Rui Wang

Background: Disability among older adults in China is becoming an increasing public health challenge due to rapid population aging. We aim to investigate how cognitive deficits, depression, and physical function limitation jointly contribute to the onset and progression of disability. Methods: We included 4226 individuals aged ≥60 years from the China Health and Retirement Longitudinal Study, who were followed for a mean of 7.8 years (2010–2020). Physical function, cognition, and depressive symptoms were assessed. Outcomes included incident activities of daily living (ADL) disability and the number of ADL and instrumental ADL disabilities. Cox regression, linear mixed‐effects models, and structural equation modeling were applied. Results: Having ≥2 conditions of cognitive deficits, depression, and physical function limitation concurrently at baseline was associated with a higher risk of incident ADL disability (hazard ratio [HR] _{2 versus 0} , 1.70 [95% CI, 1.44–2.00]; HR _{3 versus 0} , 2.10 [95% CI, 1.65–2.68]) and a faster annual increase in ADL/instrumental ADL limitations compared with those without (β _2×time =0.010 [95% CI, 0.007–0.013]; β _3×time =0.014 [95% CI, 0.010–0.019]). The association between physical function limitations and longitudinal ADL/instrumental ADL accumulation appeared to be mediated by the biannual rate of cognitive decline and increases in depression scores. Conclusions: The co‐occurrence of cognitive deficits, depression, and physical function limitations may synergistically drive long‐term disability. Our findings highlight the importance of early screening and holistic management of cognitive, mental, and physical health to reduce the burden of disability in aging populations.

Background: The potential link between data-driven classifications of individuals’ activity profiles and the occurrence of fall and dementia, including within-person transitions from dementia- or fall-only states to their co-occurrence over time, remains unclear. Method: To examine whether distinct activity profiles were associated with the risk of fall, dementia, and their transitions over time in middle-aged and older adults, this prospective longitudinal study included 288,287 adults (53.6% women) aged 40–69 years at baseline (2006–2010) from the UK Biobank. Latent class analysis was used to classify participants into distinct activity profiles based on self-reported physical activity, transportation, work, social, and sleep behaviours. Incident fall and dementia were identified through linkage to health records and the death registry up to December 2022. Multistate time-to-event analysis was conducted to examine the associations between activity profiles and the risks of fall, dementia, and their transitions over time. Results: Based on various activity levels and work status, participants were categorized into four groups: active-non-working (29.2%), inactive-non-working (14.4%), active-working (26.7%), and inactive-working (29.7%). Of them, 19,753 (6.85%) experienced a fall injury, and 4,407 (1.53%) developed dementia over an average follow-up of 13.4 years. The inactive-non-working group showed the highest risk of both fall and dementia (HR _range : 1.45—2.38) over 13.4 years. In the non-working groups, where fall and dementia occurred most often, the inactive profile was linked to a higher risk of both fall and dementia, and to an increased likelihood of transitioning between the two. Transitions from dementia to subsequent fall were associated with insufficient physical activity, whereas transitions from fall to subsequent dementia were linked to social isolation, particularly living alone and frequent loneliness. In the working groups, no differences in fall or dementia risk were observed between active and inactive profiles. Conclusions: This study highlights the important role of social and physical activity in simultaneously preventing fall, dementia, and their transitions, particularly among non-working individuals, including those on sick leave or retired.

Background/Objectives: It is unclear if adherence to healthy guidelines can modify the association between polygenic risk score (PRS) for type 2 diabetes and dementia. This study aimed to investigate interrelationships between PRS for type 2 diabetes, Life’s Essential 8 (LE8) metrics, and dementia. Methods: We included 437,732 UK Biobank participants aged ≥40 years between 2006 and 2010. PRS for type 2 diabetes was calculated by summing weighted genetic variant effects. Incident all-cause and cause-specific dementias were identified using registry records up to December 2022. LE8 scores were classified as low vs. moderate-to-high levels. Cox regression and restricted cubic splines were applied. Results: Over an average follow-up of 13.27 years (SD = 2.27), 9425 participants developed dementia. A dose–response relationship was observed between PRS and vascular dementia, with risk rising sharply beyond the 95th percentile. Individuals with low LE8 constantly showed a higher risk of all-cause dementia than those with moderate-to-high LE8 across all values of PRS for type 2 diabetes. APOE ε4 accounted for more than 35% of the population-attributable risk of dementia, whereas the PRS for type 2 diabetes contributed only 1%. The population-attributable risk of all-cause dementia could be further reduced by 5.91% to 10.46% through maintaining moderate-to-high LE8 behavioral components, even after considering APOE ε4. Conclusions: A dose–response relationship exists between PRS for type 2 diabetes and dementia, particularly vascular dementia. Adherence to optimal LE8 metrics, particularly behavioral components, may contribute to dementia prevention across genetic strata. These findings highlight the importance of multidomain lifestyle interventions in dementia prevention.

