Blood pressure from mid‐ to late life and risk of incident dementia

Objective:To determine the association between blood pressure during midlife (40–64 years) to late life (≥65 years) and risk of incident dementia.Methods:This study included 1,440 (758 women, mean age 69 ± 6 years) Framingham Offspring participants who were free of dementia and attended 5 consecutive examinations at 4-year intervals starting at midlife (1983–1987, mean age 55 years) until late life (1998–2001, mean 69 years) and subsequently were followed up for incident dementia (mean 8 years). We determined the effect of midlife hypertension (≥140/90 mm Hg), late life hypertension, lower late life blood pressure (<100/70 mm Hg), persistence of hypertension during mid- to late life, and steep decline in blood pressure from mid- to late life over an 18-year exposure period.Results:During the follow-up period, 107 participants (71 women) developed dementia. Using multivariable Cox proportional hazards models, we found that midlife systolic hypertension (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.05–2.35) and persistence of systolic hypertension into late life (HR 1.96, 95% CI 1.25–3.09) were associated with an elevated risk of incident dementia. However, in individuals with low to normal blood pressure (≤140/90 mm Hg) at midlife, a steep decline in systolic blood pressure during mid- to late life was also associated with a >2-fold increase in dementia risk (HR 2.40, 95% CI 1.39–4.15).Conclusions:Elevated blood pressure during midlife, persistence of elevated blood pressure into late life, and, among nonhypertensives, a steep decline in blood pressure during mid- to late life were associated with an increased dementia risk in a community-based cohort. Our data highlight the potential sustained cognitive benefits of lower blood pressures in midlife but also suggest that declining blood pressure in older adults with prehypertension or normotension, but not in those with hypertension, may be a risk marker for dementia.

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CUMULATIVE EXPOSURE TO ELEVATED BLOOD PRESSURE THROUGHOUT ADULTHOOD AND LATE-LIFE DEMENTIA RISK

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.07.214 ◽

2017 ◽

Vol 13 (7) ◽

pp. P586-P587

Author(s):

Elizabeth Rose Mayeda ◽

Maria Glymour ◽

Dan Mungas ◽

Paola Gilsanz ◽

Charles P. Quesenberry ◽

...

Keyword(s):

Blood Pressure ◽

Late Life ◽

Elevated Blood Pressure ◽

Cumulative Exposure ◽

Elevated Blood ◽

Dementia Risk

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Abstract MP61: Greater Late-life Physical Function Declines Among Older Adults With Higher Blood Pressure In Mid-life: The Atherosclerosis Risk In Communities (ARIC) Study

Circulation ◽

10.1161/circ.143.suppl_1.mp61 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Laura Skow ◽

J Coresh ◽

J Deal ◽

Rebecca F Gottesman ◽

Jennifer Schrack ◽

...

Keyword(s):

