Impact of different diagnostic measures on drug class association with dementia progression risk: a longitudinal prospective cohort study
Background: Clinical 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. Methods: We 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. Results: Non-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. Conclusions: Overall, 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.