INTRODUCTION: The relationship between sleep, other dementia risk factors, and dementia remains unclear. We aim to explore these associations using a two‐sample Mendelian randomization (MR) approach. METHODS: We identified genetic instrumental variables for sleep characteristics from the UK Biobank and obtained summary‐level genetic association data for dementia outcomes, including Alzheimer’s disease (AD), from the FinnGen consortium. We applied inverse‐variance weighted (IVW) MR to examine the associations between sleep characteristics and dementia outcomes. Multivariable MR was subsequently employed to assess the influence of additional dementia‐relevant factors on these relationships. RESULTS: Genetic variants for insomnia, among the sleep characteristics, were associated with elevated AD risk (odds ratio [OR] _IVW  = 3.02, 95% confidence interval [CI]: 1.28–7.10, p  = 0.01). Yet this association was largely attenuated after adjusting for education and low‐density lipoprotein (LDL). DISCUSSION: These findings indicate that the association between insomnia and AD is complex and indirect, potentially operating through social‐behavioral factors (education) and biological pathways such as LDL cholesterol.

Background: How the environment in which physical activity takes place influences brain health remains insufficiently studied. We aimed to investigate the association between outdoor physical activity and dementia in older adults, and to examine whether residential green space (GS) modifies this association. Methods: This prospective longitudinal study used UK Biobank data from 187,724 adults aged 60—73 years at baseline (2006—2010) and 36,854 with brain Magnetic Resonance Imaging (2014—2021). Outdoor activity (via Metabolic Equivalent of Task) and GS (within 300 m of homes) were assessed, with dementia incidence tracked through electronic records until December 2022. Neuroimaging markers included hippocampal and total gray-matter volumes, and white-matter hyperintensity volume. Cox proportional hazards and linear regression models were applied. Results: During a mean follow-up of 13.01 years, 7218 participants (47.1% female) developed dementia. After adjusting for covariates, higher outdoor activity is associated with a lower risk of all-cause dementia (HR_{top vs bottom quartile} = 0.84, 95% Confidence Interval [CI] 0.78—0.90). This association is most pronounced for vascular dementia (HR:0.72, 95%CI 0.63—0.83) and is stronger among those living in areas with high, compared to low, residential GS (0.73, 95%CI 0.63—0.85 vs 0.86, 95%CI 0.79—0.93, p_interaction = 0.04). Higher outdoor activity is also associated with higher hippocampal and total gray-matter volumes and fewer white-matter hyperintensities. A combined effect of outdoor activity and GS on hippocampal volume is observed. Conclusions: Outdoor activity is linked to lower dementia risk, particularly in those living in more accessible GS. These findings underscore the importance of urban planning that prioritizes accessible GS to promote brain health in the aging population.

Individuals aged 70 and older frequently experience an increased risk of deficits in both physical and cognitive functions. However, the natural progression and interrelationship of these deficits, as well as their neurologic correlates, remain unclear. We aimed to classify the data-driven physical-cognitive phenotypes and then investigate their associations with neuroimaging markers. This cross-sectional study included 70-year-old participants from the Gothenburg H70 Birth Cohort (2014-2016). Based on physical performance (grip strength, balance, walking speed, and chair stand) and cognitive measures (episodic memory, perceptual speed, executive function, verbal fluency, and visuospatial abilities), we applied latent class analysis to identify physical-cognitive phenotypes. Based on the brain MRI measurements, 3 groups of neuroimaging markers were involved-neurodegeneration, cerebral small vessel disease (cSVD), and microstructural white matter (WM) integrity. We performed multinomial logistic regressions to examine the differences between the physical-cognitive phenotypes. In total, 1,140 participants (female: 53.3%) without dementia and disability were included in the study, with 721 (female: 52.2%) undergoing MRI scans. Three physical-cognitive phenotypes were identified: an "optimal" group characterized by high performance in both physical and cognitive functions, an "intermediate" group showing a slight reduction in both domains, and a "physical deficit" group marked by a significant reduction in physical performance. Compared with the optimal group, the other 2 groups were more likely to present with vascular risk factors. The physical deficit group had higher odds of experiencing depression compared with the intermediate group (adjusted odds ratio [aOR] 2.9, 95% CI 1.4-5.9). Compared with the optimal group, the odds of presenting all 3 severe neuroimaging markers were higher in both the intermediate (aOR 3.4, 95% CI 1.5-7.9) and physical deficit (aOR 10.3, 95% CI 2.4-45.0) groups. This study highlights the variability in physical and cognitive performance among older adults and suggests that neuroimaging markers of neurodegeneration, cSVD, and microstructural WM integrity may account for these variations. Our findings indicate the potential for developing group-based strategies to prevent and manage age-related functional decline. Further research with larger sample sizes is needed to deepen our understanding of physical-cognitive decline patterns.

