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Who Progresses from Mild Cognitive Impairment to Alzheimer Disease?

Although these analyses shed light on variables that affect progression, the predictors are not accurate enough to be used for individual patients.

Mild cognitive impairment (MCI) is defined as impaired memory with preservation of the "activities of daily living." Population-based studies reveal that only approximately one third of patients with MCI ultimately progress to dementia, which, by definition, compromises the ability to function professionally and socially. Predicting whether a patient with MCI will stabilize or will decline into Alzheimer dementia is tremendously important to the patient and family. In three studies, different research groups examined the ability of cognitive and psychiatric manifestations of MCI to predict progression to Alzheimer disease (AD).

Patients with MCI may have prominent amnestic symptoms. Fleisher and colleagues examined 539 patients with amnestic MCI over 36 months and found that 212 progressed to AD. Four easily administered office-based tests best anticipated progression to AD (with 80% accuracy).

MCI may also be accompanied by anxiety or depression. Palmer and colleagues examined 185 cognitively normal individuals and 47 individuals with MCI over a 3-year period. They found that MCI patients with anxiety were more likely to progress to AD than were MCI patients without anxiety. Depressive symptoms were more common, in both the cognitively normal cohort and the MCI cohort, among those who progressed. These psychiatric symptoms may either reflect a neuropathologic change that precedes dementia or may be a subjective response to cognitive changes perceived by the patient.

Aiming to identify a biologic marker that predicts progression from MCI to AD, Kemppainen and colleagues quantified uptake of [¹¹C]PIB, a PET ligand that binds amyloid plaque, in 13 patients with amnestic MCI and in 14 cognitively normal controls. MCI patients had greater [¹¹C]PIB uptake than did controls. Approximately half of the MCI patients had [¹¹C]PIB uptake equivalent to that seen in patients with AD. Whether these are the MCI patients who will progress to AD is unknown and is a critical issue.

Comment: Because of the profoundly different clinical outcomes between patients with MCI who progress to dementia and those who do not progress, the experimental approaches reviewed here should not be employed in predicting outcome for any individual patient in the clinic.

— Warren J. Strittmatter, MD

Dr. Strittmatter is Professor of Neurology, Duke University Medical Center, Durham, NC.

Published in Journal Watch Neurology August 7, 2007

Citation(s):

Fleisher AS et al. Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology 2007 May 8; 68:1588-95.

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• Medline abstract (Free)

Palmer K et al. Predictors of progression from mild cognitive impairment to Alzheimer disease. Neurology 2007 May 8; 68:1596-602.

• Original article (Subscription may be required)
• Medline abstract (Free)

Kemppainen NM et al. PET amyloid ligand [¹¹C]PIB uptake is increased in mild cognitive impairment. Neurology 2007 May 8; 68:1603-6.

• Original article (Subscription may be required)
• Medline abstract (Free)