A team led by Professor Zhen Yuan from Centre for Cognitive and Brain Sciences at the University of Macau has made significant progress in the early detection of primary progressive aphasia frontotemporal dementia (PPA-FTD). They discovered new fMRI imaging biomarkers, which provide new ideas for the early diagnosis of PPA-FTD. The research results were published by the internationally renowned journal Neuroimage (5 year IF=6.1).

Accumulation of pathological tau is one of the primary causes of Primary Progressive Aphasia-Frontotemporal Dementia (PPA-FTD). The glymphatic system is crucial for removing metabolic waste from the brain, whereas the underlying mechanism on the interplay between impairments in glymphatic clearance and PPA-FTD is poorly understood. Therefore, the aim of this study is to inspect the role that dysregulated macroscopic cerebrospinal fluid (CSF) movement plays in the pathology of PPA-FTD.

For the present work, the coupling strength between blood-oxygen-level-dependent (BOLD) signals in the grey matter and CSF flow within the subarachnoid space and ventricular system was calculated by using Pearson correlation and made comparison between the two groups. Its associations with clinical demographic data including scores from Clinical Dementia Rating (CDR), Mini-Mental State Exam, Geriatric Depression Scale and with morphological measures in the hippocampus and entorhinal cortex were also quantified.

It was discovered that PPA-FTD group exhibited decreased global BOLD and CSF coupling as compared to that of healthy controls (HCs), indicating impaired glymphatic functions of the patients. More importantly, BOLD-CSF coupling of PPA-FTD group rather than that of the HCs demonstrated the significant correlations with the CDR scores, hippocampal volume and entorhinal cortex thickness.

The measured decoupling between global brain activation (hemodynamic response) and CSF flow and its association with symptomology and brain structural changes in PPA-FTD revealed the glymphatic dysregulation in PPA-FTD. Herein, this pilot study supports the potential role of BOLD-CSF coupling as a noninvasive biomarker for the early detection and prediction of PPA-FTD.

The corresponding author of this study is Professor Zhen Yuan from UM. Dr. Xinglin Zeng and Dr. Zhiying Zhao as Prof. Zhen Yuan’s lab members are the key members of this project. This project is supported by FDCT (FDCT 0014/2024/RIB1).

Research Articles Browsable: https://www.sciencedirect.com/science/article/pii/S105381192400421X

Fig. 1 Coupling Between Global BOLD Signal and CSF Changes. A) The global BOLD signal was averaged across the gray matter regions (the red mask on an exemplary T1-weighted image in the left column), whereas CSF signal extraction was done from CSF regions at the bottom slice of the fMRI acquisition (the middle and right column). B) Depicts the global BOLD signal and CSF signal from a representative participant. The global gray matter BOLD signal and CSF signal in percentage changes are included to illustrate signal fluctuation amplitude. Notably, substantial CSF peaks (upward black arrows) are often observed preceding large positive BOLD peaks (downward black arrows) and followed by significant negative BOLD peaks (gray arrows).

Fig. 2 The cross-correlation analysis between the BOLD and CSF signals for both healthy controls (HC) and PPA-FTD patients, in which HC show a high coupling intensity.