@article {6135, title = {Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment.}, journal = {Neuroimage Clin}, volume = {1}, year = {2012}, month = {2012}, pages = {179-87}, abstract = {

A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy. As homocysteine promotes brain atrophy, we set out to discover whether people carrying the C677T MTHFR polymorphism which increases homocysteine, might also show systematic differences in brain structure. Using tensor-based morphometry, we tested this association in 359 elderly Caucasian subjects with mild cognitive impairment (MCI) (mean age: 75~{\textpm}~7.1~years) scanned with brain MRI and genotyped as part of Alzheimer{\textquoteright}s Disease Neuroimaging Initiative. We carried out a replication study in an independent, non-overlapping sample of 51 elderly Caucasian subjects with MCI (mean age: 76~{\textpm}~5.5~years), scanned with brain MRI and genotyped for MTHFR, as part of the Cardiovascular Health Study. At each voxel in the brain, we tested to see where regional volume differences were associated with carrying one or more MTHFR {\textquoteright}T{\textquoteright} alleles. In ADNI subjects, carriers of the MTHFR risk allele had detectable brain volume deficits, in the white matter, of up to 2-8\% per risk T allele locally at baseline and showed accelerated brain atrophy of 0.5-1.5\% per T allele at 1~year follow-up, after adjusting for age and sex. We replicated these brain volume deficits of up to 5-12\% per MTHFR T allele in the independent cohort of CHS subjects. As expected, the associations weakened after controlling for homocysteine levels, which the risk gene affects. The MTHFR risk variant may thus promote brain atrophy by elevating homocysteine levels. This study aims to investigate the spatially detailed effects of this MTHFR polymorphism on brain structure in 3D, pointing to a causal pathway that may promote homocysteine-mediated brain atrophy in elderly people with MCI.

}, issn = {2213-1582}, doi = {10.1016/j.nicl.2012.09.012}, author = {Rajagopalan, Priya and Jahanshad, Neda and Stein, Jason L and Hua, Xue and Madsen, Sarah K and Kohannim, Omid and Hibar, Derrek P and Toga, Arthur W and Jack, Clifford R and Saykin, Andrew J and Green, Robert C and Weiner, Michael W and Bis, Joshua C and Kuller, Lewis H and Riverol, Mario and Becker, James T and Lopez, Oscar L and Thompson, Paul M} } @article {6592, title = {Regular fish consumption and age-related brain gray matter loss.}, journal = {Am J Prev Med}, volume = {47}, year = {2014}, month = {2014 Oct}, pages = {444-51}, abstract = {

BACKGROUND: Brain health may be affected by modifiable lifestyle factors; consuming fish and antioxidative omega-3 fatty acids may reduce brain structural abnormality risk.

PURPOSE: To determine whether dietary fish consumption is related to brain structural integrity among cognitively normal elders.

METHODS: Data were analyzed from 260 cognitively normal individuals from the Cardiovascular Health Study with information on fish consumption from the National Cancer Institute Food Frequency Questionnaire and brain magnetic resonance imaging (MRI). The relationship between fish consumption data collected in 1989-1990 and brain structural MRI obtained in 1998-1999 was assessed using voxel-based morphometry in multiple regression analyses in 2012. Covariates were age, gender, race, education, white matter lesions, MRI-identified infarcts, waist-hip ratio, and physical activity as assessed by the number of city blocks walked in 1 week. Volumetric changes were further modeled with omega-3 fatty acid estimates to better understand the mechanistic link between fish consumption, brain health, and Alzheimer disease.

RESULTS: Weekly consumption of baked or broiled fish was positively associated with gray matter volumes in the hippocampus, precuneus, posterior cingulate, and orbital frontal cortex even after adjusting for covariates. These results did not change when including omega-3 fatty acid estimates in the analysis.

CONCLUSIONS: Dietary consumption of baked or broiled fish is related to larger gray matter volumes independent of omega-3 fatty acid content. These findings suggest that a confluence of lifestyle factors influence brain health, adding to the growing body of evidence that prevention strategies for late-life brain health need to begin decades earlier.

}, keywords = {Aged, Aged, 80 and over, Animals, Brain, Cross-Sectional Studies, Diet, Fatty Acids, Omega-3, Female, Fishes, Gray Matter, Humans, Life Style, Magnetic Resonance Imaging, Male, Regression Analysis, Surveys and Questionnaires}, issn = {1873-2607}, doi = {10.1016/j.amepre.2014.05.037}, author = {Raji, Cyrus A and Erickson, Kirk I and Lopez, Oscar L and Kuller, Lewis H and Gach, H Michael and Thompson, Paul M and Riverol, Mario and Becker, James T} } @article {6593, title = {Relationship between Systemic and Cerebral Vascular Disease and Brain Structure Integrity in Normal Elderly Individuals.}, journal = {J Alzheimers Dis}, volume = {44}, year = {2015}, month = {2015}, pages = {319-28}, abstract = {

Cerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Brain, Cerebrovascular Disorders, Female, Humans, Image Processing, Computer-Assisted, Logistic Models, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Peripheral Vascular Diseases, Predictive Value of Tests, Retrospective Studies, White Matter}, issn = {1875-8908}, doi = {10.3233/JAD-141077}, author = {Riverol, Mario and Becker, James T and Lopez, Oscar L and Raji, Cyrus A and Thompson, Paul M and Carmichael, Owen T and Gach, H Michael and Longstreth, William T and Fried, Linda and Tracy, Russell P and Kuller, Lewis H} }