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The prefrontal cortex (PFC) is sensitive to the acute and chronic effects of physical activity (PA), while the anxiolytic effects of PA are well known. The current study examined the association of generalized anxiety disorder (GAD) and its interaction with PA, with resting-state, left PFC oxygenation. This cross-sectional study used data from participants (N = 2444) from The Irish Longitudinal Study on Ageing, a nationally representative prospective study of community-living adults aged 50 and older in Ireland. The Composite International Diagnostic Interview Short-Form determined fulfillment of criteria for GAD. The short-form International Physical Activity Questionnaire determined adherence to the World Health Organization PA guidelines. Resting-state, left PFC oxygenation was continuously measured via a Portalite. Tissue saturation index (TSI) was calculated as the ratio of oxygenated hemoglobin to total tissue hemoglobin (expressed as a percentage) for the final minute of a 5-minute supine-rest period. Multivariable linear regression quantified associations of GAD with TSI in the total population and population stratified by PA status. Participants with GAD had lower TSI (b = \u22121.416, p = .008) compared to those without GAD. However, this association was modified by PA. Among participants who met the PA guidelines, TSI did not differ according to GAD status (b = \u22120.800, p = .398). For participants who did not meet the guidelines, TSI was significantly lower among those with GAD (b = \u22121.758, p = .004). These findings suggest that PA may help to protect brain health among older adults with GAD.<\/jats:p>","DOI":"10.1093\/gerona\/glab090","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T17:26:19Z","timestamp":1617038779000},"page":"1391-1397","source":"Crossref","is-referenced-by-count":8,"title":["The Association Between Generalized Anxiety Disorder and Resting-State Prefrontal Cortex Oxygenation Is Modified by Self-Reported Physical Activity: Results From The Irish Longitudinal Study on Ageing"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7825-1123","authenticated-orcid":false,"given":"Cillian P","family":"McDowell","sequence":"first","affiliation":[{"name":"The Irish Longitudinal Study on Ageing and School of Medicine, Trinity College Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Newman","sequence":"additional","affiliation":[{"name":"The Irish Longitudinal Study on Ageing and School of Medicine, Trinity College Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek C","family":"Monroe","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Irvine, USA"},{"name":"Department of Kinesiology, University of North Carolina at Greensboro, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7090-9293","authenticated-orcid":false,"given":"John D","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"The Irish Longitudinal Study on Ageing and School of Medicine, Trinity College Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvin P","family":"Knight","sequence":"additional","affiliation":[{"name":"The Irish Longitudinal Study on Ageing and School of Medicine, Trinity College Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rose Anne","family":"Kenny","sequence":"additional","affiliation":[{"name":"The Irish Longitudinal Study on Ageing and School of Medicine, Trinity College Dublin, Ireland"},{"name":"Mercer\u2019s Institute for Successful Ageing, St. James\u2019s Hospital, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matt P","family":"Herring","sequence":"additional","affiliation":[{"name":"The Irish Longitudinal Study on Ageing and School of Medicine, Trinity College Dublin, Ireland"},{"name":"Department of Physical Education and Sport Sciences and Health Research Institute, University of Limerick, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"2021111806084673200_CIT0001","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and Statistical Manual of Mental Disorders (DSM-5\u00ae)","author":"American Psychiatric Association","year":"2013"},{"key":"2021111806084673200_CIT0002","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1001\/jamapsychiatry.2017.0056","article-title":"Cross-sectional comparison of the epidemiology of DSM-5 generalized anxiety disorder across the globe","volume":"74","author":"Ruscio","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"2021111806084673200_CIT0003","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/JGP.0b013e31819b87b2","article-title":"The burden of late-life generalized anxiety disorder: effects on disability, health-related quality of life, and healthcare utilization","volume":"17","author":"Porensky","year":"2009","journal-title":"Am J Geriatr Psychiatry"},{"key":"2021111806084673200_CIT0004","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1192\/bjp.bp.110.090217","article-title":"Changes in neuropsychological functioning following treatment for late-life generalised anxiety disorder","volume":"199","author":"Butters","year":"2011","journal-title":"Br J Psychiatry"},{"key":"2021111806084673200_CIT0005","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1097\/JGP.0b013e31803111f2","article-title":"Cognitive impairment in late-life generalized anxiety disorder","volume":"15","author":"Mantella","year":"2007","journal-title":"Am J Geriatr Psychiatry"},{"key":"2021111806084673200_CIT0006","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1001\/archgenpsychiatry.2010.74","article-title":"Scared to death? 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