Authors: Nicoli, Charles D. | Howard, Virginia J. | Judd, Suzanne E. | Struck, Joachim | Manly, Jennifer J. | Cushman, Mary
Article Type: Research Article
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. Show more
Keywords: Biomarkers, case-control studies, cognition disorders, cognitive dysfunction, neuropeptides, neurotensin, prospective studies
DOI: 10.3233/JAD-200456
Citation: Journal of Alzheimer's Disease, vol. 76, no. 4, pp. 1403-1412, 2020
Authors: Cushman, Mary | Callas, Peter W. | McClure, Leslie A. | Unverzagt, Frederick W. | Howard, Virginia J. | Gillett, Sarah R. | Thacker, Evan L. | Wadley, Virginia G.
Article Type: Research Article
Abstract: Background: Improved understanding of the etiology of cognitive impairment is needed to develop effective preventive interventions. Higher amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of cardiac dysfunction associated with risk of cardiovascular diseases and stroke in apparently healthy people. Objective: To study the association of NT-proBNP with risk of incident cognitive impairment. Methods: The Reasons for Geographic and Racial Differences in Stroke is a national cohort study of 30,239 black and white Americans age 45 and older at baseline, enrolled in 2003-7. Among participants without prebaseline stroke or cognitive impairment, baseline NT-proBNP was measured in 470 cases of incident …cognitive impairment and 557 controls. Cases were participants scoring below the 6th percentile of demographically-adjusted means on at least 2 of 3 serially administered tests (word list learning, word list recall and semantic fluency) over 3.5 years follow-up. Results: Adjusting for age, gender, race, region of residence, education, and income, there was an increased odds ratio of incident cognitive impairment with increasing NT-proBNP; participants in the 4th versus 1st quartile (>127 versus ≤33 pg/ml) had a 1.69-fold increased odds (95% CI 1.11–2.58). Adjustment for cardiovascular risk factors and presence of an apolipoprotein E4 allele had no substantial impact on the odds ratio. Results did not differ by age, race, gender, or presence of an apolipoprotein E4 allele. Conclusion: Higher NT-pro-BNP was associated with incident cognitive impairment in this prospective study, independent of atherogenic and Alzheimer’s disease risk factors. Future work should clarify pathophysiologic connections of NT-proBNP and cognitive dysfunction. Show more
Keywords: Biomarkers, brain, cognition disorders, natriuretic peptide, prospective study, risk factors
DOI: 10.3233/JAD-160328
Citation: Journal of Alzheimer's Disease, vol. 54, no. 2, pp. 497-503, 2016