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. 2024 Nov 26;103(10):e210014.
doi: 10.1212/WNL.0000000000210014. Epub 2024 Nov 6.

Health-Related Behaviors and Risk of Common Age-Related Brain Diseases Across Severities of Genetic Risk

Sandro Marini  1 , Tamara N Kimball  1 , Ernst Mayerhofer  1 , Reinier W P Tack  1 , Jasper R Senff  1 , Savvina Prapiadou  1 , Cyprien A Rivier  1 , Jonathan Duskin  1 , Christina Kourkoulis  1 , Guido J Falcone  1 , Nirupama Yechoor  1 , Rudolph E Tanzi  1 , Jonathan Rosand  1 , Sanjula Singh  1 , Livia Parodi  1 , Christopher D Anderson  1
Affiliations

Health-Related Behaviors and Risk of Common Age-Related Brain Diseases Across Severities of Genetic Risk

Sandro Marini et al. Neurology. .

Erratum in

Abstract

Background and objectives: The 21-point Brain Care Score (BCS) is an index that ranks behaviors and clinical measurements with the aim of encouraging lifestyle adjustments to lower the incidence of age-related brain disease, including stroke, late-life depression (LLD), and dementia. A higher BCS at baseline is associated with a lower risk of these outcomes. We aimed to investigate whether the associations between BCS and stroke, LLD, and dementia risks are independent of genetic predisposition for these conditions and quantify the effect of healthy lifestyle across genetic risk distributions for these outcomes.

Methods: Using the UK Biobank (UKB) prospective cohort study, we computed baseline BCSs and polygenic scores to estimate genetic predisposition for stroke and LLD and APOE ε allele status to stratify dementia risk. As for outcomes again in UKB, we measured incidence of stroke, LLD, and dementia. We used multivariate Cox proportional hazard models to assess associations between BCS, genetic predisposition, and these outcomes. We also conducted stratified and interaction analyses to estimate the incidence of these outcomes across quartiles of genetic risk and BCS.

Results: We included 368,340 UKB participants (median age 58 years (interquartile range 51-63 years), 46.3% male). Independent of genetic risk, a 5-point increase in BCS corresponded to lowered hazards of stroke (hazard ratio [HR] 0.70, 95% CI 0.68-0.73), LLD (HR 0.65, 95% CI 0.63-0.67), and dementia (HR 0.82, 95% CI 0.78-0.85). Incidences of all 3 outcomes were higher among participants with high genetic risk of these outcomes. However, these increased risks were offset for individuals with a higher BCS (incidence rates per 1,000 person-years were 2.76 vs 1.19 for stroke, 7.34 vs 4.46 for LLD, and 3.64 vs 2.05 for dementia, when comparing low and high BCS).

Discussion: Across different genetic predispositions for stroke, LLD, and dementia, healthier lifestyle behaviors are protective for brain health, demonstrating the nondeterminism of genetic risk. Furthermore, differences in BCS behave as aggregate risk estimators of all 3 outcomes. Further work is needed to prospectively investigate the utility and performance of the BCS as a targeted intervention in populations at elevated genetic risk of age-related brain disease.

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Conflict of interest statement

E. Mayerhofer is an employee of Regeneron Pharmaceuticals as of July 2023. The other authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

References

    1. Feigin VL, Vos T, Nichols E, et al. The global burden of neurological disorders: translating evidence into policy. Lancet Neurol. 2020;19(3):255-265. doi: 10.1016/S1474-4422(19)30411-9 - DOI - PMC - PubMed
    1. Rost NS, Salinas J, Jordan JT, et al. The brain health imperative in the 21st century-A call to action: the AAN brain health platform and position statement. Neurology. 2023;101(13):570-579. doi: 10.1212/WNL.0000000000207739 - DOI - PMC - PubMed
    1. Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology. 2013;80(19):1778-1783. doi: 10.1212/WNL.0b013e31828726f5 - DOI - PMC - PubMed
    1. Rotenstein LS, Ramos MA, Torre M, et al. Prevalence of depression, depressive symptoms, and suicidal ideation among medical students: a systematic review and meta-analysis. JAMA. 2016;316(21):2214-2236. doi: 10.1001/jama.2016.17324 - DOI - PMC - PubMed
    1. GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20(10):795-820. doi: 10.1016/s1474-4422(21)00252-0 - DOI - PMC - PubMed

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