Clinical applicability of pCASL as a substitute for FDG-PET in the etiological diagnosis of MCI and SCD: CAPE study protocol

Background: The foreseeable clinical availability in Europe of disease-modifying drugs effective in early phases of some neurodegenerative diseases (such as Alzheimer’s disease), shifts the focus to the etiological diagnosis of pre-dementia stages, such as Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD). Current diagnostic approaches employ costly and limited methods such as PET-FDG. Pseudo-continuous Arterial Spin Labeling (pCASL) is emerging as a promising non-invasive alternative, offering rapid, radiation-free brain perfusion measurements through MRI. Recent research demonstrates pCASL's comparable performance to PET-FDG in neurodegenerative dementias, revealing aligned affected brain regions. However, pCASL's suitability for diagnosing MCI and SCD remains unexplored. The CAPE study (NCT05756270) aims to evaluate pCASL's diagnostic potential in MCI and SCD during initial assessments, by correlating cerebral blood flow patterns from pCASL and PET-FDG and comparing their accuracy. Methods: CAPE primary objective will be to compare brain cerebral blood flow and glucose metabolism patterns among MCI and SCD subjects both in general and across ATN classifications of CSF biomarkers. Secondary objectives will encompass evaluating pCASL's potential in distinguishing various subgroups of SCD and MCI, examining correlations between pCASL/PET-FDG and neuropsychological tests, predicting conversion to dementia using pCASL and PET-FDG, and exploring associations between pCASL and diverse fluid biomarkers. The study will recruit up to 150 MCI and SCD subjects, with CDR ≤ 0.5 and age ≤ 80. The research will span 36 months (24-month recruitment phase, and partially overlapping 24-month follow-up). Participants will undergo baseline brain MRI, PET-FDG, neuropsychological tests, lumbar puncture, and blood tests. Neuropsychological tests will be repeated annually twice to evaluate progression to dementia. A customized pipeline for joint quantitative analysis