Dataset Information

Association of Midlife Cardiovascular Risk Profiles With Cerebral Perfusion at Older Ages.

ABSTRACT:

Importance

Poor cardiovascular health is an established risk factor for dementia, but little is known about its association with brain physiology in older adults.

Objective

To examine the association of cardiovascular risk factors, measured repeatedly during a 20-year period, with cerebral perfusion at older ages.

Design, setting, and participants

In 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.

Exposures

Framingham 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 measures

Cerebral blood flow (CBF; in milliliters per 100 g of tissue per minute) was quantified with pseudocontinuous arterial spin labeling magnetic resonance imaging.

Results

Of 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?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.

SUBMITTER: Suri S

PROVIDER: S-EPMC6593638 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Association of Midlife Cardiovascular Risk Profiles With Cerebral Perfusion at Older Ages.

Suri Sana S Topiwala Anya A Chappell Michael A MA Okell Thomas W TW Zsoldos Eniko E Singh-Manoux Archana A Kivimäki Mika M Mackay Clare E CE Ebmeier Klaus P KP

JAMA network open 20190605 6

<h4>Importance</h4>Poor cardiovascular health is an established risk factor for dementia, but little is known about its association with brain physiology in older adults.<h4>Objective</h4>To examine the association of cardiovascular risk factors, measured repeatedly during a 20-year period, with cerebral perfusion at older ages.<h4>Design, setting, and participants</h4>In this longitudinal cohort study, individuals were selected from the Whitehall II Imaging Substudy. Participants were included ...[more]

PMID: 31225888

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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).

Project description:ObjectiveAge and high blood pressure are major risk factors for cerebral microbleeds (CMBs). However, the underlying mechanisms remain unclear and arterial stiffness may be important. We investigated whether carotid arterial stiffness is associated with incidence and location of CMBs.Approach and resultsIn the prospective, population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik study, 2512 participants aged 66 to 93 years underwent a baseline brain MRI examination and carotid ultrasound in 2002 to 2006 and returned for a repeat brain MRI in 2007 to 2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain, distensibility coefficient, and Young elastic modulus. Modified Poisson regression was applied to relate carotid arterial stiffness parameters to CMB incidence. During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex, and follow-up interval, arterial stiffness measures were associated with incident CMBs (risk ratio per SD decrease in carotid arterial strain, 1.11 [95% confidence interval, 1.01-1.21]; per SD decrease in natural log-transformed distensibility coefficient, 1.14 [1.05-1.24]; and per SD increase in natural log-transformed Young elastic modulus, 1.13 [1.04-1.23]). These measures were also significantly associated with incident deep CMBs (1.18 [1.02-1.37]; 1.24 [1.08-1.42]; and 1.23 [1.07-1.42]) but not with lobar CMBs. When further adjusted for blood pressure and other baseline vascular risk factors, carotid plaque, prevalent CMBs, subcortical infarcts, and white matter hyperintensities, the associations persisted.ConclusionsOur findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially in a deep location attributable to hypertension.

Dataset Information

Association of Midlife Cardiovascular Risk Profiles With Cerebral Perfusion at Older Ages.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Publications

Association of Midlife Cardiovascular Risk Profiles With Cerebral Perfusion at Older Ages.

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