Management of mixed dementia

Alzheimer's disease (AD) and vascular dementia (VaD) are the most common causes of dementia in the elderly. Although AD can be diagnosed with a considerable degree of accuracy, the distinction between isolated AD, VaD and mixed dementia (MD) [when both pathologies coexist in the same patient] remains a controversial issue and one of the most difficult diagnostic challenges. MD represents a very common pathology, especially in the elderly, as reported in neuropathological studies. Accurate diagnosis of MD is of crucial significance for epidemiological purposes and for preventive and therapeutic strategies. Until recently, pharmacological studies have generally focused on pure disease, either AD or VaD, and have provided few data on the best therapeutic approach to MD. There is only one original randomized clinical trial on (acetyl)cholinesterase inhibitor therapy (GAL-INT-6, galantamine) for MD; the other studies are post hoc analyses of AD trial subgroups (AD2000, donepezil) or of VaD trial subgroups (VantagE, rivastigmine). Cholinesterase inhibitors have reproducible beneficial effects on cognitive and functional outcomes in patients with MD. These benefits are of a similar magnitude to those previously reported for the treatment of AD. It is likely that the beneficial effects of memantine (an NMDA receptor antagonist) in AD may also apply to MD, but randomized controlled trials are still lacking. Treatment of cardiovascular risk factors, especially hypertension, may protect brain function and should be included in prevention strategies for MD.