Phd in SENSORINEURAL PLASTICITY

Thesis title: pCASL CBF ANALYSIS IN ALZHEIMER’S DISEASE SPECTRUM PATIENTS: A PROSPECTIVE MRI STUDY

Backround and purposes: Alzheimer's disease (AD) is the leading cause of dementia, hence finding valuable biomarkers to understand pathophysiology and evolution in its pre-dementia stages is extremely important. pCASL is a non invasive MRI technique to measure brain perfusion and calculate CBF, which has shown to be reduced in several brain areas in both AD, mild cognitive impairment (MCI), with very few studies exploring its role in the first stage of AD, subjective cognitive decline (SCD). Our purpose is to use pCASL to evaluate CBF in healthy subjects (HS), SCD, MCI and AD and its relationship with cognitive function at each stage and correlate it with neuropsychological tests and brain atrophy by means of voxel-based morphometry. Methods: we prospectively enrolled patients with SCD, MCI, AD, and HS who underwent throurough neuropsychological assessment and 3T MRI both structural and with ASL. We ran one-way ANOVA for inter-group analyses and one-sample t-test for intra-group analyses comparison with clinical performances (both for CBF a VBM). Results: 206 patients (48 AD, 53 MCI, 42 SCD, 51 HS) were enrolled. AD showed CBF decrease especially in precuneus/posterior cingulate cortex (PCC) and parietal lobule compared to HS and SCD. Positive correlation between CBF and memory was found in HS and SCD but negative in MCI and AD, especially in precuneus/PCC and hippocampus. AD showed reduced gray matter volume compared to all groups, MCI compared to SCD and HS, SCD compared to HS. More represented areas were hippocampus and parahippocampal gyrus. For SCD anterior cingulate cortex. VBM showed negative correlation with memory in HS and SCD but positive in MCI and AD. Conclusions: as the disease advanced in stage, a progressive CBF reduction has been observed in critical memory areas. CBF is positively correlated with memory domain functions at early stage of the disease, while negative correlation are encountered in later phases, when more consistent structural damage is present, as shown by VBM analysis. Gray matter volume is associated more with better clinical performances in MCI and AD, while SCD and HS rely more on synaptic pruning to achieve better performances. CBF could be used as a non-invasive clinical biomarker for monitoring clinical progression, since it could anticipate visible structural damage, in particular at early stages of disease.