Vascular Dementia: Distinguishing
Characteristics, Treatment, and Prevention
Gustavo C. Roman,
Vascular dementia (VaD) is the second-most-common cause of dementia in
the elderly, after Alzheimer's disease (AD). VaD is defined as loss of cognitive function resulting from ischemic, hypoperfusive,
or hemorrhagic brain lesions due to cerebrovascular disease or cardiovascular pathology. Diagnosis requires the following
criteria: cognitive loss, often predominantly subcortical; vascular brain lesions demonstrated by imaging; a temporal link
between stroke and dementia; and exclusion of other causes of dementia. Poststroke VaD may be caused by large-vessel disease
with multiple strokes (multiinfarct dementia) or by a single stroke (strategic stroke VaD). A common form is subcortical ischemic VaD caused by small-vessel occlusions with multiple lacunas and by hypoperfusive
lesions resulting from stenosis of medullary arterioles, as in Binswanger's disease. Unlike with AD, in VaD, executive
dysfunction is commonly seen, but memory impairment is mild or may not even be present. The cholinesterase inhibitors used
for AD are also useful in VaD. Prevention strategies should focus on reduction of stroke and cardiovascular disease, with
attention to control of risk factors such as hypertension, diabetes mellitus, hypercholesterolemia,
Emerging Concepts and Therapeutic Implications
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.
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.
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.
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