How Often Does Mild Cognitive Impairment Progress to Alzheimer's Disease?
Abstract & Commentary
By F. Tuna Burgut, MD, Assistant Professor of Neurology and Psychiatry, Weill Cornell Medical College, New York Presbyterian Hospital. This abstract originally appeared in the August 2008 issue of Neurology Alert and was peer reviewed by M. Flint Beal, MD. Dr. Burgut reports no financial relationships relevant to this field of study.
Synopsis: Over a 5-year period, 16% of elderly people developed mild cognitive impairment (MCI) and had double the risk of developing Alzheimer's disease (AD) than normals; however, 30% with MCI reverted to normal.
Sources: Manly JJ, et al. Frequency and course of mild cognitive impairment in a multiethnic community. Ann Neurol 2008;63:494-506.
Correct identification of individuals with MCI and understanding the factors that affect the course of this transition between normal aging and AD or dementia is crucial in developing safe and effective disease modifying therapies. However, studies of the prevalence of MCI as well as the progression rates to AD or dementia may vary, depending on the implementation of MCI criteria, referral source, age at assessment, and duration of longitudinal follow-up. Manly et al studied the incidence rate of MCI and the progression of MCI to AD in a large population-based group of elderly adults from diverse ethnic, linguistic, and educational backgrounds over an average period of 4.7 years. They included: 2,364 subjects residing in Northern Manhattan, who were of Hispanic, African-American, and non-Hispanic white ethnicity, age 65 or older, who were at baseline free of dementia and were followed with neurological, medical, psychiatric, and neuropsychological examinations to determine the incidence rate of MCI and AD. Over 7,504 person-years of follow-up, there were 379 incident MCI cases, in which age, Hispanic/African-American ethnicity, and presence of hypertension were determined as risk factors for development of MCI. The presence of the APOE allele was, surprisingly, not associated with a greater risk for development of MCI.
After 10,517 person-years of follow-up, there were 309 cases of incident AD. Further examination revealed that subjects with MCI at their initial visit had twice the risk of developing dementia compared to those who did not have baseline MCI. Those patients with MCI involving multiple cognitive domains with memory impairment were at more risk of developing AD. Older individuals with less education, of African-American/Hispanic heritage, with a positive history of diabetes or stroke, and presence of the APOE E4 allele also were at greater risk for developing AD.
An additional finding of the study was the quantitation of reversal rates of MCI to normal status. At follow-up visits of the 564 elderly subjects diagnosed with MCI at the beginning of the study, 30% did not have MCI or dementia at any follow-up visit and 46% were stable with MCI and did not progress to dementia or revert to normal status. The authors determined that elderly subjects with isolated impairment in only one cognitive domain were most likely to revert to normal at follow-up, regardless of the nature of the cognitive domain affected.
Commentary
Interest is growing in identifying AD at an early "prodromal" phase prior to dementia and there have been several longitudinal studies examining the antecedents of MCI and AD; however, the differences in cohort types, the varying cognitive measures and cut off scores, and the differences in the use of diagnostic criteria with varying longitudinal follow-up periods have made it challenging to arrive at uniform conclusions. However, it is generally well accepted that age, gender, ethnicity, education, co-morbid medical and psychiatric conditions, severity and multiplicity of cognitive deficits, apolipoprotein E4 polymorphism, and functional and neuroanatomical changes on neuroimaging are all useful predictors of the development of MCI or conversion to AD. Manly's study is especially important as many of these risk factors were examined in an ethnically and educationally diverse large population-based group. The evaluation of longitudinal outcomes of different MCI subtypes is valuable in understanding the underlying neuropathological mechanisms leading to conversion to AD. Also, the small group of 27 cases who underwent autopsy demonstrated that antemortem diagnosis of MCI or AD had high specificity but low sensitivity for AD, emphasizing the need for larger studies that examine the accuracy of MCI diagnosis with respect to neuropathology.
The average study duration was 4.7 years but certainly a longer follow-up period will provide more information on the progression rates from normal status to MCI and AD. The course of those individuals who revert from MCI to normal status also may change if followed for a longer duration. A shortcoming of this study is the absence of brain imaging, which would allow for characterization of cerebrovascular disease in this predominantly African-American/Hispanic population with a high incidence of hypertension and diabetes, as it is likely that cerebrovascular disease was under-detected in the cohort.
Over a 5-year period, 16% of elderly people developed mild cognitive impairment (MCI) and had double the risk of developing Alzheimer's disease (AD) than normals; however, 30% with MCI reverted to normal.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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