An introduction to therapeutic approaches to vascular cognitive impairment

Abstract

Vascular cognitive impairment (VCI), encompassing vascular dementia, has been claimed as the "second-most common dementia" after Alzheimer Disease. Whether or not this is true, the clinical picture of most dementia in older people includes vascular disease. There are no validated pharmacological targets for prevention or treatment of VCI. This has inspired a multitude of potential treatment approaches, reflected by the articles in this Special Issue. These include in vitro testing of the novel oral anticoagulant dabigatran for protection against β-amyloid neurotoxicity, and an overview of neuroinflammation in VCI and the role of circulating markers (PIGF, VEGF-D) identified by the MarkVCID study. There are reviews of potential therapeutics, including adrenomedullin and nootropic preparations (exemplified by cerebrolysin). The role of sleep is reviewed, with possible therapeutic targets (5HT2A receptors). There is a clinical study protocol (INVESTIGATE-SVD) and a feasibility analysis for a secondary prevention trial in small vessel disease. Clinical data include secondary analyses of blood pressure and cerebral blood flow from a longitudinal clinical trial (NILVAD), differences between methylphenidate and galantamine responders and non-responders (STREAM-VCI), appraisal of treatment approaches in India, and primary outcomes from a randomised trial of Argentine tango dancing to preserve cognition in African American women (ACT). Treating vascular disease has great potential to improve global cognitive health, with public health impacts alongside individual benefit. Vascular disease burden varies across populations, offering the possibility of proactively addressing health inequity in dementia using vascular interventions. The next 5-10 years will witness cost-effective lifestyle interventions, repurposed drugs and novel therapeutics.

Keywords: AD, Alzheimer's disease; ADRD, Alzheimer's disease and related dementias; Clinical trials; Drugs; FTD, frontotemporal dementia; LBD, dementia with Lewy bodies; NAPA, national plan to address Alzheimer's disease; NIA, national institute on aging; PD, Parkinson's disease; SVD, small vessel disease; Treatments; VCID; VCID, vascular contributions to cognitive impairment and dementia; VaD, vascular dementia; Vascular cognitive impairment; Vascular dementia.

Fig. 1

Two common age-related pathologies contribute to clinical dementia diagnosis. The orange circle symbolises cognitive impairment, including dementia, in terms of clinical diagnoses. The two rectangles symbolize the overlap of hypothesized contributions from two major pathological contributions to these clinical diagnoses. Vascular disease pathology is shown in blue with dashed outline, Alzheimer's disease pathology (β-amyloid deposits and neurofibrillary tangles) in yellow, dotted outline. The size of the shapes and relative overlaps are indicative rather than quantitative. Nevertheless, for most cognitive impairment seen in older adults, the individual patient would lie within the “Vascular” rectangle (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).