Hypertension in midlife and early late life significantly contributes to the risk of developing dementia, even through age 90, according to study findings published in Alzheimer’s & Dementia.
“Mechanistically, sustained midlife hypertension is hypothesized to act on cognitive impairment through increased risk of arteriolar-level cerebrovascular disease,” according to researchers. Yet, late-life hypertension has been inconsistently associated with dementia risk. National and global efforts to enhance research in this field can help inform public health and clinical recommendations when it comes to the prevention of cognitive decline and dementia via midlife blood pressure (BP) management.
The researchers conducted a systematic review of studies that reported population attributable fractions (PAFs) of dementia from hypertension, 2 conditions shown to be associated in an age-dependent manner. They hypothesized that incident dementia from hypertension would differ when assessed in midlife vs late-life age groups.
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Prevalent hypertension was defined in terms of systolic BP (SBP) and diastolic BP (DBP), based on the 2017 American College of Cardiology/American Heart Association guidelines.
Normal BP: SBP <120 mm Hg and DBP <80 mm Hg
Elevated BP: SBP 120 to 129 mm Hg and DBP <80 mm Hg
Stage 1 Hypertension: SBP 130 to 139 mm Hg or DBP 80 to 80 mm Hg
Stage 2 Hypertension: SBP ≥140 mm Hg or DBP ≥90 mm Hg
If the SBP and DBP were in different categories, the higher category was used for classification purposes (eg, SBP of 140 mm Hg and DBP of 80 mm Hg was considered stage 2 hypertension).
Recognized risk factors for dementia obtained at baseline as covariates included age, sex, combined race/ARIC center, years of education, apolipoprotein E (APOE) genotype, smoking status, alcohol consumption, leisure-time physical activity, body mass index, plasma total cholesterol level, plasma high-density lipoprotein cholesterol level, and presence of diabetes.
The researchers found that the percentage of individuals with hypertension increased with age. In the age 45-54, 55-64, 65-74, and 75-84 groups, the baseline prevalence of stage 2 hypertension was 28%, 42%, 61%, and 77%, respectively.
In all age groups, the participants with hypertension — in particular, those with stage 2 hypertension — were more likely to identify as Black and to have prevalent vascular risk factors, such as diabetes.
The median age at diagnosis of dementia was 81 years, with the number of cases of dementia increasing considerably among participants aged 80 to 90. At age 80, the total number of incident dementia cases identified were:
Ages 45-54: 736 cases (10%; median follow-up, 27.2 years);
Ages 55-64: 939 cases (8%; median follow-up, 18.3 years); and
Ages 65-74: 381 cases (6%; median follow-up, 7.4 years).
By age 90, the total number of incident dementia cases increased were:
Ages 45-54: 991 cases (13%; median follow-up, 29.0 years);
Ages 55-64: 2361 cases (19%; median follow-up, 20.9 years);
Ages 65-74: 1357 cases (20%; median follow-up, 8.9 years); and
Ages 75-84: 405 cases (18%; median follow-up, 6.1 years).
The occurrence of stages 1 and 2 hypertension in midlife (ie, age groups 45-54 and 55-64), and stage 2 hypertension in early late life (ie, age group 65-74), was associated with a significantly increased hazard for dementia by age 80. By age 90, although the associations were consistent in direction, they were smaller in magnitude.
By 80 years of age, the PAFs of dementia were consistent across midlife and early late life — at approximately 15% to 20% among those with non-normal BP (ie, combination of elevated BP, stage 1 hypertension, and stage 2 hypertension).
Stage 2 hypertension, which was associated with an excess percentage of dementia cases across all age-groups, increased with age:
Ages 45-54: 11.9%; 95% CI, 6.4%-16.2%;
Ages 55-64: 14.4%; 95% CI, 8.0%-19.8%; and
Ages 65-74: 21.3%; 95% CI, 2.8%-35.4%.
The PAFs for stage 1 hypertension, which were in the range of 2.3% to 3.4%, were strongly supported only for those in the age group 55-64 (3.4%; 95% CI, 0.9%-5.5%). By age 90, the PAFs of dementia showed a trend that was consistent with dementia by age 80 across hypertension categories in midlife and early late life, although of a smaller magnitude. Overall, the PAFs from non-normal BP were:
Ages 45-54: 13.8%; 95% CI, 6.6%-20.0%;
Ages 55-64: 12.9%; 95% CI, 7.0%-18.2%;
Ages 65-74: 10.9%; 95% CI, 0.02%-21.0%; and
Ages 75-84: null.
Several limitations of the current study warrant mention. Regarding clinical assessment, these sources might capture individuals with more severe dementia and overlook those with milder stages of dementia. Further, when relative hazards were estimated, selective attrition of participants with hypertension who were at risk for dementia might have introduced an element of bias.
The researchers concluded, “Interventions targeting hypertension even in early life might reduce a sizeable proportion of dementia.”
Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Reference
Smith JR, Sharrett AR, Pike JR, et al. Dementia occurring over a 32-year follow-up attributable to hypertension observed at different ages: implications for dementia prevention. Alzheimers Dement. Published online February 18, 2023. doi:10.1002/alz.12984
This article originally appeared on Neurology Advisor
