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Patients with progressive damage to the white matter, referred to as Binswanger\u2019s disease (BD), constitute a spectrum from pure vascular disease to a mixture with neurodegenerative changes. Binswanger\u2019s disease patients are a relatively homogeneous subgroup with hypoxic hypoperfusion, lacunar infarcts, and inflammation that act synergistically to disrupt the blood\u2013brain barrier (BBB) and break down myelin. Identification of this subgroup can be facilitated by multimodal disease markers obtained from clinical, cerebrospinal fluid, neuropsychological, and imaging studies. 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