Ventral tegmental area disconnection contributes two years early to correctly classify patients converted to Alzheimer’s disease: implications for treatment

Serra, Laura, D’Amelio, Marcello, Esposito, Sharon, Di Domenico, Carlotta, Koch, Giacomo, Marra, Camillo, Mercuri, Nicola Biagio, Caltagirone, Carlo, Artusi, Carlo Alberto, Lopiano, Leonardo, Cercignani, Mara ORCID: https://orcid.org/0000-0002-4550-2456 and Bozzali, Marco 2021. Ventral tegmental area disconnection contributes two years early to correctly classify patients converted to Alzheimer’s disease: implications for treatment. Journal of Alzheimer's Disease 82 (3) , pp. 985-1000. 10.3233/JAD-210171

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Abstract

Background:Recent cross-sectional studies highlighted the loss of dopaminergic neurons in the ventral tegmental area (VTA) as an early pathophysiological event in Alzheimer’s disease (AD). Objective:In this study, we longitudinally investigated by resting-state fMRI (RS-fMRI) a cohort of patients with mild cognitive impairment (MCI) due to AD to evaluate the impact of VTA disconnection in predicting the conversion to AD. Methods:A cohort of 35 patients with MCI due to AD were recruited and followed-up for 24 months. They underwent cognitive evaluation and RS-fMRI to assess VTA connectivity at baseline and at follow-up. Results:At 24-month follow-up, 16 out of 35 patients converted to AD. Although converters and non-converters to AD did not differ in demographic and behavioral characteristics at baseline, the first group showed a significant reduction of VTA-driven connectivity in the posterior cingulate and precentral cortex. This pattern of additional disconnection in MCI-converters compared to non-converters remained substantially unchanged at 24-month follow-up. Conclusion:This study reinforces the hypothesis of an early contribution of dopaminergic dysfunction to AD evolution by targeting the default-mode network. These results have potential implications for AD staging and prognosis and support new opportunities for therapeutic interventions to slow down disease progression.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher:	IOS Press
ISSN:	1387-2877
Date of First Compliant Deposit:	11 May 2021
Date of Acceptance:	11 May 2021
Last Modified:	07 Nov 2023 02:33
URI:	https://orca.cardiff.ac.uk/id/eprint/141205

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