Spiritual Well-Being and Phenoconversion in Huntington’s Disease: Analysis from the Prospective Huntington at Risk Observational Study

<b><i>Objective:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> The study found no significant association between SWB and time to phenoconversion in individuals with the HD gene mutation. <b><i>Conclusion:</i></b> 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.