Adherence to Antihypertensive Therapy and Risk of Mild Cognitive Impairment: A Systematic Review and Meta-analysis
Leonardo Di Cosmo1, Gerardo Luna-Peralta2, Francesca Pellicanò1, Jad El Choueiri1, Jacopo Rosso Antonino3, Santiago Nieto Cuervo1, Lorenzo De Rossi1, Carlotta Ranalli4
1Department of Biomedical Sciences, Humanitas University, 2Universidad Nacional Mayor de San Marcos, 3Department of Biomedical Sciences for Health, Università degli Studi di Milano, 4Department of Neurosurgery, Università Cattolica Del Sacro Cuore
Objective:
To determine the association between adherence to antihypertensive therapy and the risk of developing mild cognitive impairment (MCI).
Background:
Hypertension is a leading modifiable risk factor for cognitive decline. While antihypertensive therapy can reduce dementia risk, its protective effect depends on continuous adherence. MCI represents an intermediate, potentially reversible stage of cognitive deterioration. Determining the role of antihypertensive adherence in preventing MCI may provide an actionable pathway to reduce cognitive decline in the aging population.
Design/Methods:
A systematic search of four databases was conducted up to October 2025 following PRISMA guidelines. Case-control, cohort, and cross-sectional studies comparing the prevalence of MCI in cohorts of patients with good versus poor adherence to antihypertensive therapy were included. A meta-analysis using a random-effects model was planned evaluating the odds ratios (OR) of developing MCI, and a narrative synthesis was provided where analyses were not feasible. Risk of bias was assessed using the ROBINS-I, and the certainty of evidence (CoE) was evaluated with GRADE criteria.
Results:
A total of 11 studies met the inclusion criteria, of which five studies (n=7,832 patients) were included in the quantitative synthesis. All studies demonstrated a low to moderate risk of bias. Good adherence to antihypertensive therapy was associated with a significantly lower risk of MCI (OR = 0.39; 95% CI 0.20–0.77; p = 0.007). Although heterogeneity was high (I² = 96%), the direction of effect consistently favored good adherence across all studies. Leave-one-out sensitivity analysis confirmed the stability of this result.
Conclusions:
Our analysis shows that poor adherence to hypertensive medication is significantly associated with the development of MCI. Despite substantial heterogeneity, these findings suggest the potential cognitive benefits of optimal and consistent blood-pressure control. Future studies should evaluate whether early interventions to improve medication adherence can delay or prevent cognitive decline in at-risk populations.
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