Affiliations: [a] University of Vermont Larner College of Medicine, Burlington, VT, USA
| [b] Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
| [c] Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA
| [d] SphingoTec GmbH, Hennigsdorf, Germany
| [e] Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
| [f] Departments of Medicine and Pathology and Laboratory Medicine, University of Vermont Larner College of Medicine, Burlington, VT, USA
Correspondence:
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Correspondence to: Mary Cushman, MD, Department of Medicine, University of Vermont Larner College
of Medicine, 360 South Park Drive, Colchester, VT 05446, USA. Tel.: +1 802 656 8968;
Fax: +1 802 656 8965; E-mail: [email protected].
Abstract: Background:The neuropeptide neurotensin (NT) has been linked to cardiometabolic disease. Cardiovascular risk factors are being recognized as risk factors for cognitive impairment. Objective:To examine the association of the stable precursor of NT, pro-neurotensin/neuromedin N (pro-NT/NMN), with incident cognitive impairment (ICI). Methods:We conducted a prospective nested case-control study in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. In 2003-2007, REGARDS enrolled 30,239 Black and White adults aged ≥45 years. ICI was identified using a 3-test cognitive battery administered biannually. Baseline pro-NT/NMN was measured by immunoassay in 393 cases of ICI and 490 controls after 3.4 years follow up. Multivariable logistic regression was used to calculate odds ratios (OR) of ICI by pro-NT/NMN quartiles. Race, age, and sex differences were studied with stratified models and interaction testing. Results:Pro-NT/NMN was higher in Black participants and those with hypertension and diabetes. Women with a 4th versus 1st-quartile pro-NT/NMN had 2.28-fold increased odds of ICI (95% CI 1.08–4.78) after adjusting for risk factors and incident stroke. There was no association of higher pro-NT/NMN quartiles with ICI in the overall group or men. There were no race or age differences in associations. Conclusion:In this biracial population-based study, elevated systemic pro-NT/NMN was associated with more than doubled risk of ICI in women but not men. Others reported sex-specific associations in women for cardiovascular mortality and diabetes with higher pro-NT/NMN, supporting a role for future research on sex differences in the neurotensinergic system.
