In the JournalsPerspective

Hypertension in midlife, late life increases risk for dementia

Patients who had sustained hypertension in midlife to late life and those with midlife hypertension and late-life hypotension had an increased risk for dementia later in life compared with patients with normal BP in midlife and late life, according to a study published in JAMA.

“The results suggest when treating blood pressure for older adults, providers may need to consider what their midlife blood pressure was, whether they were hypertensive in middle adulthood and if they were, the treating provider is going to need to be perhaps more conscious about not letting blood pressure get too low or too high, but maintaining it at a normal level and not overtreating hypertension,” Keenan A. Walker, PhD, assistant professor of neurology at Johns Hopkins Hospital, told Cardiology Today.

ARIC study data

Researchers analyzed data from 4,761 patients (59% women; mean age at fifth visit, 75 years) aged 45 to 65 years from the ARIC study. These patients underwent a cognitive battery at baseline and functional assessment at the fifth visit.

A neuropsychological battery and interview were performed at the sixth visit to assess for dementia. Researchers also defined mild cognitive impairment in patients without dementia and determined cognitive change in all patients.

From the fifth to the sixth visit, 11% of patients developed incident dementia. Patients who had normal BP at midlife and late life had an incidence rate of dementia of 1.31 per 100 person-years (95% CI, 1-1.72), whereas those with normal BP at midlife and hypertension at late life had an incidence rate of 1.99 per 100 person-years (95% CI, 1.69-2.32). Those who had hypertension at midlife and late life had an incidence rate of 2.83 per 100 person-years (95% CI, 2.4-3.35). The incidence rate for patients with normal BP at midlife and hypotension at late life was 2.07 per 100 person-years (95% CI, 1.68-2.54) and 4.26 per 100 person-years for patients with hypertension at midlife and hypotension at late life (95% CI, 3.4-5.32).

Compared with patients who had normal BP at midlife and late life, those with hypertension at midlife and late life had a significantly increased risk for subsequent dementia (HR = 1.49; 95% CI, 1.06-2.08). This was also seen in patients with hypertension at midlife and hypotension at late life (HR = 1.62; 95% CI, 1.11-2.37).

Patients with sustained hypertension in midlife had a risk for dementia regardless of their BP during late life (HR = 1.41; 95% CI, 1.17-1.71).

The risk for mild cognitive impairment was only seen in patients with hypertension at midlife and hypotension at late life compared with those who had normal BP during midlife and late life (OR = 1.65; 95% CI, 1.02-2.69).

“From our evidence, it would suggest that the guidelines seem to be in the right spot [with below 130/80 mm Hg], but also to make sure you’re not too far below that normotensive range that the guidelines suggest,” Walker said in an interview. “I suspect that most people are conscious about lowering blood pressure, but there may be less awareness about not letting blood pressure get too low in older adults.”

BP patterns did not have a significant association with cognitive changes in late life.

“If these findings do pan out, one question going forward is whether or not this pattern that we found of hypertension followed by low blood pressure is an associated feature of dementia — that is, does dementia drive the drop in blood pressure in these people who are hypertensive — or is this pattern a risk factor for dementia,” Walker told Healio. “Does this drop in blood pressure after hypertension actually cause an increase in dementia risk? Our results and the timing of what we’re seeing — one happening before the other — does suggest that this may be an actual risk factor rather than an associated feature, but we can’t tell 100% one way or the other.”

Future therapeutic approaches

“While an opportunity exists for blood pressure modification in the prevention of dementia, earlier, midlife management may be optimal, and later blood pressure-lowering interventions require careful monitoring for the potential cognitive harm associated with late-life hypotension,” Shyam Prabhakaran, MD, MS, chairman of the department of neurology at the University of Chicago, wrote in a related editorial. “It is imperative that these nuanced effects of blood pressure on brain health inform future therapeutic approaches to prevent dementia.” – by Darlene Dobkowski

For more information:

Keenan A. Walker, PhD, can be reached at Johns Hopkins Hospital, Phipps 446, 660 North Wolfe St., Baltimore, MD 21287; email: kwalke26@jhmi.edu.

Disclosures: Walker and Prabhakaran report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Patients who had sustained hypertension in midlife to late life and those with midlife hypertension and late-life hypotension had an increased risk for dementia later in life compared with patients with normal BP in midlife and late life, according to a study published in JAMA.

“The results suggest when treating blood pressure for older adults, providers may need to consider what their midlife blood pressure was, whether they were hypertensive in middle adulthood and if they were, the treating provider is going to need to be perhaps more conscious about not letting blood pressure get too low or too high, but maintaining it at a normal level and not overtreating hypertension,” Keenan A. Walker, PhD, assistant professor of neurology at Johns Hopkins Hospital, told Cardiology Today.

