Small vessel disease lesion type and brain atrophy: The role of co‐occurring amyloid

Introduction It is unknown whether different types of small vessel disease (SVD), differentially relate to brain atrophy and if co-occurring Alzheimer's disease pathology affects this relation. Methods In 725 memory clinic patients with SVD (mean age 67 ± 8 years, 48% female) we compared brain volumes of those with moderate/severe white matter hyperintensities (WMHs; n = 326), lacunes (n = 132) and cerebral microbleeds (n = 321) to a reference group with mild WMHs (n = 197), also considering cerebrospinal fluid (CSF) amyloid status in a subset of patients (n = 488). Results WMHs and lacunes, but not cerebral microbleeds, were associated with smaller gray matter (GM) volumes. In analyses stratified by CSF amyloid status, WMHs and lacunes were associated with smaller total brain and GM volumes only in amyloid-negative patients. SVD-related atrophy was most evident in frontal (cortical) GM, again predominantly in amyloid-negative patients. Discussion Amyloid status modifies the differential relation between SVD lesion type and brain atrophy in memory clinic patients.