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Association of Cardiovascular Risk Burden With Risk and Progression of Disability: Mediating Role of Cardiovascular Disease and Cognitive Decline.

ABSTRACT: Background Cardiovascular risk burden has been linked to cardiovascular disease (CVD) and cognitive decline, but its association with disability is unclear. We aimed to examined the association of cardiovascular risk burden assessed by the Framingham general cardiovascular risk score (FGCRS) with the risk and progression of disability and estimated the extent to which CVD and cognitive decline mediate this association. Methods and Results A total of 1480 older adults with no disabilities (mean age=79.32±7.38 years) from the Rush Memory and Aging Project were followed for up to 21 years. FGCRS at baseline was calculated and categorized into tertiles. Disability was assessed annually with activities of daily living. The number of CVDs was calculated by summing up the CVD events. Global cognitive function was assessed annually with a battery of 19 tests. Data were analyzed using the Cox model, linear mixed effects model, and mediation analysis. At the end of the follow-up, 713 (48.2%) participants developed disability. Compared with the lowest tertile of the FGCRS, the multiadjusted hazards ratios of disability were 1.34 (95% CI, 1.11-1.62) for the highest tertile. In addition, the highest FGCRS was associated with a change in activities of daily living score over time (?=0.057; 95% CI, 0.021-0.093). The association between FGCRS and change in activities of daily living was 13.8% mediated by the accumulation of CVDs and 25.1% by cognitive decline, respectively. Conclusions Higher cardiovascular risk burden increased the risk of disability and accelerated its progression over time. CVD accumulation and cognitive decline may partially mediate the association.

SUBMITTER: Cui K

PROVIDER: S-EPMC7726997 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Association of Cardiovascular Risk Burden With Risk and Progression of Disability: Mediating Role of Cardiovascular Disease and Cognitive Decline.

Cui KaiWang K Song Ruixue R Xu Hui H Shang Ying Y Qi Xiuying X Buchman Aron S AS Bennett David A DA Xu Weili W

Journal of the American Heart Association 20200901 18

Background Cardiovascular risk burden has been linked to cardiovascular disease (CVD) and cognitive decline, but its association with disability is unclear. We aimed to examined the association of cardiovascular risk burden assessed by the Framingham general cardiovascular risk score (FGCRS) with the risk and progression of disability and estimated the extent to which CVD and cognitive decline mediate this association. Methods and Results A total of 1480 older adults with no disabilities (mean a ...[more]

PMID: 32869681

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Project description:PurposeThis study aimed to investigate the association of the cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) with the trajectories of motor function over time and to assess the mediating effects of cardiovascular diseases (CVDs) accumulation and cognitive decline in such association.MethodsIn Rush Memory and Aging Project, a total of 1,378 physical health participants (mean age: 79.3 ± 7.3 years) were followed up for up to 22 years. FGCRS at baseline was assessed and categorized into tertiles (lowest, middle, and highest). Global motor function (including dexterity, gait, and hand strength) was assessed annually with 10 motor tests. CVDs (including stroke, congestive heart failure, and other heart diseases) were ascertained at baseline and follow-ups, and the number of CVDs accumulation over time was assessed. Global cognitive function was tested annually by 19 tests. Data were analyzed using the linear mixed-effects models and mediation analysis.ResultsAt baseline, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Over the follow-up (median: 5.3 years; interquartile range: 2.9-9.0 years), in multi-adjusted mixed-effects models, the highest FGCRS was associated with faster decline in global motor function (β = -0.0038; 95% confidence interval [CI]: -0.0069 to -0.0008), dexterity (β = -0.0056; 95% CI: -0.0093 to -0.0020), gait (β = -0.0039; 95% CI: -0.0077 to -0.0001), and hand strength (β = -0.0053; 95% CI: -0.0098 to -0.0008) compared with the lowest tertile. In mediation analysis, CVDs accumulation and cognitive decline mediated 8.4% and 42.9% of the association between FGCRS and global motor function over time, respectively.ConclusionHigher cardiovascular risk burden is associated with a faster decline in motor function including dexterity, gait, and hand strength. CVDs accumulation and cognitive decline may partially mediate the association between cardiovascular risk burden and global motor function decline.

