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Midlife Risk Factors for Impaired Physical and Cognitive Functioning at Older Ages: A Cohort Study.

ABSTRACT: Previous studies examined midlife risk factors separately for old-age impaired physical and cognitive functioning. We determined the overlap of risk factors for both domains of functioning within the same setting.Biological and behavioral risk factors at age 50 years and cognitive and physical functioning were assessed 18 (SD = 5) years later in the Whitehall II study (N = 6,316). Impaired physical functioning was defined as ?1 limitation on the activities of daily living scale. Impaired cognitive functioning was defined as Mini-Mental State Examination score <27. Two statistical analyses were employed: minimally adjusted analysis (for age, sex, and ethnicity) and mutually adjusted analysis (including all risk factors). Missing data on risk factors were imputed.After confounder adjustment, impaired physical and cognitive functioning at older ages were predicted by hypertension (odds ratios [ORs] 1.80 95% confidence interval [CI] 1.39-2.33 and 1.57 95% CI 1.07-2.31, respectively), poor lung function (1.51 95% CI 1.28-1.78 and 1.31 95% CI 1.08-1.59), and physical inactivity, marginally in the case of cognitive function (1.50 95% CI 1.19-1.90 and 1.27 95% CI 0.99-1.62) at age 50 years. Impaired physical functioning but not cognitive functioning was additionally predicted by depression and higher body mass index (1.72 95% CI 1.46-2.03 and 1.29 95% CI 1.16-1.44, respectively).Several midlife risk factors are associated with impaired physical and cognitive functioning in old age, supporting a unified prevention policy. Analysis of 12 risk factors at age 50 suggests that strategies targeting physical inactivity, hypertension, and poor lung function will reduce impairments in both cognitive and physical functioning in old age.

SUBMITTER: Brunner EJ

PROVIDER: S-EPMC5233910 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Midlife Risk Factors for Impaired Physical and Cognitive Functioning at Older Ages: A Cohort Study.

Brunner Eric J EJ Welch Catherine A CA Shipley Martin J MJ Ahmadi-Abhari Sara S Singh-Manoux Archana A Kivimäki Mika M

The journals of gerontology. Series A, Biological sciences and medical sciences 20160606 2

<h4>Background</h4>Previous studies examined midlife risk factors separately for old-age impaired physical and cognitive functioning. We determined the overlap of risk factors for both domains of functioning within the same setting.<h4>Methods</h4>Biological and behavioral risk factors at age 50 years and cognitive and physical functioning were assessed 18 (SD = 5) years later in the Whitehall II study (N = 6,316). Impaired physical functioning was defined as ≥1 limitation on the activities of d ...[more]

