Age-related white matter changes (WMC) are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC. 1. Introduction Age-related white matter changes (WMC) are prevalent findings among the elderly.WMC are considered to be etiologically related to cerebral small vessel disease and are important substrates for cognitive impairment and functional loss in the elderly [1].Although extensive studies have investigated various aspects on WMC, controversies still exist in the pathophysiology and clinical phenotypes, and consensus regarding to treatments for WMC has not been reached.In this paper, we aimed to provide an update review on the epidemiology, pathophysiology, neuroimaging, clinical importance, chemical biomarkers, and treatments of age-related WMC. The literature search was conducted using the National Center for Biotechnology Information (NCBI) PubMed/Medline to identify relevant articles related to WMC that were published until June 2011. We used the following keywords for the search: white matter, white matter changes, white matter lesions, leukoaraiosis, white matter hyperintensities, and small vessel disease. The articles were included in this paper if (1) the journal article was published in English and (2) they were related to epidemiology, pathophysiology, neuroimaging, genetics, clinical phenotypes, biomarkers, and treatment of WMC. Further searches on bibliographies in the main articles and relevant papers were performed. 2. Prevalence and Risk Factors WMC are almost endemic in community elderly with prevalence ranging from 50% to 98% [2–6]. In stroke patients, prevalence of WMC varies from 67% to 98% [7–10]. In Alzheimer’s disease, WMC are also common with prevalence ranges from 28.9% to 100% [11–13]. About 30–55% of patients with Parkinson’s disease (PD) also harbor WMC [14–16]. Age [2, 4, 6, 17–20] and hypertension [3, 18, 20–30] are established risk factors for WMC. A recent Manhattan study in community elderly found that
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