Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment

Richard John Caselli, Kewei Chen, Wendy Lee, Gene E. Alexander, Eric M. Reiman

Research output: Contribution to journalArticle

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Abstract

Background: Before symptomatic memory loss, healthy apolipoprotein E ε4 (APOE ε4) (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 ε4 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 ε4 carrier status (12 ε4 carriers [48%)]. After controlling for APOE ε4 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.

Original languageEnglish (US)
Pages (from-to)1231-1236
Number of pages6
JournalArchives of Neurology
Volume65
Issue number9
DOIs
StatePublished - Sep 2008

Fingerprint

Apolipoprotein E4
Fluorodeoxyglucose F18
Positron-Emission Tomography
Alzheimer Disease
Brain Mapping
Genetic Databases
Cognitive Dysfunction
Mild Cognitive Impairment
Glucose
Long-Term Memory
Gyrus Cinguli
Memory Disorders
Genes
Longitudinal Studies
Outcome Assessment (Health Care)
Education
Brain
Carrier
Positron Emission Tomography
Alzheimer's Disease

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment. / Caselli, Richard John; Chen, Kewei; Lee, Wendy; Alexander, Gene E.; Reiman, Eric M.

In: Archives of Neurology, Vol. 65, No. 9, 09.2008, p. 1231-1236.

Research output: Contribution to journalArticle

Caselli, Richard John ; Chen, Kewei ; Lee, Wendy ; Alexander, Gene E. ; Reiman, Eric M. / Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment. In: Archives of Neurology. 2008 ; Vol. 65, No. 9. pp. 1231-1236.
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abstract = "Background: Before symptomatic memory loss, healthy apolipoprotein E ε4 (APOE ε4) (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 ε4 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 ε4 carrier status (12 ε4 carriers [48{\%})]. After controlling for APOE ε4 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.",
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N2 - Background: Before symptomatic memory loss, healthy apolipoprotein E ε4 (APOE ε4) (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 ε4 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 ε4 carrier status (12 ε4 carriers [48%)]. After controlling for APOE ε4 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.

AB - Background: Before symptomatic memory loss, healthy apolipoprotein E ε4 (APOE ε4) (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 ε4 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 ε4 carrier status (12 ε4 carriers [48%)]. After controlling for APOE ε4 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.

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