Helen Petrovitch

Midlife blood pressure and dementia: the Honolulu–Asia aging study☆ ☆

We studied the association of mid-life blood pressure to late age dementia, specifically Alzheimers disease and vascular dementia. Data are from the cohort of 3703 Japanese-American men who were followed in the Honolulu Heart Program (HHP;1965-1971), and subsequently re-examined in 1991 for dementia. We assessed the risk (odds ratio (95% CI)) for dementia associated with categories of systolic (SBP) and diastolic blood pressure (DBP), stratified by never/ever treatment with anti-hypertensive medications, and adjusting for age, education, apolipoprotein epsilon allele, smoking and alcohol intake. Among those never treated (57% sample), the risk for dementia was OR 95% CI 3.8 (1.6-8.7) for DBP of 90-94 mm Hg, and 4. 3 (1.7-10.8) for DBP of 95 mmHg and over compared to those with DBP of 80 to 89 mm Hg. Compared to those with SBP of 110 to 139 mm Hg, the risk for dementia was 4.8 (2.0-11.0) in those with SBP 160 mm Hg and higher. Blood pressure was not associated with the risk for dementia in treated men. These results were consistent for Alzheimers disease and vascular dementia. This study suggests elevated levels of blood pressure in middle age can increase the risk for late age dementia in men never treated with anti-hypertensive medication.

Zinc and Copper Modulate Alzheimer Aβ Levels in Human Cerebrospinal Fluid

Abnormal interaction of β-amyloid 42 (Aβ42) with copper, zinc and iron induce peptide aggregation and oxidation in Alzheimers disease (AD). However, in health, Aβ degradation is mediated by extracellular metalloproteinases, neprilysin, insulin degrading enzyme (IDE) and matrix metalloproteinases. We investigated the relationship between levels of Aβ and biological metals in CSF. We assayed CSF copper, zinc, other metals and Aβ42 in ventricular autopsy samples of Japanese American men (N= 131) from the population-based Honolulu–Asia Aging Study. There was a significant inverse correlation of CSF Aβ42 with copper, zinc, iron, manganese and chromium. The association was particularly strong in the subgroup with high levels of both zinc and copper. Selenium and aluminum levels were not associated to CSF Aβ42. In vitro, the degradation of synthetic Aβ substrate added to CSF was markedly accelerated by low levels (2 μM) of exogenous zinc and copper. While excessive interaction with copper and zinc may induce neocortical Aβ precipitation in AD, soluble Aβ degradation is normally promoted by physiological copper and zinc concentrations.

Response to Hill-Burns et al. letter: An attempt to replicate interaction between coffee and CYP1A2 gene in connection to Parkinson’s disease

R. A. Popat, S. K. Van Den Eeden, C. M. Tanner, F. Kamel, D. M. Umbach, K. Marder, B. Ritz, G. Webster Ross, H. Petrovitch, B. Topol, V. McGuire and L. M. Nelson Department of Health Research and Policy, Division of Epidemiology, Stanford University, School of Medicine, Stanford, CA; Division of Research, Kaiser Foundation Research Institute, Oakland, CA; The Parkinson s Institute, Sunnyvale, CA; Epidemiology Branch, National Institute of Environmental Health Sciences, NIH Research Triangle Park, NC; Biostatistics Branch, National Institute of Environmental Health Sciences, NIH Research Triangle Park, NC; Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY; The Gertrude H Sergievsky Center and the Taub Institute, Columbia University, College of Physicians and Surgeons, New York, NY; Department of Epidemiology, School of Public Health, University of California, Los Angeles, Los Angeles, CA; Veterans Affairs Pacific Islands Health Care System, Honolulu, HI and The Pacific Health Research Institute, Honolulu, HI, USA