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Bradford C. Dickerson, MD; Reisa A. Sperling, MD; Bradley T. Hyman, MD, PhD; Marilyn S. Albert, PhD; Deborah Blacker, MD, ScD

Arch Gen Psychiatry. 2007;64(12):1443-1450. doi:10.1001/archpsyc.64.12.1443

Objective  To determine whether clinical assessment methods that grade the severity of impairments within the spectrum of mild cognitive impairment (MCI) can predict clinical course, particularly among very mildly impaired individuals who do not meet formal MCI criteria as implemented in clinical trials.

Design  Cohort.

Setting  Community volunteers.

Participants  From a longitudinal study of normal (Clinical Dementia Rating [CDR] = 0; n = 77) and mildly impaired (CDR = 0.5; n = 167) participants with 5 or more annual clinical assessments, baseline level of cognitive impairment in daily life was graded using CDR sum of boxes (CDR-SB) and level of cognitive performance impairment was graded using neuropsychological test scores.

Main Outcome Measures  Five-year outcome measures included (1) probable Alzheimer disease (AD) diagnosis and (2) clinical "decline" (CDR-SB increase  1.0). Logistic regression models were used to assess the ability of baseline measures to predict outcomes in the full sample and separately in the subjects who did not meet formal MCI criteria as implemented in a multicenter clinical trial (n = 125; "very mild cognitive impairment" [vMCI]).

Results  The presence of both higher CDR-SB and lower verbal memory and executive function at baseline predicted greater likelihood of probable AD and decline. Five-year rates of probable AD and decline in vMCI (20%, AD; 49%, decline) were intermediate between normal participants (0%, AD; 28%, decline) and participants with MCI (41%, AD; 62%, decline). Within vMCI, likelihood of probable AD was predicted by higher CDR-SB and lower executive function.

Conclusions  Even in very mildly impaired individuals who do not meet strict MCI criteria as implemented in clinical trials, the degree of cognitive impairment in daily life and performance on neuropsychological testing predict likelihood of an AD diagnosis within 5 years. The clinical determination of relative severity of impairment along the spectrum of MCI may be valuable for trials of putative disease-modifying compounds, particularly as target populations are broadened to include less impaired individuals.

Author Affiliations: Departments of Neurology (Drs Dickerson, Sperling, and Hyman) and Psychiatry (Dr Blacker), Massachusetts General Hospital and Harvard Medical School and Division of Cognitive and Behavioral Neurology, Department of Neurology, Brigham and Women's Hospital (Drs Dickerson and Sperling), Boston; and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr Albert).

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