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. 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 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. 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.
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. 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 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. 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.
Authors: Ranjan Duara; David A Loewenstein; Maria T Greig; Elizabeth Potter; Warren Barker; Ashok Raj; John Schinka; Amy Borenstein; Michael Schoenberg; Yougui Wu; Jessica Banko; Huntington Potter Journal: Am J Geriatr Psychiatry Date: 2011-11 Impact factor: 4.105
Authors: Richard J Caselli; Amylou C Dueck; Dona E C Locke; Leslie C Baxter; Bryan K Woodruff; Yonas E Geda Journal: J Int Neuropsychol Soc Date: 2015-02-09 Impact factor: 2.892
Authors: Emily H Trittschuh; Paul K Crane; Eric B Larson; Brenna Cholerton; Wayne C McCormick; Susan M McCurry; James D Bowen; Laura D Baker; Suzanne Craft Journal: J Alzheimers Dis Date: 2011 Impact factor: 4.472
Authors: Cynthia M Stonnington; Kewei Chen; Wendy Lee; Dona E C Locke; Amylou C Dueck; Xiaofen Liu; Auttawut Roontiva; Adam S Fleisher; Richard J Caselli; Eric M Reiman Journal: Alzheimers Dement Date: 2013-04-11 Impact factor: 21.566
Authors: Richard J Caselli; Amylou C Dueck; David Osborne; Marwan N Sabbagh; Donald J Connor; Geoffrey L Ahern; Leslie C Baxter; Steven Z Rapcsak; Jiong Shi; Bryan K Woodruff; Dona E C Locke; Charlene Hoffman Snyder; Gene E Alexander; Rosa Rademakers; Eric M Reiman Journal: N Engl J Med Date: 2009-07-16 Impact factor: 91.245