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While it is well known that WMHs exacerbate cognitive symptoms, the exact relation of WMHs with cognitive performance and other degenerative diseases is unknown. Furthermore, based on location, WMHs are often classified into periventricular and deep WMHs and are believed to have different pathological origins. Whether the two types of WMHs influence cognition differently is unclear. Using regression models, we assessed the independent association of these two types of WMHs with cognitive performance in two separate studies focused on distinct degenerative diseases, early Alzheimer's (mild cognitive impairment), and Parkinson's disease. We further tested if the two types of WMHs were differentially associated with reduced cortical cerebral blood flow (CBF) as measured by arterial spin labeling and increased mean diffusivity (MD, a marker of tissue injury) as measured by diffusion imaging. Our approach revealed that both deep and periventricular WMHs were associated with poor performance on tests of global cognition (Montreal cognitive Assessment, MoCA), task processing (Trail making test), and category fluency in the study of mild cognitive impairment. They were associated with poor performance in global cognition (MoCA) and category fluency in the Parkinson's disease study. Of note, more associations were detected between cognitive performance and deep WMHs than between cognitive performance and periventricular WMHs. Mechanistically, both deep and periventricular WMHs were associated with increased MD. Both deep and periventricular WMHs were also associated with reduced CBF in the gray matter.<\/jats:p>","DOI":"10.1111\/jon.12778","type":"journal-article","created":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T23:32:54Z","timestamp":1600299174000},"page":"843-850","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["White Matter Lesions in Mild Cognitive Impairment and Idiopathic Parkinson's Disease: Multimodal Advanced MRI and Cognitive Associations"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8863-3168","authenticated-orcid":false,"given":"Swati","family":"Rane","sequence":"first","affiliation":[{"name":"Department of Radiology, Integrated Brain Imaging Center University of Washington Medical Center  Seattle WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Radiology, Integrated Brain Imaging Center University of Washington Medical Center  Seattle WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel S.","family":"Hippe","sequence":"additional","affiliation":[{"name":"Department of Radiology, Integrated Brain Imaging Center University of Washington Medical Center  Seattle WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenna","family":"Cholerton","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University  Stanford CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyrus P.","family":"Zabetian","sequence":"additional","affiliation":[{"name":"Veterans Affairs Puget Sound Health Care System  Seattle WA"},{"name":"Department of Neurology University of Washington Medical Center  Seattle WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Montine","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University  Stanford CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Grabowski","sequence":"additional","affiliation":[{"name":"Department of Radiology, Integrated Brain Imaging Center University of Washington Medical Center  Seattle WA"},{"name":"Department of Neurology University of Washington Medical Center  Seattle WA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,16]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.3.652"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.19.10.1285"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.7.925"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.59.9.785"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000366411"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2015.04.012"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.01.006"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.03.024"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.JGP.0000236596.56982.1c"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2016.06.009"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.56.3.303"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25875"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.24893"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-6177(03)00039-8"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.57.11.1389"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000223"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22340"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26424"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000111"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25197"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22004"},{"key":"e_1_2_5_25_1","unstructured":"DoluiS WolfR NabavizadehSA et\u00a0al.Automated quality evaluation index for 2D ASL CBF maps.Presented at the 22nd Annual Conference of the International Society for Magnetic Resonance in Medicine; 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