Trending Clinical Topic: Blood Pressure Drugs and Dementia Risk

Ryan Syrek


January 20, 2023

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Hypertension and dementia are two concerning conditions that are rapidly increasing worldwide due to aging populations. A new study examined the effect of different types of blood pressure (BP) medications on dementia development (see Infographic). Those findings, along with new studies concerning vascular risk factors for Alzheimer's disease and related conditions, resulted in this week's top trending clinical topic.

Previous studies that suggested antihypertensive medications that stimulate types 2 and 4 angiotensin II receptors were associated with lower rates of dementia were relatively small in enrollment. However, a new retrospective cohort study included a random sample of 57,773 Medicare beneficiaries. Participants were at least 65 years of age (mean age, 73.8 years) with new-onset hypertension. Most (62.9%) were women and 86.9% were White. After adjustments, antihypertensive medication regimens that exclusively stimulated, rather than inhibited, types 2 and 4 angiotensin II receptors were associated with a 16% lower risk for incident Alzheimer's disease and related dementia (ADRD) over a follow-up of around 7 years (hazard ratio [HR], 0.84; 95% CI, 0.79-0.90; P < .001). In regard to vascular dementia, use of stimulating vs inhibiting BP drugs was associated with an 18% lower risk (HR, 0.82; 95% CI, 0.69-0.96; P = .02).

Previous findings had shown that antihypertensive medications that cross the blood-brain barrier (BBB) were potentially associated with less memory decline. A meta-analysis from 2021 assessed data on 12,849 individuals from 14 cohorts who received either BBB-crossing or non–BBB-crossing antihypertensives. Cognition was assessed for executive function, attention, verbal memory learning, language, mental status, recall, and processing speed. Those taking BBB-crossing agents had superior verbal memory (recall) compared with individuals taking non–BBB-crossing antihypertensives, with a maximum effect size of 0.07 (P = .03). Individuals in the BBB-crossing group, however, had relatively inferior attention ability, with a minimum effect size of –0.17 (P = .02). No significant differences were observed between the groups in terms of the other cognitive measures.

Experts suggest that optimizing BP interventions may be crucial in preventing cognitive decline. A meta-analysis of randomized clinical trials from 2020 showed that BP reduction with antihypertensive medications was significantly associated with decreased risk for cognitive impairment and incident dementia. A new study by Li and colleagues  shed new light on these findings. It included data from almost 17,000 cognitively healthy adults aged 50 years or older. Researchers found that higher pulse pressure and cumulative systolic BP were independently associated with faster global cognitive decline as well as increased dementia and all-cause mortality risk. These studies have prompted some experts to propose a possible target systolic BP of 110-130 mm Hg for middle-aged and older patients paired with a target diastolic BP of 70-80 mm Hg to help maintain appropriate pulse pressure.

Recent research suggests that specific vascular risk factors for dementia vary with age. New data from the Framingham Heart Study show that, at age 55 years, diabetes and high systolic BP are the most important vascular risk factors for increased 10-year incident dementia at age 55. At age 65 years, heart disease is a more important dementia risk factor. Among 4899 individuals aged 55 years (57% women), individuals with diabetes at age 55 years had a fourfold increased 10-year risk for dementia (HR, 4.31; 95% CI, 1.97-9.43). Among those patients, dementia risk also increased by about 12% for every 10-point increase in systolic BP (HR, 1.12; 95% CI, 1.02-1.24 per 10 mm Hg increment). Alternatively, patients who had cardiovascular disease when they were 65 years of age were nearly twice as likely to develop dementia (HR, 1.95; 95% CI, 1.24 – 3.07).

Tackling modifiable risk factors is essential in the absence of targeted treatments for cognitive impairment and dementia. Recent data show that nearly half of all US adults aged 45 years or older have such modifiable risk factors. Data from the Centers for Disease Control and Prevention , which included 162,000 adults aged 45 years or  older, found that nearly half had hypertension and did not achieve physical activity recommendations, the two most common modifiable risk factors. Moreover, 35% of adults had obesity, 19% had diabetes, 18% had depression, 15% smoked, 11% had hearing loss, and 10% were binge drinkers.

As the incidence of hypertension and dementia continues to rise, appropriate interventions become even more important. Insights into what interventions are most appropriate and when they should be implemented are essential components of prevention strategies. These new findings help further clarify such approaches and resulted in this week's top trending clinical topic.

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