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The objectives of this study were to determine the association between the <jats:italic>FMR1<\/jats:italic> gene gray zone expansions, AGG interspersions, and the presence of parkinsonism and motor and cognitive function in an elderly community\u2010based population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Automated <jats:italic>FMR1<\/jats:italic> polymerase chain reaction was performed on existing samples from 2 longitudinal aging studies whose subjects agreed to brain donation. A detailed clinical evaluation including a modified Unified Parkinson's Disease Rating Scale score, a composite score of global motor function, 17 cognitive tests summarized as a global measure of cognition, and neuropathological examination were obtained for genotyped participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The average age of the population (n = 2362) was 85.9\u2009\u00b1\u20097.3\u2009years, and average age at death was 88.6\u2009\u00b1\u20096.4\u2009years (n = 1326), with 72% women. The prevalence of <jats:italic>FMR1<\/jats:italic> gray zone alleles was 5.2% (122 of 2362). There was no difference between participants with gray zone expansions or those lacking AGG interspersions compared with normal participants in global cognition, global motor function, clinical diagnosis, or pathological changes. Gray zone alleles were associated with signs of parkinsonism in men (<jats:italic>P<\/jats:italic> = 0.01), and gray zone carrier men were more likely to die (hazard ratio, 2.34; 95% confidence interval, 1.31\u20134.16).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the largest study to investigate gray zone alleles in a community population. The key findings are that in men, the gray zone allele is associated with signs of parkinsonism and higher risk of death, but not with intranuclear neuronal inclusions. \u00a9 2020 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28086","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T10:27:33Z","timestamp":1590661653000},"page":"1448-1456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Fragile X Gray Zone Alleles Are Associated With Signs of Parkinsonism and Earlier Death"],"prefix":"10.1002","volume":"35","author":[{"given":"Deborah A.","family":"Hall","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukriti","family":"Nag","sequence":"additional","affiliation":[{"name":"Department of Pathology Rush University Medical Center  Chicago Illinois USA"},{"name":"Rush Alzheimer's Disease Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bichun","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"},{"name":"Rush Alzheimer's Disease Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aisha","family":"Ali","sequence":"additional","affiliation":[{"name":"University of Illinois  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Rush University Medical Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Berry\u2010Kravis","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Pediatrics Rush University Medical Center  Chicago Illinois 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Assessments of the AGG structure in more than 1000 samples reveals the risks of expansion for intermediate and small premutation fragile X alleles. 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