Project description:BackgroundUnfavorable psychosocial working conditions have been associated with cognitive decline and chronic diseases, both of which may subsequently accelerate functional dependence. This study aimed to investigate the association between job demand-control-support combinations and trajectories of disability in later life and to further explore the role of cognitive decline and the co-occurrence of chronic diseases in mediating this association.Methods and findingsIn this cohort study, 2,937 community dwellers aged 60+ years (mean age 73 ± 10.6; 62.9% female) residing in the Kungsholmen District of Stockholm, Sweden, participated in the baseline survey (2001-2004) and were followed up to 12 years. Lifelong occupational history was obtained through a standardized interview; job demands, job control, and social support at work in the longest-held occupation were graded with a psychosocial job-exposure matrix. Job control, demands, and social support were dichotomized using the median values from the matrix, respectively, to further generate demand-control-support combinations. Disability was measured by summing the number of impaired basic and instrumental activities of daily living. Global cognitive function was assessed by Mini-Mental State Examination. Chronic conditions were ascertained by clinical examinations, medical history, and patient clinical records; the total number of chronic diseases was summed. Data were analyzed using linear mixed-effects models and mediation analysis. Age, sex, education, alcohol consumption, smoking, leisure activity engagement, early-life socioeconomic status, occupational characteristic and physical demands, and baseline cognitive function and number of chronic diseases were adjusted for in the analyses. Compared with active jobs (high control/high demands; n = 1,807), high strain (low control/high demands; n = 328), low strain (high control/low demands; n = 495), and passive jobs (low control/low demands; n = 307) were all associated with a faster rate of disability progression (? = 0.07, 95% CI 0.02-0.13, p = 0.01; ? = 0.10, 95% CI 0.06-0.15, p < 0.001; ? = 0.11, 95% CI 0.05-0.18, p < 0.001). The association between high strain and disability progression was only shown in people with low social support at work (? = 0.13, 95% CI 0.07-0.19, p < 0.001), but not in those with high social support (? = 0.004, 95% CI -0.09 to 0.10, p = 0.93). Moreover, we estimated that the association between demand-control status and disability trajectories was mediated 38.5% by cognitive decline and 18.4% by accumulation of chronic diseases during the follow-up period. The limitations of this study include unmeasured confounding, self-reported work experience, and the reliance on a psychosocial job-exposure matrix that does not consider variabilities in individuals' perception on working conditions or job characteristics within occupations.ConclusionsOur findings suggest that negative psychosocial working conditions during working life may accelerate disability progression in later life. Notably, social support at work may buffer the detrimental effect of high strain on disability progression. Cognitive decline and chronic-disease accumulation, and especially the former, partially mediate the association of psychosocial working conditions with trajectories of disability. Further studies are required to explore more mechanisms that underlie the association between psychosocial working conditions and disability trajectories.

Project description:ImportanceGenetic factors have a well-known influence on Parkinson disease (PD) susceptibility. The largest genome-wide association study (GWAS) identified 26 independent single-nucleotide polymorphisms (SNPs) associated with PD risk. Among patients, the course and severity of symptom progression is variable, and little is known about the potential association of genetic factors with phenotypic variance.ObjectiveTo assess whether GWAS-identified PD risk SNPs also have a cumulative association with the progression of cognitive and motor symptoms in patients with PD.Design, setting, and participantsThis longitudinal population-based cohort study of 285 patients of European ancestry with incident PD genotyped 23 GWAS SNPs. One hundred ninety-nine patients were followed up for a mean (SD) of 5.3 (2.1) years for progression (baseline: June 1, 2001, through November 31, 2007; follow-up: June 1, 2007, through August 31, 2013, with mortality surveillance through December 31, 2016); 57 patients had died or were too ill for follow-up, and 29 withdrew or could not be contacted. Movement disorder specialists repeatedly assessed PD symptom progression.Main outcomes measuresThe combined association of PD risk loci, after creating a weighted polygenic risk score (PRS), with cognitive decline, motor progression, and survival, relying on Cox proportional hazards regression models and inverse probability weights to account for censoring.ResultsOf the 285 patients undergoing genotyping, 160 were men (56.1%) and 125 were women (43.9%); the mean (SD) age at diagnosis was 69.1 (10.4) years. The weighted PRS was associated with significantly faster cognitive decline, measured by change in the Mini-Mental State Examination (hazard ratio [HR] per 1 SD, 1.44; 95% CI, 1.00-2.07). The PRS was also associated with faster motor decline, measured by time to Hoehn & Yahr Scale stage 3 (HR, 1.34; 95% CI, 1.00-1.79) and change in Unified Parkinson's Disease Rating Scale part III score (HR, 1.42; 95% CI, 1.00-2.01).Conclusions and relevanceSusceptibility SNPs for PD combined with a cumulative PRS were associated with faster motor and cognitive decline in patients. Thus, these genetic markers may be associated with not only PD susceptibility but also disease progression in multiple domains.

