Diffuse vacuolization (spongiosis) and arteriolosclerosis in the frontal white matter occurs in vascular dementia

Objective: To examine quantitatively white-matter changes at different sites in patients with definite vascular dementia and Alzheimer's disease. Design: Prospective clinical and neuropathological series. Setting: University hospital clinics (Helsinki, Finland, and London, Ontario). Subjects: Twenty-two patients with a clinical and neuropathological diagnosis of vascular dementia and 20 patients with Alzheimer's disease. Measures: The frequencies of focal white-matter lesions, arteriolosclerosis, and cerebral amyloid angiopathy were assessed. Validated ratings and cell counts were done in the subcortical U-fiber, centrum semiovale, and periventricular areas of the frontal white matter. Degrees of abnormality (none, mild, moderate, severe) were rated for spongiosis (vacuolization of white matter), etat crible (widening of perivascular spaces), myelin loss, oligodendrocyte density, axonal loss, and overall. Densities of oligodendrocytes and astrocytes (cells per square millimeter) were determined. Results: Patients with vascular dementia showed focal white-matter lesions and arteriolosclerosis more often than patients with Alzheimer's disease. The patients with vascular dementia also had significantly greater spongiosis (P<.001), etat crible (P=.004), myelin loss (P=.005) and overall white-matter abnormality (P<.001). Arteriolosclerosis was found in association with spongiosis but not with etat crible. Cerebral amyloid angiopathy did not appear to be related to any of the white-matter changes in patients with either vascular dementia or Alzheimer's disease. The U-fiber area showed fewer changes, and the periventricular area tended to be most affected. Conclusion: In addition to focal infarcts, patients with vascular dementia showed widespread diffuse changes, including spongiosis and arteriolosclerosis, along with etat crible and myelin loss. White-matter changes in patients with Alzheimer's disease could not be related to infarction. Pathologic changes in small blood vessels are associated with diffuse white-matter changes and may have a distinct role in the genesis of vascular dementia.