• Jianping Jia, Yuye Ning, Meilin Chen, Shuheng Wang, Hao Yang, Fangyu Li, Jiayi Ding, Yan Li, Bote Zhao, Jihui Lyu, Shanshan Yang, Xin Yan, Yue Wang, Wei Qin, Qi Wang, Ying Li, Jintao Zhang, Furu Liang, Zhengluan Liao, and Shan Wang.
• From the Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital (J.J., Y.N., M.C., Shuheng Wang, H.Y., F. Li, J.D., Yan Li, B.Z., W.Q., Q.W., Ying Li), Beijing Key Laboratory of Geriatric Cognitive Disorders, Clinical Center for Neurodegenerative Disease and Memory Impairment (J.J.), the Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders (J.J.), and the Department of Neurology, Beijing Anding Hospital (Y.W.), Capital Medical University, Key Laboratory of Neurodegenerative Diseases, Ministry of Education (J.J.), the Center for Cognitive Disorders, Beijing Geriatric Hospital (J.L.), and the Department of Neurology, Beijing Jishuitan Hospital (X.Y.), Beijing, the Department of Neurology, Daqing Oilfield General Hospital, Daqing (S.Y.), the Department of Neurology, the 960th Hospital of the People's Liberation Army, Jinan (J.Z.), the Department of Neurology, Baotou Central Hospital, Baotou (F. Liang), the Department of Psychiatry, Zhejiang Provincial People's Hospital, Hangzhou (Z.L.), and the Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang (Shan Wang) - all in China.
• N. Engl. J. Med. 2024 Feb 22; 390 (8): 712722712-722.

BackgroundBiomarker changes that occur in the period between normal cognition and the diagnosis of sporadic Alzheimer's disease have not been extensively investigated in longitudinal studies.MethodsWe conducted a multicenter, nested case-control study of Alzheimer's disease biomarkers in cognitively normal participants who were enrolled in the China Cognition and Aging Study from January 2000 through December 2020. A subgroup of these participants underwent testing of cerebrospinal fluid (CSF), cognitive assessments, and brain imaging at 2-year-to-3-year intervals. A total of 648 participants in whom Alzheimer's disease developed were matched with 648 participants who had normal cognition, and the temporal trajectories of CSF biochemical marker concentrations, cognitive testing, and imaging were analyzed in the two groups.ResultsThe median follow-up was 19.9 years (interquartile range, 19.5 to 20.2). CSF and imaging biomarkers in the Alzheimer's disease group diverged from those in the cognitively normal group at the following estimated number of years before diagnosis: amyloid-beta (Aβ)42, 18 years; the ratio of Aβ42 to Aβ40, 14 years; phosphorylated tau 181, 11 years; total tau, 10 years; neurofilament light chain, 9 years; hippocampal volume, 8 years; and cognitive decline, 6 years. As cognitive impairment progressed, the changes in CSF biomarker levels in the Alzheimer's disease group initially accelerated and then slowed.ConclusionsIn this study involving Chinese participants during the 20 years preceding clinical diagnosis of sporadic Alzheimer's disease, we observed the time courses of CSF biomarkers, the times before diagnosis at which they diverged from the biomarkers from a matched group of participants who remained cognitively normal, and the temporal order in which the biomarkers became abnormal. (Funded by the Key Project of the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03653156.).Copyright © 2024 Massachusetts Medical Society.

18 keywords...

hide…