Kelsey Sewell

A substantial proportion of dementia risk may be attributable to modifiable factors, yet these are often examined in isolation despite their interrelated nature and tendency to co-occur. It remains unclear whether the relationship between modifiable factors and dementia risk is influenced by individual characteristics such as sex and genetic susceptibility. We investigated longitudinal associations between the Lifestyle for Brain health (LIBRA) score and risk of dementia, cognitive performance, and brain structure, and whether relationships differed by sex and APOE ɛ4 carrier status.Participants were aged > 50 years, dementia-free at baseline, 50% female and predominantly (97%) white/Caucasian. The LIBRA score included 11 modifiable factors (e.g., hypertension, obesity, physical inactivity). Magnetic resonance imaging estimated brain volume, domain-specific cognitive composite scores were calculated, and dementia diagnoses were determined based on self-reported and linked healthcare data.Across a mean follow-up of 10.2 years, a higher LIBRA score was associated with greater odds of developing dementia (OR = 1.20, 95% CI 1.18-1.22). This association was stronger in APOE ɛ4 non-carriers compared to ɛ4 carriers. Cross-sectionally, higher LIBRA scores related to poorer cognition, smaller whole-brain gray and white matter volumes, and increased ventricular cerebrospinal fluid (CSF), however, only the association with increased ventricular CSF persisted longitudinally (mean follow-up 3.4 years).Each one-point increase on the LIBRA score was associated with 20% increased odds of developing dementia. These results reinforce the need to target modifiable dementia risk factors and to tailor dementia prevention strategies to individual risk profiles to maximize the impact on brain health.

Background Physical activity and sleep are both related to brain health, and these lifestyle factors also share a bi‐directional relationship. However, in the context of cognitive function, sleep and physical activity are seldom considered together in cross‐sectional studies, and the influence of each lifestyle factor in the context of interventions (e.g., exercise) remains unclear. The purpose of this research is to investigate whether sleep and physical activity may interact to influence brain health in older adults. Method This will present data from two studies. The first is a previously unpublished cross‐sectional study in healthy older adults (n = 589; 69.8 ±3.7 years). Sleep was measured via the Pittsburgh Sleep Quality Index (PSQI) and both sleep and physical activity were measured via 24‐hour actigraphy for 7 days. We investigated the moderating influence of physical activity on associations between sleep and cognitive function in five domains. Secondly, we will present published data from a randomized controlled trial which was a 6‐month, supervised exercise intervention in 89 cognitively unimpaired older adults (68.76±5.32 years). We investigated the influence of baseline sleep, measured by PSQI, on exercise‐induced cognitive improvement across the course of the intervention. Result Cross‐sectionally, moderate‐to‐vigorous physical activity (MVPA) moderated the association between self‐reported sleep efficiency and episodic memory, processing speed, EF/attentional control, and working memory (β[range] = ‐0.10 – ‐0.17, all p < .05). Light physical activity moderated the association of actigraphy‐measured WASO with EF/attentional control and processing speed (βs = 0.10, all p < .05). The direction of these results was such that the association between lower sleep efficiency and greater WASO with poorer cognitive performance was stronger in those with low physical activity levels. From our exercise intervention study, we found that that those with poorer sleep efficiency at baseline showed the greatest exercise‐induced improvements in episodic memory from pre‐ to post‐intervention (β=−0.024, p = 0.004). Conclusion Our results suggest that physical activity and sleep interact to influence cognitive function, and the efficacy of exercise interventions to improve cognition may be influenced by sleep. Taken together, our data suggest that physical activity may compensate for some negative influences of poor sleep on cognition.

INTRODUCTION
The relationships between 24-h time-use composition (i.e., sleep, sedentary behavior, light physical activity, and moderate-to-vigorous physical activity [MVPA]) and brain morphology in older adulthood remain poorly understood. We examined associations between 24-h time-use composition and brain age using compositional data analysis, predicting that 24-h time use would be associated with brain age and that a greater amount of time engaged in MVPA would drive associations with younger brain age.

