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P4‐245: COMT VAL158MET polymorphism, dementia risk and cognitive development in a prospective population‐based aging study in Germany
Author(s) -
Wagner David,
Sattler Christine,
Schönknecht Peter,
Toro Pablo,
Schröder Johannes
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.2109
Subject(s) - dementia , neuropsychology , neuropsychological test , psychology , population , cohort , prospective cohort study , medicine , cognition , clinical psychology , disease , psychiatry , environmental health
different cognitive evaluations (basal plus two follow up examinations) and available genotypic information for APOE, rs11136000 (CLU), rs3851179 (PICALM), rs3818361 (CR1), rs744373 (BIN1), rs597668 (EXOC3L2) and rs1562990 (MS4A gene cluster) were selected for this study. The diagnosis and follow-up evaluations of AD were made following standard criteria. Mean differences in GDS and MMSE were evaluated using a non-parametric test (Mann-Whitney) or general linear model. The associations between loci and cognitive functions were also evaluated using linear mixed models for repeated measurements. Each chart was also reviewed for evidence of treatment with any cholinesterase inhibitor (AChEI), memantine or both. The patients were classified into four usage groups: those who never used AChEIs or Memantine, those who were taking AChEIs as monotherapy, those who were taking a combined therapy (Memantine plus AChEI), and those who were taking Memantine as monotherapy. Relationships between therapeutic protocols, genetic markers and progression were explored using Mantel-Haenszel stratified analysis looking for specific effects of genotypes on progression in each therapeutic category separately.Results:Neither calculation rendered a Bonferroni’s corrected statistical significant difference in any genetic marker. Mixed model results suggested differences in the average point in MMSE test for patients carrying PICALM GA or AA genotype compared to GG carriers at the end of the follow up (mean MMSE: PICALM GA+AA 1⁄4 16.14 versus PICALM GG 1⁄4 15.57. MMSE mean difference 1⁄4 -0,577 C.I.95% [-1.145-0.009], P 1⁄4 0.047). Furthermore, results from the variant in BIN1 were also suggestive: patients carrying minor allele for BIN1 (TC+CC) displayed a lower MMSE mean (15.7) compared with TT (16.2)(MMSE mean difference 1⁄4 0.591 C.I.95% [0.27-1.155], P1⁄4 0.04). Both observations remained unaltered after covariate adjustments although they did not resist predefined multiple testing threshold. Conclusions: None of studied genetic markers was convincingly linked to Alzheimer’s disease progression or drug response.