Effects of Antihypertensive Drug Treatment on the Risk of Dementia and Cognitive Impairment

Abstract

Dementia is a common and serious health problem that affects 33 million persons globally. With the increase in life expectancy, the prevalence of dementia is expected to reach 81.1 million persons by 2040. Dementia impairs quality of life and is associated with profound disease burden, morbidity, and mortality in both patients and caregivers. Therefore, identifying measures to prevent dementia is a research priority. Midlife hypertension has increased the risk of dementia in large prospective cohort studies. Researchers have investigated the blood pressure-lowering effects of antihypertensive drugs on the incidence of dementia. Although prospective cohort studies have shown that use of antihypertensive drugs was associated with a reduced rate of cognitive impairment and dementia, these studies were not placebo controlled. Four randomized, placebo-controlled studies-the Systolic Hypertension in Europe (Syst-Eur) study, Study on Cognition and Prognosis in the Elderly (SCOPE), Systolic Hypertension in the Elderly Program (SHEP), and Perindopril Protection Against Recurrent Stroke Study (PROGRESS)-investigated the effects of antihypertensive agents on the incidence of dementia. The Syst-Eur study found that active treatment with nitrendipine, enalapril, and/or hydrochlorothiazide reduced the rate of dementia by 50% compared with placebo (p=0.05). The PROGRESS study showed that active treatment with perindopril and indapamide was associated with reduced cognitive decline compared with placebo (risk ratio 19%, p=0.01). In contrast, the SCOPE study (candesartan or hydrochlorothiazide vs placebo) and the SHEP trial (chlorthalidone, atenolol, or reserpine vs placebo) found no significant difference between the active treatment and placebo groups on the incidence of dementia. Some researchers have suggested that certain antihypertensive drug classes, such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, diuretics, and calcium channel blockers, may offer benefit in reducing dementia risk in addition to their blood pressure-lowering effect. Further prospective randomized studies comparing different antihypertensive classes are needed to provide more evidence regarding the effects of antihypertensive drugs on dementia risk and to determine whether certain antihypertensive classes provide greater benefits than others.

Candesartan, an Angiotensin II AT1-Receptor Blocker and PPAR-γ Agonist, Reduces Lesion Volume and Improves Motor and Memory Function After Traumatic Brain Injury in Mice

“…Several large clinical studies have demonstrated that ARBs prevent the cognitive dysfunction produced by stroke in patients with and without hypertension (Fogari and Zoppi, 2004;Hansson et al, 1999;Igase et al, 2012;Meredith et al, 2004;Poon, 2008;Van Mieghem et al, 2010;Zanchetti and Elmfeldt, 2006). Furthermore, ARBs reduce the incidence and progression of Alzheimer's disease and dementia in hypertensive patients more effectively than other antihypertensive medications (Davies et al, 2011).…”

Medications and Cognition in Older Adults

“…With the possible exception of beta-blockers (see below), antihypertensives are not thought to affect cognition signi fi cantly. A review of several randomized, placebo-controlled studies and a recent metaanalysis examining the effects of antihypertension medications on dementia suggested that these medications, and angiotensin-converting enzyme (ACE) inhibitors and diuretics in particular, may help prevent or slow the progression of dementia [ 121,122 ] .…”

Blood pressure control in the elderly: Can you have too much of a good thing?

“…This question is beyond the scope of this paper. There have been several recent reviews of this topic [36][37][38].…”