Mixed dementia: emerging concepts and therapeutic implications

JAMA. 2004 Dec 15;292(23):2901-8. doi: 10.1001/jama.292.23.2901.


Context: The prevalence of mixed dementia, defined as the coexistence of Alzheimer disease (AD) and vascular dementia (VaD), is likely to increase as the population ages.

Objectives: To provide an overview of the diagnosis, pathophysiology, and interaction of AD and VaD in mixed dementia, and to provide a systematic literature review of the current evidence for the pharmacologic therapy of mixed dementia.

Data sources, study selection, and data extraction: The Cochrane Database of Systematic Reviews was searched using the keyword dementia. MEDLINE was searched for English-language articles published within the last 10 years using the keywords mixed dementia, the combination of keywords Alzheimer disease, cerebrovascular disorders, and drug therapy, and the combination of keywords vascular dementia and drug therapy.

Evidence synthesis: Dementia is more likely to be present when vascular and AD lesions coexist, a situation that is especially common with increasing age. The measured benefits in clinical trials for the treatment of mixed dementia are best described as statistically significant differences in cognitive test scores and clinician and caregiver impressions of change. In these studies, the control groups' scores typically decline while the treatment groups improve slightly or decline to a lesser degree over the study period. Nevertheless, even the patients who experience treatment benefits eventually decline. Cholinesterase inhibitor (ChI) therapy for mixed dementia shows modest clinical benefits that are similar to those found for ChI treatment of AD. The N-methyl-D-aspartate (NMDA) antagonist memantine also shows modest clinical benefits for the treatment of moderate to severe AD and mild to moderate VaD, but it has not been studied specifically in mixed dementia. The treatment of cardiovascular risk factors, especially hypertension, may be a more effective way to protect brain function as primary, secondary, and tertiary prevention for mixed dementia.

Conclusions: Currently available medications provide only modest clinical benefits once a patient has developed mixed dementia. Cardiovascular risk factor control, especially for hypertension and hyperlipidemia, as well as other interventions to prevent recurrent stroke, likely represent important strategies for preventing or slowing the progression of mixed dementia. Additional research is needed to define better what individuals and families hope to achieve from dementia treatment and to determine the most appropriate use of medication to achieve these goals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / epidemiology
  • Alzheimer Disease* / physiopathology
  • Cardiovascular Agents / therapeutic use
  • Cholinesterase Inhibitors / therapeutic use
  • Comorbidity
  • Dementia, Vascular* / diagnosis
  • Dementia, Vascular* / drug therapy
  • Dementia, Vascular* / epidemiology
  • Dementia, Vascular* / physiopathology
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Humans
  • Risk


  • Cardiovascular Agents
  • Cholinesterase Inhibitors
  • Excitatory Amino Acid Antagonists