Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) risk factors that have been linked to cognitive decline. Whether NAFLD is associated with cognitive performance in midlife remains uncertain.MethodsCoronary Artery Risk Development in Young Adults study participants with CT examination and cognitive assessment at Y25 (2010–2011; n = 2809) were included. Cognitive function was reassessed at Y30. NAFLD was defined according to liver attenuation and treated both continuously and categorically (using ≤ 40 and ≤ 51 Hounsfield units to define severity) after exclusion for other causes of liver fat. Cognitive tests including the Digit Symbol Substitution (processing speed), Rey Auditory Verbal Learning (verbal memory), and Stroop (executive function) were analyzed with standardized z-scores. Linear models were constructed to (a) examine the cross-sectional associations of NAFLD with cognitive scores and (b) evaluate its predictive role in 5-year change in cognitive performance.ResultsParticipants’ mean age (Y25) was 50.1 (SD 3.6) years (57% female; 48% black), with 392 (14%) having mild NAFLD and 281 (10%) having severe NAFLD. NAFLD was positively associated with CVD risk factors and inversely associated with cognitive scores. However, after adjustment for CVD risk factors, no associations were shown between NAFLD and cognitive scores (all βs ≈ 0). Similarly, no associations were observed with 5-year cognitive decline. CVD history, hypertension, smoking, diabetes and hypertriglyceridemia showed stronger associations with baseline cognitive scores and were predictive of subsequent cognitive decline (all P ≤ .05).ConclusionAmong middle-aged adults, inverse associations between NAFLD and cognitive scores were attenuated after adjustment for CVD risk factors, with the latter predictive of poorer cognitive performance both at baseline and follow-up.

Highlights

  • Cognitive aging has been the focus of recent scientific interest, fueled by the rapid growth of the U.S population age 65 and older [1,2,3]

  • Previous studies show that exposure to cardiovascular disease (CVD) risk factors in midlife is associated with an Gerber et al BMC Gastroenterol (2021) 21:96 increased risk of dementia [7, 8]

  • The Coronary Artery Risk Development in Young Adults (CARDIA) study is uniquely positioned to address this gap in knowledge with its diverse cohort and rigorous ascertainment of risk factors for cognitive aging repeatedly measured over time

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Summary

Introduction

Cognitive aging has been the focus of recent scientific interest, fueled by the rapid growth of the U.S population age 65 and older [1,2,3]. Previous studies show that exposure to cardiovascular disease (CVD) risk factors in midlife is associated with an Gerber et al BMC Gastroenterol (2021) 21:96 increased risk of dementia [7, 8]. Whether NAFLD is associated with cognitive decline remains an important clinical question with potential implications for preventive interventions. NAFLD has been linked to increased risk of carotid atherosclerosis [21], a potential risk factor for cognitive impairment [22, 23], and was inversely associated with measures of early brain health [24, 25]. Prospective studies evaluating NAFLD in relation to change in cognitive function in midlife are not available. Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) risk factors that have been linked to cognitive decline. Whether NAFLD is associated with cognitive performance in midlife remains uncertain

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