The enigma of mixed dementia.

Mixed type dementia (MD) refers to a combination of Alzheimer disease (AD) and vascular encephalopathy (VE) and other dementia disorders, but the distinction between these diseases is difficult. For the diagnosis of MD, the clinical/neuroimaging criteria of probable AD plus vascular cognitive impairment (VCI) as separate entities are used. Both disorders increase exponentially with age, but their interactions are common and controversial. Pathologic diagnosis is based on the combination of autopsy-proven AD with multiple vascular or ischemic brain lesions. The population-based incidence and prevalence of MD is unknown. In retrospective and prospective autopsy studies, its prevalence ranges from 2% to 58% with reasonable means of 6% to 12%, although findings from several recent studies indicated frequent coexistence of AD with multiple cerebrovascular lesions (CVLs) in cognitively impaired elderly subjects. In both AD and VCI, vascular lesions frequently involve subcortical regions (basal ganglia, thalamus, hippocampus, white matter) or are multiple microinfarcts, whereas in MD large/hemispheral infarcts and multiple microinfarcts are more frequent, suggesting different pathogenic mechanisms. There is increasing evidence that critically located small CVLs can induce/promote cognitive impairment in early-stage AD but not once AD pathology becomes more advanced. Discussion of the major pathogenic factors inducing AD, VCI, and MD suggests synergistic relations between these disorders. Currently available clinical and morphologic criteria for AD and VCI are of limited value for the diagnosis of MD, and the ability of current consensus criteria to distinguish between AD, VCI, and MD is limited. Therefore, future development of methods that more accurately characterize the impact of both AD-related and vascular brain injuries are warranted.