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Aim: To examine the associations between visceral adipose tissue (VAT) and brain structural measures at midlife and explore how these associations may be affected by age, sex and cardiometabolic factors., Methods: We used abdominal and brain magnetic resonance imaging data from a population-based cohort of people at midlife in the UK Biobank. Regression modelling was applied to study associations of VAT volume with total brain volume (TBV), grey matter volume (GMV), white matter volume, white matter hyperintensity volume (WMHV) and total hippocampal volume (THV), and whether these associations were altered by age, sex or cardiometabolic factors., Results: Complete data were available for 17 377 participants (mean age 63 years, standard deviation = 12, 53% female). Greater VAT was associated with lower TBV, GMV and THV (P < .001). We found an interaction between VAT and sex on TBV (P < .001), such that the negative association of VAT with TBV was greater in men (β = -2.89, 95% confidence interval [CI] -2.32 to -10.15) than in women (β = -1.32, 95% CI -0.49 to -3.14), with similar findings for GMV. We also found an interaction between VAT and age (but not sex) on WMHV (P < .001). The addition of other cardiometabolic factors or measures of physical activity resulted in little change to the models., Conclusions: VAT volume is associated with poorer brain health in midlife and this relationship is greatest in men and those at younger ages., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Type 2 diabetes mellitus (T2DM) is associated with brain atrophy, but the mechanisms underlying this link are unknown. Advanced glycation end products (AGEs) accumulate in T2DM, resulting in inflammation, oxidative stress, and protein cross-linking, which are known contributors to neurodegeneration. We aimed to study whether tissue AGE accumulation is associated with T2DM-related brain atrophy. We performed brain magnetic resonance imaging, cognitive tests, and noninvasive skin autofluorescence (SAF; a measure of tissue AGE levels) on people aged >55 years with and without T2DM. Multivariable linear regression was used to study the relationships among T2DM, SAF, and gray matter volume (GMV). There were 486 people included in the study. T2DM was associated with greater SAF. Greater SAF, T2DM, and cognitive impairment were each associated with lower GMV independently of age, sex, and total intracranial volume. SAF partially mediated the association between T2DM and GMV. Longitudinal studies may help confirm whether tissue AGE accumulation is associated with brain atrophy in T2DM., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

ObjectiveTo study longitudinal relationships between type 2 diabetes mellitus (T2DM), cortical thickness, and cognitive function in older people with normal cognition, mild cognitive impairment, and Alzheimer disease (AD).MethodsThe sample was derived from the Alzheimer's Disease Neuroimaging Initiative cohort who underwent brain MRI and cognitive tests annually for 5 years. Presence of T2DM was based on fasting blood glucose ≥7.0mml/L or the use of glucose-lowering agents. We used latent growth curve modeling to explore longitudinal relationships between T2DM, cortical thickness, and cognitive function, adjusting for relevant covariates and testing for interactions.ResultsThere were 124 people with T2DM (mean age 75.5 years, SD 6.2) and 693 without T2DM (mean age 75.1 years, SD 6.9) with at least 1 MRI available. AD and lower cortical thickness at study entry was associated with a lower chance of having a MRI available at each follow-up phase (all p < 0.001). T2DM was associated with lower baseline cortical thickness (p = 0.01). We found no direct effect of T2DM on decline in cortical thickness or cognitive function, but there was an indirect pathway linking T2DM and cognitive decline via baseline cortical thickness (β = -0.17, p = 0.022). There was an interaction between T2DM and education whereby the negative effect of T2DM on baseline cortical thickness was reduced in those with greater education (β = 0.34, p = 0.037). These associations changed minimally when adjusted for baseline cognitive diagnosis.ConclusionsIn an older cohort with low cerebrovascular disease burden, T2DM contributes to cognitive decline via neurodegeneration. Prior brain and cognitive reserve may protect against this effect.

Background and purposeWhite matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.MethodsHeritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies.ResultsA total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (P

Background: Physical inactivity is a risk factor for type 2 diabetes (T2D) and dementia. However, it is unknown if physical activity (PA) intensity is associated with brain health in people with T2D. Therefore, this study aimed to determine (i) associations between PA intensity and step count with both cognition and brain structure and (ii) if apolipoprotein E-ε4 or insulin therapy modifies any associations.Methods: Participants were people with T2D (n = 220; aged 55-86 years). An accelerometer worn over the right hip was used to obtain step count and moderate-to-vigorous PA (MVPA) averaged over 7 days. Cognition in 7 domains was obtained using a battery of neuropsychological tests. Brain structure was measured by Magnetic Resonance Imaging. Linear regression models were used to examine associations between step count, MVPA and each cognitive and Magnetic Resonance Imaging measure. Apolipoprotein E-ε4 × PA and insulin therapy × PA product terms were added to the models to examine effect modification.Results: The mean age of participants was 67.9 (SD = 6.3). Higher step count was associated with greater hippocampal volume (β = 0.028, 95% CI = 0.005, 0.051). Insulin therapy modified the association between MVPA and attention-processing speed, such that associations were significant in people receiving insulin therapy (p for interaction = .019). There were no other significant associations.Conclusions: Higher step count and greater time spent in MVPA may be associated with better hippocampal volume and attention-processing speed, respectively, in people with T2D. People with greater diabetes severity (receiving insulin therapy) may get more cognitive benefit from MVPA. [ABSTRACT FROM AUTHOR]

