Marcello D'Amelio, Italy
IRCCS Santa Lucia Foundation Neuroimaging LaboratoryAuthor Of 1 Presentation
VENTRAL TEGMENTAL AREA DISCONNECTION ACCOUNTS FOR A FASTER CONVERSION FROM MILD COGNITIVE IMPAIRMENT TO ALZHEIMER’S DISEASE: A LONGITUDINAL FMRI STUDY
Abstract
Aims
Dopaminergic dysfunction is an early pathophysiological event of Alzheimer’s disease (AD). This was demonstrated in animal models as well as in cross-sectional studies on AD patients. Using resting-state functional MRI (RS-fMRI), we aimed here at assessing, longitudinally, whether disconnection of the ventral tegmental area (VTA) contributes to a faster conversion from mild cognitive impairment (MCI) to AD.
Methods
We recruited 35 patients with amnestic-MCI due to AD who underwent an extensive neuropsychological assessment and MRI scanning at 3T at baseline and 24-months follow-up. At follow-up patients were reclassified in those who converted to AD (MCI-converters) and those who did not (MCI-non-Converters). MRI acquisitions included a T1-weighted volume and RS-fMRI, which was processed to quantify for each participant at each time-point, connectivity between VTA and the rest of the brain. VTA-driven connectivity was compared between MCI-converters and MCI-non-converters.
Results
Sixteen out of 35 patients converted to AD during follow-up. At baseline, MCI-converters and MCI-non-converters did not differ for demographic or neuropsychological characteristics. RS-fMRI data analysis revealed a significant reduction of VTA-driven connectivity in MCI-Converters that involved the posterior cingulate cortex and precentral gyrus. This between-group difference remained unchanged at follow-up.
Conclusions
This study indicates that a more extensive VTA disconnection precedes and predicts the occurrence of dementia in short time. The pattern of disconnection involves the posterior cingulate cortex (i.e., a key node of the default-mode-network), which was previously interpreted as exclusively due to hippocampal atrophy. These findings have relevant prognostic implications and support new opportunities for therapeutic interventions to slowdown the disease progression.