Cross-Sectional Evaluation of the Alzheimer’s Disease and Related Dementia (ADRD) Risk-Reducing Benefits Associated with HMG-CoA Reductase Inhibitors, or Statins

Background: HMG-CoA reductase inhibitors (statins) are well-established as an effective pharmacotherapy for dyslipidemia, a condition thought to trigger excess amyloid beta (Aβ) aggregation. Statins may therefore also offer prophylaxis against Alzheimer’s Disease and Related Dementias (ADRD).

Methods: To assess associations between statin use and ADRD risk, we conducted a secondary analysis of United States Medicare Current Beneficiary Survey (MCBS) data from 2019-2020. Each respondent with ADRD was matched with two other persons based on key demographic characteristics to create cases and comparisons, making for a total of 3,468 Medicare beneficiaries included in the analysis. Beneficiary ADRD diagnosis statuses were identified using MCBS’s self-reported Health Status and Functioning Questionnaire and/or the Health Status section of the MCBS Facility Instrument. Prescription utilization data, as published in the MCBS PME module, was used to identify statin users and nonusers. Associations between statin use and ADRD diagnosis were assessed via Fisher’s exact tests.

Findings: Statin utilization was associated with significantly reduced ADRD risk (OR 0.68; p<0.0001). Rosuvastatin was associated with significantly reduced ADRD risk relative to atorvastatin (OR 0.66; p=0.0193). Additionally, hydrophilic statins were associated with significantly reduced ADRD risk relative to lipophilic statins (OR 0.77; p=0.0394).

Conclusions: While statin use was found to correlate to significantly reduced ADRD risk, longitudinal research remains necessary to confirm that statins are indeed effective prophylactics against ADRD.

Keywords: Alzheimer’s Disease, Case-Control, Dementia, HMG-CoA Reductase Inhibitors, Statin.