Angiotensin Receptor Blockers: Do They Protect Against Dementia?

Discussion

The growing number of older people developing dementia places an increasing burden on families and healthcare services. The chronic nature of this condition results in the utilization of community and institutional resources for extended periods, frequently at a high economic cost. The etiology of dementia is most often related to neurodegenerative conditions, with AD being the most common. Among the important risk factors for dementia are age, female sex, previous significant head trauma, ApoE4 genotype and low education level. Cardiovascular risk factors, including hypertension, hyperlipidemia, diabetes mellitus and smoking, are considered to be important potentially treatable causes of age-related cognitive impairment and dementia. In addition, the identification of agents that are capable of exerting effects preventing vascular and neurodegenerative changes in the aging brain will probably have major ramifications on healthcare.

The results of this large, well-designed study may have important therapeutic consequences for the increasing number of older people suffering from AD and other dementias. These conditions place a significant economic and emotional burden on caregivers in particular, and on society in general. The lack of effective treatments for these conditions at the present time makes the search for other possible agents and interventions to prevent and alleviate cognitive decline and dementia all the more pressing. The clear benefit demonstrated in this study of angiotensin receptor-blocking drugs, both on the development of incident dementia and on subsequent nursing home placement and mortality, is of great interest. While this finding confirms the results of previous smaller studies demonstrating the beneficial association between angiotensin receptor blockers and cognitive function, there are a number of limitations to this study that should be emphasized. The use of a population-derived database raises the possibility of misclassification of disease, in particular that of AD and dementia, as well as other undetermined biases. In addition, the study of male veterans limits the generalizability of the findings of this study to other population groups. The study did not evaluate possible adverse effects of the therapeutic interventions in each group, and the knowledge of such effects is essential in determining the true benefit of these compounds.

The biological basis for these findings is of great interest. The authors emphasize the strong association of stroke with dementia and nursing home admission found in this study. However, this is probably not related to blood pressure control, which was similar between groups. In fact, the association between cardiovascular risk factors and AD has been questioned recently, when a systematic review found that clinically defined risk factors, such as hypertension and diabetes, were not significantly associated with an increased risk of AD.^[7] The role of the angiotensin receptor blockers on cerebral blood flow and their possible neuroprotective effects have been described; however, these and other possible mechanisms need to be studied further.

Cite this: Angiotensin Receptor Blockers: Do They Protect Against Dementia and Alzheimer’s Disease in the Elderly? - Medscape - Jun 01, 2010.

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