Background: The contribution of cerebral small vessel disease (cSVD) to the pathogenesis of frailty remains uncertain. We aimed to examine the associations between cSVD with progression of frailty in a population-based study of older people.Methods: People aged between 60 and 85 years were randomly selected form the electoral roll to participate in the Tasmanian Study of Cognition and Gait. Participants underwent self-reported questionnaires, objective gait, cognitive and sensorimotor testing over three phases ranging between 2005 and 2012. These data were used to calculate a 41-item frailty index (FI) at three time points. Baseline brain magnetic resonance imaging was performed on all participants to measure cSVD. Generalized mixed models were used to examine associations between baseline cSVD and progression of frailty, adjusted for confounders of age, sex, level of education, and total intracranial volume.Results: At baseline (n = 388) mean age was 72 years (SD = 7.0), 44% were female, and the median FI score was 0.20 (interquartile range [IQR] 0.12, 0.27). In fully adjusted models higher burden of baseline white matter hyperintensity (WMH) was associated with frailty progression over 4.4 years (β = 0.03, 95% CI: 0.01, 0.05; p = .004) independent of other SVD markers. Neither baseline infarcts (p = .23), nor microbleeds at baseline (p = .65) were associated with progression of frailty.Conclusions: We provide evidence for an association between baseline WMHs and progression of frailty. Our findings add to a growing body of literature suggesting WMH is a marker for frailty. [ABSTRACT FROM AUTHOR]

Background: Frailty is a prevalent geriatric condition associated with poor health outcomes. The pathogenesis of frailty is incompletely understood. We aimed to evaluate the relationship between cerebral small vessel disease (SVD) and frailty.Methods: People aged between 60 and 85 years were randomly selected from the electoral roll into the Tasmanian Study of Cognition and Gait. Participants completed standardized questionnaires regarding medical history and underwent objective sensorimotor, gait, and cognitive testing. These data were used to calculate a frailty index score. Magnetic resonance imaging was performed on all participants to measure SVD. Automated quantification was used to measure white matter hyperintensities (WMH), with manual consensus for subcortical infarction (SI) and cerebral microbleeds (CMB). Multivariable linear regression was used to determine the association between SVD and frailty.Results: The mean age of the sample (n = 388) was 72.0 years (SD 7.0), 44% (172/388) were female and the median Frailty Index was 0.20 (interquartile range 0.12, 0.27). WMH, SI, and CMB in unadjusted models were positively associated with higher frailty scores (p < .05). In final models including all brain variables, higher burden of WMH (β = 2.16; 95% confidence interval [CI] 0.75, 3.57; p = .003), but not SI (β = 2.96; 95% CI -0.44, 6.35; p = .09) or CMB (β = -0.46; 95% CI -4.88, 3.96; p = .84), was independently associated with a higher frailty score.Conclusions: We provide cross-sectional evidence for a positive association between larger burden of WMH and frailty. Longitudinal design is required to determine the temporality of this relationship. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease is difficult to directly visualize in vivo. Therefore, we rely on radiological phenotypes as surrogate markers of disease. The principal phenotypes of clinical interest are small, deep brain infarcts, cerebral white matter lesions, deep brain haemorrhages, and cerebral microbleeds. The causes or mechanisms underlying these phenotypes are understood in varying degrees of detail. This review aims to summarize recent knowledge regarding these phenotypes and place it in context with classical clinicopathological observations to provide mechanistic, clinical, and therapeutic insights into small vessel disease. [ABSTRACT FROM AUTHOR]

An inflammatory diet is related to poorer cognition, but the underlying brain pathways are unknown. The aim of this study was to examine associations between the Energy-Adjusted Dietary Inflammatory Index (E-DII) and brain volume, small vessel disease, and cognition in people with and without type 2 diabetes mellitus (T2DM). This is a secondary cross-sectional analysis of data from the Cognition and Diabetes in Older Tasmanians study. This study included 641 participants (n = 326 with T2DM) enrolled between 2005 and 2011 from Tasmania, Australia. The E-DII was computed from the 80-item Dietary Questionnaire for Epidemiological Studies, version 2. Brain volumes (gray matter, white matter, and white matter hyperintensities), infarcts, and microbleeds were obtained from magnetic resonance imaging. Global cognition was derived from a comprehensive battery of neuropsychological tests. Logistic and linear regressions were performed to examine associations between E-DII and brain measures and a global cognitive score, adjusting for demographics, energy, T2DM, mood, ambulatory activity, and cardiovascular risk factors. An E-DII × T2DM interaction term was tested in each model. The mean (standard deviation) age of participants was 69.8 (7.4) years. There were no associations between the E-DII and any of the brain structural measures or global cognitive function in fully adjusted models. There was a modification effect for T2DM on the association between E-DII and gray matter volume (T2DM: β = 1.38, 95% CI –3.03 to 5.79; without T2DM: β = –4.34, 95% CI, –8.52 to –0.16), but not with any of the other outcome measures. In this cross-sectional study, E-DII was not associated with brain structure or global cognition. In 1 of the 7 outcomes, a significant modification effect for T2DM was found for the associations between E-DII and gray matter. Future prospective studies are needed to clarify the associations between diet-related inflammation and brain health. [ABSTRACT FROM AUTHOR]