Blood Pressure ◽

Older Adults ◽

Physical Function ◽

Antihypertensive Medication ◽

Medication Use ◽

Late Life ◽

Elevated Blood Pressure ◽

Elevated Blood ◽

Continuous Analysis ◽

Aric Study

Introduction: Greater late-life physical function decline is associated with incident adverse outcomes including disability and death. Hypertension is the strongest risk factor for stroke, the major cause of physical disability. Hypertension in mid-life has previously been associated with poor physical functioning in late-life; however, more evidence is needed to evaluate whether higher blood pressure in mid-life is associated with the rate of physical function decline during late-late in the absence of stroke. We hypothesized that elevated blood pressure in mid-life would be associated with greater physical function declines in late life. Methods: We studied 5,559 older adults in the ARIC Study (Visit 5; mean age: 75.8 years; range: 66.7-90.9 years; 58% women; 21% Black/79% White) without prior stroke or Parkinson disease who completed the Short Physical Performance Battery (SPPB, scored 0-12). Repeated SPPB assessments occurred at Visits 6 and 7 (median follow-up: 4.2 years). The exposure was a history of elevated blood pressure (BP) (Visit 1; mean age: 52.0 years; mean gap between mid- and late-life exams: 23.7 years). BP was modeled both categorically (hypertensive: SBP 140+ mmHg, DBP 90+ mmHg, or antihypertensive medication use; pre-hypertensive: SBP 120-139 mmHg or DBP 80-89 mmHg; else normotensive) and continuously. Random-slope, random-intercept mixed models with an independent covariance structure tested the association between BP and SPPB score change, adjusted for age, sex, race-site, BMI, education, heart disease and heart failure. Continuous analysis also adjusted for antihypertensive medication use. Results: SPPB scores declined an average of 1.60 points per 10 years (95% CI: -1.75, -1.46; p<0.001) among older adults who were normotensive in mid-life. Older adults with a previous measurement of hypertension declined an additional 0.94 points per 10 years (95% CI: -1.27, -0.60; p<0.001). Prehypertension was not statistically significantly associated with additional decline compared to mid-life normotension (estimate: -0.19 SPPB points/10 years; 95% CI: -0.53, 0.16; p=0.293). In the continuous analysis, each additional 10 mmHg higher mid-life systolic blood pressure above 120 mmHg was associated with an additional 0.24 point decline in SPPB per 10 years in late-life (95% CI: -0.31,-0.14; p<0.001). Conclusions: Elevated BP in mid-life provides insight into the rate of physical function decline decades later, with higher mid-life systolic blood pressure corresponding with steeper declines in late-life physical function even in the absence of stroke. Future research should investigate whether elevated blood pressure at multiple points in mid-life further informs the association.

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Bi-directional association between epilepsy and dementia

Neurology ◽

10.1212/wnl.0000000000011077 ◽

2020 ◽

Vol 95 (24) ◽

pp. e3241-e3247 ◽

Cited By ~ 1

Author(s):

Maria Stefanidou ◽

Alexa S. Beiser ◽

Jayandra Jung Himali ◽

Teng J. Peng ◽

Orrin Devinsky ◽

...

Keyword(s):

Proportional Hazards ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Dementia Risk ◽

Incident Dementia ◽

Heart Study ◽

Allele Status ◽

Ε4 Allele ◽

Nested Case Control

ObjectiveTo assess the risk of incident epilepsy among participants with prevalent dementia and the risk of incident dementia among participants with prevalent epilepsy in the Framingham Heart Study (FHS).MethodsWe analyzed prospectively collected data in the Original and Offspring FHS cohorts. To determine the risk of developing epilepsy among participants with dementia and the risk of developing dementia among participants with epilepsy, we used separate, nested, case–control designs and matched each case to 3 age-, sex- and FHS cohort–matched controls. We used Cox proportional hazards regression analysis, adjusting for sex and age. In secondary analysis, we investigated the role of education level and APOE ε4 allele status in modifying the association between epilepsy and dementia.ResultsA total of 4,906 participants had information on epilepsy and dementia and dementia follow-up after age 65. Among 660 participants with dementia and 1,980 dementia-free controls, there were 58 incident epilepsy cases during follow-up. Analysis comparing epilepsy risk among dementia cases vs controls yielded a hazard ratio (HR) of 1.82 (95% confidence interval 1.05–3.16, p = 0.034). Among 43 participants with epilepsy and 129 epilepsy-free controls, there were 51 incident dementia cases. Analysis comparing dementia risk among epilepsy cases vs controls yielded a HR of 1.99 (1.11–3.57, p = 0.021). In this group, among participants with any post–high school education, prevalent epilepsy was associated with a nearly 5-fold risk for developing dementia (HR 4.67 [1.82–12.01], p = 0.001) compared to controls of the same educational attainment.ConclusionsThere is a bi-directional association between epilepsy and dementia. with either condition carrying a nearly 2-fold risk of developing the other when compared to controls.

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Illiteracy, dementia risk, and cognitive trajectories among older adults with low education

Neurology ◽

10.1212/wnl.0000000000008587 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2247-e2256 ◽

Cited By ~ 3

Author(s):

Miguel Arce Rentería ◽

Jet M.J. Vonk ◽

Gloria Felix ◽

Justina F. Avila ◽

Laura B. Zahodne ◽

...

