We propose to conduct a pilot study of dietary interventions to delay cognitive decline in older women. Since biomarkers may better reflect nutrients bioavailable to tissues than dietary questionnaires, we propose to prospectively examine plasma markers of a wide array of antioxidants (alpha-carotene, beta-carotene, lutein/zeaxanthin, lycopene, beta-cryptoxanthin, alpha-tocopherol and gamma-tocopherol) and homocysteine, folate and vitamins B6 and B12 and their association with cognitive decline among older participants of the Nurses Health Study (NHS). The NHS began in 1976 among 121,700 women aged 30 to 55; in 1989-1990, over 32,000 blood samples were collected. From 1995-2001, approximately 19,000+ women free of stroke and aged 70 or above completed a baseline telephone cognitive interview consisting of a variety of tests measuring general cognitive ability, episodic memory, category fluency and attention. A second wave of our cognitive tests has been administered and the third assessments are ongoing, thus allowing us to prospectively measure change in cognitive function from baseline. Several lines of evidence establish that a single plasma measure of the proposed markers well-represent long-term status and accumulating evidence indicates that earlier life exposures may be particularly important for neuroprotection in older ages. We will utilize controls from previous nested case-controls from the NHS of breast and colon cancer, colon polyps, lens opacities and heart disease for whom measurements of plasma antioxidants, homocysteine and B vitamins and cognitive function have already been completed (n=567 for homocysteine/B vitamins and 724 for plasma antioxidants). We will be able to examine both the baseline performance and longitudinal change in cognitive function on each test over time in relation to various plasma level groups, using generalized estimating equations of repeated measures with random effects.The Principal Investigator is a new, young researcher, and the proposed grant will be important in facilitating her career in aging research. Importantly, results from the proposed grant will lay the groundwork for a future, large-scale comprehensive study to examine dietary interventions to delay cognitive function.
| Kang, Jae Hee; Grodstein, Francine (2008) Plasma carotenoids and tocopherols and cognitive function: a prospective study. Neurobiol Aging 29:1394-403 |
| Grodstein, Francine; Manson, JoAnn E; Stampfer, Meir J et al. (2008) Postmenopausal hormone therapy and stroke: role of time since menopause and age at initiation of hormone therapy. Arch Intern Med 168:861-6 |
| Kang, Jae Hee; Irizarry, Michael C; Grodstein, Francine (2006) Prospective study of plasma folate, vitamin B12, and cognitive function and decline. Epidemiology 17:650-7 |
