Hypertension and Dementia—The Elephant in the Room


A recent, widely publicized report reminds us of the growing problem of dementia in the United States.[1] It is concluded that the financial burden on society from dementia is similar to the financial burden of heart disease and cancer. However, the financial burden pales in comparison to the decrease in quality of life of the afflicted and the enormous emotional impact on caregivers and family. Although it has been long suspected that hypertension is associated with the development of both vascular dementia (microinfarcts and strokes) and Alzeimer's disease, increasing evidence of the role of hypertension in the pathophysiology of dementia demands increased attention from the hypertension community to this important issue.

The association of mid-life blood pressure (BP) to late-age dementia, specifically Alzeimer's disease and vascular dementia, was studied in a cohort of 3703 Japanese American men followed in the Honolulu Heart Program.[2] Among those never treated for hypertension (57% of the sample), the risk for dementia was odds ratio (OR)=3.8 (95% confidence interval [CI], 1.6–8.7) for diastolic BP of 90 to 94 mm Hg and OR=4.3 (CI, 1.7–10.8) for diastolic BP of ≥95 mm Hg compared with those with diastolic BP of 80 to 89 mm Hg. Compared with those with systolic BP of 110 to 139 mm Hg, the risk for dementia was OR=4.8 (CI, 2.0–11) in those with systolic BP ≥160 mm Hg. Importantly, BP was not associated with the risk for dementia in men treated for hypertension. The results of the study were similar for both Alzeimer's disease and vascular dementia.

In another study, the brains of 774 Japanese American men who took part in the Honolulu Asia Aging Study were examined at necropsy.[3] Men who had been treated with antihypertensive drugs were found to have fewer microinfarcts, ie, small strokes and fewer amyloid plaques and tangles (signs of Alzeimer's disease) and less brain atrophy. Interestingly, patients who were treated with β-blockers had the healthiest brains compared with those with other treatments. In fact, the degree of cerebral pathology was approximately half as severe in patients treated with β-blockers compared with other drug classes.

The combined impact of hypertension and apolipoprotein E ε -4 carriage was studied in 118 patients aged 47 to 89 years who were participating in a brain-imaging study.[4] The cohort was comprised of well-educated middle-aged and older adults who performed normally on a battery of cognitive tests and showed no abnormalities on neurological and psychiatric testing, were free of vascular disease on clinical examination, and had at least one apolipoprotein E ε-4 allele. Patients with uncontrolled hypertension had a greater deposition of β-amyloid as quantitated by brain positron emission tomography imaging with radiotracer fluorine 18-labeled florbetapir. Participants in the hypertension group with at least one ε4 allele showed significantly greater amyloid burden than those with only one risk factor or no risk factors. Notably, increased pulse pressure was strongly associated with increased mean cortical amyloid level for patients with at least one ε4 allele.

The above studies should make us pause and wonder whether we are measuring the correct BPs to better understand the natural history of target organ damage associated with hypertension. Although we have spoken often of the need for ambulatory 24-hour BP monitoring, it is possible that we should be measuring central BP throughout the day.[5] Additional study is required to resolve this issue.

The “elephant in the room” refers to an obvious truth that is either ignored or unaddressed. While dementia is certainly the focus of attention for a large number of the scientific community, the topic has not been given the attention it deserves from hypertension specialists.

Life has breadth as well as length

While outcome studies of patients with hypertension often focus on hard endpoints of stroke, myocardial infarction, kidney failure, and death, the slow erosion of cognitive function that characterizes progressive dementia deprives patients of the pleasure of living out their lives while enjoying the interaction with family and loved ones and continuing to be amazed at the wonderful world in which we live. Thus, when drawing conclusions from the usual randomized clinical trials, we must be aware of not only what is being studied, but also what is not being studied.