National Psychiatry Center, Semmelweis University, Budapest, Hungary.
Neurodegener Dis. 2013;11(2):72-8. doi: 10.1159/000341997. Epub 2012 Oct 3.
BACKGROUND/AIMS: α-Synuclein (SNCA) may be a key factor in dopaminergic neurotransmission, reward processing, and neurodegeneration in Parkinson's disease (PD). We investigated delay discounting of reward and caudate volume in SNCA gene duplication carriers before and after the development of PD.
Participants were 7 presymptomatic SNCA duplication carriers who later developed PD (follow-up period: 5.4 years) and 10 matched non-carrier controls. At the follow-up assessment, patients received levodopa (L-DOPA) therapy. Delay discounting of reward was assessed with the Kirby discounting questionnaire. We measured the volume of the caudate nucleus and cerebral cortex using structural MRI and FreeSurfer software.
In the presymptomatic stage, carriers showed similar delay discounting and caudate volume to that of non-carrier controls. However, after the development of PD, we observed a significant elevation in delay discounting (impulsive decisions) and reduced caudate volume. There was no cortical atrophy.
Impaired reward-related decision making and caudate volume loss are not detectable in the presymptomatic stage in SNCA duplication carriers. These behavioral and neuroanatomical alterations are observed after the development of clinical symptoms when there is extensive neurodegeneration. Study limitations include a small sample size as well as the potential confounding effect of general cognitive decline.
背景/目的：α-突触核蛋白（SNCA）可能是帕金森病（PD）中多巴胺能神经传递、奖励处理和神经退行性变的关键因素。我们研究了 SNCA 基因重复携带者在 PD 发生前后的奖励延迟折扣和尾状核体积。
参与者为 7 名有 SNCA 基因重复但尚未出现症状的携带者，这些携带者后来发展为 PD（随访期：5.4 年），并匹配了 10 名非携带者对照。在随访评估时，患者接受了左旋多巴（L-DOPA）治疗。使用 Kirby 折扣问卷评估奖励的延迟折扣。我们使用结构 MRI 和 FreeSurfer 软件测量尾状核和大脑皮层的体积。
在无症状阶段，携带者的延迟折扣和尾状核体积与非携带者对照组相似。然而，在 PD 发生后，我们观察到延迟折扣（冲动决策）显著升高，尾状核体积减少。没有皮质萎缩。
在 SNCA 基因重复携带者的无症状阶段，无法检测到与奖励相关的决策和尾状核体积损失。这些行为和神经解剖学改变在出现临床症状后，当出现广泛的神经退行性变时才会出现。研究的局限性包括样本量小以及认知能力普遍下降的潜在混杂影响。
