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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)985-1000
Number of pages16
JournalJournal of Alzheimer's Disease
Volume82
Issue number3
DOIs
Publication statusPublished - 2021

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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