Impact of cerebral white matter changes on functionality in older adults: An overview of the LADIS Study results and future directions.

The evidence on the clinical significance of cerebral white matter changes (WMC) has mounted over the past few decades. WMC 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 Disability (LADIS) Study has contributed substantially to this body of knowledge. LADIS is a European multicenter collaboration aimed at assessing the role of WMC as an independent predictor of the transition to disability in initially non-disabled patients aged 65-84 years. Besides the demonstration that severe WMC cause a more than double risk of transition from an autonomous to a dependent status after 3 years of follow-up, the LADIS Study has also provided evidence on the role of WMC 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-weighted imaging changes in normal appearing brain tissue and in WMC) has also been investigated. In the present article, we review the main results of the LADIS Study and offer some considerations for future developments in the field, paying attention to the potential use of WMC 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 WMC.