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Associations of Serum Magnesium with Brain Morphology and Subclinical Cerebrovascular Disease: The Atherosclerosis Risk in Communities-Neurocognitive Study.

ABSTRACT: Circulating magnesium has been associated with a lower risk of dementia, but the physiologic effects by which magnesium may prevent neurological insults remain unclear. We studied 1466 individuals (mean age 76.2 ± 5.3, 28.8% black, 60.1% female) free of prevalent stroke, with measured serum magnesium and with available MRI scans obtained in 2011-2013, participating in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Cross-sectional differences in frontal, temporal, parietal, and occipital lobe volume, along with deep grey matter, total brain, and white matter hyperintensity volume across serum magnesium (categorized into quintiles and per standard deviation increases) were assessed using multiple linear regression. We also examined associations of magnesium with the prevalence of cortical, subcortical, and lacunar infarcts using multiple logistic regression. After adjusting for demographics, biomarkers, medications, and cardiometabolic risk factors, higher circulating magnesium was associated with greater total brain volume and frontal, temporal, and parietal lobe volumes (volumes 0.14 to 0.19 standard deviations higher comparing Q5 to Q1). Elevated magnesium was also associated with lower odds of subcortical infarcts (OR (95%CI): 0.44 (0.25, 0.77) comparing Q5 to Q1) and lacunar infarcts (OR (95%CI): 0.40 (0.22, 0.71) comparing Q5 to Q1). Elevated serum magnesium was cross-sectionally associated with greater brain volumes and lower odds of subclinical cerebrovascular disease, suggesting beneficial effects on pathways related to neurodegeneration and cerebrovascular damage. Further exploration through prospective analyses is needed to assess increasing circulating magnesium as a potential neuroprotective intervention.

SUBMITTER: Alam AB

PROVIDER: S-EPMC8703422 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo examine the associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA1c and diabetes duration) with brain volumes and vascular pathology on brain MRI and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology.Research design and methodsCross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011-2013. Participants were categorized by diabetes-HbA1c status as without diabetes (<5.7% [reference]), with prediabetes (5.7 to <6.5%), and with diabetes ([defined as prior diagnosis or HbA1c ?6.5%] <7.0% vs. ?7.0%), with further stratification by diabetes duration (<10 vs. ?10 years).ResultsIn adjusted analyses, compared with participants without diabetes and HbA1c <5.7%, participants with prediabetes and those with diabetes and HbA1c <7.0% did not have significantly different brain volumes or vascular pathology (all P > 0.05), but those with diabetes and HbA1c ?7.0% had smaller total brain volume (? -0.20 SDs, 95% CI -0.31, -0.09), smaller regional brain volumes (including frontal, temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus [all P < 0.05]), and increased burden of white matter hyperintensities (WMH) (P = 0.016). Among participants with diabetes, those with HbA1c ?7.0% had smaller total and regional brain volumes and an increased burden of WMH (all P < 0.05) compared with those with HbA1c <7.0%. Similarly, participants with longer duration of diabetes (?10 years) had smaller brain volumes and higher burden of lacunes (all P < 0.05) than those with a diabetes duration <10 years. We found no evidence for mediation by WMH in associations of diabetes with smaller brain volumes by structural equation models (all P > 0.05).ConclusionsMore-severe diabetes (defined by higher HbA1c and longer disease duration) but not prediabetes or less-severe diabetes was associated with smaller brain volumes and an increased burden of brain vascular pathology. No evidence was found that associations of diabetes with smaller brain volumes are mediated by brain vascular pathology, suggesting that other mechanisms may be responsible for these associations.

Project description:IMPORTANCE:Vitamin D deficiency has been associated with hypertension, diabetes mellitus, and incident stroke. Little is known about the association between vitamin D and subclinical cerebrovascular disease. OBJECTIVE:To examine the relationship of 25-hydroxyvitamin D (25[OH]D) levels with cerebrovascular abnormalities as assessed on brain magnetic resonance imaging (MRI) among participants of the Atherosclerosis Risk in Communities (ARIC) Brain MRI study. DESIGN, SETTING, AND PARTICIPANTS:Participants were white and black adults aged 55 to 72 years with no history of clinical stroke who underwent a cerebral MRI at ARIC visit 3 (n?=?1622) and a second cerebral MRI approximately 10 years later (n?=?888). EXPOSURES:The 25(OH)D level was measured by mass spectrometry at visit 3, with levels adjusted for calendar month and categorized using race-specific quartiles. MAIN OUTCOMES AND MEASURES:The cross-sectional and prospective associations of 25(OH)D levels with white matter hyperintensities (WMHs) and MRI-defined infarcts were investigated using multivariable regression models. RESULTS:The mean age of the participants was 62 years, 59.6% were women, and 48.6% were black. Lower 25(OH)D levels were not significantly associated with WMH score of severity, prevalent high-grade WMH score (?3), or prevalent infarcts in cross-sectional, multivariable-adjusted models (all P?>?.05). Similarly, no significant prospective associations were found for lower 25(OH)D levels with change in WMH volume, incident high WMH score (?3), or incident infarcts on the follow-up MRI, which occurred approximately 10 years later. CONCLUSIONS AND RELEVANCE:A single measure of 25(OH)D was not cross-sectionally associated with WMH grade or prevalent subclinical infarcts and was not prospectively associated with WMH progression or subclinical brain infarcts seen on serial cerebral MRIs obtained approximately 10 years apart. These findings do not support optimizing vitamin D levels for brain health.

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Associations of Serum Magnesium with Brain Morphology and Subclinical Cerebrovascular Disease: The Atherosclerosis Risk in Communities-Neurocognitive Study.

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