ACHE and Alzheimer disease: Memantine is also a possibility although it was neutral in MND-SMART.42 A recent network metanalysis provides mixed results as to whether AChE-I improve cognition in VCI/VaD.43 However, it remains unclear whether AChE-i and memantine only modulate symptoms in AD, also have some disease modifying/neuroprotective properties or even address AD pathology which may often be present in VCI/VaD.44 In this respect, cSVD would be an interesting target for testing whether AChE-Is do have disease-modifying effects in view of the longer natural history for cognitive decline in cSVD.