The results indicate a significant association of UGT1A1 phenotype and genotype based on in vitro phenotypic measurements. The clinical significance of our finding remains to be established.

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ObjectivesTo perform a systematic review of reported HRs of all cause dementia, Alzheimer's disease (AD) and vascular dementia (VaD) for late-life depression and depressive symptomatology on specific screening instruments at specific thresholds.DesignMeta-analysis with meta-regression.Setting and participantsPubMed, PsycInfo, and Cochrane databases were searched through 28 February 2014. Articles reporting HRs for incident all-cause dementia, AD and VaD based on published clinical criteria using validated measures of clinical depression or symptomatology from prospective studies of general population of adults were selected by consensus among multiple reviewers. Studies that did not use clinical dementia diagnoses or validated instruments for the assessment of depression were excluded. Data were extracted by two reviewers and reviewed by two other independent reviewers. The most specific analyses possible using continuous symptomatology ratings and categorical measures of clinical depression focusing on single instruments with defined reported cut-offs were conducted.Primary outcome measuresHRs for all-cause dementia, AD, and VaD were computed where possible for continuous depression scores, or for major depression assessed with single or comparable validated instruments.ResultsSearches yielded 121 301 articles, of which 36 (0.03%) were eligible. Included studies provided a combined sample size of 66 532 individuals including 6593 cases of dementia, 2797 cases of AD and 585 cases of VaD. The increased risk associated with depression did not significantly differ by type of dementia and ranged from 83% to 104% for diagnostic thresholds consistent with major depression. Risk associated with continuous depression symptomatology measures were consistent with those for clinical thresholds.ConclusionsLate-life depression is consistently and similarly associated with a twofold increased risk of dementia. The precise risk estimates produced in this study for specific instruments at specified thresholds will assist evidence-based medicine and inform policy on this important population health issue.