[en] Lewy body dementia is the second most common neurodegenerative dementia after Alzheimer’s disease. Disease-modifying therapies for this disabling neuropsychiatric condition are critically needed. To identify drugs associated with risk of developing Lewy body dementia, we performed a population-based case-control study of 148,170 United States Medicare participants diagnosed with Lewy body dementia between January 1, 2008, and December 31, 2014, and 1,253,043 frequency-matched controls. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of Lewy body dementia risk with 1,017 prescription drugs overall and separately for the three major racial groups (Black, Hispanic, White Americans). We identified significantly reduced Lewy body dementia risk associated with drugs used to treat cardiovascular diseases (antihypertensives: OR = 0.72, 95% CI = 0.70–0.74, p-value = 0; cholesterol-lowering agents: OR = 0.85, 95% CI = 0.83–0.87, p-value = 0; antidiabetics: OR = 0.83, 95% CI = 0.62–0.72, p-value = 0). Notably, antidiabetic medications were associated with a larger risk reduction among Black Lewy body dementia patients compared to other racial groups (Black: OR = 0.67, 95% CI = 0.62–0.72, p-value = 0; Hispanic: OR = 0.86, 95% = 0.80–0.92, p-value = 5.16 x 10-5; White: OR = 0.85, 95% CI = 0.82–0.88, p-value = 0). To independently confirm the epidemiological findings, we looked for evidence of genetic overlap between Lewy body dementia and cardiovascular traits using whole-genome sequence data generated for 2,652 Lewy body dementia patients and 4,027 controls. Bivariate mixed modeling identified shared genetic risk between Lewy body dementia and low-density lipoprotein cholesterol levels, type 2 diabetes, and hypertension. By combining epidemiological and genomic data, we demonstrated that drugs treating cardiovascular diseases are associated with reduced Lewy body dementia risk, and these associations varied across racial groups. Future randomized clinical trials need to confirm our findings, but our data suggest that assiduous management of cardiovascular diseases may be beneficial in this understudied form of dementia.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) LIH - Luxembourg Institute of Health Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Disciplines :
Neurology Cardiovascular & respiratory systems Genetics & genetic processes
Author, co-author :
Scholz, Sonja W ; Department of Neurology, Johns Hopkins University Medical Center , Baltimore, MD 21287 , USA ; Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 , USA
Moroz, Brian E; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892 , USA
Saez-Atienzar, Sara; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA
Chia, Ruth ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA
Cahoon, Elizabeth K; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892 , USA
Dalgard, Clifton L; Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD 20814 , USA ; The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences , Bethesda, MD 20814 , USA
Dalgard, Clifton L
Adeleye, Adelani
Soltis, Anthony R
Alba, Camille
Viollet, Coralie
Bacikova, Dagmar
Hupalo, Daniel N
Sukumar, Gauthaman
Pollard, Harvey B
Wilkerson, Matthew D
Martinez, Elisa McGrath
Black, Sandra E
Gan-Or, Ziv
Keith, Julia
Masellis, Mario
Rogaeva, Ekaterina
Brice, Alexis
Lesage, Suzanne
Xiromerisiou, Georgia
Calvo, Andrea
Canosa, Antonio
Chio, Adriano
Logroscino, Giancarlo
Mora, Gabriele
KRÜGER, Rejko ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
MAY, Patrick ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Alcolea, Daniel
Clarimon, Jordi
Fortea, Juan
Gonzalez-Aramburu, Isabel
Infante, Jon
Lage, Carmen
Lleó, Alberto
Pastor, Pau
Sanchez-Juan, Pascual
Brett, Francesca
Aarsland, Dag
Al-Sarraj, Safa
Attems, Johannes
Gentleman, Steve
Hardy, John A
Hodges, Angela K
Love, Seth
McKeith, Ian G
Morris, Christopher M
Morris, Huw R
Palmer, Laura
Pickering-Brown, Stuart
Ryten, Mina
Thomas, Alan J
Troakes, Claire
Albert, Marilyn S
Barrett, Matthew J
Beach, Thomas G
Bekris, Lynn M
Bennett, David A
Boeve, Bradley F
Dalgard, Clifton L
Dawson, Ted M
Dickson, Dennis W
Ferman, Tanis
Ferrucci, Luigi
Flanagan, Margaret E
Foroud, Tatiana M
Ghetti, Bernardino
Gibbs, J Raphael
Goate, Alison
Goldstein, David S
Graff-Radford, Neill R
Kantarci, Kejal
Kaufmann, Horacio
Kukull, Walter A
Leverenz, James B
Mao, Qinwen
Masliah, Eliezer
Monuki, Edwin
Newell, Kathy L
Palma, Jose-Alberto
Perkins, Matthew
Pletnikova, Olga
Renton, Alan E
Resnick, Susan M
Rosenthal, Liana S
Ross, Owen A
Scherzer, Clemens R
Serrano, Geidy E
Shakkottai, Vikram G
Sidransky, Ellen
Tanaka, Toshiko
Topol, Eric
Torkamani, Ali
Traynor, Bryan J
Troncoso, Juan C
Woltjer, Randy
Wszolek, Zbigniew K
Scholz, Sonja W
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Pfeiffer, Ruth M; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892 , USA
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