Association of Midlife to Late-Life Blood Pressure Patterns With Incident Dementia

Abstract

Importance: The association between late-life blood pressure (BP) and cognition may depend on the presence and chronicity of past hypertension. Late-life declines in blood pressure following prolonged hypertension may be associated with poor cognitive outcomes.

Objective: To examine the association of midlife to late-life BP patterns with subsequent dementia, mild cognitive impairment, and cognitive decline.

Design, setting, and participants: The Atherosclerosis Risk in Communities prospective population-based cohort study enrolled 4761 participants during midlife (visit 1, 1987-1989) and followed-up over 6 visits through 2016-2017 (visit 6). BP was examined over 24 years at 5 in-person visits between visits 1 and 5 (2011-2013). During visits 5 and 6, participants underwent detailed neurocognitive evaluation. The setting was 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis, Minnesota. Follow-up ended on December 31, 2017.

Exposures: Five groups based on longitudinal patterns of normotension, hypertension (>140/90 mm Hg), and hypotension (<90/60 mm Hg) at visits 1 to 5.

Main outcomes and measures: Primary outcome was dementia onset after visit 5, based on Ascertain Dementia-8 informant questionnaires, Six-Item Screener telephone assessments, hospital discharge and death certificate codes, and the visit 6 neurocognitive evaluation. Secondary outcome was mild cognitive impairment at visit 6, based on the neurocognitive evaluation.

Results: Among 4761 participants (2821 [59%] women; 979 [21%] black race; visit 5 mean [SD] age, 75 [5] years; visit 1 mean age range, 44-66 years; visit 5 mean age range, 66-90 years), there were 516 (11%) incident dementia cases between visits 5 and 6. The dementia incidence rate for participants with normotension in midlife (n = 833) and late life was 1.31 (95% CI, 1.00-1.72 per 100 person-years); for midlife normotension and late-life hypertension (n = 1559), 1.99 (95% CI, 1.69-2.32 per 100 person-years); for midlife and late-life hypertension (n = 1030), 2.83 (95% CI, 2.40-3.35 per 100 person-years); for midlife normotension and late-life hypotension (n = 927), 2.07 (95% CI, 1.68-2.54 per 100 person-years); and for midlife hypertension and late-life hypotension (n = 389), 4.26 (95% CI, 3.40-5.32 per 100 person-years). Participants in the midlife and late-life hypertension group (hazard ratio [HR], 1.49 [95% CI, 1.06-2.08]) and in the midlife hypertension and late-life hypotension group (HR, 1.62 [95% CI, 1.11-2.37]) had significantly increased risk of subsequent dementia compared with those who remained normotensive. Irrespective of late-life BP, sustained hypertension in midlife was associated with dementia risk (HR, 1.41 [95% CI, 1.17-1.71]). Compared with those who were normotensive in midlife and late life, only participants with midlife hypertension and late-life hypotension had higher risk of mild cognitive impairment (37 affected individuals (odds ratio, 1.65 [95% CI, 1.01-2.69]). There was no significant association of BP patterns with late-life cognitive change.

Conclusions and relevance: In this community-based cohort with long-term follow-up, sustained hypertension in midlife to late life and a pattern of midlife hypertension and late-life hypotension, compared with midlife and late-life normal BP, were associated with increased risk for subsequent dementia.

