Neuropsychological and neuroimaging characteristics of patients with mild cognitive impairment and negative-amyloid deposition.

Frontiers in neurology 2025

Dai X, Zhang J, Li X, Chen Y, Qiao Y, Zhang S, Chen K, Ai L, Peng D, Zhang Z

Abstract

OBJECTIVES: Accumulating studies have reported that some mild cognitive impairment (MCI) patients without significant β-amyloid (Aβ) deposition on amyloid positron emission tomography (PET) can later develop Alzheimer’s disease (AD). Therefore, this study profiled the cognitive and neural characteristics of MCI patients with negative Aβ deposition to better understand potential features associated with an increased risk of AD progression. METHODS: Thirty-seven MCI patients and 32 normal controls (NCs) underwent neuropsychological assessments, structural magnetic resonance imaging, and diffusion tensor imaging scans. MCI patients were stratified into amyloid-positive (Aβpos; n = 18) and amyloid-negative (Aβneg; n = 19) groups based on 18F-florbetapir PET. We compared cognitive performance, white matter (WM) integrity, and gray matter volume (GMV) across the three groups and further examined the interplay among brain structural alterations and cognitive changes. RESULTS: Cognitively, relative to NCs, participants in Aβneg MCI group showed significant deficits in multiple cognitive domains including episodic memory, attention, and executive function, as those in Aβpos MCI group did. Both MCI subgroups exhibited extensive disruptions of WM integrity. Direct comparisons between the Aβneg and Aβpos groups revealed that Aβ-related structural changes were predominantly localized to the left hippocampus and adjacent regions. The increased Aβ deposition was closely associated with elevated mean diffusivity in the left hippocampal portion of the cingulum and reduced GMV of the left hippocampus. Moreover, the GMV of hippocampus could mediate the impact of WM disruption on episodic memory performance. CONCLUSION: Aβneg MCI patients who exhibit AD-like cognitive and structural abnormalities, particularly involving the hippocampus, may be associated with advanced cognitive decline or dementia progression. These results may help identify high-risk individuals within the heterogeneous Aβneg MCI population.

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