Association of metabolic syndrome with neuroimaging and cognitive outcomes in the UK Biobank

Objective: Metabolic syndrome (MetS) has been previously linked to dementia. This study examines the association of MetS with neuroimaging and cognition in dementia-free adults, offering insight into the impact of MetS on brain health prior to dementia onset. Research Design and Methods: We included 37,395 dementia-free adults from the UK Biobank. MetS was defined as ≥3 of the following components: elevated waistcircumference, triglycerides, blood-pressure, HbA1c, or reduced HDL-cholesterol. Multivariable-adjusted linear regression was used to assess associations of MetS with structural neuroimaging and cognitive domains. Results: MetS was associated with lower total brain (Standardised Beta-coefficient (β): - 0.06, 95%CI: -0.08, -0.04), grey matter (β: -0.10, 95%CI: -0.12, -0.08) and hippocampal volumes (Left-β: -0.03, 95%CI: -0.05, -0.01; Right-β: -0.04, 95%CI: -0.07, -0.02), and greater white matter hyperintensities (WMH) volume (β: 0.08, 95%CI: 0.06, 0.11). MetS participants performed poorer on cognitive tests of working memory (β: -0.10, 95%CI: -0.13, -0.07), verbal-declarative memory (β: -0.08, 95%CI: -0.11, -0.05), processing speed (β: -0.06, 95%CI: -0.09, -0.04), verbal and numerical reasoning (β: -0.07, 95%CI: -0.09, -0.04), nonverbal reasoning (β: -0.03, 95%CI: -0.05, -0.01), and on executive function, where higher scores indicated poorer performance (β: 0.05, 95%CI: 0.03, 0.08). An increasing number of MetS components were also associated with lower brain volumes, greater WMH, and poorer cognition across all domains. Conclusions: MetS was associated poorer brain health in dementia-free adults, characterised by lower brain volumes, greater vascular pathology, and poorer cognition. Further research is necessary to understand whether reversal or improvement of MetS can improve brain health

Vitamin D and Memory Decline: Two Population-Based Prospective Studies

BACKGROUND: Vitamin D deficiency has been linked with dementia risk, cognitive decline, and executive dysfunction. However, the association with memory remains largely unknown. OBJECTIVE: To investigate whether low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with memory decline. METHODS: We used data on 1,291 participants from the US Cardiovascular Health Study (CHS) and 915 participants from the Dutch Longitudinal Aging Study Amsterdam (LASA) who were dementia-free at baseline, had valid vitamin D measurements, and follow-up memory assessments. The Benton Visual Retention Test (in the CHS) and Rey's Auditory Verbal Learning Test (in the LASA) were used to assess visual and verbal memory, respectively. RESULTS: In the CHS, those moderately and severely deficient in serum 25(OH)D changed -0.03 SD (95% CI: -0.06 to 0.01) and -0.10 SD (95% CI: -0.19 to -0.02) per year respectively in visual memory compared to those sufficient (p = 0.02). In the LASA, moderate and severe deficiency in serum 25(OH)D was associated with a mean change of 0.01 SD (95% CI: -0.01 to 0.02) and -0.01 SD (95% CI: -0.04 to 0.02) per year respectively in verbal memory compared to sufficiency (p = 0.34). CONCLUSIONS: Our findings suggest an association between severe vitamin D deficiency and visual memory decline but no association with verbal memory decline. They warrant further investigation in prospective studies assessing different memory subtypes.National Heart, Lung, and Blood Institute (NHLBI)National Institute of Neurological Disorders and Stroke (NINDS)National Institute on Aging (NIA)Alzheimer’s AssociationMary Kinross Charitable TrustHalpin TrustAge Related Diseases and Health TrustNorman Family Charitable TrustRosetrees TrustJames Tudor FoundationUK National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsul

Vitamin D and cognitive function: A Mendelian randomisation study

The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, pcurvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life

Vitamin D and cognitive function:a Mendelian randomisation study

Abstract The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, pcurvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life