@article {1054, title = {Anemia is associated with the progression of white matter disease in older adults with high blood pressure: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Oct}, pages = {1867-72}, abstract = {

OBJECTIVES: To investigate whether anemia predicts worsening white matter hyperintensities (WMHs) in older community-dwellers.

DESIGN: Prospective cohort study.

SETTING: Older community-dwellers.

PARTICIPANTS: One thousand eight hundred forty-six Cardiovascular Health Study (CHS) participants (mean age 73.7 +/- 4.4, 41\% male, 15.6\% African American).

MEASUREMENTS: Participants had hemoglobin measured and brain magnetic resonance imaging (MRI) in 1992/93 and a second brain MRI in 1997/98. Anemia was defined according to World Health Organization criteria (hemoglobin <12 g/dL in women and <13 g/dL in men). Worsening WMHs were determined according to standardized side-by-side readings.

RESULTS: After 5 years, WMHs worsened in 517 participants (28\%). Progression was not associated with anemia in the whole sample, in sex or race strata, or in other prespecified subgroups (participants with renal dysfunction or diabetes mellitus), except in participants with high blood pressure (>or=140/90 mmHg). Of the 678 participants with high blood pressure, those with anemia (10.5\%) had a 1.79 times greater risk of WMHs worsening (95\% confidence interval=1.06-2.98; P for interaction between anemia and high blood pressure=.01) independent of demographics, baseline WMHs, cardiovascular risk factors and comorbidities, medications, renal function, inflammation, and incident stroke (logistic regression models). There was no greater risk in participants with anemia with normal blood pressure.

CONCLUSION: Anemia may contribute to worsening of WMHs in older adults with high blood pressure.

}, keywords = {Aged, Anemia, Brain, Cardiovascular Diseases, Disease Progression, Female, Humans, Hypertension, Leukoaraiosis, Magnetic Resonance Imaging, Male}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.01950.x}, author = {Inzitari, Marco and Studenski, Stephanie and Rosano, Caterina and Zakai, Neil A and Longstreth, William T and Cushman, Mary and Newman, Anne B} } @article {1279, title = {Association of HSP70 and its co-chaperones with Alzheimer{\textquoteright}s disease.}, journal = {J Alzheimers Dis}, volume = {25}, year = {2011}, month = {2011}, pages = {93-102}, abstract = {

The heat shock protein (HSP) 70 family has been implicated in the pathology of Alzheimer{\textquoteright}s disease (AD). In this study, we examined common genetic variations in the 80 genes encoding HSP70 and its co-chaperones. We conducted a study in a series of 462 patients and 5238 unaffected participants derived from the Rotterdam Study, a population-based study including 7983 persons aged 55 years and older. We genotyped a total of 12,053 Single Nucleotide Polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. Replication was performed in two independent cohort studies, the Framingham Heart study (FHS; n = 806) and Cardiovascular Health Study (CHS; n = 2150). When adjusting for multiple testing, we found a small but consistent, though not significant effect of rs12118313 located 32 kb from PFDN2, with an OR of 1.19 (p-value from meta-analysis = 0.003). However this SNP was in the intron of another gene, suggesting it is unlikely this SNP reflects the effect of PFDN2. In a formal pathway analysis we found nominally significant evidence for an association of BAG, DNAJA and prefoldin with AD. These findings corroborate with those of a study of 2032 AD patients and 5328 controls, in which several members of the prefoldin family showed evidence for association to AD. Our study did not reveal evidence for a genetic variant if the HSP70 family with a major effect on AD. However, our findings of the single SNP analysis and pathway analysis suggest that multiple genetic variants in prefoldin are associated with AD.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Cohort Studies, Genetic Association Studies, Genetic Variation, HSP70 Heat-Shock Proteins, Humans, Middle Aged, Molecular Chaperones, Polymorphism, Single Nucleotide}, issn = {1875-8908}, doi = {10.3233/JAD-2011-101560}, author = {Broer, Linda and Ikram, Mohammad Arfan and Schuur, Maaike and DeStefano, Anita L and Bis, Joshua C and Liu, Fan and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Beiser, Alexa S and Longstreth, William T and Hofman, Albert and Aulchenko, Yurii and Seshadri, Sudha and Fitzpatrick, Annette L and Oostra, Ben A and Breteler, Monique M B and van Duijn, Cornelia M} } @article {5849, title = {Adiposity and cognitive decline in the cardiovascular health study.}, journal = {Neuroepidemiology}, volume = {40}, year = {2013}, month = {2013}, pages = {274-81}, abstract = {

BACKGROUND: Studies relating adiposity to cognition in the elderly show conflicting results, which may be explained by the choice of adiposity measures. Thus, we studied the longitudinal associations of different adiposity measures, fat mass by bioelectrical impedance analysis, body mass index (BMI) and waist circumference (WC), with cognitive performance in the Cardiovascular Health Study.

METHODS: Cognitive performance was assessed with the modified Mini-Mental State Examination, the Digit Symbol Substitution Test, and a composite of both. We used linear mixed models to estimate rates of change in cognitive function scores associated with adiposity measured at baseline.

RESULTS: The final sample was comprised of 2,681 women (57.9\%) and 1,949 men (42.1\%) aged 73 {\textpm} 5.2 and 73.9 {\textpm} 5.6 years, respectively. Adiposity was associated with slower cognitive decline in most analyses. Results were similar for fat mass, BMI and WC. Higher fat-free mass was also related to slower cognitive decline. Results were similar in analyses excluding persons with cancer, smokers, and persons with short follow-up, poor self-reported health, or persons with cardiovascular disease.

CONCLUSIONS: Higher adiposity and higher fat-free mass in the elderly was related to better cognitive performance. This finding was not explained by confounding by preexisting conditions.

}, keywords = {Adiposity, Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Cognition Disorders, Electric Impedance, Female, Humans, Male, Risk Factors, Waist Circumference, Waist-Hip Ratio}, issn = {1423-0208}, doi = {10.1159/000345136}, author = {Luchsinger, Jos{\'e} A and Biggs, Mary L and Kizer, Jorge R and Barzilay, Joshua and Fitzpatrick, Annette and Newman, Anne and Longstreth, William T and Lopez, Oscar and Siscovick, David and Kuller, Lewis} } @article {6815, title = {Association of Alzheimer{\textquoteright}s disease GWAS loci with MRI markers of brain aging.}, journal = {Neurobiol Aging}, volume = {36}, year = {2015}, month = {2015 Apr}, pages = {1765.e7-16}, abstract = {

Whether novel risk variants of Alzheimer{\textquoteright}s disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta {\textpm} SE = -0.047 {\textpm} 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.

}, keywords = {Aging, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Female, Genome-Wide Association Study, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Organ Size, Polymorphism, Single Nucleotide, Risk, Sialic Acid Binding Ig-like Lectin 3}, issn = {1558-1497}, doi = {10.1016/j.neurobiolaging.2014.12.028}, author = {Chauhan, Ganesh and Adams, Hieab H H and Bis, Joshua C and Weinstein, Galit and Yu, Lei and T{\"o}glhofer, Anna Maria and Smith, Albert Vernon and van der Lee, Sven J and Gottesman, Rebecca F and Thomson, Russell and Wang, Jing and Yang, Qiong and Niessen, Wiro J and Lopez, Oscar L and Becker, James T and Phan, Thanh G and Beare, Richard J and Arfanakis, Konstantinos and Fleischman, Debra and Vernooij, Meike W and Mazoyer, Bernard and Schmidt, Helena and Srikanth, Velandai and Knopman, David S and Jack, Clifford R and Amouyel, Philippe and Hofman, Albert and DeCarli, Charles and Tzourio, Christophe and van Duijn, Cornelia M and Bennett, David A and Schmidt, Reinhold and Longstreth, William T and Mosley, Thomas H and Fornage, Myriam and Launer, Lenore J and Seshadri, Sudha and Ikram, M Arfan and Debette, Stephanie} }