Midlife, Late-Life Blood Pressure Trends Linked to Dementia Risk

Nancy A. Melville

November 24, 2016

BALTIMORE — Elevated blood pressure in mid-life and a rapid decline in blood pressure later in life are each strongly associated with risk of dementia, a new study using data from the Framingham Offspring Cohort suggests.

"This is the first study to reliably report an association between midlife systolic hypertension (140 mmHg or higher) and clinically confirmed dementia in late life," the authors conclude.

Senior author Sudha Seshadri, MD, a professor of neurology at Boston University School of Medicine, Massachusetts, noted that the results did not vary according to use of antihypertensive medications.

"If an individual's blood pressure was high, being on a medication did not result in a higher or lower risk overall," she told Medscape Medical News.

She noted that the findings offer important insights specifically about dementia. "Although the cross-sectional relationship between midlife hypertension and cognitive function in persons who are dementia-free has been clear for many years [demonstrated in] landmark studies, the relationship with clinical dementia has not been clear," Dr Seshadri said.

"No prior study has looked at midlife blood pressure and the endpoint of clinical dementia as an outcome."

A position paper published online in October by the American Heart Association in Hypertension to assess the state of knowledge of the role of chronic arterial hypertension and its treatment on cognition concluded that data are still insufficient to make recommendations.

The authors concluded, however, that "judicious treatment of hypertension, taking into account goals of care and individual characteristics (age and comorbidities), seems justified to safeguard vascular health and, as a consequence, brain health."

Their findings were presented at the American Neurological Association (ANA) 2016 Annual Meeting.

Midlife increases in blood pressure and later-life low blood pressure have been shown to be associated with cognitive decline in major studies; however, less is understood regarding their role in the development of clinical dementia.

For the study, researchers evaluated data from the Framingham Offspring Cohort of 1440 participants who had been examined on five sequential occasions at four yearly intervals, beginning in midlife (1983–1987; mean age 55 years) and continuing to late life (1998–2001; mean age 69 years).

Participants who were dementia-free at the fifth examination were subsequently followed for a mean of 8 years to evaluate the development of dementia. Of these patients, 107 went on to be diagnosed with dementia, including 50% who used antihypertensive medication during the period.

Midlife systolic hypertension, defined as 140/90 mmHg or higher, was associated with an increased risk of dementia (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.14 - 2.53), as was late-life systolic hypertension (HR, 1.48; 95% CI, 1.01 - 2.19).

Systolic hypertension that was persistent over the course of the study was associated with a significant increase in risk of dementia (HR, 2.15; 95% CI, 1.37 - 3.35), and a rapid decline in systolic blood pressure from mid-to-late life was also associated with an increased risk (HR, 1.62; 95% CI, 1.08 - 2.44 for slope of change < –0.5 vs > –0.5).

Dr Seshadri added that a broad array of mechanisms could explain the link between hypertension and dementia.

"Hypertension impacts dementia risk in many ways," Dr Seshadri said. "It increases the risk of ischemic and hemorrhagic strokes and promotes atherosclerosis, arteriosclerosis, and stiffness of large and smaller vessels, reducing the ability of the brain to autoregulate its blood flow."

"[In addition], hypertension damages the heart, and thus reduces cardiac output reaching the brain; it may damage the kidneys, resulting in accumulation of molecules adversely affecting the brain; and damages the endothelium of the blood–brain barrier."

Trajectory of Change

Costantino Iadecola, MD, who led the committee on the recent AHA position paper on hypertension and cognition, said Dr Seshadri's new study contributes to the need for more evidence, describing the link between midlife hypertension and late-life dementia.

"These prospective data are novel and provide new insight into the association between blood pressure and dementia," Dr Iadecola, who is director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medical College, New York, NY, told Medscape Medical News.

"Individuals with steady, persistent hypertension or a rapid blood pressure decline were at greater risk [for dementia]."

A key strength of the study is that sufficient blood pressure measurements were available to understand the trajectory of blood pressure change, he noted.

"[This is] a critical variable and much more informative that spot checking blood pressure over decades."

In addition to the noted effects of persistent hypertension and dementia, different pathophysiological mechanisms could be involved in the heightened dementia risk seen with rapid blood pressure decline late in life, Dr Iadecola added.

"One possibility is that the reduction in blood pressure was the effect of damage to the brain induced by previous hypertension or other brain pathology, for example Alzheimer's disease, which is also associated with midlife hypertension and late-life hypotension," he explained.

"The brain is vital for maintaining normal levels of blood pressure by neurohumoral mechanisms regulating intravascular volume and peripheral vascular resistance. Dysfunction and damage to brain regions involved in such regulation may have been responsible for the reduction in blood pressure."

Furthermore, hypertension leads to a shift to the right of the "autoregulatory curve," describing the relationship between blood pressure and cerebral blood flow, Dr Iadecola explained.

"Such right-shift would result in the brain getting 'accustomed' to run at higher levels of blood pressure. In individuals with a rapid reduction in cerebral blood flow caused by the declining blood pressure failure of autoregulation may have led to a reduction in blood flow resulting in brain dysfunction and damage."

More research is needed to better understand the relationships, he said.

"Additional clinical biomarker data, such as concurring Alzheimer's disease and information about the cause of hypertension, if known, would be required to gain insight into why in some individuals there was a reduction in blood pressure, while in others there was persistent hypertension."

The authors and Dr Iadecola have reported no relevant financial relationships.

American Neurological Association (ANA) 2016 Annual Meeting. Abstract M148. Presented October 17, 2016.

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