Association between statin therapy and dementia risk: evidence from All of Us and UK Biobank with coenzyme Q7-related mediation analysis
5 affiliations
- 1College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University
- 2College of Pharmacy, Chungbuk National University
- 3Human-Centered Artificial Intelligence Research Institute, Ewha Womans University
- 4Department of Pharmacy, Kangwon National University
- 5School of Pharmacy, Sungkyunkwan University
Abstract
Background: Statins are widely prescribed for cardiovascular disease prevention in older adults; however, their association with dementia remains controversial. Given the high prevalence of both statin use and cognitive decline in aging populations, clarifying this relationship has critical implications for geriatric clinical practice and shared decision-making.
Methods: We conducted a population-based retrospective cohort study using the All of Us Research Program (discovery cohort, n = 83,355; 31,513 statin users) and UK Biobank (replication cohort, n = 173,282; 43,976 statin users). Participants were adults aged ≥40 years who self-identified as White, followed from 2006 through 2023 (discovery) and 2017 (replication). Inverse probability of treatment weighting balanced baseline characteristics. Dementia risk was estimated using Cox proportional hazards models. An exploratory mediation analysis examined low-density lipoprotein cholesterol (LDL-C) and coenzyme Q7, a protein involved in CoQ10 biosynthesis, as potential pathways linking statin use and dementia.
Results: Statin use was associated with significantly increased dementia risk in both cohorts (discovery: adjusted HR 2.22, 95% CI 2.02–2.44; replication: adjusted HR 2.54, 95% CI 1.98–3.33). Clear intensity-dependent relationships were observed, with high-intensity statins conferring 14% greater risk than moderate-to-low intensity therapy. In the exploratory mediation analysis, the estimated indirect effect through coenzyme Q7 was statistically significant and accounted for 8.2% of the total association, whereas the indirect effect through LDL-C was not statistically significant.
Conclusion: Statin use was associated with higher dementia risk in both cohorts, and exploratory mediation findings suggested a modest statistical indirect association through COQ7, which should be considered hypothesis-generating. Given the observational design and conflicting evidence in the literature, these findings warrant further investigation before informing clinical decisions about statin therapy.
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BibTeX
@article{lee2026association,
title = {{Association between statin therapy and dementia risk: evidence from All of Us and UK Biobank with coenzyme Q7-related mediation analysis}},
author = {Da Hoon Lee and Yoon-A. Park and Jung Sun Kim and Jeong Yee and Ji Min Han and Hye Sun Gwak},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1915633},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1915633/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association between statin therapy and dementia risk: evidence from All of Us and UK Biobank with coenzyme Q7-related mediation analysis
AU - Da Hoon Lee
AU - Yoon-A. Park
AU - Jung Sun Kim
AU - Jeong Yee
AU - Ji Min Han
AU - Hye Sun Gwak
PY - 2026
DA - 2026/10/29
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1915633
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1915633/full
AB - Background: Statins are widely prescribed for cardiovascular disease prevention in older adults; however, their association with dementia remains controversial. Given the high prevalence of both statin use and cognitive decline in aging populations, clarifying this relationship has critical implications for geriatric clinical practice and shared decision-making. Methods: We conducted a population-based retrospective cohort study using the All of Us Research Program (discovery cohort, n = 83,355; 31,513 statin users) and UK Biobank (replication cohort, n = 173,282; 43,976 statin users). Participants were adults aged ≥40 years who self-identified as White, followed from 2006 through 2023 (discovery) and 2017 (replication). Inverse probability of treatment weighting balanced baseline characteristics. Dementia risk was estimated using Cox proportional hazards models. An exploratory mediation analysis examined low-density lipoprotein cholesterol (LDL-C) and coenzyme Q7, a protein involved in CoQ10 biosynthesis, as potential pathways linking statin use and dementia. Results: Statin use was associated with significantly increased dementia risk in both cohorts (discovery: adjusted HR 2.22, 95% CI 2.02–2.44; replication: adjusted HR 2.54, 95% CI 1.98–3.33). Clear intensity-dependent relationships were observed, with high-intensity statins conferring 14% greater risk than moderate-to-low intensity therapy. In the exploratory mediation analysis, the estimated indirect effect through coenzyme Q7 was statistically significant and accounted for 8.2% of the total association, whereas the indirect effect through LDL-C was not statistically significant. Conclusion: Statin use was associated with higher dementia risk in both cohorts, and exploratory mediation findings suggested a modest statistical indirect association through COQ7, which should be considered hypothesis-generating. Given the observational design and conflicting evidence in the literature, these findings warrant further investigation before informing clinical decisions about statin therapy.
SN - 1663-9812
ER -