Aging, Hypertension, and Dementia: Resolving the Mystery

As we age, heart disease, often presenting first as hypertension in mid-life, develops with an association to development of late-life dementia.  Dementia affects almost 50 million persons world-wide making it a public health challenge.^1-2 Preventing heart disease by effective longitudinal treatment of hypertension is an attractive goal, but does it prevent, delay, or reduce dementia? 

Relationship of Longitudinal Cardiovascular Disease With Cognitive Decline:

In a study of 1600 persons from northeastern Illinois, mean age 79.5±7.5 years; 75.8% female, who were followed for a mean of 21 years, their mean Framingham General Cardiovascular Score (FGCRS) was 15.6±3.7.³  The participants were stratified into three quartiles (lowest, middle, and highest) by their baseline FGCRS.  Compared with the lowest tertile, the highest tertile had a faster decline in global cognition, episodic memory, working memory, and perceptual speed over the follow-up.  Magnetic resonance imaging studies showed the higher FGCRS had smaller hippocampus volumes, grey matter, and total brain to volume of white matter hyperintensities.  These findings suggest that greater cardiovascular burden over time may predict faster declines in memory and speed of thought associated with neurodegeneration.

Association of Long-term Blood Pressure Lowering With Dementia:

A systematic review and meta-analysis of the benefit of blood pressure lowering for the prevention of dementia or cognitive decline blood pressure lowering was significantly associated with a lower risk of dementia and cognitive impairment.⁵ Mean age of the included participants was 69±5.4 years with 42.2% women.  Mean systolic and diastolic blood pressure was 154±14.9/83.3±9.9 mmHg.  The mean duration of follow-up was 49.2 months.  Blood pressure lowering with antihypertensive agents was significantly associated with reduced risk of dementia or cognitive impairment [OR] 0.93; 95% CI: 0.88-0.98).  Blood pressure lowering was not significantly associated with a change in cognitive test scores.  This study adds to the data from the SPRINT MIND trial supporting that blood pressure lowering is important in reducing the risk of dementia.⁵

Type of Antihypertension Class and Risk for Dementia:

A separate meta-analysis of 14 randomized trials with a total of 96.158 community-dwelling dementia-free adults > 55 years old participants followed for a mean of 4.1 years there were 3728 incident cases of dementia and 1741 incident Alzheimer’s disease diagnoses.⁶ In patients with hypertension (n-15,537) and using antihypertensive medication the risk of developing dementia was a hazard ratio [HR] 0.88; 95% CI: 0-29-0.98; p=0.019 and for Alzheimer’s disease [HR] 0.84; 95% CI: 0.73-0.97; p=0.021.  The study did not find any significant differences between antihypertensive drug classes and incidence dementia or Alzheimer’s disease.  

The risk of dementia is a major public health challenge.  Development of cardiovascular disease at middle-age is associated with accelerated declines in memory and speed of thought associated with neurodegeneration.  There is good news!  Chronic blood pressure lowering is associated with a modest decrease in the risk of dementia and cognitive decline, independent of antihypertensive class(es) prescribed.  What remains elusive is what target blood pressure to achieve during chronic antihypertensive treatment.  The SPRINT MIND trial was underpowered to determine whether intensive blood pressure control (< 120 mmHg SBP) vs. standard blood pressure control (< 140 mmHg SBP) is the best target.  However, all patients reached a SBP of <135 mmHg which provides a generalized achievable target. 

Given the high incidence of dementia in an ever-growing aging population, these studies provide a foundation to lower blood pressure early in patients, especially those with underlying cardiovascular disease.  Postponing blood pressure treatment with antihypertensive drugs or treatment apathy in lowering blood pressure to goal-directed targets is not good practice. 

Mark A. Munger, PharmD, FCCP, FACC, is a professor of pharmacotherapy and adjunct professor of internal medicine, at the University of Utah, where he also serves as the associate dean of Academic Affairs for the College of Pharmacy. 

References:

1. Livingston G, Sommerlad A, Orgeta V,et al. Dementia, Prevention, intervention and care. Lancet 2017;390:2673-734
2. Response to the growing dementia burden must be faster. Lancet Neurol 2018;17:651
3. Song R, Xu H, Dintica CS, Pan K-Y, Qi X, Buchman AS, Bennett DA, Xu W. Associates between cardiovascular risk structural brain changes, and cognitive decline. JACC 2020;75(20):2525-34.
4. Hughes D, Judge C, Murphy “R, Loughlin E, Costello M, Whitely W, Bosch J, O’Donnell MJ, Canavan M. Association of blood pressure lowering with incident dementia or cognitive impairment. A systematic review and meta-analysis. JAMA 2020:323(19):1934-44.
5. The SPRINT MIND Investigators for the SPRINT Research Group. Effect of intensive vs. standard blood pressure control on probably dementia. A randomized clinical trial. JAMA 2019;32(6):553-61.
6. Ding J, Davis-Plourde KL, Sedaghat S, et al.  Antihypertensive medications and risk for incident dementia and Alzheimer’s disease: A meta-analysis of individual participant data from prospective cohort studies. Lancet 2020 Jan;19(1):61-70.