METHODS
Baseline data from the Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE; n = 648) were analyzed. Brain age was estimated using T1-weighted magnetic resonance imaging data. Time-use composition was derived from wrist-worn triaxial accelerometers. Regression models examined associations between 24-h time-use composition (expressed as isometric log ratios) and brain age, adjusting for age, sex, apolipoprotein E4 (APOE4) carriage, education, body mass index, image quality, and site. Compositional isotemporal substitution evaluated how hypothetical reallocations of time between behaviors related to brain age.

RESULTS
The final sample included 573 adults (69.8±3.7 years, 407 females). It was found that 24-h time-use composition was associated with brain age (F = 2.72, p = 0.004). Post hoc modeling indicated that time spent in MVPA primarily drove these associations, such that less MVPA was associated with greater brain age, irrespective of whether time was taken from sleep, sedentary behavior, or light physical activity.

DISCUSSION
These results suggest that 24-h time use, especially time spent in MVPA, relates to structural brain age in late adulthood. Maintaining or increasing MVPA may help preserve younger brain age, irrespective of which behaviors this time was reallocated from. Future research should examine whether systematically shifting 24-h time use toward MVPA alters brain aging trajectories.

INTRODUCTION
Arterial stiffness (carotid-femoral pulse wave velocity [cfPWV]) and plasma neurofilament light (NfL), markers of vascular and neuroaxonal aging, are linked to cognitive decline. Whether higher cfPWV amplifies the NfL–cognition relationship remains unclear.

METHODS
Cognitively unimpaired older adults (N = 570) were assessed using composite cognitive scores from confirmatory factor analysis. cfPWV was dichotomized at the median. Plasma NfL was quantified on a Single Moleculte Array-High Definition, model X (SIMOA-HD X).

RESULTS
Higher NfL correlated with poorer performance across all cognitive domains (p < 0.05), and higher cfPWV was linked to worse episodic memory, working memory, and processing speed (p < 0.05). NfL× cfPWV interactions were significant for episodic (β = 0.289, p = 0.048) and working memory (β = 0.287, p = 0.025), with stronger NfL–cognition associations in the higher cfPWV group (episodic memory: β = -0.324, p < 0.01; working memory: β = -0.343, p < 0.01).

DISCUSSION
Greater cfPWV amplified the association between NfL-related axonal degeneration and cognitive decline.

Background
Globally, coffee and tea are consumed extensively, potentially providing neuroprotection through anti-inflammatory and antioxidative stress effects.

Objective
This study aimed to investigate associations between coffee and tea intake and cognitive function.

Methods
In a longitudinal prospective cohort study, dementia-free (n = 8715; age range 60.0–85.2 years) older adults from the UK Biobank self-reported coffee and tea intake over the previous year; ‘never’, ‘moderate’ (1–3 cups/day), or ‘high’ (≥4 cups/day). Participants completed cognitive assessments at ≥2 timepoints (mean of 9.11 years).

Results
Those ‘never’ consuming coffee and ‘moderate’ coffee consumers (β = 0.06, p = 0.005; β = 0.07, p < 0.001, respectively), as well as ‘moderate’ tea consumers and ‘high’ tea consumers (β = 0.06, p = 0.009; β = 0.06, p = 0.003, respectively) had slower fluid intelligence decline. Additionally, those ‘never’ consuming coffee and ‘moderate’ coffee consumers had a slower increase in pairs matching errors (β = −0.05, p = 0.022; β = 0.05, p = 0.013) compared to ‘high’ consumers.

Conclusions
‘Moderate’ coffee, and ‘moderate’ and ‘high’ tea intake may be a protective factor against cognitive decline. Randomized controlled trials are required to establish causal relationships leading to evidence-based recommendations regarding benefits of coffee and tea intake.

Introduction
This study examined longitudinal associations between self-reported exercise and cognition, with moderation by sex, in individuals with autosomal dominant Alzheimer's disease (ADAD) mutations. We also examined whether changes in exercise over time differed in ADAD mutation carriers versus non-carriers in the years preceding first cognitive symptom onset.

