Work

Association between amyloid-β deposition and cognitive function in cognitively normal adults: a multilevel meta-analysis

Year: 2026

Type: article

Study designs: Systematic Review, Meta-Analysis

Abstract: BACKGROUND: The association between cerebral amyloid-β (Aβ) burden and cognitive performance in cognitively normal (CN) older adults remains uncertain. This meta-analysis aimed to provide an updated and modality-sensitive synthesis of the relationship between Aβ burden and cognitive performance in CN ageing. METHODS: We searched major electronic databases for observational studies investigating the relationship between Aβ biomarkers (positron emission tomography [PET], cerebrospinal fluid [CSF], or plasma) and cognitive outcomes in CN adults. Effect sizes were transformed to Fisher’s z. To account for within-study dependencies, we applied a multilevel random-effects meta-analytic model, followed by subgroup analyses by biomarker modality, study design, and cognitive domain. RESULTS: Sixty-two studies involving 27,320 CN participants (197 effect sizes) met the inclusion criteria. Overall, higher Aβ burden was modestly but significantly associated with poorer cognition (Fisher’s z = − 0.092, p < 0.001), with substantial heterogeneity. Modality-specific analyses showed significant negative associations for PET (Fisher’s z = − 0.098, p < 0.001) and plasma (Fisher’s z = − 0.103, p = 0.012), but not for CSF. By study design, significant associations were observed in both longitudinal studies (Fisher’s z = − 0.109, p = 0.002) and cross-sectional studies (Fisher’s z = − 0.070, p = 0.002). By cognitive domain, the association appeared to be strongest for episodic memory (Fisher’s z = − 0.156, p < 0.001), with significant associations also noted for global cognition, language, executive function, and attention (Fisher’s z = − 0.130 to − 0.057, p ≤ 0.038). DISCUSSION: In CN ageing, higher Aβ burden was associated with slightly poorer cognition. Associations were more consistently detected for PET-based measures and were most pronounced for episodic memory. These findings highlight the importance of biomarker modality and domain-targeted outcomes in preclinical AD research.

Source: Alzheimer s Research & Therapy

DOI: 10.1186/s13195-026-02061-0

Authors: Yanlu Huang, Qiong Gong, Zhuoyi Zhong, Qihao Guo

Institutions: Jinan University, First Affiliated Hospital of Jinan University, Shanghai Jiao Tong University, Shanghai Sixth People's Hospital

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,290