Date of Award
Open Access Thesis
Medical Doctor (MD)
Chistopher van Dyck
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.
Zdanys, Kristina Frances Victoria, "BDNF Variants Influence Educational Attainment But Not Disease Characteristics in Alzheimers Disease" (2009). Yale Medicine Thesis Digital Library. 476.