Cognitive impairment in neurological diseases: lessons from apolipoprotein E.

Apolipoprotein E4 (ApoE4) has been considered to have detrimental effects on the age of onset and progression in Alzheimer's disease. Evidence continues to accumulate regarding the effects of ApoE isoforms in a number of other neurological diseases. Recent studies demonstrate an increase in cognitive deficits in ApoE4 patients with traumatic brain injury, cerebrovascular disease, and delirium. Evidence of the role ApoE isoforms played in cognition in multiple sclerosis has illuminated the neurodegenerative aspects of this disease. It further provides evidence of the effect neuroinflammation has in increasing susceptibility to cognitive decline in younger patients. Determining where these diverse diseases intersect and diverge in their relationship to ApoE provides insight into the two-hit mechanism in cognitive decline.