Different mechanisms of episodic memory failure in mild cognitive impairment.

Mild cognitive impairment (MCI), defined as episodic memory impairment beyond what is expected in normal aging, is often associated with hippocampal atrophy (HA) and may represent incipient Alzheimer's disease. However, recent studies suggest that MCI is very heterogeneous and multiple etiologies likely exist. One possibility is small vessel cerebrovascular disease (CVD). Specifically, we hypothesized that white matter hyperintensities (WMH), an MRI marker for CVD, would lead to impairments in executive control processes critical for working memory that may, in turn, result in episodic memory impairment. To test this hypothesis, we examined a group of subjects clinically diagnosed with MCI and used MRI to further subcategorize individuals as either MCI with severe white matter hyperintensities (MCI-WMH) or MCI with severe hippocampal atrophy (MCI-HA). MCI-WMH, MCI-HA, and matched control subjects each performed a battery of working memory and episodic memory tasks. Results showed that MCI-HA and MCI-WMH were equally impaired on the episodic memory task relative to controls, but MCI-WMH were additionally impaired on tests tapping verbal and spatial working memory abilities and attentional control processes. These results suggest that CVD and hippocampal dysfunction are associated with distinct neuropsychological profiles. Although both syndromes are associated with episodic memory deficits, CVD is additionally associated with working memory and executive control deficits.