Background: Cumulative exposures to obesity, hypertension, and physical inactivity from midlife (40-65 years) onwards are three known cardiovascular risk factors for dementia and associated cerebral structural damage. Exactly how early in the lifespan sensitive periods for exposure to these risk factors begin is yet to be established, specifically with respect to onset of cerebral structural changes. We aimed to investigate whether cardiovascular risk across childhood and adolescence is already associated with cerebral structure in regions previously linked with dementia, during young adulthood.
View Article and Find Full Text PDFObese adults are often reported to have smaller brain volumes than their non-obese peers. Whether this represents evidence of accelerations in obesity-driven atrophy or is instead a legacy of developmental differences established earlier in the lifespan remains unclear. This study aimed to investigate whether early-life differences in adiposity explain differences in numerous adult brain traits commonly attributed to mid-life obesity.
View Article and Find Full Text PDFThe hypothalamus is part of the hypothalamic-pituitary-adrenal axis which activates stress responses through release of cortisol. It is a small but heterogeneous structure comprising multiple nuclei. In vivo human neuroimaging has rarely succeeded in recording signals from individual hypothalamus nuclei.
View Article and Find Full Text PDFEpidemiological studies suggest lifestyle factors may reduce the risk of dementia. However, few studies have examined the association of diet and waist-to-hip ratio with hippocampus connectivity. In the Whitehall II Imaging Sub-study, we examined longitudinal changes in diet quality in 512 participants and waist-to-hip ratio in 665 participants.
View Article and Find Full Text PDFBiol Psychiatry Cogn Neurosci Neuroimaging
November 2023
Background: Cognitive deficits are often comorbid with mood disorders and can cause significant functional impairment even after resolution of the primary mood symptoms. We do not currently have pharmacological treatments that adequately address these deficits. 5-HT receptor agonists show promise as potential procognitive agents in animal and early human translational studies.
View Article and Find Full Text PDFIntroduction: Stakeholder engagement remains scarce in basic brain research. However, it can greatly improve the relevance of investigations and accelerate the translation of study findings to policy. The Lifebrain consortium investigated risk and protective factors influencing brain health using cognition, lifestyle and imaging data from European cohorts.
View Article and Find Full Text PDFCumulative evidence suggests that impaired cerebrovascular reactivity (CVR), a regulatory response critical for maintaining neuronal health, is amongst the earliest pathological changes in dementia. However, we know little about how CVR is affected by dementia risk, prior to disease onset. Understanding this relationship would improve our knowledge of disease pathways and help inform preventative interventions.
View Article and Find Full Text PDFThe menopause transition involves changes in oestrogens and adipose tissue distribution, which may influence female brain health post-menopause. Although increased central fat accumulation is linked to risk of cardiometabolic diseases, adipose tissue also serves as the primary biosynthesis site of oestrogens post-menopause. It is unclear whether different types of adipose tissue play diverging roles in female brain health post-menopause, and whether this depends on lifetime oestrogen exposure, which can have lasting effects on the brain and body even after menopause.
View Article and Find Full Text PDFVascular smooth muscle cells (VSMCs) are the key moderators of cerebrovascular dynamics in response to the brain's oxygen and nutrient demands. Crucially, VSMCs may provide a sensitive biomarker for neurodegenerative pathologies where vasculature is compromised. An increasing body of research suggests that VSMCs have remarkable plasticity and their pathophysiology may play a key role in the complex process of neurodegeneration.
View Article and Find Full Text PDFIt is well documented that some brain regions, such as association cortices, caudate, and hippocampus, are particularly prone to age-related atrophy, but it has been hypothesized that there are individual differences in atrophy profiles. Here, we document heterogeneity in regional-atrophy patterns using latent-profile analysis of 1,482 longitudinal magnetic resonance imaging observations. The results supported a 2-group solution reflecting differences in atrophy rates in cortical regions and hippocampus along with comparable caudate atrophy.
View Article and Find Full Text PDFThe sources of inter- and intra-individual variability in age-related cognitive decline remain poorly understood. We examined the association between 20-year trajectories of cognitive decline and multimodal brain structure and morphology in older age. We used the Whitehall II Study, an extensively characterised cohort with 3T brain magnetic resonance images acquired at older age (mean age = 69.
