Treatment of Hypertension Can Reduce the Risk of Dementia in Later Life
Treatment of Hypertension Can Reduce the Risk of Dementia in Later Life
Abstract & Commentary
By Matthew E. Fink, MD, Interim Chair and Neurologist-in-Chief, Department of Neurology and Neuroscience, Weill Cornell Medical College. Dr. Fink reports no financial relationships relevant to this field of study.
Synopsis: Antihypertensive treatment may reduce the risk of dementia as well as Alzheimer's-type pathology.
Sources: Haag MDM, Hofman A, Koudstaal PJ, et al. Duration of antihypertensive drug use and risk of dementia: A prospective cohort study. Neurology 2009;72:1727-1734; Hoffman LB, Schmeidler J, Lesser GT, et al. Less Alzheimer disease pathology in medicated hypertensive than nonhypertensive persons. Neurology 2009;72:1720-1726
Two recent companion papers in neurology have added to the growing evidence that antihypertensive treatment can reduce the risk of dementia, including Alzheimer's disease.
The study by Haag and colleagues was a prospective, population-based cohort study in Rotterdam, that followed 6,249 people older than age 55 who were screened and found to be free of dementia at the time of enrollment (1990-1993) and were followed until 2005 for incident dementia. Continuous data regarding medication use was determined from pharmacy records and antihypertensive use was expressed in years. A Cox regression model was used to calculate hazard ratios (HRs) of all dementia and Alzheimer's disease, with or without the use of antihypertensive medications. Compared to people who never used them, antihypertensive medication use was associated with a reduced risk of all dementia (HR per year = 0.95; CI 0.91-0.99). In persons age 75 or younger, there was an 8% risk reduction in dementia risk per year of antihypertensive use. The risk reduction was 4% per year in those older than 75 years of age. Similar findings were found for Alzheimer's disease alone. No apparent differences were found among different classes of antihypertensive medications.
Hoffman and colleagues approached this issue in a way that may shed light on the mechanisms of action of antihypertensive medications as a strategy to reduce the risk of dementia. This was a postmortem study of 291 brains of patients who were at least 60 years of age at time of death, and had either normal brain tissue, or primary neuropathology with only Alzheimer's-associated lesions. Brains with significant vascular pathology were excluded. Medical records were reviewed for a diagnosis of hypertension and whether antihypertensive medications were taken, and three groups were compared - medicated hypertensives, nonmedicated hypertensives, and nonhypertensives. Neuritic plaques and neurofibrillary tangles were quantified according to the Consortium to Establish a Registry for Alzheimer's Disease criteria. Based on an objective scoring system, there was less Alzheimer's disease pathology in the medically-treated hypertension group than the nonhypertensive group. The untreated hypertensive group and the nonhypertensive group had similar degrees of Alzheimer's pathology.
Commentary
Previous studies of the effects of antihypertensive medications on the risk of developing dementia have shown mixed results, but there were many weaknesses in earlier study design and relatively short follow-up periods. The Rotterdam study was a well-designed, prospective cohort study, with a large number of study subjects and accurate medical records and pharmacy records, and the results are compelling and reliable. We would conclude from the Rotterdam study that treatment of mid-life hypertension will reduce the risk of late-life dementia. The study also suggests that in the very elderly-older than age 75, there is less benefit to blood pressure treatment, indicating that age is a major risk factor for dementia that cannot be modified.
But why does treatment of high blood pressure reduce the risk of dementia? The simple answer is that it works by reducing the risk of both small and large brain infarcts as people age, thereby reducing the risk of vascular dementia or the mixed forms that are probably the most common. However, the Hoffman neuropathology study specifically excluded brains that had vascular pathology and showed that there was less Alzheimer's-type pathology in brains of people who were treated with antihypertensive medications, compared to those who were never treated. The logical conclusion is that antihypertensive treatment has a more specific effect on Alzheimer's pathology that is independent of its effects on the cardiovascular system. Both calcium-channel blockers and angiotensin-II receptor blockers have intracellular effects on glia and neurons, and these effects need more study. However, all of the drug types, including diuretics, seem to have equal effects on Alzheimer's-type pathology. Could microcirculatory effects at the arteriolar and capillary level of the brain be playing a role? Do these drugs have an effect on the transport of amyloid-beta into the brain? All of these questions are intriguing and exciting and warrant further investigation to try to understand the relationship between the vascular system and Alzheimer's disease.
Antihypertensive treatment may reduce the risk of dementia as well as Alzheimer's-type pathology.Subscribe Now for Access
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