Belinda Brown

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 The first is a previously unpublished cross‐sectional study in healthy older adults (n = 589; 69.8 ±3.7 years).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.

Background
Sarcopenia, an age-related loss of skeletal muscle strength, mass and function, is linked with dementia and Alzheimer's disease (AD). Current guideline-recommended tools to diagnose sarcopenia, such as appendicular skeletal muscle mass (ASM), calculated as the sum of lean muscle mass in the arms and legs via dual-energy X-ray absorptiometry (DXA), are not commonly done in AD studies. However, brain magnetic resonance imaging (MRI) is regularly performed in AD studies, and temporalis muscle thickness (TMT) has been suggested as a potential sarcopenia biomarker. As a first step in evaluating whether TMT could be a useful sarcopenia diagnostic tool, we aimed to ascertain if TMT correlates with ASM in healthy older adults.

Method
We conducted a retrospective study of healthy cognitively-unimpaired older adults in the Intense Physical Activity and Cognition study, in whom MRI and DXA had been performed on the same visit. TMT was measured on axial T1-weighted MRIs bilaterally perpendicular to the long-axis of the temporalis muscle using the orbital roof and Sylvian fissure as anatomical landmarks, and average TMT used for analysis. ASM was adjusted for body size (height2). Sarcopenia was defined as ASM< 7.0 kg/m2 for males and <5.5 kg/m2 for females as per the 2019 European working group on sarcopenia in older people criteria. Pearson correlation assessed the relationship between TMT and ASM or age.

Result
There were 95 participants (mean±standard deviation [SD] age 69.1±5.2 years, 53% female, median Montreal Cognitive Assessment score 27 [Interquartile range 25 – 28],11% had sarcopenia). The mean±SD ASM was 7.0±1.2 kg/m2 and TMT was 7.3±1.2 mm. TMT and ASM were moderately correlated (r = 0.41, 95% confidence interval 0.23 – 0.56). TMT did not correlate with age but differed significantly between those with (mean±SD 7.4±1.2) and without sarcopenia (mean±SD 6.2±0.8, p = 0.004).

Conclusion
Among a cohort of cognitively-unimpaired older adults, TMT demonstrated moderate correlation with ASM. While futher studies are needed, these findings suggest that MRI-based assessement of TMT could be a practical tool to diagnose sarcopenia in AD studies. Future studies in AD patients should explore the relationship between TMT and long-term clinical and functional outcomes.

Background
Alzheimer's disease (AD), the most common form of dementia, is marked by significant reductions in glucose metabolism. Such hypometabolism reflects underlying synaptic dysfunction, correlating with cognitive decline. Our study aimed to explore the impact of dietary patterns—specifically, the Western Diet and Prudent Diet—on change in glucose metabolism in brain regions associated with AD risk, [18F]Fluorodeoxyglucose positron emission tomography (FDG‐PET) imaging as a biomarker.

Method
Longitudinal data from 133 cognitively unimpaired older adults were analysed from the Western Australian Memory Study. Participants underwent dietary assessment using the Cancer Council of Victoria Food Frequency Questionnaire and completed FDG‐PET imaging up to three times over 43 months. Dietary patterns were identified through principal component analysis, yielding two patterns—named Western Diet and Prudent Diet. Pattern scores were computed by summing food group intakes weighted by their respective factor loadings. Linear mixed‐effect models evaluated the association between dietary adherence and brain glucose metabolism, including potential confounders. The cohort was stratified by apolipoprotein E (APOE) ε4 carrier status, a genetic risk factor for AD, to investigate potential differing effects.

Result
Adherence to a Western Diet, characterised by high sugars and saturated fats, was associated with a faster decline in glucose metabolism in the right fusiform gyrus among APOE ε4 carriers (β = ‐0.00012; SE = 0.00004; false discover rate adjusted p = .032), with no significant associations in APOE ε4 non‐carriers. Similarly, no significant associations were observed between the Prudent Diet, characterised by high intake of fruits, vegetables, and whole grains, and glucose metabolism, in both APOE ε4 carriers and non‐carriers.

Conclusion
Our study highlights the potential detrimental impact of a Western Diet on brain glucose metabolism, particularly for individuals at genetic risk for AD. The decline in glucose metabolism in the fusiform gyrus, a region essential for cognitive functions like facial recognition, emphasises the role of diet in brain health. Future research should examine the mechanisms linking diet to neurodegeneration and explore dietary interventions as preventive strategies against cognitive decline and dementia.

Background
Type 2 diabetes is associated with increased Alzheimer’s disease risk and brain beta amyloid (Aβ) burden, suggesting an underlying mechanistic relationship between Alzheimer’s disease and type 2 diabetes. Animal studies show exercise reduces levels of brain Aβ and tau, and while human studies are somewhat limited, some studies have reported physical activity is associated with lower brain Aβ and tau levels. Exercise has well established links to reductions in insulin resistance; thus, as physical activity can impact both insulin resistance and Alzheimer’s disease pathology and/or biomarkers, it is reasonable to hypothesise that a mediating relationship may exist. The objective of this review was to identify what evidence exists that examines the association between insulin, physical activity, Aβ and tau in research conducted on animal models and in human cohorts. We specifically aimed to identify whether insulin resistance has a mediating role in the relationship between physical activity and Aβ and tau.

Methods
A systematic search was performed in Cochrane library, PsycINFO, PubMed and World of Science to identify publications. The search identified 343 articles with 20 articles meeting the full inclusion criteria.

Results
Most animal studies showed that exercise could simultaneously reduce insulin resistance and Alzheimer’s disease pathology and/or biomarkers. We found limited evidence from human research that physical activity was associated with both reduced insulin resistance and Aβ or tau levels. We did not find any evidence that insulin resistance mediates the physical activity – Aβ or tau relationship.

