DIFFERENTIAL EFFECTS OF PHARMACOLOGIC AND NON-PHARMACOLOGIC TREATMENTS OF ALZHEIMER’S DISEASE: A COMPREHENSIVE SUMMARY OF EVIDENCE AND META-ANALYSIS

Abstract

The objective of any Alzheimer's disease (AD) treatment is to achieve clinically meaningful symptom reductions without compromising the quality of life (QOL) in patients. Despite the promise of emerging therapies, existing pharmacological treatments have dominated the AD treatment landscape. The acceptance of these treatment norms, especially in comparison to non-pharmacological treatments has not been adequately examined. We performed an exhaustive, quantitative review of their comparative effects, based on all published clinical data, which has not been methodologically feasible until now. This investigation applies novel clinical data extraction and aggregation technologies developed by MedAware Systems, Inc. It is a patent-pending process where two scientists, blinded to each other, extract data from the same study. Intelligent software compares each data field for matches (or mismatches). Where there is a mismatch, a senior scientist reconciles the data mismatch. This methodology is used to thoroughly profile the differences in efficacy and QOL/ADL outcomes among leading pharmacologic and non-pharmacologic treatments to identify the complete domain of AD literature, to extract information on intervention, efficacy, and cohort-level evidence available, and to elucidate the great variation in therapy effect. A total of 795 clinical studies reporting AD interventions and outcome data were located. Of those, 280 and 84 publications were identified that investigated drug and non-pharmacologic treatments, respectively, and were included in the analysis. Overall, no significant reduction in cognitive decline or improvement in QOL/ADL scores was demonstrated with either pharmacologic (MSI-E = 0.17±7.41) or non-pharmacologic (MSI-E = -0.49±2.33) treatments. While acetylcholinesterase inhibitors showed the most overall cognitive benefit (MSI-E = 0.56±7.05), the class was also associated with significant reduction in ADL/QOL (MSI-E = -1.13±11.92) and the greatest variability in effect. Within non-pharmacologic treatments, integrative therapies showed the poorest efficacy (MSI-E = -1.77±3.73) but suggested conserved ADL/QOL (MSI-E = 0.01±2.76). The MedAware Systems, Inc. literature database and meta-analytic methodology readily profiles the diversity, poor efficacy, and the corresponding QOL effect of leading drug and non-pharmacologic AD treatments. The roles of publication-, treatment-, and patient-level factors in reported safety and efficacy profiles warrant further investigation .