@article {660, title = {Alcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study.}, journal = {Stroke}, volume = {32}, year = {2001}, month = {2001 Sep}, pages = {1939-46}, abstract = {

BACKGROUND AND PURPOSE: Subclinical findings on MRI of the brain are associated with poorer cognitive and neurological function among older adults. We sought to determine how alcohol consumption is related to these findings.

METHODS: As part of the Cardiovascular Health Study, 3660 adults aged 65 years and older underwent MRI of the brain from 1992 to 1994. We excluded 284 participants with a confirmed history of cerebrovascular disease. We assessed self-reported intake of beer, wine, and liquor at the annual clinic visit closest to the date of the MRI and grouped participants into 6 categories: abstainers, former drinkers, <1 drink weekly, 1 to <7 drinks weekly, 7 to <15 drinks weekly, and >/=15 drinks weekly. Neuroradiologists assessed white matter grade, infarcts, ventricular size, and sulcal size in a standardized and blinded manner. We used multivariate regression to control for sociodemographic and clinical characteristics.

RESULTS: We found a U-shaped relationship between alcohol consumption and white matter abnormalities. Compared with abstainers, individuals consuming 1 to <7 drinks had an OR of 0.68, and those consuming >/=15 drinks weekly had an OR of 0.95 (p for quadratic term=0.01). Heavier alcohol consumption was associated with a lower prevalence of infarcts (OR for >/=15 drinks weekly relative to abstainers 0.59; P for trend=0.004), but larger ventricular size (OR for >/=15 drinks weekly relative to abstainers 1.32; P for trend=0.006) and sulcal size (OR for >/=15 drinks weekly relative to abstainers 1.53; P for trend=0.007).

CONCLUSIONS: Moderate alcohol consumption is associated with a lower prevalence of white matter abnormalities and infarcts, thought to be of vascular origin, but with a dose-dependent higher prevalence of brain atrophy on MRI among older adults. The extent to which these competing associations influence overall brain function will require further study.

}, keywords = {Aged, Aging, Alcohol Drinking, Atrophy, Brain, Brain Diseases, Cerebral Infarction, Comorbidity, Demography, Female, Health Surveys, Humans, Logistic Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Odds Ratio, Prospective Studies, Sensitivity and Specificity, United States}, issn = {1524-4628}, doi = {10.1161/hs0901.095723}, author = {Mukamal, K J and Longstreth, W T and Mittleman, M A and Crum, R M and Siscovick, D S} } @article {1298, title = {Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium.}, journal = {Ann Neurol}, volume = {69}, year = {2011}, month = {2011 Jun}, pages = {928-39}, abstract = {

OBJECTIVE: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified.

METHODS: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts.

RESULTS: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (p(discovery) = 4.0 {\texttimes} 10(-9) ; p(replication) = 1.3 {\texttimes} 10(-7) ; p(combined) = 4.0 {\texttimes} 10(-15) ). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 {\texttimes} 10(-9) ), rs11869977 (p = 5.7 {\texttimes} 10(-9) ), rs936393 (p = 6.8 {\texttimes} 10(-9) ), rs3744017 (p = 7.3 {\texttimes} 10(-9) ), and rs1055129 (p = 4.1 {\texttimes} 10(-8) ). Variant alleles at these loci conferred a small increase in WMH burden (4-8\% of the overall mean WMH burden in the sample).

INTERPRETATION: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH.

}, keywords = {Aged, Aged, 80 and over, Cerebral Cortex, Chromosomes, Human, Pair 17, Cognition Disorders, Cohort Studies, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Leukoencephalopathies, Magnetic Resonance Imaging, Male, Middle Aged, Movement Disorders, Nerve Fibers, Myelinated, Polymorphism, Single Nucleotide, Residence Characteristics, RNA, Messenger}, issn = {1531-8249}, doi = {10.1002/ana.22403}, author = {Fornage, Myriam and Debette, Stephanie and Bis, Joshua C and Schmidt, Helena and Ikram, M Arfan and Dufouil, Carole and Sigurdsson, Sigurdur and Lumley, Thomas and DeStefano, Anita L and Fazekas, Franz and Vrooman, Henri A and Shibata, Dean K and Maillard, Pauline and Zijdenbos, Alex and Smith, Albert V and Gudnason, Haukur and de Boer, Renske and Cushman, Mary and Mazoyer, Bernard and Heiss, Gerardo and Vernooij, Meike W and Enzinger, Christian and Glazer, Nicole L and Beiser, Alexa and Knopman, David S and Cavalieri, Margherita and Niessen, Wiro J and Harris, Tamara B and Petrovic, Katja and Lopez, Oscar L and Au, Rhoda and Lambert, Jean-Charles and Hofman, Albert and Gottesman, Rebecca F and Garcia, Melissa and Heckbert, Susan R and Atwood, Larry D and Catellier, Diane J and Uitterlinden, Andr{\'e} G and Yang, Qiong and Smith, Nicholas L and Aspelund, Thor and Romero, Jose R and Rice, Kenneth and Taylor, Kent D and Nalls, Michael A and Rotter, Jerome I and Sharrett, Richey and van Duijn, Cornelia M and Amouyel, Philippe and Wolf, Philip A and Gudnason, Vilmundur and van der Lugt, Aad and Boerwinkle, Eric and Psaty, Bruce M and Seshadri, Sudha and Tzourio, Christophe and Breteler, Monique M B and Mosley, Thomas H and Schmidt, Reinhold and Longstreth, W T and DeCarli, Charles and Launer, Lenore J} } @article {1310, title = {Progression of magnetic resonance imaging-defined brain vascular disease predicts vascular events in elderly: the Cardiovascular Health Study.}, journal = {Stroke}, volume = {42}, year = {2011}, month = {2011 Oct}, pages = {2970-2}, abstract = {

BACKGROUND AND PURPOSE: To determine whether progression of MRI-defined vascular disease predicts subsequent vascular events in the elderly.

METHODS: The Cardiovascular Health Study, a longitudinal cohort study of vascular disease in the elderly, allows us to address this question because its participants had 2 MRI scans≈5 years apart and have been followed for ≈9 years since the follow-up scan for incident vascular events.

RESULTS: Both MRI-defined incident infarcts and worsened white matter grade were significantly associated with heart failure, stroke, and death, but not transient ischemic attacks, angina, or myocardial infarction. Strongest associations occurred when both incident infarcts and worsened white matter grade were present for heart failure (hazard ratio, 1.79; 95\% confidence interval, 1.18-2.73), stroke (hazard ratio, 2.58; 95\% confidence interval, 1.53-4.36), death (hazard ratio, 1.69; 95\% confidence interval, 1.28-2.24), and cardiovascular death (hazard ratio, 1.97; 95\% confidence interval, 1.24-3.14).

CONCLUSIONS: Progression of MRI-defined vascular disease identifies elderly people at increased risk for subsequent heart failure, stroke, and death. Whether aggressive risk factor management would reduce risk is unknown.

}, keywords = {Aged, Brain, Disease Progression, Female, Follow-Up Studies, Heart Failure, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Predictive Value of Tests, Prognosis, Stroke}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.111.622977}, author = {Longstreth, W T and Arnold, Alice M and Kuller, Lewis H and Bernick, Charles and Lefkowitz, David S and Beauchamp, Norman J and Manolio, Teri A} }