This chapter reviews the mechanism of action of cladribine, summarizes data from clinical trials in patients with multiple sclerosis (MS), and provides guidance on the management of these patients in clinical practice. The study of parenteral cladribine showed encouraging results, which lead to the development of an oral tablet formulation. Cladribine is rapidly absorbed with Cmax within 30- 50 minutes after oral administration. CLARITY, a 96-week, placebo-controlled Phase 3 study of cladribine tablets as an annual short-course oral monotherapy in RRMS, was recently completed and the principal results published. Benefit of doses of cladribine over placebo was demonstrated for a variety of clinical and imaging end-points. The most common adverse events in the patients were lymphopenia, headache, nasopharyngitis, and upper respiratory tract infections (URTI). The outcomes observed during the CLARITY study were associated with a reduced consumption of health care resources and a decreased need for medical and societal support.

This chapter discusses the potential role that vascular risk factors and asymptomatic cerebrovascular disease (CVD) may have on lifetime risk for dementia. It examines evidence regarding the extent and character by which vascular cognitive impairment (VCI) influences cognition and by what mechanism VCI may contribute to incident dementia whether the dementia syndrome results from Alzheimer's disease (AD), vascular dementia (VaD) or a mixed dementia. The chapter reviews the concept of VCI, and also discusses the spectrum and potentially long time course of vascular-related brain injury, and the potentially important role of cerebral white matter in relation to widely distributed cognitive processes such as memory. It addresses cognitive changes associated with aging, and the potential role of asymptomatic vascular brain injury in these processes. The chapter outlines the identification of clinically relevant episodic memory impairment (amnestic mild cognitive impairment (aMCI)) due solely to presumed brain vascular disease.