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Independent Effect ◽

Growth Curve Models ◽

Cox Proportional Hazards Models ◽

Dementia Risk ◽

Incident Dementia ◽

Low Education

ObjectiveTo investigate whether illiteracy was associated with greater risk of prevalent and incident dementia and more rapid cognitive decline among older adults with low education.MethodsAnalyses included 983 adults (≥65 years old, ≤4 years of schooling) who participated in a longitudinal community aging study. Literacy was self-reported (“Did you ever learn to read or write?”). Neuropsychological measures of memory, language, and visuospatial abilities were administered at baseline and at follow-ups (median [range] 3.49 years [0–23]). At each visit, functional, cognitive, and medical data were reviewed and a dementia diagnosis was made using standard criteria. Logistic regression and Cox proportional hazards models evaluated the association of literacy with prevalent and incident dementia, respectively, while latent growth curve models evaluated the effect of literacy on cognitive trajectories, adjusting for relevant demographic and medical covariates.ResultsIlliterate participants were almost 3 times as likely to have dementia at baseline compared to literate participants. Among those who did not have dementia at baseline, illiterate participants were twice as likely to develop dementia. While illiterate participants showed worse memory, language, and visuospatial functioning at baseline than literate participants, literacy was not associated with rate of cognitive decline.ConclusionWe found that illiteracy was independently associated with higher risk of prevalent and incident dementia, but not with a more rapid rate of cognitive decline. The independent effect of illiteracy on dementia risk may be through a lower range of cognitive function, which is closer to diagnostic thresholds for dementia than the range of literate participants.

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Association of Mid- to Late-Life Blood Pressure Patterns With Risk of Subsequent Coronary Heart Disease and Death

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.632514 ◽

2021 ◽

Vol 8 ◽

Author(s):

Menghui Liu ◽

Shaozhao Zhang ◽

Xiaohong Chen ◽

Xiangbin Zhong ◽

Zhenyu Xiong ◽

...

Keyword(s):

Blood Pressure ◽

Coronary Heart Disease ◽

Heart Disease ◽

Proportional Hazards ◽

Late Life ◽

Cox Proportional Hazards ◽

Atherosclerosis Risk In Communities ◽

Cox Proportional Hazards Models ◽

Significant Difference ◽

All Cause Mortality

Background: The elevated blood pressure (BP) at midlife or late-life is associated with cardiovascular disease and death. However, there is limited research on the association between the BP patterns from middle to old age and incident coronary heart disease (CHD) and death.Methods: A cohort of the Atherosclerosis Risk in Communities (ARIC) Study enrolled 9,829 participants who attended five in-person visits from 1987 to 2013. We determined the association of mid- to late-life BP patterns with incident CHD and all-cause mortality using multivariable-adjusted Cox proportional hazards models.Results: During a median of 16.7 years of follow-up, 3,134 deaths and 1,060 CHD events occurred. Compared with participants with midlife normotension, the adjusted hazard ratio for all-cause mortality and CHD was 1.14 (95% CI, 1.04–1.25) and 1.28 (95% CI, 1.10–1.50) in those with midlife hypertension, respectively. In further analyses, compared with a pattern of sustained normotension from mid- to late-life, there was no significant difference for the risk of incident death (HR, 1.15; 95% CI, 0.96–1.37) and CHD (HR, 1.33; 95% CI, 0.99–1.80) in participants with a pattern of midlife normotension and late-life hypertension with effective BP control. A higher risks of death and CHD were found in those with pattern of mid- to late-life hypertension with effective BP control (all-cause mortality: HR, 1.24; 95% CI, 1.08–1.43; CHD: HR, 1.65; 95% CI 1.30–2.09), pattern of midlife normotension and late-life hypertension with poor BP control (all-cause mortality: HR, 1.27; 95% CI, 1.12–1.44; CHD: HR, 1.53; 95% CI, 1.23–1.92), and pattern of mid- to late-life hypertension with poor BP control (all-cause mortality: HR, 1.49; 95% CI, 1.30–1.71; CHD: HR, 1.87; 95% CI, 1.48–2.37).Conclusions: The current findings underscore that the management of elderly hypertensive patients should not merely focus on the current BP status, but the middle-aged BP status. To achieve optimal reductions in the risk of CHD and death, it may be necessary to prevent, diagnose, and manage of hypertension throughout middle age.