PMID: 27271050

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Project description:ImportancePoor cardiovascular health is an established risk factor for dementia, but little is known about its association with brain physiology in older adults.ObjectiveTo examine the association of cardiovascular risk factors, measured repeatedly during a 20-year period, with cerebral perfusion at older ages.Design, setting, and participantsIn this longitudinal cohort study, individuals were selected from the Whitehall II Imaging Substudy. Participants were included if they had no clinical diagnosis of dementia, had no gross brain structural abnormalities on magnetic resonance imaging scans, and had received pseudocontinuous arterial spin labeling magnetic resonance imaging. Cardiovascular risk was measured at 5-year intervals across 5 phases from September 1991 to October 2013. Arterial spin labeling scans were acquired between April 2014 and December 2014. Data analysis was performed from June 2016 to September 2018.ExposuresFramingham Risk Score (FRS) for cardiovascular disease, comprising age, sex, high-density lipoprotein cholesterol level, total cholesterol level, systolic blood pressure, use of antihypertensive medications, cigarette smoking, and diabetes, was assessed at 5 visits.Main outcomes and measuresCerebral blood flow (CBF; in milliliters per 100 g of tissue per minute) was quantified with pseudocontinuous arterial spin labeling magnetic resonance imaging.ResultsOf 116 adult participants, 99 (85.3%) were men. At the first examination, mean (SD) age was 47.1 (5.0) years; at the last examination, mean (SD) age was 67.4 (4.9) years. Mean (SD) age at MRI scan was 69.3 (5.0) years. Log-FRS increased with time (B = 0.058; 95% CI, 0.044 to 0.072; P < .001). Higher cumulative FRS over the 20-year period (measured as the integral of the rate of change of log-FRS) was associated with lower gray matter CBF (B = -0.513; 95% CI -0.802 to -0.224; P < .001) after adjustment for age, sex, education, socioeconomic status, cognitive status, arterial transit time, use of statins, and weekly alcohol consumption. Voxelwise analyses revealed that this association was significant in 39.6% of gray matter regions, including the posterior cingulate, precuneus, lateral parietal cortex, occipital cortex, hippocampi, and parahippocampal gyrus. The strength of the association of higher log-FRS with lower CBF decreased progressively from the first examination (R2 = 0.253; B = -10.816; 99% CI -18.375 to -3.257; P < .001) to the last (R2 = 0.188; B = -7.139; 99% CI -14.861 to 0.582; P = .02), such that the most recent FRS measurement at mean (SD) age 67.4 (4.9) years was not significantly associated with CBF with a Bonferroni-corrected P < .01 .Conclusions and relevanceCardiovascular risk in midlife was significantly associated with lower gray matter perfusion at older ages, but this association was not significant for cardiovascular risk in later life. This finding could inform the timing of cardiovascular interventions so as to be optimally effective.

Project description:Cardiovascular health in midlife is an established risk factor for cognitive function later in life. Knowing mechanisms of this association may allow preventative steps to be taken to preserve brain health and cognitive performance in older age. In this study, we investigated the association of the Framingham stroke-risk score, a validated multifactorial predictor of 10-year risk of stroke, with brain measures and cognitive performance in stroke-free individuals. We used a large (N?=?800) longitudinal cohort of community-dwelling adults of the Whitehall II imaging sub-study with no obvious structural brain abnormalities, who had Framingham stroke risk measured five times between 1991 and 2013 and MRI measures of structural integrity, and cognitive function performed between 2012 and 2016 [baseline mean age 47.9 (5.2) years, range 39.7-62.7?years; MRI mean age 69.81 (5.2) years, range 60.3-84.6?years; 80.6% men]. Unadjusted linear associations were assessed between the Framingham stroke-risk score in each wave and voxelwise grey matter density, fractional anisotropy and mean diffusivity at follow-up. These analyses were repeated including socio-demographic confounders as well as stroke risk in previous waves to examine the effect of residual risk acquired between waves. Finally, we used structural equation modelling to assess whether stroke risk negatively affects cognitive performance via specific brain measures. Higher unadjusted stroke risk measured at each of the five waves over 20?years prior to the MRI scan was associated with lower voxelwise grey and white matter measures. After adjusting for socio-demographic variables, higher stroke risk from 1991 to 2009 was associated with lower grey matter volume in the medial temporal lobe. Higher stroke risk from 1997 to 2013 was associated with lower fractional anisotropy along the corpus callosum. In addition, higher stroke risk from 2012 to 2013, sequentially adjusted for risk measured in 1991-94, 1997-98 and 2002-04 (i.e. 'residual risks' acquired from the time of these examinations onwards), was associated with widespread lower fractional anisotropy, and lower grey matter volume in sub-neocortical structures. Structural equation modelling suggested that such reductions in brain integrity were associated with cognitive impairment. These findings highlight the importance of considering cerebrovascular health in midlife as important for brain integrity and cognitive function later in life (ClinicalTrials.gov Identifier: NCT03335696).

Dataset Information

Midlife Risk Factors for Impaired Physical and Cognitive Functioning at Older Ages: A Cohort Study.

Publications

Midlife Risk Factors for Impaired Physical and Cognitive Functioning at Older Ages: A Cohort Study.

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