Does Use of Antihypertensive Drugs Affect the Incidence or Progression of Dementia? A Systematic Review

Background: Hypertension appears to contribute to the development of dementia. Antihypertensive drugs may play an important role in altering the incidence or progression of dementia, particularly dementia of the vascular type; however, the neuroprotective effects of these agents in other types of dementia are not well characterized. Objectives: The main aims of this review were to examine the relationship between use of antihypertensive agents and the incidence and progression of Alzheimer's dementia (AD), vascular dementia (VaD), and unspecified dementia, and to consider whether these agents may be neuroprotective. Methods: A search of the English-language literature (January 1996-August 2009) was conducted using PubMed, Ovid MEDLINE, EBSCO MEDLINE, and the Cochrane Database of Systematic Reviews for publications mentioning both antihypertensive drugs and dementia. A combination of searches was performed using the following terms: antihypertensive drugs, dementia, cognitive impairment, Alzheimer's dementia, vascular dementia, progression of cognitive impairment, severity of cognitive impairment, severity of dementia, prevalence, and incidence. Searches were also performed using the names of antihypertensive drug classes. The bibliographies of all retrieved articles were reviewed for additional relevant publications. The focus was on randomized controlled trials, cohort studies, and case-control studies, excluding studies in animals, patients aged <45 years, drugs other than antihypertensive agents, and the role in cognition of hormones, receptors, and enzymes. Results: Sixty-five potentially relevant articles were identified from the 536 publications retrieved by the literature search. After application of the exclusion criteria, 12 original studies were included in the review, all published between 1999 and 2008 and most involving patients with AD or VaD. The most frequently studied antihypertensive agents were calcium channel blockers (7 studies), diuretics (6 studies), and angiotensin-converting enzyme (ACE) inhibitors (6 studies). Overall, these medications appeared to be beneficial in dementia, but only ACE inhibitors and diuretics significantly reduced the risk for and progression of dementia in the majority of studies. Conclusions: Antihypertensive medications-particularly ACE inhibitors and diuretics-may be helpful in reducing the risk for and progression of dementia. Large randomized clinical trials are warranted to further explore the relationship between antihypertensive drugs and dementia. (Am J Geriatr Pharmacother. 2009;7:250-261) (C) 2009 Excerpta Medica Inc.