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Differential effects of four types of genetic variation in\n                      <jats:italic>GBA<\/jats:italic>\n                      on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 10.3% of patients with PD and\n                      <jats:italic>GBA<\/jats:italic>\n                      sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60\u20136.25) and a hastened decline in Mini\u2013Mental State Exam scores compared to noncarriers (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0009). Carriers of complex\n                      <jats:italic>GBA<\/jats:italic>\n                      alleles (0.7%) had an HR of 3.22 (95% CI, 1.18\u20138.73;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.022). By contrast, the common, non\u2010neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92\u20134.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89\u20132.05) did not reach significance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Mutations in the\n                      <jats:italic>GBA<\/jats:italic>\n                      gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into \u201chigh gear.\u201d These findings suggest a relationship between specific types of\n                      <jats:italic>GBA<\/jats:italic>\n                      mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674\u2013685\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24781","type":"journal-article","created":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T10:59:40Z","timestamp":1474541980000},"page":"674-685","source":"Crossref","is-referenced-by-count":264,"title":["Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's"],"prefix":"10.1002","volume":"80","author":[{"given":"Ganqiang","family":"Liu","sequence":"first","affiliation":[{"name":"Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham &amp; Women's Hospital Cambridge MA"},{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendon","family":"Boot","sequence":"additional","affiliation":[{"name":"Biomarkers Program, Harvard NeuroDiscovery Center Boston MA"},{"name":"Department of Neurology 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Cerveau et de la Moelle Epini\u00e8re, Assistance Publique H\u00f4pitaux de Paris, D\u00e9partement de Neurologie et de G\u00e9n\u00e9tique, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Ravina","sequence":"additional","affiliation":[{"name":"Voyager Therapeutics, Clinical Development Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacobus J.","family":"van Hilten","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Cormier\u2010Dequaire","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Universit\u00e9 Pierre et Marie Curie Paris 06 UMR S 1127, Institut National de Sant\u00e9 et en Recherche M\u00e9dicale U 1127 and Centre d'Investigation Clinique 1422, Centre National de Recherche Scientifique U 7225, Institut du Cerveau et de la Moelle Epini\u00e8re, Assistance Publique H\u00f4pitaux de Paris, D\u00e9partement de Neurologie et de G\u00e9n\u00e9tique, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Christophe","family":"Corvol","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Universit\u00e9 Pierre et Marie Curie Paris 06 UMR S 1127, Institut National de Sant\u00e9 et en Recherche M\u00e9dicale U 1127 and Centre d'Investigation Clinique 1422, Centre National de Recherche Scientifique U 7225, Institut du Cerveau et de la Moelle Epini\u00e8re, Assistance Publique H\u00f4pitaux de Paris, D\u00e9partement de Neurologie et de G\u00e9n\u00e9tique, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger 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