, induces RAGE-mediated neuroinflammation and amyloid deposition in CD1 mice. Methods: Mice received intranasal FA at environmentally relevant 0.02 mg/day or 0.2 mg/day doses for seven days; an additional group was co-treated with insulin. Cognitive function was assessed using passive avoidance (PA) and radial arm maze (RAM) tests, and synaptic plasticity was evaluated by electrophysiology. Hippocampal tissue was analyzed for RAGE expression, ADAM10/BACE1 gene balance, Aβ42 monomer levels, and amyloid deposits using optimized Thioflavin-S (Th-S) staining. Results: We observed cognitive decline in mice receiving intranasal FA administration. Elevated blood glucose levels were also observed following intranasal FA exposure. Sustained impairment of glucose metabolism led to overexpression of the RAGE in the hippocampus. There was also an imbalance of ADAM10 and BACE1 expression in the hippocampus. This was caused by overexpression of RAGE, as the enhanced interaction of the ligand and RAGE is a key factor disrupting this balance. Finally, Th-S staining confirmed amyloid deposition in mice subjected to intranasal FA exposure. Conclusions: This study provides new insights into the RAGE-mediated mechanisms by which FA contributes to the pathogenesis of AD. Full article

Background/Objectives: Daily sleep patterns are associated with cognitive health and Alzheimer’s disease (AD). However, it remains unclear how suboptimal irregular sleep manifests in AD from the preclinical stage to dementia. This study aimed to establish the dose–response association between sleep irregularity and psychometrically defined stage-specific AD as well as executive dysfunction, among adults with subjective cognitive and sleep issues. Methods: Cross-sectional data were obtained from 532 Japanese adults (mean age = 63.9 years) between March 2023 and April 2024. Sleep irregularity was quantified using the Sleep Regularity Index (SRI) with 24/7 accelerometer data. A modified Poisson regression with cubic splines was performed to establish the dose–response association. Results: This study identified novel non-linear associations. The prevalence ratios of cognitive impairment, defined as being in the preclinical and more advanced stages of AD, significantly declined beyond a median SRI of 60. Participants within this SRI range also showed significantly lower prevalence ratios of poorer Trail Making Test B performance. All results were independent of age, sleep duration, and risk of depression. Conclusions: Maintaining balanced-to-regular daily sleep patterns might be optimal for AD progress from its preclinical stages, with a potential benchmark at SRI of 60, especially for those individuals at risk for cognitive decline and sleep disorders. Further research is needed to replicate this benchmark in diverse populations and to evaluate the effect of rigid sleep regularity on cognitive health. Full article

Dementia represents a major healthcare challenge, as pathological changes often occur years before overt symptoms. Early manifestations such as mild cognitive impairment (MCI) and subjective cognitive decline (SCD) represent critical transitional stages between normal aging and dementia. Thus, distinguishing these conditions (i.e., MCI and SCD) and determining their potential evolution into dementia remains crucial. However, current clinical tools, mainly neuroimaging and neuropsychological assessments, are not always clearly interpretable and are often resource-intensive. In recent years, artificial intelligence (AI), including machine learning (ML) and deep learning (DL), has demonstrated promising potential in early detection, progression prediction, and differential diagnosis of neurocognitive disorders. This systematic review aims to synthesize current evidence on the application of AI-based approaches to improve diagnostic accuracy and prognostic assessments in dementia. A comprehensive literature search of studies published between 2015 and 2025 was conducted across PubMed/MEDLINE, Scopus, and Web of Science, following PRISMA 2020 guidelines. Studies were evaluated for data modality, methodological rigor, performance metrics, and clinical applicability. Seventeen (17) studies, of which twelve (12) are primary studies and five (5) are secondary studies, examining AI applications in detecting and diagnosing neurocognitive disorders (NCDs) in adults with dementia, MCI, or SCD were included. Results indicate that AI models, particularly DL applied to neuroimaging, electrophysiological data, speech and language features, biomarkers, and digital behavioral data, achieve high diagnostic accuracy in distinguishing MCI, Alzheimer’s disease, and healthy aging. Predictive models also show potential in forecasting conversion from MCI to dementia and monitoring cognitive trajectories via wearable or smart-home technologies. Nonetheless, heterogeneity, limited external validation, and methodological inconsistencies hinder clinical translation. In conclusion, AI represents a rapidly evolving and promising tool for early detection and monitoring of neurocognitive disorders. Collectively, the reviewed studies underscore the need for standardized pipelines, larger multicenter datasets, and explainable AI frameworks to enable effective clinical implementation. Full article

