Multimodal Markers of Inflammation in the Subcortical Ischemic Vascular Disease Type of Vascular Cognitive Impairment

Introduction

Vascular cognitive impairment (VCI) is a heterogeneous disease that is caused by a wide variety of vascular factors.¹ Pathological studies have shown that both large- and small-vessel damage occurs in patients with VCI.^2,3 Large-vessel disease leads to strokes with a stepwise course as a result of multiple infarctions that result in concomitant loss of intellect. Small-vessel disease has several forms: it may either produce lacunes mainly in the basal ganglia without white matter damage or extensive changes in the white matter with or without lacunes (Table I in the online-only Data Supplement). The term subcortical ischemic vascular disease is often used for both lacunar state and white matter disease, but there may be different pathophysiologies involved, particularly when there is cerebral hypoperfusion, which has a major effect on the vulnerable deep white matter.⁴

Binswanger disease (BD) was first described in 1894 in patients with arteriolosclerotic demyelination.⁵ Patients with BD have a symptom complex that includes vascular risk factors, cognitive impairment, small stroke-like events, hyperreflexia, and imbalance (Table II in the online-only Data Supplement).^6,7 Neuropsychological testing shows executive dysfunction, whereas difficulties with memory and language occur more commonly in Alzheimer disease (AD); overlap occurs in neuropsychological testing in BD and AD, making patterns of cognitive dysfunction only suggestive of diagnoses. The Montreal Cognitive Assessment, which includes tests of executive function, when compared with minimental status examination is more often abnormal in patients with BD, making it a better screening test.⁸

Clinical features alone may be insufficient to diagnose BD, and a multimodal approach with biomarkers may be helpful. The biomarkers that have been suggested include neuropsychological testing, brain imaging, and cerebrospinal fluid (CSF) studies. Routine MRI shows white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery imaging, which are nonspecific and are …