Figure 1.. Study Timeline and Longitudinal Blood Pressure Patterns

^aOf the participants who attended visit 4, 3304 died before visit 5 and 2247 did not attend visit 5. There were 433 participants who did not attend visit 4 but attended visit 5. ^bBetween visits 5 and 6, 1777 participants in the analytic sample were excluded (see panel C), 198 died, and 1284 did not attend visit 6. ^cBlood pressure pattern groups based on blood pressure levels at Visits 1 to 5. Dotted lines represent the approximate 24-year blood pressure pattern. Hypertension was defined as systolic blood pressure >140 mm Hg, or diastolic blood pressure >90 mm Hg, or use of antihypertensive medication. Hypotension was defined as systolic blood pressure <90 or diastolic blood pressure <60, irrespective of current antihypertensive medication use or hypertension diagnosis. Blood pressure patterns were defined using the standard hypertension definition. Midlife hypertension was defined as meeting hypertension criteria for two consecutive visits between Visits 1 and 4; persons not meeting this criterion were classified as midlife normotensive. Late-life normotension, hypertension, and hypotension were defined at Visit 5. Participants with midlife hypertension/late-life normotension were not included in the standard hypertension definition analyses because of small sample size (n = 23). ^dParticipants were excluded for missing information regarding the following: smoking status (n = 687), drinking status (n = 321), body mass index (n = 185), coronary heart disease (n = 100), total cholesterol (n = 85), total high-density lipoprotein cholesterol (n = 85), diabetes (n = 56), previous stroke (n = 10), and education (n = 9). A subset of participants were missing information for more than 1 covariate; these values are not mutually exclusive. ^eParticipants missing information (blood pressure or antihypertensive medication use) necessary to determine visit 5 hypertension status using the standard hypertension criteria were excluded.

Figure 2.. Kaplan-Meier Curves for Time to Dementia Onset for Standard Hypertension Definition Blood Pressure Groups

Kaplan-Meier curves for time to dementia onset in the full analytic sample (N = 4738), and among younger (n = 2053) and older (n = 2685) subgroups based on 24-year midlife to late-life blood pressure patterns. Younger and older groups were defined based on median split (<74 vs ≥74 years of age). The median interquartile range (IQR) follow-up times for the midlife and late-life group were 5.0 (4.4-5.3) for normotension and normotension, 4.9 (4.4-5.3) for normotension and hypertension, 4.9 (4.3-5.3) for hypertension and hypertension, 4.9 (4.3-5.2) for hypertension and normotension, and 4.9 (4.2-5.2) years for the hypertension and hypotension group. The median (IQR) follow-up time for the groups with participants younger than 74 years of age were 5.0 (4.5-5.3) for normotension and normotension, 5.0 (4.4-5.3) for normotension and hypertension, 4.9 (4.4-5.3) for hypertension and hypertension, 5.0 (4.5-5.4) for hypertension and normotension, and 4.9 (4.3-5.3) years for the hypertension and hypotension group. The median (IQR) follow-up times for the groups with participants aged 74 years or older were 4.9 (4.3-5.2) for normotension and normotension, 4.9 (4.3-5.2) for normotension and hypertension, 4.8 (4.2-5.2) for hypertension and hypertension, 4.9 (4.2-5.2) for hypertension and normotension, and 4.9 (4.2-5.2) years for the hypertension and hypotension group. Participants with midlife hypertension and late-life normotension were not included in the standard hypertension definition analyses because of small sample size (n = 23).

Figure 3.. Adjusted Hazard Ratios (95% CI) for the Association of Midlife and Late-Life Systolic Blood Pressure With Incident Dementia

A, The association of mean midlife systolic blood pressure (SBP) (measured at visits 1-4) with dementia risk (n=4662). B, The association of late-life SBP with dementia risk among individuals with a mean midlife SBP lower than 120 mm Hg (n=2583). C, The association of late-life SBP with dementia risk among individuals with a mean midlife SBP greater than or equal to 120 mm Hg (n=2068). Hazard ratios (indicated by a bold blue line) and 95% CIs (lighter-faced blue lines) are derived from Cox proportional hazard regression models adjusted for baseline age, sex, race-center, education, apolipoprotein E ε4 (APOEε4) status, and body mass index, total cholesterol, high-density lipoprotein cholesterol, cigarette smoking status, alcohol use status, prevalent diabetes, coronary heart disease, heart failure, and previous stroke defined at visit 5. Models used to examine late-life blood pressure were also adjusted for mean midlife SBP. SBP values were centered at the sample median and modeled using a restricted cubic spline with knots at the 5th, 35th, 65th, and 95th percentiles. Histograms of time-averaged SBP are displayed as solid bars. Participants with extreme blood pressure values (in the bottom first and top 99th percentile) were excluded from these analyses.