Combination therapies delay cognitive decline over 10 years in Alzheimer’s NACC participants

INTRODUCTION Delaying cognitive decline in Alzheimer’s disease can significantly impact both function and quality of life. METHODS Longitudinal analysis of National Alzheimer’s Coordinating Center (NACC) dataset of 7,653 mild dementia CDR-SB AD participants at baseline with prescriptions for diabetes (DBMD), lipid-lowering (LIPL), anti-hypertensive (AHTN), and non-steroidal anti-inflammatory (NSD) medications over 10 years was evaluated for change in cognitive function relative to non-treated stratified by sex and APOE genotype. RESULTS Combination therapy of DBMD+LIPL+AHTN+NSD resulted in a 44% / 35% (MMSE/CDR-SB) delay in cognitive decline at 5 years and 47% / 35% (MMSE/CDR-SB) delay at 10 years. Females and APOE4 carriers exhibited greatest cognitive benefit of combination therapy. DISCUSSION Combination therapies significantly delayed cognitive decline in NACC AD participants at a magnitude comparable to or greater than beta-amyloid immunomodulator interventions. These data support combination precision medicine targeting AD risk factors to alter the course of the disease that persists for a decade. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement National Institute of Aging P01AG026572 5R01AG057931-02 Women's Alzheimer's Movement University of Arizona Center for Innovation in Brain Science ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors