Etiology of MCI

Given the preliminary and general nature of the concept of MCI, a clear and concise list of possible etiologies is unlikely although systemic diseases likely account for some cases. Clearly, a significant percentage of the cases represent early stages of dementia, most commonly AD. Petersen et al. (2001) reviewed six longitudinal studies of patients who fit the general description of MCI and found that the annual rate of conversion to a diagnosis of dementia ranged from 6 to 25 percent, with the majority of the studies falling in the range of 12 to 15 percent. This is higher than the annual incidence of dementia, which ranges from 1.1 percent for 60 to 64 years of age to 8.7 percent for individuals who are 95 years or older (Bachman et al., 1993).

Some authors have theorized that the progression of MCI varies depending on the specific cognitive domains impaired at the time of initial presentation. Individuals with impairment in multiple cognitive domains may progress to AD or vascular dementia or show no progression. Purely amnestic MCI is believed to progress to AD. In contrast, MCI that presents with prominent deficits other than memory may develop into a frontotemporal dementia, dementia with Lewy bodies, primary progressive aphasia, Parkinson's dementia, or AD. In the case of dementia with Lewy bodies, an initial presentation of amnestic MCI may be less likely than nonamnestic MCI because individuals with diffuse Lewy body disease (DLBD) demonstrate relative preservation of the hippocampi in comparison to those with AD (Petersen et al., 2001).

Given the association between MCI and subsequent diagnosis of AD, or dementia in general, the AAN has recommended that persons who meet the basic criteria for MCI be monitored clinically. However, it should be emphasized that not all cases of MCI develop into dementia. Indeed, according to data reviewed by Hogan and McKeith (2001), the majority of persons identified with MCI do not convert to dementia within the first 2 to 3 years after identification (Ritchie et al., 2001).

There appear to be several causes of MCI in the elderly population other than preclinical dementia. The association between several systemic disease states common in the elderly and MCI is well known. For example, several studies have demonstrated that hypoxemic chronic obstructive pulmonary disease (COPD) results in cognitive dysfunction that is measurable with neuropsychological instruments and that the severity of the cognitive dysfunction is related to the severity of hypoxemia as well as quality of life (Grant et al., 1987; McSweeny and Labuhn, 1996). However, the nature of the cognitive dysfunction associated with hypoxemic COPD is different than that associated with AD and most other forms of progressive dementia. Rather than prominent memory deficits, individuals with chronic hypoxemia demonstrate impaired complex perceptual-motor learning and cognitive flexibility (Grant et al., 1987). Other studies have demonstrated associations between MCI and obstructive sleep apnea, nondement-ing cerebrovascular disorders, and other health problems (Brown et al., 1996; Rourke and Adams, 1996). In addition, depression, which is common in the elderly, is sometimes associated with memory difficulties, although this is by no means universally true, and depression-associated memory deficits appear to be quite different than those observed in AD (King and Caine, 1996).

In summary, while MCI is certainly associated with progressive dementia, it is not specific to dementia, and a diagnosis of MCI is a poor predictor of dementia risk over a 3-year period following initial identification (Ritchie et al., 2001). The fact that MCI is not specific to dementia has led to some controversy regarding the AAN identification and monitoring recommendation noted above. As Hogan and McKeith (2001) have pointed out, there are significant psychological and social problems associated with being labeled "at risk" for dementia, including personal distress and curtailment of driving privileges. Accordingly, more specific indicators of dementia risk and long-term studies of MCI as a risk factor are needed.

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