Background: The successful FINGER multidomain intervention model combined dietary intervention (healthy Nordic diet) with exercise, cognitive training, social activities, and cardiovascular risk monitoring. The FINGER model is being tested and optimized in the World‐Wide FINGERS network of multidomain dementia prevention trials (45+ countries). Advanced FINGER 2.0 models combine lifestyle interventions with multi‐nutrients and/or putative disease‐modifying drugs.Method: The 11‐year extended follow‐up of FINGER trial participants (N:1260, at‐risk general population) was completed in Q1‐2023. The MIND‐AD pilot‐trial (N:93, prodromal Alzheimer’s disease (AD)) included medical food (Fortasyn Connect), tested alone or in combination with multidomain lifestyle intervention for 6 months. The MET‐FINGER trial (N:600, at‐risk general population enriched with APOE4‐carriers, 2‐year intervention) includes different dosages of metformin (in combination with upgraded FINGER lifestyle intervention).Result: New nutrition/metabolic related data will be presented from FINGER where eg. adherence to healthier diet was still relatively high in the multidomain arm after the extended follow‐up. Higher adherence was also related to better cognition. Several dietary and metabolic biomarkers have been analyzed revealing underlying mechanisms and responders (eg persons with insulin resistance, higher HOMA, responded less). In the MIND‐AD trial, participants from 4 European countries were randomized to the multidomain lifestyle intervention alone (N:32), or in combination with medical food (N:31), and 30 to the control group. Adherence was high for all intervention domains (78‐87%). Compared with the control group, the group with lifestyle+medical food showed a decrease in vascular risk burden (P = 0.027) and an increase in healthy diet patterns (P = 0.045), and better cognition after the intervention (CDR‐SOB). There were no significant differences between the lifestyle only and control group. MET‐FINGER trial recruitment started in January 2023 (preliminary data presented).Conclusion: Longer‐term dietary and lifestyle changes are feasible and effective in older adults in the at‐risk spectrum of AD/dementia. Beneficial effects (adherence to and effects of interventions) seemed to improve with the inclusion of medical food in prodromal AD. The unique long follow‐up of FINGER provides important information about long‐term effects and methodological aspects. The MET‐FINGER trial will provide data on synergistic effects between FINGER intervention and a drug targeting both glucose metabolism and AD pathology.

Background: Previous evidence supports a beneficial effect of physical activity on executive function across the whole lifespan. Yet, the interrelationships of the intensities of physical activity, cardiorespiratory fitness, and executive function require further investigation in adults.Aim: Using unfiltered accelerometry data and high-resolution intensity classification, we sought to estimate the associations of physical activity with cardiorespiratory fitness and executive function in adult office workers.Methods: We included 343 full-time office workers (mean age: 42.41 years, range of age: 36−49 years). Executive function was assessed using Stroop, Trail making tests (part-B), and 2-back tests, and a composite score was produced to reflect the general executive function performance. Physical activity was assessed using the Actigraph GT3X+-monitor, worn by each participant for seven days at the hip. Raw accelerometry data were processed by the 10 Hz frequency extended method and divided into 22 intensity bins and sleep time. Cardiorespiratory fitness was estimated using the submaximal Ekblom-Bak cycle ergometer test. Data were analyzed using partial least squares regressions.Results: In adults, cardiorespiratory fitness was closely correlated with a wide range of absolute physical activity intensity patterns. A higher level of executive function in adults was associated with both higher absolute physical activity intensities and cardiorespiratory fitness, which was independent of age, sex, and education levels. A very weak association between intensities, fitness, and executive function was observed in high-fit adults. Among low-fit adults, although a positive association started already toward the upper end of moderate intensity, there still appeared to be an association between intensities, cardiorespiratory fitness, and executive function. That is, cardiorespiratory fitness may mediate the association between absolute physical activity intensities and executive function up to a certain level.Conclusion: The maintenance of executive function in adulthood was related to both physical activity intensities and cardiorespiratory fitness, while their interrelationship was not equal across fitness levels. It is highly recommended to consider the cardiorespiratory fitness level in future studies that focus on executive functions in aging as well when designing individualized physical activity training programs.