Negida Ahmed, Vohra Hiba, Lageman Sarah, Mukhopadhyay Nitai, Berman Brian, Weintraub Daniel, Barrett Matthew
Virginia Commonwealth University.
University of Pennsylvania, Philadelphia Veterans Affairs Medical Center.
Res Sq. 2024 Nov 11:rs.3.rs-5278177. doi: 10.21203/rs.3.rs-5278177/v1.
Subtyping Parkinson's disease with mild cognitive impairment (PD-MCI) could improve clinical trial design and personalized treatments. Cholinergic nucleus 4 (Ch4) volume has been linked to cognitive impairment severity and future decline in PD. This study investigates whether PD-MCI patients with MRI evidence of Ch4 degeneration have distinct clinical profiles and cognitive trajectories. Baseline MRI scans of 148 PD-MCI participants from the Parkinson's Progression Markers Initiative (PPMI) were analyzed. Patients with low Ch4 grey matter density (GMD) had worse motor, autonomic, and olfactory symptoms, and were more likely to belong to the diffuse malignant PD subtype (51.6% vs. 23.4%; P < 0.01). They also had faster progression to cognitive milestones (P = 0.0046). These findings identify PD-MCI with low Ch4 as a distinct subtype with more severe symptoms and faster cognitive decline, highlighting the importance of considering this group in PD-MCI clinical trials, particularly for cholinergic therapies.
对帕金森病合并轻度认知障碍（PD-MCI）进行亚型分类可以改善临床试验设计和个性化治疗。胆碱能核4（Ch4）的体积与PD患者的认知障碍严重程度及未来病情恶化有关。本研究调查了有Ch4变性MRI证据的PD-MCI患者是否具有独特的临床特征和认知轨迹。对帕金森病进展标志物计划（PPMI）中148名PD-MCI参与者的基线MRI扫描进行了分析。Ch4灰质密度（GMD）低的患者运动、自主神经和嗅觉症状更严重，且更有可能属于弥漫性恶性PD亚型（51.6%对23.4%；P<0.01）。他们向认知里程碑进展的速度也更快（P=0.0046）。这些发现确定Ch4低的PD-MCI为一种具有更严重症状和更快认知衰退的独特亚型，突出了在PD-MCI临床试验中考虑该群体的重要性，特别是对于胆碱能疗法。
