Carlo Caltagirone (Italy)
S. Lucia Foundation IRCCS Rome NeurorehabilitationAuthor Of 2 Presentations
VENTRAL TEGMENTAL AREA DISCONNECTION CONTRIBUTES TWO YEARS EARLY TO CORRECTLY CLASSIFY PATIENTS CONVERTED TO ALZHEIMER’S DISEASE: IMPLICATIONS FOR TREATMENT.
- Marco Bozzali (Italy)
Abstract
Background and Aims:
The loss of dopaminergic neurons in the ventral tegmental area (VTA) has been recently recognised as an early pathophysiological event of Alzheimer’s disease (AD). Using resting-state fMRI (RS-fMRI), we aimed here to investigate longitudinally, in a group of patients with mild cognitive impairment (MCI) due to AD, the impact of VTA-driven brain disconnection in predicting the conversion to AD.
Methods:
a cohort of 35 MCI patients were recruited and followed-up for 24 months. They underwent cognitive evaluation and MR scanning at 3T in two occasions, at baseline and at follow-up. RS-fMRI data were analysed to obtain in each subject VTA-driven connectivity maps to be used in group analyses.
Results:
At 24-month follow-up, 46% of patients converted to AD. Although MCI-converters and non-converter did not differ in demographic and behavioral characteristics at baseline, the former group showed already a significant reduction of VTA-driven connectivity in the posterior cingulate and precentral cortex. The patterns of connectivity observed at baseline remained substantially unchanged in both groups, MCI converters and nonconverters, when comparing them on fMRI data collected at follow-up. Moreover, a discriminant analysis showed that baseline VTA-disconnection together with hippocampal atrophy, correctly classify patients as converters and non-converter with high sensitivity, specificity and accuracy (all parameters above 68%).
Conclusions:
This study indicates a substantial contribution of dopaminergic dysfunction to AD progression since early clinical stages, by targeting the default-mode network. These results have implications for patient stratification in pharmacological and non-pharmacological clinical trials.
INTERACTION BETWEEN COGNITIVE RESERVE AND BRAIN COMPLEXITY TO MITIGATE THE IMPACT OF ATROPHY IN EARLY ALZHEIMER’S DISEASE.
- Marco Bozzali (Italy)
Abstract
Background and Aims:
We aimed here at investigating the effect of cognitive reserve (CR) in modulating cortical brain architecture across Alzheimer’s disease (AD) progression.
Methods:
278 individuals (110 AD, 104 mild-cognitive-impairment (MCI) due to AD patients, 64 healthy controls) underwent neuropsychological testing and MR scanning at 3T. T1-weighted volumes were processed using CAT-12 to assess cortical thickness (CTh) and fractal dimension (FD) (a measure of cortical complexity). Education was used as proxy measure of CR to divide each studied group in individuals with high (HCR) and low CR (LCR). Differences in cortical complexity explained by CR were assessed within groups using a t-test model in SPM12. Correlations were also investigated between cognitive scores and cortical complexity.
Results:
No significant demographic differences were observed within groups stratified by CR. HCR- compared to LCR-MCI patients showed smaller CTh in the right temporal and left prefrontal lobes, and increased FD in the right temporal and left temporo-parietal lobes. HCR-AD against LCR-AD patients showed smaller CTh in several cortical regions alongside reduced FD in left temporal cortices. HCR- compared to LCR-controls showed increased CTh in prefrontal areas bilaterally, and in the right parieto-occipital cortex. A positive association was found between brain complexity and performance on memory and executive tests in HCR-MCI patients.
Conclusions:
CR accounts for cortical complexity in patients (but not in healthy subject) at the stage of MCI showing both atrophic changes (neurodegeneration) and richer patterns of brain folding (reserve mechanisms) in temporo-parietal areas. This further confirms a strict time-window for CR effects and possible interventions.