Pro-neurotensin/neuromedin N is Associated With Incident Cognitive Impairment in Women

Introduction: Neurotensin (NT) is a neuropeptide implicated in cardiovascular and metabolic disease. As such, it is a candidate risk factor for cognitive impairment. We are not aware of studies reporting the relationship of NT and incident cognitive impairment (ICI). NT can be estimated in plasma by measuring its stable equimolar precursor, pro-neurotensin/neuromedin N (pro-NT/NMN). Hypothesis: Higher fasting plasma pro-NT/NMN is associated with risk of ICI. Methods: Prospective nested case-control study in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. REGARDS enrolled 30,239 Black and White adults aged ≥45 from 2003-2007. Baseline pro-NT/NMN was measured by immunoassay in 497 controls and 399 cases of ICI over 3.5 years follow up. ICI was identified using a 3-test cognitive battery biannually. Multivariable logistic regression was used to calculate odds ratios (OR) of ICI by pro-NT/NMN quartiles. Race and sex differences were studied with stratified models and interaction testing (with p <0.10 significant). Results: There was no association of 4 th vs. 1 st -quartile proNT/NMN with ICI in the overall group (see table), nor significant associations of the 2 nd and 3 rd quartiles with ICI in any group The OR differed significantly by sex; women had a 90% increased odds in the demographic-adjusted model, only slightly attenuated by risk factor adjustment. There was no race difference in associations. Conclusions: Higher circulating pro-NT/NMN was associated with ICI in women but not men. This could be due to cerebral vasoconstrictive effects of NT and estrogen-mediated differences in transcription. Confirmatory study is required.