Neuroimaging Laboratory, Fondazione Santa Lucia, IRCCS, Rome, Italy.
Laboratory Molecular Neurosciences, Fondazione Santa Lucia, IRCCS, Rome, Italy.
J Alzheimers Dis. 2021;82(3):985-1000. doi: 10.3233/JAD-210171.
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).
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.
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.
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.
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.
最近的横断面研究强调，腹侧被盖区（VTA）中多巴胺能神经元的丧失是阿尔茨海默病（AD）的早期病理生理事件。
在这项研究中，我们通过静息态 fMRI（rs-fMRI）对一组由于 AD 导致的轻度认知障碍（MCI）患者进行了纵向研究，以评估 VTA 失连接对预测向 AD 转化的影响。
我们招募了 35 名由于 AD 导致的 MCI 患者，并对他们进行了 24 个月的随访。他们接受了认知评估和 rs-fMRI 检查，以评估基线和随访时 VTA 的连通性。
在 24 个月的随访中，35 名患者中有 16 名转化为 AD。尽管转化组和非转化组在基线时的人口统计学和行为特征上没有差异，但第一组在后扣带回和中央前回的 VTA 驱动连通性显著降低。与非转化组相比，MCI 转化组中这种额外的失连接模式在 24 个月的随访中基本保持不变。
这项研究通过靶向默认模式网络，进一步支持了多巴胺能功能障碍对 AD 进展的早期贡献的假说。这些结果对 AD 的分期和预后具有潜在的影响，并为减缓疾病进展的治疗干预提供了新的机会。
