Association among white matter lesions, rseeg rhythms, amyloid tau markers, and cognitive status in mild cognitive impairment patients

Objective Abnormalities in posteriorly dominant resting-state eyes-closed electroencephalographic (rsEEG) alpha rhythms are associated with cerebrospinal fluid (CSF) tau neuropathology and Mini-Mental Status Examination (MMSE) score, reflecting global cognition, in patients with mild cognitive impairment due to Alzheimer’s disease (MCI-AD). The present study examined the relationships between white matter cerebrovascular lesions (WMLs) and CSF amyloid-tau markers, posterior rsEEG alpha rhythms, and cognitive status in patients with MCI-AD versus those with mild cognitive impairment not due to Alzheimer’s disease (MCI-noAD). Methods An international database provided clinical, demographic, CSF amyloid-tau, rsEEG, and magnetic resonance imaging (MRI) datasets for 68 MCI-AD and 44 MCI-noAD patients. The WMLs were segmented from T2-weighted and FLAIR MRI images. Cortical rsEEG sources at individual delta, theta, and alpha frequencies were estimated using eLORETA freeware. Results In MCI-AD patients, greater WMLs were not associated with increased AD neuropathology, greater alterations in rsEEG alpha or other source activities, or worse MMSE scores. In contrast, higher WMLs were associated with lower MMSE scores in patients with MCI-noAD. Conclusions These results suggest that WMLs had a limited role in prodromal AD, while it affects global cognitive status in patients with MCI-noAD. Significance These findings highlight the stage-dependent, region-specific, and pathology-specific nature of cerebrovascular-neurodegenerative interactions. The limited role of WMLs in MCI-AD may indicate that synergistic neurotoxic effects between vascular burden and AD pathology require more advanced disease stages or higher thresholds of vascular burden to manifest clinically.