View Article and Find Full Text PDFCardiometabolic risk (CMR) factors are associated with accelerated brain aging and increased risk for sex-dimorphic illnesses such as Alzheimer's disease (AD). Yet, it is unknown how CMRs interact with sex and apolipoprotein E-ϵ4 (APOE4), a known genetic risk factor for AD, to influence brain age across different life stages. Using age prediction based on multi-shell diffusion-weighted imaging data in 21,308 UK Biobank participants, we investigated whether associations between white matter Brain Age Gap (BAG) and body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage (BF%), and APOE4 status varied (i) between males and females, (ii) according to age at menopause in females, and (iii) across different age groups in males and females.
View Article and Find Full Text PDFThis study aimed to evaluate whether engagement in leisure activities is linked to measures of brain structure, functional connectivity, and cognition in early old age. We examined data collected from 7,152 participants of the United Kingdom Biobank (UK Biobank) study. Weekly participation in six leisure activities was assessed twice and a cognitive battery and 3T MRI brain scan were administered at the second visit.
View Article and Find Full Text PDFis a widely used index for quantifying individuals' brain health as deviation from a normative brain aging trajectory. Higher-than-expected is thought partially to reflect above-average rate of brain aging. Here, we explicitly tested this assumption in two independent large test datasets (UK Biobank [main] and Lifebrain [replication]; longitudinal observations ≈ 2750 and 4200) by assessing the relationship between cross-sectional and longitudinal estimates of models were estimated in two different training datasets (n ≈ 38,000 [main] and 1800 individuals [replication]) based on brain structural features.
View Article and Find Full Text PDFWe characterize the associations of total cerebral small vessel disease (SVD) burden with brain structure, trajectories of vascular risk factors, and cognitive functions in mid-to-late life. Participants were 623 community-dwelling adults from the Whitehall II Imaging Sub-study with multi-modal MRI (mean age 69.96, SD = 5.
View Article and Find Full Text PDFHigher socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. We ask whether relationships between SES, brain volumes and cognitive ability differ across cohorts, by age and national origin. European and US cohorts covering the lifespan were studied (4-97 years, N = 500 000; 54 000 w/brain imaging).
View Article and Find Full Text PDFLarge scale neuroimaging datasets present the possibility of providing normative distributions for a wide variety of neuroimaging markers, which would vastly improve the clinical utility of these measures. However, a major challenge is our current poor ability to integrate measures across different large-scale datasets, due to inconsistencies in imaging and non-imaging measures across the different protocols and populations. Here we explore the harmonisation of white matter hyperintensity (WMH) measures across two major studies of healthy elderly populations, the Whitehall II imaging sub-study and the UK Biobank.
View Article and Find Full Text PDFThe high prevalence of unhealthy dietary patterns and related brain disorders, such as dementia, emphasizes the importance of research that examines the effect of dietary factors on brain health. Identifying markers of brain health, such as volume and connectivity, that relate to diet is an important first step towards understanding the lifestyle determinants of healthy brain ageing. We conducted a systematic review of 52 studies (total n = 21,221 healthy participants aged 26-80 years, 55 % female) that assessed with a range of MRI measurements, which brain areas, connections, and cerebrovascular factors were associated with dietary markers.
View Article and Find Full Text PDFAims: Existing evidence suggests links between brain and cardiovascular health. We investigated associations between cognitive performance and cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank, considering a range of potential confounders.
Methods And Results: We studied 29 763 participants with CMR and cognitive testing, specifically, fluid intelligence (FI, 13 verbal-numeric reasoning questions), and reaction time (RT, a timed pairs matching exercise); both were considered continuous variables for modelling.
Background: It is well-established that what is good for the heart is good for the brain. Vascular factors such as hypertension, diabetes, and high cholesterol, and genetic factors such as the apolipoprotein E4 allele increase the risk of developing both cardiovascular disease and dementia. However, the mechanisms underlying the heart-brain association remain unclear.
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