Hypometabolism in Alzheimer-affected brain regions in cognitively healthy latino individuals carrying the apolipoprotein E ε4 allele

Jessica B S Langbaum, Kewei Chen, Richard J. Caselli, Wendy Lee, Cole Reschke, Daniel Bandy, Gene E Alexander, Christine M. Burns, Alfred W Kaszniak, Stephanie A. Reeder, Jason J. Corneveaux, April N. Allen, Jeremy Pruzin, Matthew J. Huentelman, Adam S. Fleisher, Eric M. Reiman

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Objective: To investigate with fluorodeoxyglucose positron emission tomography whether regional reductions in the cerebral metabolic rate for glucose (CMRgl) previously found in cognitively healthy latemiddle-aged apolipoprotein E (APOE) ε4 carriers extend to members of the Latino Mexican American community. Design: Prospective cohort study. Setting: Banner Alzheimer's Institute, Phoenix, Arizona. Patients or Other Participants: Eleven APOE ε4 carriers and 16 noncarriers from Arizona's Latino community (mean [SD] age, 54.6 [6.4] years) matched for sex, mean age, and educational level and who were predominantly of self-designated Mexican origin. Main Outcome Measure: A brain mapping algorithm was used to compare cross-sectional regional CMRgl in Latino APOE ε4 carriers vs noncarriers. Results: Participant groups had similar distributions for age, sex, education, family history of dementia, clinical ratings, and neuropsychological test scores. Latino APOE ε4 carriers had lower CMRgl than the noncarriers in the posterior cingulate, precuneus, and parietal regions previously found to be preferentially affected in patients with Alzheimer disease (AD) and cognitively healthy non-Latino APOE ε4 carriers. Additionally, the Latino APOE ε4 carriers had lower CMRgl in the middle and anterior cingulate cortex, hippocampus, and thalamus. Conclusions: This study provides support for the relationship between APOE ε4 and risk of AD in Latino individuals. It illustrates the role of positron emission tomography as a presymptomatic endophenotype for the assessment of AD risk factors and supports the inclusion of Latino APOE ε4 carriers in proof-of-concept studies using fluorodeoxyglucose PET to evaluate promising presymptomatic treatments in cognitively healthy carriers of this common AD susceptibility gene.

Original languageEnglish (US)
Pages (from-to)462-468
Number of pages7
JournalArchives of Neurology
Volume67
Issue number4
DOIs
StatePublished - Apr 2010

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Apolipoprotein E4
Hispanic Americans
Alleles
Brain
Alzheimer Disease
Glucose
Parietal Lobe
Gyrus Cinguli
Positron-Emission Tomography
Brain Mapping
Endophenotypes
Sex Education
Allele
Carrier
Alzheimer
Latinos
Neuropsychological Tests
Disease Susceptibility
Age Distribution
Thalamus

ASJC Scopus subject areas

  • Clinical Neurology

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Hypometabolism in Alzheimer-affected brain regions in cognitively healthy latino individuals carrying the apolipoprotein E ε4 allele. / Langbaum, Jessica B S; Chen, Kewei; Caselli, Richard J.; Lee, Wendy; Reschke, Cole; Bandy, Daniel; Alexander, Gene E; Burns, Christine M.; Kaszniak, Alfred W; Reeder, Stephanie A.; Corneveaux, Jason J.; Allen, April N.; Pruzin, Jeremy; Huentelman, Matthew J.; Fleisher, Adam S.; Reiman, Eric M.

In: Archives of Neurology, Vol. 67, No. 4, 04.2010, p. 462-468.

