Ventral tegmental area disconnection contributes two years early to correctly classify patients converted to alzheimer's disease: Implications for treatment

Camillo Marra, Laura Serra, Marcello D'Amelio, Sharon Esposito, Carlotta Di Domenico, Giacomo Koch, Nicola Biagio Mercuri, Carlo Caltagirone, Carlo Alberto Artusi, Leonardo Lopiano, Mara Cercignani, Marco Bozzali

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)985-1000
Numero di pagine16
RivistaJournal of Alzheimer's Disease
Volume82
DOI
Stato di pubblicazionePubblicato - 2021

Keywords

  • Alzheimer's disease
  • amnestic mild cognitive impairment
  • ventral tegmental area
  • functional connectivity
  • restingstate MRI
  • dopaminergic system

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