{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:23:08Z","timestamp":1791228188623,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T00:00:00Z","timestamp":1450224000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Geriatrics Gerontology Int"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>The evidence on the clinical significance of cerebral white matter changes (<jats:styled-content style=\"fixed-case\">WMC<\/jats:styled-content>) has mounted over the past few decades. <jats:styled-content style=\"fixed-case\">WMC<\/jats:styled-content> are recognized as one of the neuroimaging features of cerebral small vessel disease, and are associated with various disturbances and a poor prognosis. The Leukoaraiosis and <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>isability (<jats:styled-content style=\"fixed-case\">LADIS<\/jats:styled-content>) Study has contributed substantially to this body of knowledge. <jats:styled-content style=\"fixed-case\">LADIS<\/jats:styled-content> is a European multicenter collaboration aimed at assessing the role of <jats:styled-content style=\"fixed-case\">WMC<\/jats:styled-content> as an independent predictor of the transition to disability in initially non\u2010disabled patients aged 65\u201384 years. Besides the demonstration that severe <jats:styled-content style=\"fixed-case\">WMC<\/jats:styled-content> cause a more than double risk of transition from an autonomous to a dependent status after 3 years of follow\u2010up, the <jats:styled-content style=\"fixed-case\">LADIS<\/jats:styled-content> Study has also provided evidence on the role of <jats:styled-content style=\"fixed-case\">WMC<\/jats:styled-content> in relation to the decline of cognitive and motor performances, depressive symptoms associated with aging and cerebrovascular diseases, the presence of urinary disturbances, and various neurological abnormalities. The possible role of other lesions (lacunar infarcts, cerebral atrophy, corpus callosum morphology) and microstructural abnormalities (diffusion\u2010weighted imaging changes in normal appearing brain tissue and in <jats:styled-content style=\"fixed-case\">WMC<\/jats:styled-content>) has also been investigated. In the present article, we review the main results of the <jats:styled-content style=\"fixed-case\">LADIS<\/jats:styled-content> Study and offer some considerations for future developments in the field, paying attention to the potential use of <jats:styled-content style=\"fixed-case\">WMC<\/jats:styled-content> progression as a surrogate marker in intervention trials in cerebral small vessel diseases. We also discuss some therapeutic perspectives regarding the beneficial impact of physical activity on the risk of vascular cognitive impairment in patients with <jats:styled-content style=\"fixed-case\">WMC<\/jats:styled-content>. <jats:bold>Geriatr Gerontol Int 2015; 15 (Suppl. 1): 10\u201316.<\/jats:bold><\/jats:p>","DOI":"10.1111\/ggi.12665","type":"journal-article","created":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T08:55:54Z","timestamp":1450256154000},"page":"10-16","source":"Crossref","is-referenced-by-count":70,"title":["Impact of cerebral white matter changes on functionality in older adults: An overview of the LADIS Study results and future directions"],"prefix":"10.1111","volume":"15","author":[{"given":"Leonardo","family":"Pantoni","sequence":"first","affiliation":[{"name":"NEUROFARBA Department Neuroscience Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Fierini","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department Neuroscience Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Poggesi","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department Neuroscience Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"LADIS Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.3.652"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70104-6"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70124-8"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000081050"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2007.01590.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2006.00798.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.167.1.81"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2477"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23802"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2006.110361"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000179092.59909.42"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000207442"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.160440"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.576629"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000202010"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e7ca05"},{"key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3233\/JAD-2011-110494","article-title":"Self\u2010perceived memory complaints predict progression to Alzheimer disease. 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