Pharmacological signatures of the reduced incidence and the progression of cognitive decline in ageing populations suggest the protective role of beneficial polypharmacy
Abstract
Preventive treatments for dementia are warranted. Here we show that utilization of certain combinations of prescription medications and supplements correlates with reduced rates of cognitive decline. More than 1,900 FDA-approved agents and supplements were collapsed into 53 mechanism-based groups and traced in electronic medical records (EMRs) for >50,000 patients. These mechanistic groups were aligned with the data presented in more than 300 clinical trials, then regression model was built to fit the signals from EMRs to clinical trial performance. While EMR signals of each single agents correlated with clinical performance relatively weakly, the signals produced by combinations of active compounds were highly correlated with the clinical trial performance (R = 0.93, p = 3.8 x10^-8). Higher ranking pharmacological modalities were traced in patient profiles as their combinations, producing protective complexity estimates reflecting degrees of exposure to beneficial polypharmacy. For each age strata, the higher was the protective complexity score, the lower was the prevalence of dementia, with maximized life-long effects for the highest regression score /diversity compositions. The connection was less strong in individuals already diagnosed with cognitive impairment. Confounder analysis confirmed an independent effect of protective complexity in multivariate context. A sub-cohort with lifelong odds of dementia decreased > 5-folds was identified; this sub-cohort should be…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 50,000 participants or records.
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