Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment.
BACKGROUND
Before symptomatic memory loss, healthy apolipoprotein E epsilon4 (APOE epsilon4) (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 epsilon4 gene dose.


METHODS
Longitudinal study.


METHODS
Academic medical center.


METHODS
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.


METHODS
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 epsilon4 carrier status (12 epsilon4 carriers [48%)]. After controlling for APOE epsilon4 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.


CONCLUSIONS
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.
Caselli
Richard J
RJ
Department of Neurology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA. Caselli.Richard@Mayo.edu
Chen
Kewei
K
Lee
Wendy
W
Alexander
Gene E
GE
Reiman
Eric M
EM
D000368:Aged; D000647:Amnesia / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005544:Forecasting; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged