, new research shows. In a retrospective study of more than 15,000 participants, hypertension during middle age was associated with memory decline, and onset at later ages was linked to worsening memory and global cognition.
The investigators found that prehypertension, defined as systolic pressure of 120-139 mm Hg or diastolic pressure of 80-89 mm Hg, was also linked to accelerated cognitive decline.
Although duration of hypertension was not associated with any marker of cognitive decline, blood pressure control “can substantially reduce hypertension’s deleterious effect on the pace of cognitive decline,” said study investigator Sandhi M. Barreto, MD, PhD, professor of medicine at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
The findings were published online Dec. 14 in Hypertension.
Unanswered questions
Hypertension is an established and highly prevalent risk factor for cognitive decline, but the age at which it begins to affect cognition is unclear. Previous research suggests that onset during middle age is associated with more harmful cognitive effects than onset in later life. One reason for this apparent difference may be that the duration of hypertension influences the magnitude of cognitive decline, the researchers noted.
Other studies have shown that prehypertension is associated with damage to certain organs, but its effects on cognition are uncertain. In addition, the effect of good blood pressure control with antihypertensive medications and the impact on cognition are also unclear.
To investigate, the researchers examined data from the ongoing, multicenter ELSA-Brasil study. ELSA-Brasil follows 15,105 civil servants between the ages of 35 and 74 years. Dr. Barreto and team assessed data from visit 1, which was conducted between 2008 and 2010, and visit 2, which was conducted between 2012 and 2014.
At each visit, participants underwent a memory test, a verbal fluency test, and the Trail Making Test Part B. The investigators calculated Z scores for these tests to derive a global cognitive score.
Blood pressure was measured on the right arm, and hypertension status, age at the time of hypertension diagnosis, duration of hypertension diagnosis, hypertension treatment, and control status were recorded. Other covariables included sex, education, race, smoking status, physical activity, body mass index, and total cholesterol level.
The researchers excluded patients who did not undergo cognitive testing at visit 2, those who had a history of stroke at baseline, and those who initiated antihypertensive medications despite having normotension. After exclusions, the analysis included 7,063 participants (approximately 55% were women, 15% were Black).
At visit 1, the mean age of the group was 58.9 years, and 53.4% of participants had 14 or more years of education. In addition, 22% had prehypertension, and 46.8% had hypertension. The median duration of hypertension was 7 years; 29.8% of participants with hypertension were diagnosed with the condition during middle age.
Of those who reported having hypertension at visit 1, 7.3% were not taking any antihypertensive medication. Among participants with hypertension who were taking antihypertensives, 31.2% had uncontrolled blood pressure.
Independent predictor
Results showed that prehypertension independently predicted a significantly greater decline in verbal fluency (Z score, –0.0095; P < .01) and global cognitive score (Z score, –0.0049; P < .05) compared with normal blood pressure.
At middle age, hypertension was associated with a steeper decline in memory (Z score, –0.0072; P < .05) compared with normal blood pressure. At older ages, hypertension was linked to a steeper decline in both memory (Z score, –0.0151; P < .001) and global cognitive score (Z score, –0.0080; P < .01). Duration of hypertension, however, did not significantly predict changes in cognition (P < .109).
Among those with hypertension who were taking antihypertensive medications, those with uncontrolled blood pressure experienced greater declines in rapid memory (Z score, –0.0126; P < .01) and global cognitive score (Z score, –0.0074; P < .01) than did those with controlled blood pressure.
The investigators noted that the study participants had a comparatively high level of education, which has been shown to “boost cognitive reserve and lessen the speed of age-related cognitive decline,” Dr. Barreto said. However, “our results indicate that the effect of hypertension on cognitive decline affects individuals of all educational levels similarly,” she said.
Dr. Barreto noted that the findings have two major clinical implications. First, “maintaining blood pressure below prehypertension levels is important to preserve cognitive function or delay cognitive decline,” she said. Secondly, “in hypertensive individuals, keeping blood pressure under control is essential to reduce the speed of cognitive decline.”
The researchers plan to conduct further analyses of the data to clarify the observed relationship between memory and verbal fluency. They also plan to examine how hypertension affects long-term executive function.
‘Continuum of risk’
Commenting on the study, Philip B. Gorelick, MD, MPH, adjunct professor of neurology (stroke and neurocritical care) at Northwestern University, Chicago, noted that, so far, research suggests that the risk for stroke associated with blood pressure levels should be understood as representing a continuum rather than as being associated with several discrete points.
“The same may hold true for cognitive decline and dementia. There may be a continuum of risk whereby persons even at so-called elevated but relatively lower levels of blood pressure based on a continuous scale are at risk,” said Dr. Gorelick, who was not involved with the current study.
The investigators relied on a large and well-studied population of civil servants. However, the population’s relative youth and high level of education may limit the generalizability of the findings, he noted. In addition, the follow-up time was relatively short.
“The hard endpoint of dementia was not studied but would be of interest to enhance our understanding of the influence of blood pressure elevation on cognitive decline or dementia during a longer follow-up of the cohort,” Dr. Gorelick said.
The findings also suggest the need to better understand mechanisms that link blood pressure elevation with cognitive decline, he added.
They indicate “the need for additional clinical trials to better elucidate blood pressure lowering targets for cognitive preservation in different groups of persons at risk,” such as those with normal cognition, those with mild cognitive impairment, and those with dementia, said Dr. Gorelick. “For example, is it safe and efficacious to lower blood pressure in persons with more advanced cognitive impairment or dementia?” he asked.
The study was funded by the Brazilian Coordination for the Improvement of Higher Education Personnel. Dr. Barreto has received support from the Research Agency of the State of Minas Gerais. Although Dr. Gorelick was not involved in the ELSA-Brasil cohort study, he serves on a data monitoring committee for a trial of a blood pressure–lowering agent in the preservation of cognition.
A version of this article first appeared on Medscape.com.