Cognitively Unimpaired Multiparous Women Have Higher CSF p‐tau181 Levels Which Have More Deleterious Effects on Neurodegeneration and Executive Function

Abstract

AbstractBackgroundEpidemiologic studies show that multiparity (≥3 children) is associated with a higher risk of clincal AD in cognitively unimpaired (CU) women. However, studies exploring the impact of parity on AD biomarkers are scarce. We explored the association between number of children and imaging and fluid AD biomarkers, and the related interaction with neurodegeneration and cognition.MethodWe included 210 CU parous women from the ALFA+ cohort with 34 nulliparous women and 152 men with children as controls. The number of children was dichotomized as <3 children vs ≥3 children. All CSF biomarkers were measured using the Roche NeuroToolKit and Elecsys® immunoassays (both Roche Diagnostics International Ltd), except p‐tau231 and GAP‐43 (ELISA). All plasma biomarkers were measured using the Simoa HD‐X (Quanterix Corp) except sICAM1 (MSD). Jack’s cortical thickness AD signature was used as a marker of neurodegeneration. Cognitive change (3‐year follow‐up) was measured with a PACC‐like composite as well as for individual cognitive domains. Biomarkers differences between parity groups were analyzed with ANCOVA adjusted by age. Independent linear models with biomarkers, AD signature and cognitive change as dependent variable were constructed. The number of children was set as predictor, and age, APOE‐ε4, and age at first birth as covariates in all models. Interaction terms between number of children and biomarkers were modeled. p‐values <0.05 were considered as significant.ResultSeveral biomarkers were significantly higher in grand multiparours women (Table 1). Linear regression results (Table 2, Fig. 1A) showed that multiparity was associated with higher CSF p‐tau181 levels. Moreover, multiparity interacted with CSF p‐tau181 to predict thinner cortical thickness in AD‐sensitive regions and a steeper decline in executive function (Table 2, Fig. 1B & 1C). No significant associations in men and nulliparous women were found.ConclusionHaving ≥3 children increases the risk of higher CSF p‐tau181 levels in CU middle‐aged women, with CSF p‐tau181 having a more deleterious effect on cortical thickness and change on executive function performance. These findings contribute to our understanding of the higher risk for AD observed in CU multiparous women, who show higher susceptibility and more adverse downstream consequences to tau pathology.