Search

BACKGROUND: Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity. METHODS AND RESULTS: Cross-sectional data from The Maastricht Study, a Dutch population-based cohort (n=4326; age, 59.4±8.6 years; 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers, composite scores of flicker light-induced retinal arteriolar and venular dilation, and plasma biomarkers of endothelial dysfunction (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor). White matter connectivity was calculated from 3T diffusion magnetic resonance imaging to quantify the number (average node degree) and organization (characteristic path length, global efficiency, clustering coefficient, and local efficiency) of white matter connections. A higher plasma biomarkers of endothelial dysfunction composite score was associated with a longer characteristic path length (β per SD, 0.066 [95% CI, 0.017-0.114]) after adjustment for sociodemographic, lifestyle, and cardiovascular factors but not with any of the other white matter connectivity measures. After multiple comparison correction, this association was nonsignificant. None of the other microvascular function measures were associated with any of the connectivity measures. CONCLUSIONS: These findings suggest that microvascular dysfunction as measured by indirect markers is not associated with whole-brain white matter connectivity.

Type 2 diabetes (T2DM) is associated with increased risk for cardiovascular disease (CVD). Whether screen-detected T2DM, based on fasting plasma glucose (FPG) or on HbA1c, are associated with different risks of incident CVD in high-risk populations and which one is preferable for diabetes screening in these populations, remains unclear. A total of 8,274 high-risk CVD participants were included from the UCC-SMART cohort. Participants were divided into groups based on prior T2DM diagnosis, and combinations of elevated/non-elevated FPG and HbA1c (cut-offs at 7 mmol/L and 48 mmol/mol, respectively): Group 0: known T2DM; group 1: elevated FPG/HbA1c; group 2: elevated FPG, non-elevated HbA1c; group 3: non-elevated FPG, elevated HbA1c; group 1 + 2: elevated FPG, regardless of HbA1c; group 1 + 3: elevated HbA1c, regardless of FPG; and group 4 (reference), non-elevated FPG/HbA1c. During a median follow-up of 6.3 years (IQR 3.3–9.8), 712 cardiovascular events occurred. Compared to the reference (group 4), group 0 was at increased risk (HR 1.40; 95 % CI 1.16–1.68), but group 1 (HR 1.16; 95 % CI 0.62–2.18), 2 (HR 1.18; 95 % CI 0.84–1.67), 3 (HR 0.61; 95 % CI 0.15–2.44), 1 + 2 (HR 1.17; 95 % CI 0.86–1.59) and 1 + 3 (HR 1.01; 95 % CI 0.57–1.79) were not. However, spline interpolation showed a linearly increasing risk with increasing HbA1c/FPG, but did not allow for identification of other cut-off points. Based on current cut-offs, FPG and HbA1c at screening were equally related to incident CVD in high-risk populations without known T2DM. Hence, neither FPG, nor HbA1c, is preferential for diabetes screening in this population with respect to risk of incident CVD. [ABSTRACT FROM AUTHOR]

Aims: To develop and externally validate the LIFE‐T1D model for the estimation of lifetime and 10‐year risk of cardiovascular disease (CVD) in individuals with type 1 diabetes. Materials and Methods: A sex‐specific competing risk‐adjusted Cox proportional hazards model was derived in individuals with type 1 diabetes without prior CVD from the Swedish National Diabetes Register (NDR), using age as the time axis. Predictors included age at diabetes onset, smoking status, body mass index, systolic blood pressure, glycated haemoglobin level, estimated glomerular filtration rate, non‐high‐density lipoprotein cholesterol, albuminuria and retinopathy. The model was externally validated in the Danish Funen Diabetes Database (FDDB) and the UK Biobank. Results: During a median follow‐up of 11.8 years (interquartile interval 6.1–17.1 years), 4608 CVD events and 1316 non‐CVD deaths were observed in the NDR (n = 39 756). The internal validation c‐statistic was 0.85 (95% confidence interval [CI] 0.84–0.85) and the external validation c‐statistics were 0.77 (95% CI 0.74–0.81) for the FDDB (n = 2709) and 0.73 (95% CI 0.70–0.77) for the UK Biobank (n = 1022). Predicted risks were consistent with the observed incidence in the derivation and both validation cohorts. Conclusions: The LIFE‐T1D model can estimate lifetime risk of CVD and CVD‐free life expectancy in individuals with type 1 diabetes without previous CVD. This model can facilitate individualized CVD prevention among individuals with type 1 diabetes. Validation in additional cohorts will improve future clinical implementation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We first examined the role of age at cardiovascular disease (CVD) onset for incident dementia, and then examined whether lifestyle factors at guideline‐recommended levels in individuals with CVD mitigates dementia risk. METHODS: We used population‐based data (Whitehall II: n = 10,308/baseline 1985–1988/examinations every 4–5 years). Lifestyle factors (non‐smoking, body mass index [BMI], physical activity, diet) were extracted post‐CVD. RESULTS: Over a median of 31.6 years, 3275 (32.1%) developed CVD. At age 70, risk of dementia was higher in individuals with CVD onset before (hazard ratio [HR] of incident dementia for participants with CVD before age 60, using participants without CVD at age 70 as the reference: 1.56, 95% confidence interal [CI] 1.18–2.08) but not after 60 years. In participants with CVD, a greater number of lifestyle factors at recommended levels post‐CVD was associated with a lower dementia risk (per lifestyle factor at recommended level HR: 0.73, 95% CI 0.59–0.92). DISCUSSION: Our results suggest that early onset CVD is associated with a higher dementia risk at older ages. In those with CVD, the dementia risk was lower if lifestyle factors are at recommended levels following CVD diagnosis. Highlights: CVD in midlife but not in late life is associated with a higher risk of dementia.Dementia risk in CVD patients is lower if their lifestyle factors are at recommended levels.These findings provide evidence to promote CVD prevention in midlife or earlier.Study findings also show the importance of a healthy lifestyle in those with CVD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The retina may provide non‐invasive, scalable biomarkers for monitoring cerebral neurodegeneration. METHODS: We used cross‐sectional data from The Maastricht study (n = 3436; mean age 59.3 years; 48% men; and 21% with type 2 diabetes [the latter oversampled by design]). We evaluated associations of retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses with cognitive performance and magnetic resonance imaging indices (global grey and white matter volume, hippocampal volume, whole brain node degree, global efficiency, clustering coefficient, and local efficiency). RESULTS: After adjustment, lower thicknesses of most inner retinal layers were significantly associated with worse cognitive performance, lower grey and white matter volume, lower hippocampal volume, and worse brain white matter network structure assessed from lower whole brain node degree, lower global efficiency, higher clustering coefficient, and higher local efficiency. DISCUSSION: The retina may provide biomarkers that are informative of cerebral neurodegenerative changes in the pathobiology of dementia. [ABSTRACT FROM AUTHOR]