Sokol Leonard L, Ashner Marissa C, Bega Danny, Kluger Benzi M, Smith Alexander K, Marder Karen S, Garcia Tanya P
The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
McGaw Bioethics Scholars Program, Center for Bioethics and Humanities, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
J Palliat Med. 2025 Jun;28(6):803-807. doi: 10.1089/jpm.2024.0227. Epub 2025 Mar 5.
Spiritual well-being (SWB) has been shown to delay the onset of cognitive decline among older adults predisposed to Alzheimer's disease and related neurodegenerative dementias. It was, however, unknown if SWB is also associated with delay in disease manifestation ("phenoconversion") in rare, genetic neurodegenerative dementias, such as Huntington's disease (HD). Thus, we sought to evaluate the association between SWB and phenocovnersion in people at-risk for HD. The "Prospective Huntington At Risk Observation Study" (PHAROS), a large-scale national prospective research study, recruited a substantial cohort of 1001 participants. These participants, who were first-degree relatives of individuals diagnosed with HD and had a 50% chance of carrying the HD genetic mutation, were blinded to their genetic status and underwent repeated clinical assessments every 12 months. The study used Cox proportional models to examine the relationship between SWB and time to phenoconversion while also considering subcomponents of SWB and adjusting for age, sex, and CAG repeat length. The study found no significant association between SWB and time to phenoconversion in individuals with the HD gene mutation. While existing data suggest that SWB may be an actionable target to improve health-related quality of life in HD and other serious illnesses, there is a lack of evidence supporting the role of SWB in attenuating phenoconversion in people with the HD genetic mutation. Unlike Alzheimer's, HD may be less responsive to analogous factors in delaying disease onset.
精神幸福感（SWB）已被证明可延缓易患阿尔茨海默病及相关神经退行性痴呆症的老年人认知能力下降的发病时间。然而，在罕见的遗传性神经退行性痴呆症，如亨廷顿舞蹈症（HD）中，精神幸福感是否也与疾病表现延迟（“表型转换”）相关尚不清楚。因此，我们试图评估精神幸福感与HD高危人群表型转换之间的关联。“亨廷顿舞蹈症高危人群前瞻性观察研究”（PHAROS）是一项大规模的全国性前瞻性研究，招募了1001名参与者组成了一个相当大的队列。这些参与者是被诊断患有HD的个体的一级亲属，携带HD基因突变的几率为50%，他们对自己的基因状况不知情，并且每12个月接受一次重复的临床评估。该研究使用Cox比例模型来检验精神幸福感与表型转换时间之间的关系，同时还考虑了精神幸福感的子成分，并对年龄、性别和CAG重复长度进行了调整。该研究发现，携带HD基因突变的个体中，精神幸福感与表型转换时间之间没有显著关联。虽然现有数据表明，精神幸福感可能是改善HD及其他严重疾病中与健康相关生活质量的一个可采取行动的目标，但缺乏证据支持精神幸福感在减轻携带HD基因突变者表型转换方面的作用。与阿尔茨海默病不同，HD在延缓疾病发作方面可能对类似因素的反应较小。
