Alzheimer's & dementia (Amsterdam, Netherlands) · 2026
Individualized cholinergic pathway degeneration in Alzheimer's disease characterized by normative modeling.
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Feng Shuoyun, Zhuang Huixiang, Xu Chang, Guo Xinyu, Cao Li, Liu Yaou, Guan Yue, Li Yao, Alzheimer's Disease Neuroimaging Initiative
Аннотация
INTRODUCTION: Cholinergic pathway degeneration is implicated in Alzheimer's disease (AD), but its individualized characterization in AD and mild cognitive impairment (MCI) remains limited.
METHODS: We constructed lifespan normative models of medial and lateral cholinergic pathways using >6000 diffusion MRI scans from healthy individuals. These models were applied to 1742 scans from 725 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Individualized diffusion abnormalities were integrated into a composite cholinergic pathway degeneration index (CPDI). Group differences and longitudinal associations with cognitive decline and progression were evaluated.
RESULTS: CPDI was higher in MCI and AD participants than in controls, and increased longitudinally in patients with AD and in patients with MCI who progressed to AD. Higher baseline CPDI was associated with an increased risk of progression from MCI to AD and faster decline in global cognition, memory, language, and executive function.
DISCUSSION: CPDI provides an individualized biomarker of cholinergic pathway degeneration with prognostic relevance in AD.
METHODS: We constructed lifespan normative models of medial and lateral cholinergic pathways using >6000 diffusion MRI scans from healthy individuals. These models were applied to 1742 scans from 725 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Individualized diffusion abnormalities were integrated into a composite cholinergic pathway degeneration index (CPDI). Group differences and longitudinal associations with cognitive decline and progression were evaluated.
RESULTS: CPDI was higher in MCI and AD participants than in controls, and increased longitudinally in patients with AD and in patients with MCI who progressed to AD. Higher baseline CPDI was associated with an increased risk of progression from MCI to AD and faster decline in global cognition, memory, language, and executive function.
DISCUSSION: CPDI provides an individualized biomarker of cholinergic pathway degeneration with prognostic relevance in AD.