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Hypertension is strongly associated with cognitive decline and a promising target for dementia prevention. Our aim was to investigate the association between different antihypertensive treatments and cognitive performance in elderly hypertensive patients presenting with subjective memory complaints.Three hundred and seventy-eight elderly hypertensive patients more than 60 years (mean age 70.4 ± 6.3 years) treated with at least one antihypertensive agent and presenting with subjective memory complaints but without dementia were prospectively recruited and underwent a combination of neuropsychological tests, brain magnetic resonance imaging with semiquantification of white matter hyperintensities, carotid echotracking, brachial endothelial function, and ambulatory blood pressure assessments.None of the three composite scores (memory score, verbal fluency, and visual memory capacity) was found associated with blood pressure levels. On the other hand, age-adjusted and sex-adjusted analyses showed a significant and positive association between memory score and use of calcium channel blockers (CCBs) (users: +0.14 ± 0.09 versus nonusers: −0.12 ± 0.06; P = 0.016). Multivariate analyses also revealed that CCB use was significantly associated with a better memory score, independently of age, male sex, white matter hyperintensities, and carotid wall cross-sectional area, all of which were associated with worse memory scores.In elderly hypertensive treated patients with subjective memory complaints, CCB use was associated with better memory performance independently of blood pressure level and macrovascular and microvascular alterations, suggesting a specific neuroprotective effect of this pharmacological class. Interventional controlled trials are required to confirm the specific protective effect of CCBs on cognitive decline.