Distinct patterns of spontaneous brain activity in mild cognitive impairment patients stratified by cerebrospinal fluid biomarkers

Background This study aimed to explore the alterations in the Amplitude of Low-Frequency Fluctuation (ALFF) among mild cognitive impairment (MCI) patients with varying cerebrospinal fluid (CSF) biomarker levels, including abnormal Amyloid-beta (Aβ42) and phosphorylated tau protein (p-tau) (A + T +), abnormal Aβ42 and normal p-tau (A + T-), and normal Aβ42 and p-tau (A-T-), and to investigate their longitudinal changes. Methods A total of 134 MCI patients were enrolled in this study and stratified into three groups, including 54 A-T- group, 28 A + T- group, and 52 A + T + group based on CSF Aβ and p-tau levels. The baseline ALFF values derived from blood oxygen level-dependent signals were employed to quantify spontaneous brain activity patterns. Comparisons were made among the three groups regarding ALFF differences, and their correlations with cognitive functions and CSF biomarkers were investigated. Additionally, a subset of participants with 2-year follow-up data underwent a mixed-effects model analysis to examine group-by-time interactions in ALFF. Results At baseline, compared to the A-T- group, the A + T- group showed decreased ALFF in the bilateral cerebellar posterior lobe (CPL) and increased ALFF in the bilateral middle frontal gyrus (MFG), while the A + T + group displayed decreased ALFF in the bilateral CPL. In contrast to the A + T- group, the A + T + group exhibited decreased ALFF in the bilateral MFG. Additionally, there was a significant negative correlation between the bilateral MFG and p-tau levels, while the left MFG was positively correlated with RAVLT-learning performance, and the right MFGs was positively correlated with Aβ levels. Longitudinally, a significant group-by-time interaction was observed in the right inferior temporal gyrus (ITG), where A + T + patients exhibited a more pronounced ALFF decline over 2 years compared to A + T- patients. Conclusion This study highlights distinct and evolving patterns of brain activity associated with Aβ and tau pathology in MCI. The combination of cross-sectional and longitudinal analyses reveals that tau pathology may drive accelerated functional decline in specific brain regions, particularly the right ITG, offering insights into the progression of AD-spectrum disorders.