ARIC study data

Researchers analyzed data from 4,761 patients (59% women; mean age at fifth visit, 75 years) aged 45 to 65 years from the ARIC study. These patients underwent a cognitive battery at baseline and functional assessment at the fifth visit.

A neuropsychological battery and interview were performed at the sixth visit to assess for dementia. Researchers also defined mild cognitive impairment in patients without dementia and determined cognitive change in all patients.

From the fifth to the sixth visit, 11% of patients developed incident dementia. Patients who had normal BP at midlife and late life had an incidence rate of dementia of 1.31 per 100 person-years (95% CI, 1-1.72), whereas those with normal BP at midlife and hypertension at late life had an incidence rate of 1.99 per 100 person-years (95% CI, 1.69-2.32). Those who had hypertension at midlife and late life had an incidence rate of 2.83 per 100 person-years (95% CI, 2.4-3.35). The incidence rate for patients with normal BP at midlife and hypotension at late life was 2.07 per 100 person-years (95% CI, 1.68-2.54) and 4.26 per 100 person-years for patients with hypertension at midlife and hypotension at late life (95% CI, 3.4-5.32).

Compared with patients who had normal BP at midlife and late life, those with hypertension at midlife and late life had a significantly increased risk for subsequent dementia (HR = 1.49; 95% CI, 1.06-2.08). This was also seen in patients with hypertension at midlife and hypotension at late life (HR = 1.62; 95% CI, 1.11-2.37).

Patients with sustained hypertension in midlife had a risk for dementia regardless of their BP during late life (HR = 1.41; 95% CI, 1.17-1.71).

The risk for mild cognitive impairment was only seen in patients with hypertension at midlife and hypotension at late life compared with those who had normal BP during midlife and late life (OR = 1.65; 95% CI, 1.02-2.69).

“From our evidence, it would suggest that the guidelines seem to be in the right spot [with below 130/80 mm Hg], but also to make sure you’re not too far below that normotensive range that the guidelines suggest,” Walker said in an interview. “I suspect that most people are conscious about lowering blood pressure, but there may be less awareness about not letting blood pressure get too low in older adults.”

BP patterns did not have a significant association with cognitive changes in late life.

“If these findings do pan out, one question going forward is whether or not this pattern that we found of hypertension followed by low blood pressure is an associated feature of dementia — that is, does dementia drive the drop in blood pressure in these people who are hypertensive — or is this pattern a risk factor for dementia,” Walker told Healio. “Does this drop in blood pressure after hypertension actually cause an increase in dementia risk? Our results and the timing of what we’re seeing — one happening before the other — does suggest that this may be an actual risk factor rather than an associated feature, but we can’t tell 100% one way or the other.”

Future therapeutic approaches

“While an opportunity exists for blood pressure modification in the prevention of dementia, earlier, midlife management may be optimal, and later blood pressure-lowering interventions require careful monitoring for the potential cognitive harm associated with late-life hypotension,” Shyam Prabhakaran, MD, MS, chairman of the department of neurology at the University of Chicago, wrote in a related editorial. “It is imperative that these nuanced effects of blood pressure on brain health inform future therapeutic approaches to prevent dementia.” – by Darlene Dobkowski

For more information:

Keenan A. Walker, PhD, can be reached at Johns Hopkins Hospital, Phipps 446, 660 North Wolfe St., Baltimore, MD 21287; email: kwalke26@jhmi.edu.

Disclosures: Walker and Prabhakaran report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Carl J. Pepine

    Carl J. Pepine

    In addition to the publication of this study, results from the SPRINT MIND trial were also published (Nasrallah IM, et al. JAMA. 2019;doi:10.1001/jama.2019.10551), which found that patients with hypertension who had a target systolic BP less than 120 mm Hg had a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume compared with those with a target BP of less than 140 mm Hg. These are two very important publications that directly relate to the increasing numbers of patients that we are seeing with cognitive impairment as well as hypertension.

    While both are associated with the development of atherosclerosis (larger vessel disease), it is known that a major component of cognitive impairment and hypertension is related to microvascular disease/dysfunction. But the mechanisms are not completely understood, and why these two conditions are much more prevalent among older women than men remain unclear.

    These recent reports help to shed light on the timing of this relationship throughout life and its remarkable sensitivity to only a few years of lower BP. The latter data from SPRINT MIND are also important because this beneficial response to lower BP was observed in a relatively low-risk cohort for cerebral vascular disease (eg, no diabetes or prior stroke).

    More recently, the gut microbiota has emerged as a contributor to both hypertension and cognitive impairment via the “brain-gut axis” and its influence on vascular, neural, immune and metabolic pathways. Altering the “bugs” in our GI tract may emerge as a novel management tool for these conditions. This is clearly a hot area, so stay tuned!

    • Carl J. Pepine, MD, MACC
    • Cardiology Today Chief Medical Editor
      University of Florida, Gainesville

    Disclosures: Pepine reports no relevant financial disclosures.