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Abstract WP479: Associations Between Vascular Risk, Amyloid Burden and Incident Dementia: The ARIC-PET Study

Stroke ◽

10.1161/str.51.suppl_1.wp479 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Rebecca F Gottesman ◽

Aozhou Wu ◽

Josef Coresh ◽

Clifford R Jack ◽

David S Knopman ◽

...

Keyword(s):

Risk Factors ◽

Proportional Hazards ◽

Brain Mri ◽

Amyloid Β ◽

Standardized Uptake Value ◽

Cox Proportional Hazards ◽

Vascular Risk ◽

Brain Volumes ◽

Dementia Risk ◽

Incident Dementia

Background: Midlife vascular risk factors (MVRF) are associated with incident dementia. Similarly, amyloid β(Aβ) and neurodegeneration (e.g.brain volumes), as parts of the Alzheimer’s Disease (AD) ATN framework, are associated with cognition. Whether vascular and AD-associated factors contribute to dementia independently or interact synergistically to reduce cognitive ability is not well understood. Methods: Recruited from 3 U.S. communities, ARIC-PET participants were followed from 1987-89 (45-64 yo) through 2016-17 (74-94 yo). Cognition was evaluated in 2011-13 (ages 69-88), and twice more, every 2-3 years. In 2011-13, nondemented ARIC-PET participants had a brain MRI, with measurement of white matter hyperintensities (WMH) and brain volumes, with florbetapir (Aβ) PET scans in 2012-14; global cortical standardized uptake value ratio (SUVR) was log-transformed and standardized. Dementia was classified by expert review, as well as phone and medical record surveillance. The relative contributions of vascular risk (MVRF, WMH volume) and AD pathology (elevated Aβ SUVR, smaller AD signature region volumes) to incident dementia were evaluated with Cox proportional hazards regression. Results: In 298 individuals, 36 developed dementia. In models with key MVRF, demographics, and Aβ SUVR, hypertension and Aβ each independently predicted dementia risk (per SD of Aβ SUVR: HR 2.57, 95% CI 1.72-3.84; hypertension: HR 2.57, 95% CI 1.16-5.67), but didn’t interact on dementia risk. WMH (per SD: HR 1.51, 95% CI 1.03-2.20) and Aβ SUVR (per SD: HR 2.52, 95% CI 1.83-3.47) each contributed to incident dementia but WMH lost significance when MVRF were added to the model. Smaller AD signature regions were associated with incident dementia, independent of Aβ SUVR, and remained significant after adjustment for MVRF (HR per SD 2.18, 95% CI 1.18-4.01). Conclusions: Midlife hypertension and late-life Aβ independently contribute to dementia risk, but don’t synergize on a multiplicative scale. Neurodegeneration (e.g.smaller AD signature region volume) is also associated with incident dementia, independent of Aβ and MVRF. Multiple pathways leading to dementia should be considered when evaluating risk factors and interventions to reduce the burden of dementia.

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Abstract P160: Long-term Blood Pressure Variability And Cognitive Decline And Dementia Among Community-dwelling Elderly

Hypertension ◽

10.1161/hyp.76.suppl_1.p160 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Michael E Ernst ◽

Joanne Ryan ◽

Enayet K Chowdhury ◽

Anne M Murray ◽

Robyn L Woods ◽

...