Project description:BackgroundThe impact of cardiovascular risk burden on cognitive trajectories and brain structure changes remains unclear.ObjectivesThis study aimed to examine whether cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) is associated with cognitive decline and structural brain differences.MethodsWithin the Rush Memory and Aging Project, 1,588 dementia-free participants (mean age: 79.5 years) were followed for up to 21 years. FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with a battery of 19 tests, from which composite scores were derived. A subsample (n = 378) of participants underwent magnetic resonance imaging. Structural total and regional brain volumes were estimated. Data were analyzed using linear mixed-effects models and linear regression models.ResultsIn all participants, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Compared with the lowest tertile of FGCRS, the highest tertile was associated with faster decline in global cognition (β = -0.019; 95% confidence interval [CI]: -0.035 to -0.003), episodic memory (β = -0.023; 95% CI: -0.041 to -0.004), working memory (β = -0.021; 95% CI: -0.035 to -0.007), and perceptual speed (β = -0.027; 95% CI: -0.042 to -0.011) over the follow-up. In magnetic resonance imaging data analyses, higher FGCRS was related to smaller volumes of the hippocampus (β = -0.021; 95% CI: -0.042 to -0.000), gray matter (β = -1.569; 95% CI: -2.757 to -0.382), and total brain (β = -1.588; 95% CI: -2.832 to -0.344), and greater volume of white matter hyperintensities (β = 0.035; 95% CI: 0.001 to 0.069).ConclusionsHigher cardiovascular risk burden may predict decline in episodic memory, working memory, and perceptual speed and is associated with neurodegeneration and vascular lesions in the brain.

Project description:Importance:The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical ?-amyloid [A?] and tau) provides an important opportunity to understand the basis of SCD and AD risk. Objective:To examine associations between SCD and global A? and tau burdens in regions of interest in clinically healthy older adults. Design, Setting, and Participants:This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11-labeled PET (PiB-PET) imaging for A?. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. Main Outcomes and Measures:Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The A? level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of A?, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. Results:Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high A? burden. Greater SCD was associated with increasing entorhinal cortical tau burden (??=?0.35; 95% CI, 0.19-.52; P?<?.001) and A? burden (??=?0.24; 95% CI, 0.08-.40; P?=?.005), but not inferior temporal tau burden (??=?0.10; 95% CI, -0.08 to 0.28; P?=?.27). This association between entorhinal cortical tau burden and SCD was largely unchanged after accounting for A? burden (??=?0.36; 95% CI, 0.15-.58; P?=?.001), and no interaction influenced SCD (??=?-0.36; 95% CI, -0.34 to 0.09; P?=?.25). An exploratory post hoc whole-brain analysis also indicated that SCD was predominantly associated with greater tau burden in the entorhinal cortex. Conclusions and Relevance:Subjective cognitive decline is indicative of accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of A?. Our findings suggest multiple underlying pathways that motivate SCD that do not necessarily interact to influence SCD endorsement. As such, multiple biological factors must be considered when assessing SCD in clinically healthy older adults.

Dataset Information

Association of Cardiovascular Risk Burden With Risk and Progression of Disability: Mediating Role of Cardiovascular Disease and Cognitive Decline.

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Association of Cardiovascular Risk Burden With Risk and Progression of Disability: Mediating Role of Cardiovascular Disease and Cognitive Decline.

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