Objective: We hypothesized that elevated parathyroid hormone (PTH) levels will be independently associated with 20-year cognitive decline in a large population-based cohort. Methods: We studied 12,964 middle-aged white and black ARIC participants without a history of prior stroke who, in 1990-1992 (baseline), had serum PTH levels measured and cognitive function testing, with repeat cognitive testing performed at up to 2 follow-up visits. Cognitive testing included the Delayed Word Recall, the Digit Symbol Substitution, and the Word Fluency tests, which were summed as a global Z score. Using mixed-effects models, we compared the relative decline in individual and global cognitive scores between each of the top 3 quartiles of PTH levels to the reference bottom quartile. We adjusted for demographic variables, education, vascular risk factors, and levels of calcium, phosphate, and vitamin D. We imputed missing covariate and follow-up cognitive data to account for attrition. Results: The mean (SD) age of our cohort was 57 (6) years, 57% were women, and 24% were black. There was no cross-sectional association of elevated PTH with cognitive global Z score at baseline (p > 0.05). Over a median of 20.7 years, participants in each PTH quartile showed a decline in cognitive function. However, there was no significant difference in cognitive decline between each of the top 3 quartiles and the lowest reference quartile (p > 0.05). In a subset, there was also no association of higher mid-life PTH levels with late-life prevalent adjudicated dementia (p > 0.05). Conclusions: Our work does not support an independent influence of PTH on cognitive decline in this population-based cohort study.
Bibliographical noteFunding Information:
From the Ciccarone Center for the Prevention of Heart Disease (S.M.K., E.D.M.) and Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine; Department of Epidemiology (D.Z., E.G., R.F.G., E.D.M.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Northeast Ohio Medical University (S.K.K.), Rootstown; Division of Epidemiology and Community Health (P.L.L.), School of Public Health, University of Minnesota, Minneapolis; Department of Epidemiology (A.A.), Rollins School of Public Health, Emory University, Atlanta, GA; and Department of Medicine (B.G.W.), Division of Geriatrics, University of Mississippi Medical Center, Jackson. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
This work was supported by grants from NIH/National Institute of Neurological Disorders and Stroke (R01NS072243 to Dr. Michos), the NIH/NHLBI (R01HL103706 to Dr. Lutsey), and the NIH Office of Dietary Supplements (R01HL103706-S1 to Dr. Lutsey). The Atherosclerosis Risk in Communities Study is a collaborative research supported by the National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). ARIC-NCS was funded by U01 HL096812, HL096814, HL096899, HL096902, and HL096917, with additional support from the National Institute of Neurological Disorders and Stroke. Dr. Michos and Dr. Zhao are also supported by the Blumenthal Scholars Fund for Preventive Cardiology research.