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Source: Morris JC, et al. Mild cognitive impairment represents early-stage Alzheimer’s disease. Arch Neurol. 2001;58:397-405.
Persons having mild cognitive impairment (MCI) display deficits that are greater than expected for their age, but less than would be considered diagnostic of dementia. MCI is considered a state of increased risk for Alzheimer’s disease (AD), to the extent that persons with MCI develop AD at a higher rate than comparably aged individuals without cognitive impairments. The issue of whether MCI actually represents an early, transitional stage of AD in all cases is a hotly debated topic.
Researchers at Washington University (St. Louis) have added fuel to this fire by carrying out a nearly decade-long observational study of individuals with MCI that included careful clinical-neuropathological correlations. The study used the Clinical Dementia Rating Scale (CDR). MCI is taken to be equivalent to a CDR score of 0.5, while normal cognition is rated as 0 and mild dementia as 1. A unique feature of the Washington University study was the further stratification of CDR 0.5 group into 3 subcategories based on the rater’s confidence that the condition was an early manifestation of dementia of the AD type (DAT). When the rater had the highest confidence of likely progression to AD, the participants were scored as 0.5/DAT. Moderate confidence of progression merited a 0.5/incipient DAT rating, while lowest confidence led to a 0.5/uncertain dementia label. In general, patients with memory loss as part of the primary presentation and greater degree of initial impairment were more likely to be placed in the 0.5/DAT group.
Morris and colleagues found that all of the persons given a designation of 0.5/DAT went on to become demented over 9.5 years. Approximately 61% of MCI patients developed dementia in 5 years, while only 35.7% of the 0.5/incipient DAT and 19.9% of the 0.5/uncertain group went on to develop clear-cut dementia over that time. Thus, the rate of progression of MCI to dementia depended on the level of impairment at presentation. A total of 25 MCI patients came to autopsy, and 21 (84%) were found to have AD. Morris et al concluded that there is sufficient correlation between the state of MCI and subsequent autopsy findings of AD to indicate that MCI actually represents an early stage of AD.
This study makes the important observation that persons given a CDR rating of 0.5 and the clinical designation of MCI do not all share the same risk level of developing AD. MCI can represent a possible transition state to dementia, but it is heterogenous in terms of the degree of impairment on presentation and the cognitive domains initially involved. It appears that the previously reported rates of conversion from MCI to AD of 10-15% per year are most applicable to individuals with slightly more advanced cognitive decline and memory loss as an initial feature of their presentation.
In clinical practice, it can be difficult to reliably identify MCI patients without using the kind of detailed assessment tools used in clinical research studies. It would be even more difficult for practicing neurologists to draw distinctions among subgroups of MCI patients as was done in this study. This emphasizes the need for caution in applying the MCI construct outside of a research context. Persons already labeled as having MCI may need reassurance that their risk of developing AD may not be as high as some sources have previously indicated.
This study and others like it prove that it is possible to identify a select population of mildly impaired persons who have a high likelihood of developing AD within a few years. It remains to be seen whether the broader group of patients in the state currently defined as MCI are all suffering from an early stage of AD. —Norman R. Relkin