Analysis of Clinical Traits Associated With Cardiovascular Health, Genomic Profiles, and Neuroimaging Markers of Brain Health in Adults Without Stroke or Dementia

Acosta, Julián; Both, Cameron; Rivier, Cyprien; Szejko, Natalia; Leasure, Audrey C; Gill, Thomas M; Payabvash, Seyedmehdi; Sheth, Kevin N; Falcone, Guido J

doi:10.1001/jamanetworkopen.2022.15328

Cited by 8 publications

(7 citation statements)

References 23 publications

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“…These findings were consistent with previous cross-sectional 17,18 and longitudinal findings 40 . They were also in line with a UKB study by Falcone et al 19 , who reported that higher LS7 was associated with lower WMH and larger BV, and another study in New York by Glodzik et al 41 , who suggested that elevated Framingham cardiovascular risk was correlated with reduced hippocampal response. These findings supported the potential role of favorable behavioral CVH profile in maintaining brain health.…”

Section: Discussionsupporting

confidence: 87%

“…Increasing longitudinal studies have investigated the associations between LS7 and dementia in American cohorts 13,14 and some European countries 15 , including the UK 16 . Beyond these clinical endpoints, few studies have evaluated whether enhanced CVH is associated with enhanced brain health, as measured by cognitive performance tests 17,18 and neuroimaging markers 19,20 . By contrast, no studies have yet explored the longitudinal associations between the newly launched LE8 score and multiple neurocognitive outcomes in European populations.…”

Section: Introductionmentioning

confidence: 99%

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Associations of “Life’s Essential 8” cardiovascular health with dementia risk, cognition, and neuroimaging markers of brain health

Zhou

2023

Preprint

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Importance:The American Heart Association (AHA)’s Life’s Essential 8 (LE8) score, a recently updated metric for promoting cardiovascular health (CVH), has addressed the limitations of the original metrics (Life’s Simple 7) and is able to quantify CVH. Objective:To evaluate the associations of LE8 score with the risk of incident dementia and its subtypes, cognition, and neuroimaging outcomes and to determine whether these associations differ among apolipoprotein E (APOE)-ε4 genotypes. Design, Setting, and Participants:UK Biobank participants without prior cardiovascular disease nor dementia at baseline (2006–2010) were enrolled in this prospective cohort study. Data analysis was conducted from December 20, 2022, to February 15, 2023. Exposures:A modified version of the LE8 score was created (range: 0–100) and categorized into poor (0–49), intermediate (50–79), and optimal (80–100) CVH. Main Outcomes and Measures:The outcomes included incident dementia (all-cause, vascular [VaD], and Alzheimer’s disease ascertained through hospital inpatient and death records), cognitive test scores (fluid intelligence and numeric memory), and neuroimaging markers (total brain volume [BV], white matter hyperintensity [WMH], and hippocampal volume). Adjusted Cox proportional hazard and multivariable linear regression models were used. Results: A subsample of 316,669 participants (mean [SD] age, 56.3 [8.1] years) were included. Higher LE8 scores were associated with reduced risk of all-cause dementia and VaD, the adjusted hazard ratios (HRs) in the optimal CVH versus the poor CVH group were 0.56 (95% confidence interval [CI], 0.48–0.64) and 0.29 (95% CI, 0.22–0.38), respectively. A 10-point increment in LE8 was associated with higher fluid intelligence (β, 0.088; 95% CI, 0.073–0.102) and numeric memory (β, 0.054; 95% CI, 0.043–0.065), and was also associated with lower WMH volume (β, −0.673; 95% CI, from −0.751 to −0.596) and larger BV (β, 77.93; 95% CI, 62.03–93.84) and hippocampal volume (β, 0.197; 95% CI, 0.106–0.288). These associations were more evident in APOE-ε4 noncarriers. Conclusions and Relevance: Individuals with a higher LE8 score experienced less dementia events (driven especially by incident VaD) and were associated with better neurocognitive brain health profiles. CVH optimization may be beneficial to the maintenance of brain health.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Associations of “Life’s Essential 8” cardiovascular health with dementia risk, cognition, and neuroimaging markers of brain health

Zhou

2023

Preprint

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“…The previous studies on the association of LS7 score with neuroimaging markers, including WMHs and brain volume, showed consistent results [20,28]. Moreover, other studies found that WMHs including higher glucose levels [17,29], BP [13,14,17], blood lipids [17,30], BMI and smoking status [17,31,32], as has been previously indicated.…”

Section: Discussionsupporting

confidence: 70%

“…A recent study shows that cardiovascular health optimization was associated with improved health and confirms the role of genetic predisposition of LS7 metrics in brain health. However, whether adherence to these recommendations could reduce brain microstructural damage is still unclear [20].…”

Section: Introductionmentioning

confidence: 99%

Associations of Life's Simple 7 with cerebral white matter hyperintensities and microstructural integrity: UK Biobank cohort study

