Subtype division of mild cognitive impairment based on cluster analysis and the risk of progression to AD
10.3760/cma.j.issn.0254-9026.2025.04.021
- VernacularTitle:基于聚类分析方法的轻度认知功能障碍亚型划分及其阿尔茨海默病进展风险研究
- Author:
Yingxue PENG
1
;
Xianxian LONG
1
;
Manqiong YUAN
1
;
Ya FANG
1
Author Information
1. 卫生技术评估福建省高校重点实验室 厦门大学公共卫生学院老年健康研究中心，厦门 361005
- Publication Type:Journal Article
- Keywords:
Mild cognitive impairment;
Cluster analysis;
Subtype;
Survival analysis;
Alzheimer's disease
- From:
Chinese Journal of Geriatrics
2025;44(4):538-543
- CountryChina
- Language:Chinese
-
Abstract:
Objective:Mild cognitive impairment(MCI)is characterized by its heterogeneity in pathology, clinical outcomes, and the degree of cognitive impairment.This study aims to identify distinct subtypes of MCI and examine their associated risk of progression to Alzheimer's disease(AD).Methods:Four cognitive domains—memory, language, attention/executive function, and visuospatial ability—were evaluated using seven neuropsychological tests.K-means cluster analysis was employed to categorize MCI into distinct subtypes.Kaplan-Meier survival analysis and Cox regression were utilized to estimate the median survival time and the risk of progression to AD for each subtype, with cognitively normal(CN)individuals at baseline serving as the control group.Only participants with a minimum of two follow-up visits were included in this analysis.Results:A total of 1, 020 subjects with baseline MCI were included in the study, with an age range of 60 to 90 years and a mean age of 73.6 years.Among these subjects, 40.5% were female, and the mean length of education was 16.0 years.The MCI subtypes were classified based on their characteristics as follows: amnestic(n=485), mixed(n=147), and derived normal(n=388).The mixed subtype performed poorly across all neuropsychological tests, particularly demonstrating significantly worse results than the other two subtypes in attention/executive ability and visuospatial functioning.The amnestic subtype primarily exhibited deficits in the memory cognition dimension, while the derived normal subtype scored poorly on the delayed recall aspect of memory cognition.For the survival analysis, a total of 1, 427 subjects were included, with a mean follow-up duration of 50 months.The proportions of subjects who progressed to AD during follow-up were 48.8% for amnestic MCI, 60.0% for mixed MCI, 16.0% for derived normal MCI, and 6.4% for CN individuals at baseline.The mean time to conversion to AD was 29.1 months for amnestic MCI, 19.6 months for mixed MCI, 53.6 months for derived normal MCI, and 85.9 months for CN subjects.There were statistically significant differences in survival time among the subtypes( P<0.001), with the mixed subtype exhibiting the shortest median survival time and the highest risk of progression to AD( HR=20.0, 95% CI: 13.0-30.8).In contrast, the derived normal subtype had the longest survival time and the lowest risk of progression to AD( HR=2.7, 95% CI: 1.7-4.1). Conclusions:MCI subtypes exhibit significant heterogeneity regarding cognitive impairment, progression risk, and time to AD.Individuals with mixed MCI demonstrate the shortest progression time and the highest risk of transitioning to AD.Consequently, early prevention and intervention strategies for AD should prioritize this particular subgroup.
