Rainer Malik1, Marios K Georgakis1, Julia Neitzel1, Kristiina Rannikmäe2, Michael Ewers1, Sudha Seshadri3, Cathie L M Sudlow4,5, Martin Dichgans1,6,7. 1. Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University LMU, Munich, Germany. 2. Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK. 3. The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, Texas, USA. 4. Center for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. 5. Nine Bioquarter, Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK. 6. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. 7. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Abstract
INTRODUCTION: Midlife clustering of vascular risk factors has been associated with late-life dementia, but causal effects of individual biological and lifestyle factors remain largely unknown. METHODS: Among 229,976 individuals (mean follow-up 9 years), we explored whether midlife cardiovascular health measured by Life's Simple 7 (LS7) is associated with incident all-cause dementia and whether the individual components of the score are causally associated with dementia. RESULTS: Adherence to the biological metrics of LS7 (blood pressure, cholesterol, glycemic status) was associated with lower incident dementia risk (hazard ratio = 0.93 per 1-point increase, 95% confidence interval [CI; 0.89-0.96]). In contrast, there was no association between the composite LS7 score and the lifestyle subscore (smoking, body mass index, diet, physical activity) and incident dementia. In Mendelian randomization analyses, genetically elevated blood pressure was associated with higher risk of dementia (odds ratio = 1.31 per one-standard deviation increase, 95% CI [1.05-1.60]). DISCUSSION: These findings underscore the importance of blood pressure control in midlife to mitigate dementia risk.
INTRODUCTION: Midlife clustering of vascular risk factors has been associated with late-life dementia, but causal effects of individual biological and lifestyle factors remain largely unknown. METHODS: Among 229,976 individuals (mean follow-up 9 years), we explored whether midlife cardiovascular health measured by Life's Simple 7 (LS7) is associated with incident all-cause dementia and whether the individual components of the score are causally associated with dementia. RESULTS: Adherence to the biological metrics of LS7 (blood pressure, cholesterol, glycemic status) was associated with lower incident dementia risk (hazard ratio = 0.93 per 1-point increase, 95% confidence interval [CI; 0.89-0.96]). In contrast, there was no association between the composite LS7 score and the lifestyle subscore (smoking, body mass index, diet, physical activity) and incident dementia. In Mendelian randomization analyses, genetically elevated blood pressure was associated with higher risk of dementia (odds ratio = 1.31 per one-standard deviation increase, 95% CI [1.05-1.60]). DISCUSSION: These findings underscore the importance of blood pressure control in midlife to mitigate dementia risk.
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