Roshni Biswas, MBBS, PhD, MPH
(Credit: ResearchGate)
In a newly presented study, researchers reported that combination therapies involving antihypertensive, lipid-lowering, and antidiabetes medications were associated with slower cognitive decline and less dementia-related neuropathologies. Presented at the 2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada, these results suggest that combination therapies targeting vascular metabolic risk factors may have the potential to prevent dementia.1
Across 5 cohort studies (n = 4651), findings showed baseline therapies with the 3 medication classes associated with slower decline in global cognition (estimate = .02; P = .02), particularly semantic and working memory, compared with no medication use. Among a subgroup of autopsied participants (n = 1896), use of the 3 classes was linked to lower odds of atherosclerosis (OR = 0.47; P < .01) and arteriolosclerosis (OR = 0.53; P = .01), but higher odds of brain infarcts (OR = 1.74; P = .01), especially macroinfarcts (OR = 1.66; P = .03).
Presented by Roshni Biswas, MBBS, PhD, MPH, research scientist at Rush Alzheimer’s Disease Center, combination therapy was associated with less global Alzheimer disease (AD) pathology (estimate = –0.22; P < .01), including reduced amyloid and tangle burden, and with lower odds of TDP-43 pathology (OR = 0.46; P < .01) and hippocampal sclerosis (OR = 0.27; P = .03). The analysis included older adults from cohort studies of aging who had no baseline dementia and at least 2 annual cognitive assessments, with medication use visually inspected and recorded annually.
Authors noted that the indicator for combination therapy was based on the number of class medications used (range, 0 – 3). Mixed effects models were used to evaluate associations between baseline therapy and cognitive decline. In the subgroup of deceased and autopsied participants, neuropathologic assessments examined cerebrovascular disease, AD pathology, and other dementia-related features. Researchers analyzed associations between medication use at the last clinical visit before death and neuropathology outcomes using linear and logistic regression models, adjusting for age, sex, and education.
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All told, baseline use of 2 medication classes was also associated with slower decline in global cognition (estimate = .01; P <.01), particularly episodic, semantic and working memory domains. In autopsied participants, use of 2 medication classes was linked with lower odds of atherosclerosis (OR = .63; P <.01), less global AD pathology (estimate = – 0. 09; P = .03) and tangles (estimate = – 0.22; P = .03), and lower odds of TDP-43 (OR = .71; P = .02). Additionally, baseline therapy with only 1 medication class was associated with slower semantic memory decline (estimate = .10; P = .02) and in autopsied participants, with less tangles (estimate = -.20; P = .02) and lower odds of TDP-43 (OR = .73; P = .02).
Previously published in Alzheimer’s & Dementia, researchers conducted a case control study to explore the association between duration and combination of multiple cardiovascular therapy classes and incident dementia, similar to the AAIC 2025 presented study. The findings suggested that preventing dementia through cardiovascular drug pathways could be possible; however, it may be important to consider the potential long-term negative cognitive effect of antiplatelets.2
Investigators used data from the Swedish national registers, including 8,065 incident dementia cases aged at least 70 years at diagnosis between 2011 and 2016 and 880,650 age- and sex-matched controls. Results showed that long-term users of multiple cardiovascular therapy classes had statistically significantly fewer dementia diagnoses (OR, 0.75–0.91) compared with non-users. Notably, antiplatelets use was linked with more dementia diagnoses (OR, 1.13–1.25). Furthermore, use of antihypertensives in combination with diuretics, lipid-lowering drugs, and oral anticoagulants for at least 5 years was related to fewer dementia diagnoses (OR, 0.66–0.84).
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