Is the time ripe for new diagnostic criteria of cognitive impairment due to cerebrovascular disease? Consensus report of the International Congress on Vascular Dementia working group

Background: Long before Alzheimer's disease was established as the leading cause of dementia in old age, cerebrovascular lesions were known to cause cognitive deterioration and associated disability. Since the middle of the last century, different diagnostic concepts for vascular dementia and related syndromes were put forward, yet no widely accepted diagnostic consensus exists to date. Discussion: Several international efforts, reviewed herein, are ongoing to define cognitive impairment due to cerebrovascular disease in its different stages and subtypes. The role of biomarkers is also being discussed, including cerebrospinal fluid proteins, structural and functional brain imaging, and genetic markers. The influence of risk factors, such as diet, exercise and different comorbidities, is emphasised by population-based research, and lifestyle changes are considered for the treatment and prevention of dementia. Conclusion: To improve the diagnosis and management of vascular cognitive impairment, further progress has to be made in understanding the relevant pathomechanisms, including shared mechanisms with Alzheimer's disease;bringing together fragmented research initiatives in coordinated international programs;testing if known risk factors are modifiable in prospective interventional studies;and defining the pre-dementia and pre-clinical stages in line with the concept of mild cognitive impairment due to Alzheimer's disease

Preventing post-stroke dementia. The MARCH Trial. Protocol and statistical analysis plan of a randomized clinical trial testing the safety and efficacy of Maraviroc in post-stroke cognitive impairment

BackgroundCurrent evidence suggest that 25%-33% of stroke-survivors develop post-stroke cognitive impairment (PSCI). The licensed drug Maraviroc, a CCR5-antagonist, is postulated to act via a neuroprotective mechanism that may offer the potential of preventing progression to vascular dementia. Our hypothesis: Maraviroc may have the potential to augment learning skills and cognitive performance by affecting synaptic plasticity, along with neuro-inflammatory modulation in patients with cerebral small vessel disease (SVD) and PSCI.DesignMARCH is a multi-center, double-blind randomized-control Phase-II trial of Maraviroc 150 or 600 mg/day versus placebo for 12-months in five stroke centers in Israel. Included are patients diagnosed with recent (1-24 months) subcortical stroke who experience mild PSCI and have evidence of white matter lesions and SVD on neuroimaging.OutcomesPrimary outcomes: 1. Change in cognitive scores. 2. Drug related adverse events. Secondary outcomes: change in functional and affective scores, MRI-derived measures, inflammatory markers, carotid atherosclerosis, cerebrospinal-fluid biomarkers in a sub-study. A sample size of 60 in each treatment group and 30 in the placebo group (total - 150 participants) provides 80% power between the treatment and the placebo groups.ConclusionsThe results of this work could lead to a novel, readily available, therapeutic avenue to reduce PSCI, and possibly other pathologies. This study will test safety and effectiveness of Maraviroc in limiting cognitive deterioration and/or post stroke cognitive impairment in patients with cerebral small vessel disease.ScheduleFirst-patient first-visit was May 2021. Recruitment to complete in 2023, follow-up to complete in 2024