Older women, blood pressure, and cognition
Authors: Philip B Gorelick, Farzaneh Sorond
Journal: The Lancet Healthy Longevity (2022)

Controversy exists regarding the management of blood pressure (BP) in older people for the prevention of cognitive impairment or dementia.1Gorelick PB Sorond F Cognitive function in SPRINT: where do we go next?.Lancet Neurol. 2020; 19: 880-881Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar Is it safe and effective to substantially lower BP in older patients or will there be untoward effects such as stroke and worsening of cognition, syncope, or other adverse events?1Gorelick PB Sorond F Cognitive function in SPRINT: where do we go next?.Lancet Neurol. 2020; 19: 880-881Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar On the basis of observational epidemiological studies, it has long been held that raised BP in midlife predicts cognitive impairment or dementia in later life. However, the association of elevated BP as a predictor of dementia is less clear in older people.2Gorelick PB Whelton PK Sorond F Carey RM Blood pressure management in stroke.Hypertension. 2020; 76: 1688-1695Crossref PubMed Scopus (7) Google Scholar A major guideline on BP control from from the American College of Cardiology, American Heart Association, and other expert groups concludes that it is reasonable to lower BP in people with hypertension to prevent cognitive decline and dementia, but the guidance does not set a firm target for BP lowering.3Whelton PK Carey RM Aronow WS et al.2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines.Hypertension. 2018; 71: e13-115Crossref PubMed Scopus (1787) Google Scholar The Systolic Blood Pressure Intervention Trial (SPRINT) allayed some clinical concerns by showing that targeting systolic blood pressure (SBP) to less than 120 mm Hg compared with standard therapy (<140 mm Hg) was relatively safe and improved the secondary cognitive outcomes, mild cognitive impairment, and the composite of MCI and probable dementia, although there was no significant reduction of the primary outcome, probable dementia.4The SPRINT RESEARCH GroupA randomized trial of intensive versus standard blood-pressure control.N Engl J Med. 2015; 373: 2103-2116Crossref PubMed Scopus (3579) Google Scholar, 5The SPRINT MIND Investigators for the SPRINT Research GroupEffect of intensive vs standard blood pressure control on probable dementia. A randomized clinical trial.JAMA. 2019; 321: 553-561Crossref PubMed Scopus (460) Google Scholar There remain subgroups of study participants such as older women who have not been well represented in randomised controlled trials or observational studies of BP and cognition. In The Lancet Healthy Longevity Liu and colleagues report the findings of the Women's Health Initiative Memory Study (WHIMS), 6Liu L Hayden KM May NS et al.Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the women's Health Initiative Memory Study.Lancet Health Longev. 2022; 3: e42-e53Summary Full Text Full Text PDF Scopus (1) Google Scholar a sample of 7207 community-dwelling women aged 65–79 years, and the association of BP and hypertension treatment on the occurrence of mild cognitive impairment and dementia in older women.6Liu L Hayden KM May NS et al.Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the women's Health Initiative Memory Study.Lancet Health Longev. 2022; 3: e42-e53Summary Full Text Full Text PDF Scopus (1) Google Scholar WHIMS participants originated from the WHI hormone trials, and later transitioned to the WHIMS-Epidemiology of Cognitive Health Outcomes (ECHO) post-trial study. Cognitive function was assessed annually and defined by a central adjudication process. BP was measured at baseline, and pulse pressure (PP) was calculated. The main outcomes were mild cognitive impairment, probable dementia, and cognitive loss (a composite of mild cognitive impairment or probable dementia, or both). The median follow-up was 9 years, and 15·7% of participants were classified as having mild cognitive impairment, 10·3% as having probable dementia, and 21·3% as having cognitive loss.6Liu L Hayden KM May NS et al.Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the women's Health Initiative Memory Study.Lancet Health Longev. 2022; 3: e42-e53Summary Full Text Full Text PDF Scopus (1) Google Scholar Incidence rates per 1000 person-years were 15·3 for mild cognitive impairment, 9·7 for dementia, and 20·3 for cognitive loss. Elevated SBP and PP predicted increased risk of mild cognitive impairment and cognitive loss (test for trend across strata: p<0·01); however, participants with hypertension with SBP lower than 120 mm Hg were not at increased risk of mild cognitive impairment (hazard ratio [HR] 1·33, 95% CI 0·98–1·82; p=0·071) or cognitive loss (1·09, 0·82–1·44; p=0·57) compared with those with normal BP. Participants on BP-lowering medication with a PP lower than 50 mm Hg did not have an increased risk of mild cognitive impairment (1·26, 0·98–1·62; p=0·07) or cognitive loss (1·17, 0·94–1·46; p=0·16). There were no significant associations of probable dementia and the aforementioned BP metrics, and BP and PP variability did not predict cognitive outcome. BP metrics are complex and can be analysed in different ways.7Mahinrad S, Sorond F, Gorelick PB. Hypertension and cognitive dysfunction: a review of mechanisms, life-course observational studies and clinical trials. Reviews in Cardiovascular Medicine (in press).Google Scholar For example, mean SBP and PP at baseline and BP variability can be analysed, as was done in the current study.6Liu L Hayden KM May NS et al.Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the women's Health Initiative Memory Study.Lancet Health Longev. 2022; 3: e42-e53Summary Full Text Full Text PDF Scopus (1) Google Scholar Other metrics of interest and beyond baseline BP can include time-dependent cumulative SBP and BP trajectories during given time periods.7Mahinrad S, Sorond F, Gorelick PB. Hypertension and cognitive dysfunction: a review of mechanisms, life-course observational studies and clinical trials. Reviews in Cardiovascular Medicine (in press).Google Scholar Therefore, one must consider the effect of BP over time on cognition rather than a single baseline measure. An additional associated factor of interest is the class of antihypertensive therapy. Although some doctors favour administration of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, a class effect favouring one BP lowering class over another for perseveration of cognition has not been conclusively shown.8Peters R Yasar S Anderson CS et al.Investigation of antihypertensive class, dementia, and cognitive decline: a meta-analysis.Neurology. 2020; 94: e267-e291Crossref PubMed Scopus (37) Google Scholar This WHI observational study6Liu L Hayden KM May NS et al.Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the women's Health Initiative Memory Study.Lancet Health Longev. 2022; 3: e42-e53Summary Full Text Full Text PDF Scopus (1) Google Scholar provides unique information as it emphasises the association of BP and PP on cognitive outcomes in a large cohort of older women.6Liu L Hayden KM May NS et al.Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the women's Health Initiative Memory Study.Lancet Health Longev. 2022; 3: e42-e53Summary Full Text Full Text PDF Scopus (1) Google Scholar The main findings show that older women with hypertension and SBP of 120 mm Hg or higher were at increased risk of mild cognitive impairment and cognitive loss, whereas those treated to an SBP of less than 120 mm Hg were not at a significantly increased risk of the aforementioned outcomes.6Liu L Hayden KM May NS et al.Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the women's Health Initiative Memory Study.Lancet Health Longev. 2022; 3: e42-e53Summary Full Text Full Text PDF Scopus (1) Google Scholar The association between hypertension or elevation of SBP or PP and probable dementia seemed to be increased but did not reach significance. The latter finding for SBP and probable dementia were similar to those of SPRINT,4The SPRINT RESEARCH GroupA randomized trial of intensive versus standard blood-pressure control.N Engl J Med. 2015; 373: 2103-2116Crossref PubMed Scopus (3579) Google Scholar, 5The SPRINT MIND Investigators for the SPRINT Research GroupEffect of intensive vs standard blood pressure control on probable dementia. A randomized clinical trial.JAMA. 2019; 321: 553-561Crossref PubMed Scopus (460) Google Scholar but both were underpowered studies for the outcome of probable dementia. Overall, these observational findings6Liu L Hayden KM May NS et al.Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the women's Health Initiative Memory Study.Lancet Health Longev. 2022; 3: e42-e53Summary Full Text Full Text PDF Scopus (1) Google Scholar complement those of SPRINT,4The SPRINT RESEARCH GroupA randomized trial of intensive versus standard blood-pressure control.N Engl J Med. 2015; 373: 2103-2116Crossref PubMed Scopus (3579) Google Scholar, 5The SPRINT MIND Investigators for the SPRINT Research GroupEffect of intensive vs standard blood pressure control on probable dementia. A randomized clinical trial.JAMA. 2019; 321: 553-561Crossref PubMed Scopus (460) Google Scholar and as we await additional clinical trial data,9Daillare-Theroux C Quesnal-Olivo M-H Brochu K et al.Evaluation of intensive vs. standard blood pressure reduction and association with cognitive decline and dementia. A systematic review and meta-analysis.JAMA Netw Open. 2021; 4e2134553Crossref PubMed Scopus (2) Google Scholar they provide support to consider intensive BP lowering, specifically as it relates to older women, to an SBP target of less than 120 mm Hg. PBG serves as a member of a data and safety monitoring committee for a Novartis-sponsored trial of LCZ696 for cognition in heart failure. Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the Women's Health Initiative Memory StudyResults of our study show significant associations of hypertension and elevated SBP and PP levels with risk of mild cognitive impairment and the combined endpoint of either mild cognitive impairment or probable dementia, suggesting that intensive control of hypertension, SBP, and PP can preserve cognitive health in older women. Full-Text PDF Open Access