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Richard J. Caselli, MD; Kewei Chen, PhD; Wendy Lee, MS; Gene E. Alexander, PhD; Eric M. Reiman, MD

Arch Neurol. 2008;65(9):1231-1236.

Background  Before symptomatic memory loss, healthy apolipoprotein E 4 (APOE 4) (OMIM 104310) carriers demonstrate accelerated longitudinal decline on memory tests, suggesting the existence of a transitional state between normal aging and mild cognitive impairment (MCI), which we have called amnestic pre-MCI.

Objective  To support our neuropsychological construct of pre-MCI by characterizing and comparing the relationship between measurements of baseline regional hypometabolism and subsequent rates of memory decline in a group of individuals with neuropsychologically defined asymptomatic memory decline (pre-MCI group) and in nondecliners after controlling for APOE 4 gene dose.

Design  Longitudinal study.

Setting  Academic medical center.

Participants  Of 139 healthy individuals in the Arizona APOE Cohort aged 50 to 69 years who underwent longitudinal neuropsychological testing and fludeoxyglucose F 18–positron emission tomography (FDG-PET) since 1994, 10 met our criteria for amnestic pre-MCI, and 15 showed no decline.

Main Outcome Measures  Correlations between lower regional cerebral metabolic rates for glucose (CMRgl) and rates of verbal memory test decline that occurred at a mean of 41 months after baseline FDG-PET using an automated brain mapping algorithm (SPM5).

Results  The pre-MCI and nondecliner groups did not differ in mean (SD) age (56.8 [4.8] years), education (16.5 [2.3] years), sex (19 women [76%]), or APOE 4 carrier status (12 4 carriers [48%)]. After controlling for APOE 4 gene dose, the pre-MCI group had significant correlations between lower baseline CMRgl in the posterior cingulate, bilateral parietal, and left prefrontal regions (known to be preferentially affected by Alzheimer disease) and subsequent verbal memory decline. Nondecliners had significant correlations bilaterally in the posterior and midcingulate cortices. Correlations in the left parietal, left temporal, and bilateral frontal regions were significantly greater in the pre-MCI group than those in the nondecliner group.

Conclusion  Individuals with amnestic pre-MCI showed significantly greater correlations between cerebral hypometabolism and subsequent long-term memory decline than nondecliners in Alzheimer disease–affected brain regions.

Author Affiliations: Departments of Neurology (Dr Caselli), Psychiatry (Drs Chen and Reiman and Ms Lee), and Psychology (Dr Alexander), Mayo Clinic, Scottsdale, Arizona; Banner Alzheimer's Institute and Banner Good Samaritan Medical Center (Drs Chen and Reiman and Ms Lee) and Arizona Alzheimer's Research Consortium (Drs Caselli, Chen, Alexander, and Reiman and Ms Lee), Phoenix, Arizona; and Department of Psychology, University of Arizona, Tucson (Dr Alexander).

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