Yoshimura Kenji, Shima Atsushi, Kambe Daisuke, Furukawa Koji, Nishida Akira, Wada Ikko, Sakato Yusuke, Sakamaki-Tsukita Haruhi, Terada Yuta, Yamakado Hodaka, Taruno Yosuke, Nakanishi Etsuro, Sawamura Masanori, Fujimoto Koji, Fushimi Yasutaka, Okada Tomohisa, Nakamoto Yuji, Hanakawa Takashi, Takahashi Ryosuke, Sawamoto Nobukatsu
Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Eur J Neurol. 2025 Jan;32(1):e70022. doi: 10.1111/ene.70022.
A dual-syndrome hypothesis, which states the cognitive impairments in Parkinson's disease (PD) are attributable to frontostriatal dopaminergic dysregulation and cortical disturbance-each associated with attention/executive and memory/visuospatial dysfunction, respectively-has been widely accepted. This multisystem contribution also underlies highly heterogeneous progression rate to dementia.
Nondemented PD patients who underwent [I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([I]FP-CIT) SPECT and neuropsychological examinations were enrolled. Patients who agreed to participate and age- and sex-matched healthy controls (HCs) also underwent 7-T MRI. Patients were classified as cognitively normal (PD-CN) or mild cognitive impairment (PD-MCI) following the level II criteria of Movement Disorder Society Guideline.
A total of 155 patients (PD-CN/PD-MCI 74/81) were enrolled, whereas 76 patients (PD-CN/PD-MCI 35/41) and 56 HCs underwent 7 T-MRI. The caudate [I]FP-CIT uptake in PD was correlated with the performance of attention/working memory (trail-making test [TMT]-A and symbol digit modality test) and executive (TMT-B) domains. In contrast, the regional cortical thickness in the left frontotemporal and right frontal lobes in PD was correlated with performance of memory (Hopkins verbal learning test-revised delayed recall) and visuospatial (judgment of line orientation) domains. Moreover, compared to 37 HCs with a Montreal Cognitive Assessment score of >25, PD-CN patients showed broad occipitoparietal cortical thinning.
We demonstrated distinctive impairments of dopaminergic frontostriatal deficits and cortical degeneration as neural bases for the dual-syndrome hypothesis. Our findings suggest that occipitoparietal lobe thinning occurs at a cognitively normal stage, and additional frontotemporal lobe thinning underlies impairments in the memory and visuospatial domains at the PD-MCI stage.
一种双重综合征假说已被广泛接受，该假说认为帕金森病（PD）中的认知障碍归因于额纹状体多巴胺能调节异常和皮质功能紊乱，分别与注意力/执行功能及记忆/视觉空间功能障碍相关。这种多系统作用也是导致痴呆进展速度高度异质性的基础。
纳入接受[I]N-ω-氟丙基-2β-甲氧羰基-3β-（4-碘苯基）去甲托烷（[I]FP-CIT）单光子发射计算机断层扫描（SPECT）和神经心理学检查的非痴呆PD患者。同意参与的患者以及年龄和性别匹配的健康对照（HCs）也接受了7-T磁共振成像（MRI）检查。根据运动障碍协会指南的二级标准，将患者分为认知正常（PD-CN）或轻度认知障碍（PD-MCI）。
共纳入155例患者（PD-CN/PD-MCI分别为74/81例），而76例患者（PD-CN/PD-MCI分别为35/41例）和56例HCs接受了7-T MRI检查。PD患者尾状核的[I]FP-CIT摄取与注意力/工作记忆（连线测验 [TMT]-A和符号数字模式测验）及执行功能（TMT-B）领域的表现相关。相比之下，PD患者左侧额颞叶和右侧额叶的区域皮质厚度与记忆（霍普金斯词语学习测验修订版延迟回忆）及视觉空间功能（直线定向判断）领域的表现相关。此外，与蒙特利尔认知评估得分>25的37例HCs相比，PD-CN患者表现出广泛的枕顶叶皮质变薄。
我们证明了多巴胺能额纹状体缺陷和皮质变性的独特损害是双重综合征假说的神经基础。我们的研究结果表明，枕顶叶变薄发生在认知正常阶段，而额外的额颞叶变薄是PD-MCI阶段记忆和视觉空间领域损害的基础。
