ABSTRACTHypertension has been shown to be a risk factor for development of dementia. However, medical treatment of hypertension failed to reduce consistently the risk of dementia. Experimental study pointed to the possibility of difference between different calcium channel blockers (CCB) in their neuro-protective effect. The aim of our study was to evaluate the risk of dementia during treatment of hypertension with different CCBs. This is a retrospective cohort study based on electronic database of a large public health care organization. Study period was 11 years and it included patients aged 40–75 years old, having diagnosis of hypertension without diagnosis of dementia at the starting point, treated with either single specific CCB (study group) or with other than CCBs antihypertensive medications (control group) for at least 30 months during the study period. A total of 15,664 patients that satisfied these criteria were identified: 3,884 were treated with amlodipine, 2,062 were treated with nifedipine, 609 were treated with lercanidipine, and 9,109 never received CCBs. Dementia developed in 765 (4.9%) patients. Adjusted hazard ratio (HR) for dementia in patients treated with amlodipine, nifedipine, and lercanidipine was 0.60 (p < 0.001), 0.89 (NS), and 0.90 (NS). Decreased adjusted HR of dementia with amlodipine was demonstrated in the patients aged 60 or more (HR 0.61 [0.49–0.77], p < 0.001), but not in the patients aged less than 60 years old.This study shows that amlodipine therapy may be associated with a decreased dementia risk in hypertensive individuals older than 60 years, compared to those treated without CCBs.