Keyword(s):

Blood Pressure ◽

Cognitive Decline ◽

Blood Pressure Variability ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Immortal Time Bias ◽

Incident Dementia ◽

The Impact

Greater blood pressure variability (BPV) in midlife increases the risk of dementia, but the impact of BPV in cognitively intact older adults is unknown. We examined the risk of incident dementia and cognitive decline associated with long-term, visit-to-visit BPV in participants of the ASPirin in Reducing Events in the Elderly (ASPREE) study, a randomized primary prevention trial of daily low-dose aspirin in community-dwelling adults in Australia and the US aged 70 and older (65 if US minority), who were free of dementia or evidence of cognitive impairment at enrollment. The mean of three BPs using an automated cuff was recorded at baseline and annually; participants also underwent baseline and biennial standardized assessments of global cognition, delayed episodic memory, verbal fluency, processing speed and attention. Cognitive decline was pre-specified as a >1.5 standard deviation (SD) decline in score from baseline on any of the cognitive tests, while incident dementia was a pre-specified secondary endpoint of ASPREE which was adjudicated using DSM-IV criteria. BPV was estimated using within-individual SD of mean systolic BP across baseline and the first two annual visits, and participants with cognitive decline or incident dementia during this period were excluded from the analysis to avoid immortal time bias. After adjustment for key covariates, Cox proportional hazards regression revealed increased risks for dementia and cognitive decline during follow-up for individuals in the highest SD tertile of BPV (Table). Our findings suggest that high BPV in older ages should be considered a potential therapeutic target to preserve cognitive function.

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Risk of incident dementia in late-life depression treated with antidepressants: A nationwide population cohort study

Journal of Psychopharmacology ◽

10.1177/0269881120944152 ◽

2020 ◽

Vol 34 (10) ◽

pp. 1134-1142

Author(s):

Jian-An Su ◽

Chih-Cheng Chang ◽

Yao-Hsu Yang ◽

Ko-Jung Chen ◽

Yueh-Ping Li ◽

...

Keyword(s):

Confidence Interval ◽

Proportional Hazards ◽

Late Life ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Late Life Depression ◽

Design Data ◽

High Exposure ◽

Incident Dementia ◽

Exposure Dosage

Background: Antidepressants are frequently used to treat depression in patients with dementia. In addition, late-life depression is associated with the incidence of subsequent cognitive impairment or dementia. However, the association between exposure to antidepressants in late-life depression and the development of incident dementia remains understudied. Methods: Through a population-based retrospective cohort design, data were extracted from the Taiwan National Health Insurance Research Dataset of medical claims registered from 1998–2013. We collected data of individuals who had received a new diagnosis of depression between 2000 and 2007. We excluded those who received a diagnosis of depression and were given antidepressants before 2000 and those younger than 60 years. The primary outcome was the occurrence of incident dementia. The time from the prescription of antidepressants or the diagnosis of depression until the outcome or the end of 2013 was calculated as the time to event. A total of 563,918 cases were included and were divided into either antidepressant users or antidepressant nonusers. Cox proportional hazards models were used to calculate the hazard ratio and 95% confidence interval. Results: Exposure to antidepressants did not increase the risk of dementia in patients with late-life depression at either a low exposure dosage (hazard ratio: 1.06, 95% confidence interval: 0.91–1.23) or a high exposure dosage (hazard ratio: 1.07, 95% confidence interval: 0.95–1.20). To confirm the validity of our results, we performed a sensitivity analysis and subgroup analysis, and the post-hoc results were consistent with the main results. Conclusion: Antidepressants did not increase the risk of incident dementia in patients with late-life depression.

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Homocysteine Predicts Incident Isolated Systolic Hypertension in Older Adults

Circulation ◽

10.1161/circ.103.suppl_1.9999-19 ◽

2001 ◽

Vol 103 (suppl_1) ◽

pp. 1347-1347

Author(s):

Rachel P Wildman ◽

Lewis H Kuller

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Older Adults ◽

Systolic Hypertension ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Isolated Systolic Hypertension ◽

