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

## TL;DR

This study compares cognitive and brain differences in mild cognitive impairment patients with and without amyloid buildup, focusing on those at risk of developing Alzheimer's disease.

## Contribution

The study identifies hippocampal structural and cognitive patterns in amyloid-negative MCI patients that may indicate future Alzheimer's risk.

## Key findings

- Aβneg MCI patients show cognitive deficits similar to Aβpos MCI in memory, attention, and executive function.
- Both MCI groups exhibit disrupted white matter integrity, with Aβpos showing more localized hippocampal changes.
- Hippocampal gray matter volume mediates the relationship between white matter disruption and memory decline.

## Abstract

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.

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.

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.

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.