Aims

to assess the pontine noradrenergic nucleus Locus Coeruleus (LC) by 3T MRI neuromelanin (NM)-sensitive sequence in cognitive intact subjects (HC) and in patients suffering from Amnestic Mild Cognitive Impairment (aMCI), Alzheimer’s Disease Dementia (ADD), Lewy Body Dementia/Parkinson’s Disease Dementia (LBD/PDD) and Frontotemporal Dementia (FTD).

Methods

We submitted 234 subjects (HC=60; MCI=80; ADD=40; LBD/PDD=36; FTD=18) to a 3T Brain MR scan, which included a NM-sensitive T1-weighted sequence for LC assessment. MRI scans were then processed profiting of an in-house developed semi-automatic software, which was run by blinded operators. Results were expressed using two parameters: VOX, which is the total number of voxels recognized as belonging to LC; AVG, which is the average intensity of selected voxels.

Results

We found that ADD patients showed a significantly lower value of VOX, when compared to HC and FTD. No significant differences were observed between aMCI and HC, even if the former had lower values of VOX compared to the latter. DLB/PDD showed the lowest values of VOX, significantly different from HC, FTD, and even ADD. Interestingly, in early-onset ADD patients (<65 yy), we observed a reduction of VOX as marked as the one we found in DLB/PDD.

Conclusions

We observed a marked reduction of LC in patients suffering from ADD; even though we did not find a statistically significant involvement of LC in aMCI patients, these showed lower values compared to HC. These findings are in line with neuropathological findings, which showed an early and dramatic degeneration of LC in AD pathogenesis.

Funding: Italian Ministry of Health, PE-2013-02359574-(P.I.: FSG).