Silvia Paola Caminiti, Micol Avenali, Alice Galli, Rachele Malito, Giada Cuconato, Caterina Galandra, Rosaria Calabrese, Andrea Pilotto, Alessandro Padovani, Fabio Blandini, Daniela Perani, Cristina Tassorelli, Enza Maria Valente
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引用次数: 0
摘要
我们评估了来自帕金森进展标志物计划的128名GBA和432名非ongba帕金森病(PD)受试者。评估基线临床特征和多巴胺能活性,并进行临床随访(6.87±3.2年)。生存分析评估了性别和GBA1突变对认知能力下降的独立和相互作用影响。在基线时,GBA-PD男性表现出严重的运动障碍、睡眠障碍和记忆缺陷。尽管运动缺陷较轻,但与男性相比,女性表现出更大的多巴胺能失神经支配,提示神经储备的作用。在纵向评估中,与GBA-PD女性和non - ba - pd相比,GBA-PD男性表现出更高的MoCA年变化率和更大的认知障碍风险。在GBA- pd男性中,发病年龄较晚和“严重/轻度”GBA变异均与认知障碍风险增加相关。男性和GBA1携带者在PD患者认知能力下降的风险增加中具有附加价值。性别对gba1相关病理的影响值得进一步研究,以解决未来的试验设计和患者选择问题。
Male sex accelerates cognitive decline in GBA1 Parkinson’s disease
We evaluated 128 GBA and 432 nonGBA Parkinson’s disease (PD) subjects available from Parkinson’s Progression Markers Initiative. Baseline clinical features and dopaminergic activity were assessed, together with clinical follow-up (6.87 ± 3.2 years). Survival analyses assessed the independent and interactive effects of sex and GBA1 mutations on cognitive decline. At baseline, GBA-PD males showed severe motor impairment, sleep disorders and memory deficits. Despite milder motor deficit, compared to GBA-PD males, GBA-PD females showed greater dopaminergic denervation, suggesting the effect of neural reserve. In longitudinal assessment, GBA-PD males showed greater MoCA rate of change per year and greater risk of cognitive impairment than GBA-PD females and nonGBA-PD. In GBA-PD males, both late age at onset and “severe/mild” GBA variants were associated with increased risk of cognitive impairment. Male sex and GBA1 carrier status have an additive value in increasing the risk of cognitive decline in PD. The effect of sex on GBA1-related pathology warrants further examination to address future trials design and patients’ selection.
期刊介绍:
npj Parkinson's Disease is a comprehensive open access journal that covers a wide range of research areas related to Parkinson's disease. It publishes original studies in basic science, translational research, and clinical investigations. The journal is dedicated to advancing our understanding of Parkinson's disease by exploring various aspects such as anatomy, etiology, genetics, cellular and molecular physiology, neurophysiology, epidemiology, and therapeutic development. By providing free and immediate access to the scientific and Parkinson's disease community, npj Parkinson's Disease promotes collaboration and knowledge sharing among researchers and healthcare professionals.