TY - JOUR
T1 - Health-Related Behaviors and Risk of Common Age-Related Brain Diseases Across Severities of Genetic Risk
AU - Marini, Sandro
AU - Kimball, Tamara N.
AU - Mayerhofer, Ernst
AU - Tack, Reinier W.P.
AU - Senff, Jasper R.
AU - Prapiadou, Savvina
AU - Rivier, Cyprien A.
AU - Duskin, Jonathan
AU - Kourkoulis, Christina
AU - Falcone, Guido J.
AU - Yechoor, Nirupama
AU - Tanzi, Rudolph E.
AU - Rosand, Jonathan
AU - Singh, Sanjula
AU - Parodi, Livia
AU - Anderson, Christopher D.
N1 - Publisher Copyright:
© 2024 American Academy of Neurology.
PY - 2024/11/26
Y1 - 2024/11/26
N2 - 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 e 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.
AB - 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 e 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.
UR - http://www.scopus.com/inward/record.url?scp=85208688740&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000210014
DO - 10.1212/WNL.0000000000210014
M3 - Article
C2 - 39504504
AN - SCOPUS:85208688740
SN - 0028-3878
VL - 103
JO - Neurology
JF - Neurology
IS - 10
M1 - e210014
ER -