Methods
Participants (n = 491) were ADAD mutation carriers (63%) and non-carriers (37%) from the Dominantly Inherited Alzheimer Network aged 37.6 ± 11.1 years. Participants reported their average time partaking in various leisure-time exercise activities over the past 12 months.

Results
Greater baseline exercise predicted better longitudinal cognitive performance. Sex did not moderate these associations. In the years preceding first cognitive symptoms or last follow-up visit, mutation carriers showed a decline in their exercise engagement compared to mutation non-carriers.

Discussion
Self-reported exercise is associated with preserved cognitive function in those with ADAD mutations; however, AD-related pathways may influence the level of engagement in exercise prior to cognitive symptom onset.

Highlights
• Greater weekly exercise predicts slower cognitive decline in ADAD mutation carriers.
• These associations varied dependent on closeness to estimated symptom onset.
• These associations were not moderated by sex.
• Weekly exercise declined in ADAD mutation carriers compared to non-carriers.
• Results may suggest a bidirectional relationship between exercise and AD risk.

Background
Worldwide, coffee and tea are two of the most popular beverages consumed. Studies have suggested a protective role of coffee and tea, including reduced risk of Alzheimer’s disease. However, longitudinal data from large cohorts of older adults reporting associations of coffee and tea intake with cognitive decline is limited.

Method
Cognitively unimpaired participants (n = 8,451) from UK BioBank (≥60 years of age) with at least 2 follow up visits (average follow up time 8.83 years) were included. Baseline self-report coffee and tea intake (cups per day) were collected using a questionnaire. Cognitive assessment included Pairs Matching test (errors), Reaction Time test, Numeric Memory test, and Fluid Intelligence. Linear mixed models assessed the relationship between categorical coffee and tea intake and cognitive outcomes, including covariates age, sex, qualification, Townsend deprivation index, ethnicity, Apolipoprotein E ε4 status, and body mass index.

Result
Daily coffee intake predicted the slope of decline in Fluid Intelligence across follow-up (β = -0.02, SE = 0.007, FDR corrected p = .004). Those never consuming coffee and those with moderate coffee consumption (1-3 cups) had slower declines in Fluid Intelligence compared to those with high coffee consumption (³4 cups, β = 0.06, SE = 0.02, p = .005; β = 0.07, SE = 0.02, p<.001, respectively).

Daily tea intake predicted decline in Fluid Intelligence across follow-up (β = 0.02, SE = 0.007, FDR corrected p = .044), such that those who never drank tea showed a greater decline in Fluid Intelligence compared to those who had moderate and high tea consumption (β = 0.06, SE = 0.02, p = .009; β = 0.06, SE = 0.02, p = .003, respectively).

Conclusion
Our results support the hypothesis that coffee and tea intake may be a protective factor against cognitive decline, particularly for maintaining Fluid Intelligence. However, our results show an upper limit to coffee intake with a maximum of 3 cups/day being consumed for beneficial effects, and no coffee intake being more beneficial than ³4 cups. Conversely, high tea consumption provided positive effects on cognition in addition to moderate consumption, with high tea consumption being more beneficial than no tea consumption. Additional longitudinal observational and intervention studies are required to validate our findings and confirm this hypothesis.

This research has been conducted using the UK Biobank Resource under Application Number 108907.