Kaplan Meier ◽

Blood Pressures ◽

Amino Acid Methionine

0019 Untreated isolated systolic hypertension (ISH) indicates arterial stiffening and carries a risk for both stroke and cardiovascular disease. Elevated plasma homocysteine, a metabolite of the essential amino acid methionine, has been linked to vascular stiffness. 187 normotensive (defined as systolic blood pressure (SBP) < 160 mmHg and diastolic blood pressure < 90 mmHg) men and women (mean age 71.29 + 6.3 yrs) were followed for an average of 7 years for incident ISH. ISH was defined as a SBP ≥160 mmHg (while maintaining a DBP of < 90 mmHg) at least one time at 3 year follow-up visits, or the initiation of antihypertensive therapy. The mean baseline systolic and diastolic blood pressures (DBP) were 127 and 69 mmHg, respectively. Over the 7 year period, 59(31.5%) participants developed ISH, 76% qualified by antihypertensive use, and 24% by blood pressure values. The Kaplan Meier Estimate of 7 year survival free from ISH was 67% (95% CI: 61%, 74%). The relationship between incident ISH and the traditional cardiovascular risk factors, creatinine, homocysteine, and carotid artery intima-media wall thickness (IMT) was assessed by Cox proportional hazards regression. The strongest predictor of incident ISH was baseline SBP. For participants with baseline SBPs of < 130, 130-139, and 140+ mmHg, the corresponding 7 year survival free from ISH was 80% (95% CI: 73%, 88% ), 53% (95%CI: 38%, 67%), and 44% (95% CI: 26%, 62%). Factors independently associated with time to ISH were higher triglycerides (upper tertile,RR=2.0, p=0.012), homocysteine levels (> 12.0 μmol/l, RR=2.2, p=0.005), and baseline SBP (per 10 mmHg,RR=1.4, p=0.003). The results were similar when the analysis was restricted to the 157 participants with a baseline SBP of < 140 mmHg. Baseline IMT was found to be univariately related to time to ISH (RR per each 1.0 mm increment=3.0; p=0.016). In multivariate analysis, this association remained independent of triglycerides and homocysteine, but not baseline SBP (RR per each 1.0 mm increment=2.5; p=0.049). In conclusion, among normotensive older adults, 32% can be expected to develop ISH over a 7 year period, and higher triglyceride and homocysteine levels are risk factors.

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Diabetes, disability, and dementia risk: Results from the Hispanic Established Populations for the Epidemiologic Studies of the Elderly (H-EPESE)

International Journal of Social Psychiatry ◽

10.1177/00207640211037722 ◽

2021 ◽

pp. 002076402110377

Author(s):

Elizabeth Vásquez ◽

Meghana A Gadgil ◽

Weihui Zhang ◽

Jacqueline L Angel

Keyword(s):

Cognitive Impairment ◽

Proportional Hazards ◽

Epidemiologic Study ◽

The Elderly ◽

Epidemiologic Studies ◽

Cox Proportional Hazards ◽

Self Report ◽

Dementia Risk ◽

Incident Dementia ◽

Diabetes Status

Background: Emerging research has elucidated pathophysiological relationships among diabetes, disability, cognitive impairment, and incident dementia. However, the relationships between diabetes, disability, and dementia have been largely underexamined in Latino populations, which have a disproportionate prevalence of diabetes and its complications. Aims: This study examines diabetes as a risk factor for subsequent disability and dementia risk in a Mexican-origin older adult sample. Methods: The data are drawn from eight waves (1993–2013) of the Hispanic Established Populations for the Epidemiologic Study of the Elderly (HEPESE; N = 3,050, mean age at baseline = 73.6 (±6.8)). Respondents’ diabetes status at baseline was ascertained by self-report. Disability was assessed using eight functional domains assessed through the Lawton Instrumental Activities of Daily Living (IADL) Scale. Dementia risk was assessed using a Mini-Mental Status Exam (MMSE) score below 18 and the need for aid with at least two IADLs. We used multivariable Cox proportional hazards models to predict the relation between diabetes and time to disability, cognitive impairment, and incident dementia, adjusting for age at migration, socioeconomic status, acculturation, and health status. Results: At baseline, diabetes prevalence was 28.1%, and 37.7% had IADL disability. Diabetes was associated with a higher risk of developing dementia (Hazard Ratio (HR) = 1.22, p < .001) over the approximetely 20 year study period. In addition, immigrants who migrated at age 50 or older had a higher dementia risk (HR = 1.35, p = .01) when compared to their US-born counterpart. Conclusion: Our results highlight the importance of better characterizing the role of diabetes and nativity in the co-occurrence of disability and dementia risk.

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