Sun

Wang

et al. 2023

Euro J of Neurology

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Background and purpose:The American Heart Association Life's Simple 7 (LS7) metric was used to define optimal cardiovascular and brain health, but the associations with macrostructural hyperintensities and microstructural white matter damage are unclear.The objective was to determine the association of LS7 ideal cardiovascular health factors with macrostructural and microstructural integrity. Method: A total of 37,140 participants with available LS7 and imaging data from UK Biobank were included in this study. Linear associations were implemented to examine the associations of LS7 score and subscores with white matter hyperintensity load (WMH) (WMH volume normalized by total white matter volume and logit-transformed) and diffusion imaging indices (fractional anisotropy [FA], mean diffusivity, orientation dispersion index [OD], intracellular volume fraction, isotropic volume fraction [ISOVF]). Results:In individuals (mean age 54.76 years; 19,697 females, 52.4%), higher LS7 score and subscores were strongly associated with lower WMH and microstructural white matter injury, including OD, ISOVF, FA. Both interaction analyses and stratified analyses of LS7 score and subscores with age and sex showed a strong association with microstructural damage markers, with remarkable age and sex differences. The association of OD was pronounced in females and populations younger than 50 years and FA, mean diffusivity and ISOVF were pronounced in males and populations older than 50 years. Conclusion:These findings suggest that healthier LS7 profiles are associated with better profiles of both macrostructural and microstructural markers of brain health, and indicate that ideal cardiovascular health is associated with improved brain health.

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“…With every fifth child aged 6 to 11 years in the US being obese, childhood obesity is a growing health concern . While the concept of brain health is not universally agreed upon yet, it broadly refers to optimal brain integrity and function . The US Centers for Disease Control and Prevention defined brain health as an ability to “perform all the mental processes… of cognition, including the ability to learn and judge, use language, and remember.” Quantitative multimodal neuroimaging can provide objective tools for indirect assessment of different aspects of brain health .…”

Section: Introductionmentioning

confidence: 99%

Association of Body Mass Index and Waist Circumference With Imaging Metrics of Brain Integrity and Functional Connectivity in Children Aged 9 to 10 Years in the US, 2016-2018

et al. 2023

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ImportanceAside from widely known cardiovascular implications, higher weight in children may have negative associations with brain microstructure and neurodevelopment.ObjectiveTo evaluate the association of body mass index (BMI) and waist circumference with imaging metrics that approximate brain health.Design, Setting, and ParticipantsThis cross-sectional study used data from the Adolescent Brain Cognitive Development (ABCD) study to examine the association of BMI and waist circumference with multimodal neuroimaging metrics of brain health in cross-sectional and longitudinal analyses over 2 years. From 2016 to 2018, the multicenter ABCD study recruited more than 11 000 demographically representative children aged 9 to 10 years in the US. Children without any history of neurodevelopmental or psychiatric disorders were included in this study, and a subsample of children who completed 2-year follow-up (34%) was included for longitudinal analysis.ExposuresChildren’s weight, height, waist circumference, age, sex, race and ethnicity, socioeconomic status, handedness, puberty status, and magnetic resonance imaging scanner device were retrieved and included in the analysis.Main Outcomes and MeasuresAssociation of preadolescents’ BMI z scores and waist circumference with neuroimaging indicators of brain health: cortical morphometry, resting-state functional connectivity, and white matter microstructure and cytostructure.ResultsA total of 4576 children (2208 [48.3%] female) at a mean (SD) age of 10.0 years (7.6 months) were included in the baseline cross-sectional analysis. There were 609 (13.3%) Black, 925 (20.2%) Hispanic, and 2565 (56.1%) White participants. Of those, 1567 had complete 2-year clinical and imaging information at a mean (SD) age of 12.0 years (7.7 months). In cross-sectional analyses at both time points, higher BMI and waist circumference were associated with lower microstructural integrity and neurite density, most pronounced in the corpus callosum (fractional anisotropy for BMI and waist circumference at baseline and second year: P &lt; .001; neurite density for BMI at baseline: P &lt; .001; neurite density for waist circumference at baseline: P = .09; neurite density for BMI at second year: P = .002; neurite density for waist circumference at second year: P = .05), reduced functional connectivity in reward- and control-related networks (eg, within the salience network for BMI and waist circumference at baseline and second year: P &lt; .002), and thinner brain cortex (eg, for the right rostral middle frontal for BMI and waist circumference at baseline and second year: P &lt; .001). In longitudinal analysis, higher baseline BMI was most strongly associated with decelerated interval development of the prefrontal cortex (left rostral middle frontal: P = .003) and microstructure and cytostructure of the corpus callosum (fractional anisotropy: P = .01; neurite density: P = .02).Conclusions and RelevanceIn this cross-sectional study, higher BMI and waist circumference among children aged 9 to 10 years were associated with imaging metrics of poorer brain structure and connectivity as well as hindered interval development. Future follow-up data from the ABCD study can reveal long-term neurocognitive implications of excess childhood weight. Imaging metrics that had the strongest association with BMI and waist circumference in this population-level analysis may serve as target biomarkers of brain integrity in future treatment trials of childhood obesity.

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Analysis of Clinical Traits Associated With Cardiovascular Health, Genomic Profiles, and Neuroimaging Markers of Brain Health in Adults Without Stroke or Dementia

Cited by 8 publications

References 23 publications

Associations of “Life’s Essential 8” cardiovascular health with dementia risk, cognition, and neuroimaging markers of brain health

Associations of “Life’s Essential 8” cardiovascular health with dementia risk, cognition, and neuroimaging markers of brain health

Associations of Life's Simple 7 with cerebral white matter hyperintensities and microstructural integrity: UK Biobank cohort study

Association of Body Mass Index and Waist Circumference With Imaging Metrics of Brain Integrity and Functional Connectivity in Children Aged 9 to 10 Years in the US, 2016-2018

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