Poor sleep is commonly associated with poorer cognition in older adults. Unfortunately, effective sleep improvement therapies for older adults are limited in their accessibility and have shown only subtle effects on cognition. Physical activity, however, is associated with better cognition in older adults and may compensate for cognitive deficits related to poor sleep. This study examined whether greater engagement in physical activity moderates the association between sleep and cognitive function in older adults.
We utilized baseline data from the Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) study. Cognitively unimpaired older adults (
 = 589, mean age ± SD: 69.8 ± 3.7, 70% female) underwent a comprehensive cognitive assessment. Sleep was measured via the Pittsburgh Sleep Quality Index (PSQI), and both sleep and physical activity were measured using 24-h actigraphy for 7 days.
Moderate-to-vigorous physical activity (MVPA) accumulated in at least 10-min bouts moderated the association between self-reported sleep efficiency and episodic memory, processing speed, executive function (EF)/attentional control, and working memory (β
 = -0.10 to -0.17, all
< 0.05). In addition, light-intensity physical activity moderated the association of actigraphy-measured wake after sleep onset (WASO) with EF/attentional control and processing speed (β
 = 0.10, all
 < 0.05). The direction of these results was such that lower sleep efficiency and greater WASO was associated with poorer cognitive performance, but this association was attenuated by engaging in greater amounts of physical activity.
These results support the hypothesis that physical activity may mitigate the association between poor sleep and cognitive deficits in older adulthood. We highlight the need for further longitudinal studies and randomized clinical trials of exercise to further examine these associations. These results suggest that even small amounts of MVPA or light intensity physical activity mitigate the association between poor sleep and cognitive deficits in older adulthood.
Moderate-to-vigorous physical activity moderated the association of self-reported sleep efficiency with cognition.Light physical activity moderated the association of wake after sleep onset with cognition.Physical activity may mitigate sleep-related cognitive deficits in older adults.Further longitudinal studies and randomized controlled trials are needed.

Poor sleep is associated with worse cognitive function in older adults. However, nuanced associations between sleep and cognition might be masked by the multidimensional nature of sleep which requires multiple approaches (e.g., self-report and actigraphy) to gain meaningful insight. We investigated associations of sleep with cognition and hypothesized that the most consistent association would be between self-reported sleep duration and actigraphy-measured wake after sleep onset (WASO). We utilized baseline data from the Investigating Gains in Neurocognition in an Intervention Trial of Exercise study. Cognitively unimpaired older adults (n=589, aged 65-80) completed a comprehensive cognitive assessment with generation of five domain-specific cognitive composite scores. Sleep was measured via the Pittsburgh Sleep Quality Index (PSQI) and 24-h actigraphy (GT9X Link). Greater actigraphy WASO and shorter self-reported sleep duration were associated with poorer performance in all five cognitive domains (β
= -0.14 to -0.19, all p<0.05; β
= 0.08-0.15, all p<0.05). Shorter actigraphy sleep duration was also associated with poorer EF/attentional control (β=0.09, p=0.020) and processing speed (β=0.10, p=0.013). Actigraphy and self-reported sleep were more strongly associated with episodic memory in older (74 years) and younger (66 years) individuals, respectively. Actigraphy-derived WASO was consistently and robustly associated with cognitive performance. Additionally, our results suggest that self-reported sleep duration provides insight into sleep behaviors related to brain health (e.g., long periods of still wakefulness), beyond actigraphy-measured sleep duration. Thus, both self-report and actigraphy measures of sleep provide critical and unique information for interpreting relationships with cognitive performance.

INTRODUCTION
The utility of blood-based biomarkers for discriminating Alzheimer's disease (AD)-related versus non-AD-related cognitive deficits in preclinical populations remains poorly understood. Here, we tested the capability of blood markers to detect and discriminate variation in performance across multiple cognitive domains in a cognitively unimpaired sample.

METHODS
Participants (n = 648, aged 69.9 ± 3.8, 71% female) underwent a comprehensive cognitive assessment and assays for plasma-based biomarkers amyloid beta (Aβ)1-42/1-40 by mass spectrometry, phosphorylated tau (p-tau) 181 and 217, p-tau217/Aβ1-42, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL).

RESULTS
Greater p-tau217 was exclusively associated with poorer episodic memory performance (β = −0.11, SE = 0.04, p = .003), and remained so after covarying for NfL. Higher NfL was non-specifically associated with poorer performance across a range of cognitive domains and remained so after covarying for p-tau217.

DISCUSSION
Blood-based biomarkers may differentiate non-AD-related versus AD-related cognitive deficits. This characterization will be important for early intervention and disease monitoring for AD.