A Brain Care Score to Mitigate the Genetic Risk of Adverse Brain Health Outcomes
Tamara Kimball1, Ernst Mayerhofer2, Jasper Senff2, Sandro Marini2, Cyprien A. Rivier 3, Christina Kourkoulis 2, Tin Oreskovic4, Sinclair Carr5, Guido Falcone3, Nirupama Yechoor6, Jonathan Rosand2, Sanjula Singh2, Livia Parodi2, Christopher Anderson7
1Neurology, Mass General Brigham-Harvard Medical School, 2Neurology, Massachusetts General Hospital-Harvard Medical School, 3Yale School of Medicine, 4Big Data Institute, Nuffield Department of Population Health, 5Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 6Neurology, MassGeneral Brigham-Harvard Medical School, 7Neurology, Brigham and Women's Hospital-Harvard Medical School
Objective:
Investigate whether the association between Brain Care Score (BCS) and outcomes is independent of genetic predisposition for the same outcomes and whether improving the BCS among UK Biobank (UKB) participants could mitigate the effect of high genetic risk of dementia, stroke, and depression.
Background:
The 21-point BCS is a novel tool derived through a modified Delphi process, developed to encourage lifestyle adjustments to lower dementia, stroke, and late-life depression risks. A lower BCS is associated with a higher risk of these outcomes.
Design/Methods:
Data from 176,693 UKB participants with primary care records were utilized. Polygenic risk scores (PRS) for stroke and depression were generated using PRS-CS and GWAS summary data. APOE genotype determined all-cause dementia risk, stratified by APOE e4 alleles. Baseline and 12-year follow-up BCS data were collected. Sex and age-adjusted Cox Proportional Hazard models were performed to assess associations between BCS at baseline and changes in BCS over time with stroke, depression, and dementia stratified by tertiles of genetic risk.
Results:
Even among those with high genetic risk, participants with high BCS exhibited lowered hazards: stroke (HR: 0.55; 95%CI 0.48-0.62), depression (HR: 0.48; 95%CI 0.45-0.52), and dementia (HR: 0.80; 95%CI 0.70-0.91). Similarly, a 5-point longitudinal increase in total BCS during follow-up lowered the risks among those at the highest genetic risk of stroke (HR: 0.69; 95%CI 0.59-0.81) and depression (HR:0.57; 95%CI 0.51-0.63).
Conclusions:
A higher BCS mitigates conferred genetic risk for stroke, dementia, and depression. Improvements in the BCS over the 12-year observation period were shown to lessen genetic risk effects for these adverse brain health outcomes, adding further weight to the utility of the BCS as a tool for brain care.