Date of Award

7-9-2009

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Chistopher van Dyck

Abstract

This study aimed to determine whether brain-derived neurotrophic factor (BDNF) variants are related to premorbid educational attainment, progression of cognitive and functional decline, and associated neuropsychiatric symptoms in patients with Alzheimers disease (AD). A sample of n = 341 AD subjects was genotyped for the BDNF polymorphisms val66met, C270T, and G-712A. Subjects received tests of cognition and daily function at baseline and at multiple subsequent time points during their participation in a variety of research protocols. Cognition was measured by the Mini-Mental State Examination (MMSE) and Alzheimers Disease Assessment Scale (ADAS-Cog). Functional performance was assessed using the Instrumental Activities of Daily Living questionnaire (IADL) as well as the Alzheimers Disease Cooperative Study-Activities of Daily Living inventory (ADCS-ADL). Subjects were also characterized for the frequency and severity of neuropsychiatric symptoms using the Neuropsychiatric Inventory (NPI). There was a significant effect of val66met genotype on educational attainment (F = 7.42, df = 2, 329, P = .00070), with met homozygotes having significantly fewer years of education than both the val/met and val/val groups. No association was observed between any BDNF polymorphism and measures of cognitive or functional decline. The C270T-T allele was associated with a higher prevalence of neuropsychiatric symptoms (Z = -2.11, N = 241, p = .035) and specifically with the presence of hallucinations (OR = 3.25, 95% CI = [1.22-8.62], p = .018). In summary, the val66met polymorphism appears to be associated with lower premorbid educational attainment in AD patients. The C270T-T allele demonstrated association with total neuropsychiatric symptoms and specifically hallucinations. BDNF genotypes in this sample do not confer a more rapid rate of cognitive or functional decline.

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