Conclusion
Exercise can simultaneously impact insulin resistance and Alzheimer’s disease pathology in animal models. Results from human research are limited, and no robust evaluation of the potential mediating role of insulin resistance in the physical activity – Aβ or tau relationship exists. Future research should focus on identifying the mediating pathways that may link physical activity to biomarkers of Alzheimer’s disease.

Background
Central adiposity is a modifiable risk factor for age-related cognitive decline and has been linked to lipid dysregulation. However, the mechanisms underlying this relationship, particularly the role of plasma lipids at the species level, remain poorly understood. This study investigates whether lipids mediate the relationship between central adiposity and cognition in cognitively unimpaired older adults.

Methods
Ninety-four cognitively normal older adults (n = 94, mean age 69.0 ± 5.0 years, 54% female) were included in this study. Cognitive composite scores were derived from z-standardised neuropsychological assessments, and central adiposity was measured using the waist–hip ratio (WHR). Lipidomic profiling identified 918 lipid species, which were clustered into modules of highly correlated lipids using a Weighted Gene Co-Expression Network Analysis (WGCNA). Modules associated with the WHR and cognition were identified via partial Spearman’s correlation analysis, followed by a mediation analysis.

Results
Of the 39 lipid modules identified, 1 enriched with phosphatidylglycerol (PG) lipids containing an arachidic acid (20:0) sidechain was positively correlated with cognition (ρ = 0.32, FDR p < 0.05) and negatively correlated with the WHR (ρ = −0.43, FDR p < 0.001). Mediation analysis revealed that this arachidic acid-carrying PG lipid-enriched module mediated the WHR–cognition relationship, with individual species PG (20:0_16:1), PG (20:0_18:1), and PG (20:0_18:2) also contributing individually. Conclusions: Arachidic acid-carrying PG lipids statistically mediate the WHR–cognition relationship in cognitively unimpaired older adults. These findings suggest that adiposity-related lipid pathways are detectable in cognitively unimpaired older adults and may represent targets for early intervention to preserve cognitive health.

Background
Mental health issues among young university students have increased in recent years, driven by academic stress and sedentary lifestyles. The YoungFitT Project aims to explore well-being strategies and the psychobiological mechanisms behind their effects on university students. The project includes two studies: the first evaluates the effectiveness of High-Intensity Functional Training (HIFT), Mindfulness-Based Stress Reduction (MBSR), and Qigong (QG) on psychological well-being and cognitive functions, and also explores whether socio-demographic, mental (mindful thinking, sleep quality), physical (physical fitness, physical activity), physiological (heart rate variability), and biological (microbiota) factors mediate or moderate intervention effects on university students. Given that immersive virtual reality (VR) can enhance adherence and provide additional benefits, the second study will explore the feasibility and efficacy of HIFT-VR, MBSR-VR, and QG-VR on university students’ psychological well-being and cognitive functions.

Methods
Two mixed-methods randomized controlled trials will be conducted. In Study 1, participants will be randomly assigned to one of three groups (HIFT, MBSR, QG) using a 1:1:1 ratio. Psychological, cognitive, physical, physiological, and biological measures will be evaluated two weeks before and after the interventions. The interventions include three weekly sessions for 12 weeks. Subsequently, a follow-up will be conducted 12 weeks after the intervention to assess psychological well-being. Study 2 is a proof-of-concept study in which VR interventions will be co-designed with input from university students and professionals. Twelve participants from each study will also complete semi-structured interviews to explore their experiences and perceived impact.

Discussion
The proposed interventions are expected to produce differential effects on psychological well-being and cognitive function. VR environments may enhance adherence and offer added benefits over conventional training. Findings will inform effective, personalized strategies for the mental and physical health of university youth.

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
Dietary nitrate, as a nitric oxide (NO) precursor, may support brain health and protect against dementia.

Objective
Our primary aim was to investigate whether dietary nitrate is associated with neuroimaging markers of brain health linked with Alzheimer's disease (AD).

Participants
Study participants were cognitively unimpaired individuals from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) who had β-amyloid positron emission tomography (PET) scans (n = 554) and magnetic resonance imaging (MRI) scans (n = 335) and had completed a Food Frequency Questionnaire at baseline.

Methods
Source-specific nitrate intakes were estimated using comprehensive nitrate food composition databases. Rates of cerebral β-amyloid (Aβ) deposition, measured using PET, and rates of brain atrophy, measured using MRI, were assessed between baseline and 126-months follow-up, at intervals of 18 months. Multivariable-adjusted linear mixed effect models were used to examine associations between baseline source-specific nitrate intake and rates of (i) cerebral Aβ deposition and (ii) brain atrophy, over the 126 months of follow-up. Analyses were carried out following stratification of the sample by established dementia Alzheimer's disease (AD) risk factors including sex and presence or absence of the apolipoprotein E (APOE) ε4 allele.

Results
In women carriers of the APOE ε4 allele, higher plant sourced nitrate intake (median intake 121 mg/day), was associated with a slower rate of cerebral Aβ deposition [β: 4.47 versus 8.99 Centiloid (CL) /18 months, p < 0.05] and right hippocampal atrophy [-0.01 versus -0.03 mm3 /18 months, p < 0.01], after multivariable adjustments. Moderate intake showed protective associations in men carriers and in both men and women non-carriers of APOE ε4.

Conclusions
Associations were observed between plant-derived nitrate intake and cerebral Aβ deposition, particularly in high-risk populations (women and APOE ε4 carriers). Associations were also observed for brain volume atrophy, however these exhibited subgroup variability without clear patterns relative to sex and APOE ε4 allele carriage. These findings suggest a potential link between plant-sourced nitrate and AD related neuroimaging markers of brain health improved brain health, but further validation in larger studies is required.