Identification of circulating risk biomarkers for cognitive decline in a large community-based population in Chongqing China

Yu Kang; Zijuan Feng; Qian Zhang; Mingjing Liu; Yanhua Li; Huan Yang; Lingling Zheng; Chunjiang Cheng; Weitao Zhou; Dandan Lou; Xiaoyong Li; Liangping Chen; Yi Feng; Xiaoling Duan; Jianzhong Duan; Mengjiao Yu; Shou Yang; Yuhang Liu; Xin Wang; Bo Deng; Chenghui Liu; Xiuqing Yao; Chi Zhu; Chunrong Liang; Xiaolong Zeng; Sisi Ren; Qunying Li; Yin Zhong; Yong Yan; Huaqing Meng; Zhaohui Zhong; Yong Zhang; Jun Kang; Xiaoqian Luan; Sipei Pan; Yili Wu; Tingyu Li; Weihong Song; Yun Zhang

doi:10.1002/alz.14443

Identification of circulating risk biomarkers for cognitive decline in a large community-based population in Chongqing China

Alzheimers Dement. 2024 Dec 23. doi: 10.1002/alz.14443. Online ahead of print.

Authors

Yu Kang^{1

2}, Zijuan Feng¹, Qian Zhang³, Mingjing Liu¹, Yanhua Li¹, Huan Yang¹, Lingling Zheng¹, Chunjiang Cheng¹, Weitao Zhou¹, Dandan Lou¹, Xiaoyong Li¹, Liangping Chen¹, Yi Feng¹, Xiaoling Duan¹, Jianzhong Duan¹, Mengjiao Yu¹, Shou Yang¹, Yuhang Liu¹, Xin Wang⁴, Bo Deng⁴, Chenghui Liu⁴, Xiuqing Yao⁴, Chi Zhu⁴, Chunrong Liang⁴, Xiaolong Zeng⁴, Sisi Ren⁵, Qunying Li⁴, Yin Zhong⁵, Yong Yan⁶, Huaqing Meng⁷, Zhaohui Zhong⁵, Yong Zhang⁵, Jun Kang⁵, Xiaoqian Luan^{8

9}, Sipei Pan^{8

9}, Yili Wu⁸, Tingyu Li¹, Weihong Song^{1

2

8

9}, Yun Zhang^{10

11}

Affiliations

¹ Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
² Townsend Family Laboratories, Department of Psychiatry, The University of British Columbia, Vancouver, British Columbia, Canada.
³ Clinical Research Support Unit, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
⁴ Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
⁵ School of Public Health and Management, Chongqing Medical University, Chongqing, China.
⁶ Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
⁷ Department of psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
⁸ Center for Geriatric Medicine, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁹ Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, China.
¹⁰ Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
¹¹ The National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China.

PMID: 39713874
DOI: 10.1002/alz.14443

Abstract

Introduction: This study aims to investigate the relationship between blood-based pathologies and established risk factors for cognitive decline in the community-based population of Chongqing, a region with significant aging.

Methods: A total of 26,554 residents aged 50 years and older were recruited. Multinomial logistic regression models were applied to assess the risk factors of cognition levels. Propensity score matching and linear mixed effects models were used to evaluate the relationship between key risk factors and the circulating biomarkers.

Results: Shared and distinct risk factors for MCI and dementia were identified. Age, lower education, medical history of stroke, hypertension, and epilepsy influenced mild cognitive impairment (MCI) progression to dementia. Correlations between key risk factors and circulating neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), amyloid β protein (Aβ)40, and Aβ42/Aβ40 ratio suggest underlying mechanisms contributing to cognitive impairment.

Discussion: The common and distinct risk factors across cognitive decline stages emphasize the need for tailored interventions. The correlations with blood biomarkers provide insights into potential management targets.

Highlights: From a large community-based cohort study on the residents in Chongqing, we have identified that mild cognitive impairment (MCI) and dementia share several common risk factors, including age, female gender, rural living, lower education levels, and a medical history of stroke. However, each condition also has its own unique risk factors. Several factors contribute to the progression of MCI into dementia including age, education levels, occupation, and a medical history of hypertension and epilepsy. We discover the correlations between the risk factors for dementia and blood biomarkers that indicate the presence of axonal damage, glial activation, and Aβ pathology.

Keywords: Alzheimer's disease; blood biomarkers; dementia; elderly population; mild cognitive impairment.

Abstract

Grants and funding