The Presence and Severity of NAFLD are Associated With Cognitive Impairment and Hippocampal Damage

Yingwen Miao; Bing Zhang; Xitai Sun; Xuelin Ma; Da Fang; Wen Zhang; Tianyu Wu; Xiang Xu; Congcong Yu; Yinjiao Hou; Qun Ding; Sijue Yang; Linqing Fu; Zhou Zhang; Yan Bi

doi:10.1210/clinem/dgad352

The Presence and Severity of NAFLD are Associated With Cognitive Impairment and Hippocampal Damage

J Clin Endocrinol Metab. 2023 Nov 17;108(12):3239-3249. doi: 10.1210/clinem/dgad352.

Authors

Yingwen Miao^{1

2}, Bing Zhang³, Xitai Sun⁴, Xuelin Ma^{1

2}, Da Fang^{1

2}, Wen Zhang³, Tianyu Wu^{1

2}, Xiang Xu^{1

2}, Congcong Yu^{1

2}, Yinjiao Hou^{1

2}, Qun Ding^{1

2}, Sijue Yang^{1

2}, Linqing Fu³, Zhou Zhang^{1

2}, Yan Bi^{1

2}

Affiliations

¹ Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
² Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China.
³ Department of Radiology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
⁴ Department of General Surgery, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, China.

PMID: 37310344
DOI: 10.1210/clinem/dgad352

Abstract

Context: Although cognitive impairment in nonalcoholic fatty liver disease (NAFLD) has received attention in recent years, little is known about detailed cognitive functions in histologically diagnosed individuals.

Objective: This study aimed to investigate the association of liver pathological changes with cognitive features and further explore the underlying brain manifestations.

Methods and patients: We performed a cross-sectional study in 320 subjects who underwent liver biopsy. Among the enrolled participants, 225 underwent assessments of global cognition and cognitive subdomains. Furthermore, 70 individuals received functional magnetic resonance imaging scans for neuroimaging evaluations. The associations among liver histological features, brain alterations, and cognitive functions were evaluated using structural equation model.

Results: Compared with controls, patients with NAFLD had poorer immediate memory and delayed memory. Severe liver steatosis (odds ratio, 2.189; 95% CI, 1.020-4.699) and ballooning (OR, 3.655; 95% CI, 1.419-9.414) were related to a higher proportion of memory impairment. Structural magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis exhibited volume loss in left hippocampus and its subregions of subiculum and presubiculum. Task-based magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis had decreased left hippocampal activation. Path analysis demonstrated that higher NAFLD activity scores were associated with lower subiculum volume and reduced hippocampal activation, and such hippocampal damage contributed to lower delayed memory scores.

Conclusions: We are the first to report the presence and severity of NAFLD to be associated with an increased risk of memory impairment and hippocampal structural and functional abnormalities. These findings stress the significance of early cognitive evaluation in patients with NAFLD.

Keywords: cognitive impairment; functional MRI; hippocampal damage; nonalcoholic fatty liver disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cognitive Dysfunction* / diagnostic imaging
Cognitive Dysfunction* / etiology
Cross-Sectional Studies
Hippocampus / diagnostic imaging
Hippocampus / pathology
Humans
Non-alcoholic Fatty Liver Disease* / complications
Non-alcoholic Fatty Liver Disease* / diagnostic imaging
Non-alcoholic Fatty Liver Disease* / pathology

Associated data

figshare/10.6084/m9.figshare.22769345.v4

Abstract

Publication types

MeSH terms

Associated data

Grants and funding