Impact of different diagnostic measures on drug class association with dementia progression risk: a longitudinal prospective cohort study

Abstract

AbstractBackgroundClinical Dementia Rating Sum of Boxes (CDRSOB) scale is known to be highly indicative of cognitive-functional status, but it is unclear whether it is consistent with clinician diagnosis in evaluating drug class associations with risk of progression to mild cognitive impairment (MCI) and dementia.MethodsWe employed multivariate logistic regression on longitudinal NACC data, to identify drug classes associated with disease progression risk, using clinician diagnosis and CDRSOB as the outcome.ResultsNon-steroidal anti-inflammatory drugs, anxiolytics, antidiabetics, and Parkinson’s medications were significantly associated with decreased progression to mild cognitive impairment (MCI)/dementia, and antihypertensives and Alzheimer’s medications significantly associated with increased progression risk. Associations were however dependant on the diagnostic measure used, e.g., antihypertensives were associated with increased Healthy-to-Dementia risk using clinical diagnosis as the outcome (OR:2.05, FDR p<0.001), but not for CDRSOB. Additionally, some associations appear to be gender specific; for instance, antidiabetics had lower MCI-to-Dementia risk for women (OR:0.58, FDR p=0.006) using CDRSOB. Further, in accordance with existing literature, acetylcholinesterase inhibitors were not beneficial in delaying dementia.ConclusionsOverall, we demonstrate that choice of diagnostic measure can influence the magnitude of risk or protection attributed to drug classes. A consensus must be reached within the research community with respect to the most accurate diagnostic outcome to identify risk and improve reproducibility.FundingThis project was supported by the European Union’s INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB (Centre for Personalised Medicine, IVA 5036)), with additional support by the Northern Ireland Functional Brain Mapping Project Facility (1303/101154803), funded by invest Northern Ireland and the University of Ulster (K.W.-L.), Alzheimer’s Research UK (ARUK) NI Pump Priming (M.B.,S.T.,K.W.-L.,P.L.M.), Ulster University Research Challenge Fund (M.B.,S.T.,K.W.-L.,M.B.), and the Dr George Moore Endowment for Data Science at Ulster University (M.B.).