Mild behavioral impairment (MBI) constitutes a late-life transition state that is associated with an increased risk of cognitive impairment and dementia. Herein, we cross-sectionally describe the MBI construct and its relationship with cognitive status in Mexican-Mestizos (MM) older adults. Participants were classified according to their cognitive and behavioral statuses using tests administered to older adults and their informants. APOE_rs429358/rs7412 variants were genotyped by real-time PCR. Multivariate correlation and Principal Components Analysis (PCA) were used in statistical analysis. A total of 246 participants were included, 56.1% were classified as individuals with NC, 13.0% had subjective cognitive decline, and 30.9% had mild cognitive impairment. A total of 37% (91/246) of participants from all over the cognitive spectrum met the MBI criteria; among this group, APOEε4 homozygosity was associated with two subdomains of the MBI. Subjective cognitive complaint, symptoms of depression, and cognitive decline reported by the informant were associated with an increased risk for MBI (ORs in the range of 4.7–15.89). The first three components of PCA explained 68.0% of the variance of the dataset, including the MBI-checklist total score as a main contributor. Well-known risk factors for dementia also correlated with this PCA. MBI could be a potential marker for cognitive decline in non-demented MM elderly people; however, observed associations should be confirmed in future longitudinal studies. Full article

As population aging accelerates, age-related declines in visual sensitivity and attentional control make older drivers more vulnerable to suboptimal in-vehicle interface designs. Head-up displays (HUDs) are intended to reduce gaze shifts by overlaying information within the forward field of view, yet empirical evidence remains limited on how specific HUD presentation strategies reshape older drivers’ visual attention allocation. Grounded in theories of visual attention and cognitive load, this study systematically investigates three design variables that are increasingly common in contemporary HUDs (including AR-HUDs): (1) dynamic versus static navigation cues, (2) pedestrian warning strategies under different lighting conditions, and (3) the spatial placement of high-priority information. We first conducted a formative user study to define variables and operationalizations, and then carried out three within-subject driving-simulator experiments using controlled HUD stimuli and eye tracking. Objective gaze measures (e.g., fixation count, total fixation duration, and time to first fixation) were combined with subjective preference ratings to characterize attentional capture, search efficiency, and potential attentional costs. Findings reveal a robust trade-off: continuously changing navigation cues enhance attentional capture but can also increase attentional “stickiness,” unnecessarily consuming older drivers’ limited attentional resources. In pedestrian hazard tasks, real-time overlay warnings that were spatially aligned with the hazard significantly improved visual localization under low-light conditions, outperforming early warnings and multi-stage strategies. Across tasks and layout conditions, the central HUD region showed a stable attentional advantage—placing critical information centrally elicited greater visual attention and stronger subjective preference. These results provide mechanistic evidence for how HUD parameters modulate older drivers’ attention and yield actionable implications for prioritization, temporal pacing of dynamic navigation cues, and a “center-first” layout strategy to guide age-friendly HUD design. Full article

Objective: Alzheimer’s disease (AD) is traditionally characterized by amyloid-β and tau pathology; however, accumulating evidence indicates that metabolic and inflammatory dysfunctions are early, central contributors to disease development. This narrative review explores how metabolic disturbances influence AD pathophysiology. Methods: A comprehensive literature search was performed on PubMed, Embase, and Scopus. Selected studies were original studies or reviews published in English within the past five years involving human subjects. Case reports, case series, editorials, and non-human studies were excluded. A total of 64 articles were reviewed and summarized. Results: Cerebral glucose hypometabolism, mitochondrial impairment, insulin resistance, oxidative stress, and neuroinflammation were observed throughout the AD spectrum. These metabolic changes often appeared before significant amyloid accumulation and were more closely linked to tau pathology and cognitive decline. Early microglial activation was linked to transient glucose hypermetabolism, progressing to glucose hypometabolism and neurodegeneration as the disease advanced. Conclusions: AD is associated with a gradual breakdown of metabolic and inflammatory homeostasis, which occurs before and promotes the development of traditional neuropathological features. Addressing early metabolic vulnerabilities may be essential for effective disease intervention and prevention. Full article