Research output: Contribution to journalArticle

Langbaum, JBS, Chen, K, Caselli, RJ, Lee, W, Reschke, C, Bandy, D, Alexander, GE, Burns, CM, Kaszniak, AW, Reeder, SA, Corneveaux, JJ, Allen, AN, Pruzin, J, Huentelman, MJ, Fleisher, AS & Reiman, EM 2010, 'Hypometabolism in Alzheimer-affected brain regions in cognitively healthy latino individuals carrying the apolipoprotein E ε4 allele', Archives of Neurology, vol. 67, no. 4, pp. 462-468. https://doi.org/10.1001/archneurol.2010.30
Langbaum, Jessica B S ; Chen, Kewei ; Caselli, Richard J. ; Lee, Wendy ; Reschke, Cole ; Bandy, Daniel ; Alexander, Gene E ; Burns, Christine M. ; Kaszniak, Alfred W ; Reeder, Stephanie A. ; Corneveaux, Jason J. ; Allen, April N. ; Pruzin, Jeremy ; Huentelman, Matthew J. ; Fleisher, Adam S. ; Reiman, Eric M. / Hypometabolism in Alzheimer-affected brain regions in cognitively healthy latino individuals carrying the apolipoprotein E ε4 allele. In: Archives of Neurology. 2010 ; Vol. 67, No. 4. pp. 462-468.
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abstract = "Objective: To investigate with fluorodeoxyglucose positron emission tomography whether regional reductions in the cerebral metabolic rate for glucose (CMRgl) previously found in cognitively healthy latemiddle-aged apolipoprotein E (APOE) ε4 carriers extend to members of the Latino Mexican American community. Design: Prospective cohort study. Setting: Banner Alzheimer's Institute, Phoenix, Arizona. Patients or Other Participants: Eleven APOE ε4 carriers and 16 noncarriers from Arizona's Latino community (mean [SD] age, 54.6 [6.4] years) matched for sex, mean age, and educational level and who were predominantly of self-designated Mexican origin. Main Outcome Measure: A brain mapping algorithm was used to compare cross-sectional regional CMRgl in Latino APOE ε4 carriers vs noncarriers. Results: Participant groups had similar distributions for age, sex, education, family history of dementia, clinical ratings, and neuropsychological test scores. Latino APOE ε4 carriers had lower CMRgl than the noncarriers in the posterior cingulate, precuneus, and parietal regions previously found to be preferentially affected in patients with Alzheimer disease (AD) and cognitively healthy non-Latino APOE ε4 carriers. Additionally, the Latino APOE ε4 carriers had lower CMRgl in the middle and anterior cingulate cortex, hippocampus, and thalamus. Conclusions: This study provides support for the relationship between APOE ε4 and risk of AD in Latino individuals. It illustrates the role of positron emission tomography as a presymptomatic endophenotype for the assessment of AD risk factors and supports the inclusion of Latino APOE ε4 carriers in proof-of-concept studies using fluorodeoxyglucose PET to evaluate promising presymptomatic treatments in cognitively healthy carriers of this common AD susceptibility gene.",
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T1 - Hypometabolism in Alzheimer-affected brain regions in cognitively healthy latino individuals carrying the apolipoprotein E ε4 allele

AU - Langbaum, Jessica B S

AU - Chen, Kewei

AU - Caselli, Richard J.

AU - Lee, Wendy

AU - Reschke, Cole

AU - Bandy, Daniel

AU - Alexander, Gene E

AU - Burns, Christine M.

AU - Kaszniak, Alfred W

AU - Reeder, Stephanie A.

AU - Corneveaux, Jason J.

AU - Allen, April N.

AU - Pruzin, Jeremy

AU - Huentelman, Matthew J.

AU - Fleisher, Adam S.

AU - Reiman, Eric M.

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N2 - Objective: To investigate with fluorodeoxyglucose positron emission tomography whether regional reductions in the cerebral metabolic rate for glucose (CMRgl) previously found in cognitively healthy latemiddle-aged apolipoprotein E (APOE) ε4 carriers extend to members of the Latino Mexican American community. Design: Prospective cohort study. Setting: Banner Alzheimer's Institute, Phoenix, Arizona. Patients or Other Participants: Eleven APOE ε4 carriers and 16 noncarriers from Arizona's Latino community (mean [SD] age, 54.6 [6.4] years) matched for sex, mean age, and educational level and who were predominantly of self-designated Mexican origin. Main Outcome Measure: A brain mapping algorithm was used to compare cross-sectional regional CMRgl in Latino APOE ε4 carriers vs noncarriers. Results: Participant groups had similar distributions for age, sex, education, family history of dementia, clinical ratings, and neuropsychological test scores. Latino APOE ε4 carriers had lower CMRgl than the noncarriers in the posterior cingulate, precuneus, and parietal regions previously found to be preferentially affected in patients with Alzheimer disease (AD) and cognitively healthy non-Latino APOE ε4 carriers. Additionally, the Latino APOE ε4 carriers had lower CMRgl in the middle and anterior cingulate cortex, hippocampus, and thalamus. Conclusions: This study provides support for the relationship between APOE ε4 and risk of AD in Latino individuals. It illustrates the role of positron emission tomography as a presymptomatic endophenotype for the assessment of AD risk factors and supports the inclusion of Latino APOE ε4 carriers in proof-of-concept studies using fluorodeoxyglucose PET to evaluate promising presymptomatic treatments in cognitively healthy carriers of this common AD susceptibility gene.

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