{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T10:46:48Z","timestamp":1792579608950,"version":"4.5.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"5","funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["ZIA HG200336-19"],"award-info":[{"award-number":["ZIA HG200336-19"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012737","name":"Department of Health and Human Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012737","id-type":"DOI","asserted-by":"publisher"}]},{"name":"United States Government"},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tracking non-motor symptoms and neuropsychological function is critical for assessing neurodegenerative progression. We characterized differences among individuals with Gaucher disease, GBA1 variant carriers and GBA1-associated Parkinson disease to identify candidate markers of Parkinson disease-related change in Gaucher disease or GBA1 variant carriers. We analysed data from 161 adults evaluated at the National Institutes of Health between 1983 and 2024, including 79 with Gaucher disease, 52 GBA1 variant carriers and 30 with GBA1-associated Parkinson disease. Assessments included questionnaires for non-motor symptoms, depression, anxiety, fatigue, sleepiness, olfaction and intelligence quotient measures. Eighty-seven participants contributed longitudinal data from at least two visits. Linear mixed-effects models, adjusted for age, sex and education, examined baseline differences and longitudinal trajectories. At baseline, the GBA1-associated Parkinson disease group showed lower olfactory performance (compared with both groups, P &amp;lt; 0.0001), greater daytime sleepiness (compared with GBA1 variant carriers, P = 0.003; compared with Gaucher disease, P = 0.0002) and higher non-motor symptom burden (compared with both groups, P &amp;lt; 0.0001). Only olfaction declined longitudinally, most steeply in GBA1-associated Parkinson disease (P &amp;lt; 0.0001; rate: 0.65 points per year, P = 0.032). In this longitudinal cohort, olfactory decline was the most robust marker differentiating GBA1-associated Parkinson disease from Gaucher disease and GBA1 variant carriers. Intelligence quotient and non-motor symptom measures did not demonstrate a comparable decline, reflecting their limited sensitivity to longitudinal change, and reinforcing the need for objective, biologically based measures. Among participants without Parkinson disease at study onset, test scores remained stable over follow-up and phenoconversion was rare, underscoring the very low observed Parkinson disease penetrance among individuals with biallelic or heterozygous GBA1 variants.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag377","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:49:30Z","timestamp":1792064970000},"source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal olfactory and neuropsychological trajectories across the\n                    <i>GBA1<\/i>\n                    spectrum"],"prefix":"10.1093","volume":"8","author":[{"given":"Yonatan","family":"Serlin","sequence":"first","affiliation":[{"name":"Neurophysiology of Epilepsy Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20814 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Branch, National Human Genome Research Institute, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grisel","family":"Lopez","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3019-8500","authenticated-orcid":false,"given":"Ellen","family":"Sidransky","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health , Bethesda, MD 20892 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