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Since the neuroprotective effects of n-3 PUFA have been widely validated, the role of n-6 PUFA remains debated, with their underlying mechanisms still not fully understood. Methods: In this study, 169,295 participants from the UK Biobank were included to analyze the associations between dietary n-6 PUFA intake and neurodegenerative diseases using Cox regression models with full adjustments for potential confounders. In addition, multiple linear regression models were utilized to estimate the impact of n-6 PUFA intake on brain imaging phenotypes. Results: Results indicated that low dietary n-6 PUFA intake was associated with increased risks of incident dementia (hazard ratio [95% confidence interval] = 1.30 [1.13, 1.49]), Parkinson\u2019s disease (1.42 [1.16, 1.74]), and multiple sclerosis (1.65 [1.03, 2.65]). Moreover, the low intake was linked to diminished volumes of various brain structures, including the hippocampus (\u03b2 [95% confidence interval] = \u22120.061 [\u22120.098, \u22120.025]), thalamus (\u22120.071 [\u22120.105, \u22120.037]), and others. White matter integrity was also found to be compromised in individuals with low n-6 PUFA intake. Conclusions: These findings enhanced our understanding of how dietary n-6 PUFA intake might affect neurological health, thereby providing epidemiological evidence for future clinical and public health interventions.<\/jats:p>","DOI":"10.3390\/nu16244272","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T06:44:05Z","timestamp":1733899445000},"page":"4272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Dietary N-6 Polyunsaturated Fatty Acid Intake and Brain Health in Middle-Aged and Elderly Adults"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiawei","family":"Gu","sequence":"first","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxuan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Hua","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobei","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Center for Mental Health, Beijing 100121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Mathematics and Physics, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2684-6341","authenticated-orcid":false,"given":"Jinjun","family":"Ran","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"20","author":"Feigin","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_2","unstructured":"(2024). 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