Vascular dementia and Alzheimer's disease - are we in a dead-end road?

Abstract

Background: Diagnostic criteria separating vascular dementia from other dementias, particularly Alzheimer's disease (AD) neglect the real world in which most AD cases present with at least some vascular brain lesions. Most importantly, vascular lesions, even if subtle, exert significant effects on the patients' cognitive functioning if they coexist with AD pathology.

Objectives: To emphasize the need for an integrative dementia concept in which the vascular component represents an important end point in trial planning and a possibility for disease modification along the whole spectrum of combined vascular and primary degenerative pathology.

Methods: Review of the literature on possible surrogate markers to study the contribution of vascular brain damage in dementia.

Results: The longitudinal change in volume of white matter lesions is the best elaborated putative surrogate marker for the study of the vascular component in dementia. Validation of the role of lacunes and microbleeds as surrogate end points is poor. Loss of brain volume is an important adjunct outcome measure even though the vascular origin of atrophy remains uncertain.

Conclusions: A focus on pure vascular dementia distracts from the importance of vascular factors in dementia. Consideration of the vascular component in future clinical trials will improve our pathophysiological understanding and provide options for treatment.