The apolipoprotein e genotype predicts longitudinal transitions to mild cognitive impairment but not to alzheimer's dementia: Findings from a nationally representative study

C. J. Brainerd, V. F. Reyna, Ronald Carl Petersen, G. E. Smith, A. E. Kenney, C. J. Gross, E. S. Taub, B. L. Plassman, G. G. Fisher

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Objective: The ε4 allele of the apolipoprotein E (APOE) genotype is the most widely accepted genetic risk factor for Alzheimer's dementia (AD), but findings on whether it is a risk factor for the AD prodrome, mild cognitive impairment (MCI), have been inconsistent. In a prospective longitudinal design, we investigated (a) whether transitions to MCI and other forms of neurocognitive impairment without dementia (CIND) are more frequent among normal ε4 carriers than among noncarriers and (b) whether subsequent transitions to AD from MCI and from other forms of CIND are more frequent among ε4 carriers than among noncarriers. Method: The frequency of the ε4 allele was studied in older adults (mean age 70), who had participated in two or more waves of neuropsychological testing and diagnosis in the Aging, Demographics, and Memory Study (ADAMS) of the United States Department of Health and Human Services, National Institutes of Health, National Institute on Aging's Health and Retirement Study, conducted by the University of Michigan. The association between ε4 and longitudinal transitions to specific types of CIND and dementia can be determined with this data set. Results: Epsilon 4 increased the rate of progression from normal functioning to MCI (58% of new diagnoses were carriers) but not to other forms of CIND. The rate of progression to AD from MCI or from other forms of CIND was not increased by ε4. Conclusions: The results support the hypothesis that ε4 is a risk factor for transitions from normal functioning to MCI but not for subsequent transitions to AD. In the ADAMS sample, the reason ε4 is elevated in AD individuals is because it is already elevated in MCI individuals, who are the primary source of new AD diagnoses.

Original languageEnglish (US)
Pages (from-to)86-94
Number of pages9
JournalNeuropsychology
Volume27
Issue number1
DOIs
StatePublished - 2013

Fingerprint

Apolipoproteins
Alzheimer Disease
Genotype
Population Dynamics
Dementia
National Institute on Aging (U.S.)
United States Dept. of Health and Human Services
Apolipoprotein E4
Retirement
National Institutes of Health (U.S.)
Cognitive Dysfunction
Alzheimer
Mild Cognitive Impairment
Gene Frequency
Alleles
Health

Keywords

  • Alzheimer's dementia
  • APOE genotype
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Arts and Humanities (miscellaneous)

Cite this

The apolipoprotein e genotype predicts longitudinal transitions to mild cognitive impairment but not to alzheimer's dementia : Findings from a nationally representative study. / Brainerd, C. J.; Reyna, V. F.; Petersen, Ronald Carl; Smith, G. E.; Kenney, A. E.; Gross, C. J.; Taub, E. S.; Plassman, B. L.; Fisher, G. G.

In: Neuropsychology, Vol. 27, No. 1, 2013, p. 86-94.

Research output: Contribution to journalArticle

Brainerd, C. J. ; Reyna, V. F. ; Petersen, Ronald Carl ; Smith, G. E. ; Kenney, A. E. ; Gross, C. J. ; Taub, E. S. ; Plassman, B. L. ; Fisher, G. G. / The apolipoprotein e genotype predicts longitudinal transitions to mild cognitive impairment but not to alzheimer's dementia : Findings from a nationally representative study. In: Neuropsychology. 2013 ; Vol. 27, No. 1. pp. 86-94.
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abstract = "Objective: The ε4 allele of the apolipoprotein E (APOE) genotype is the most widely accepted genetic risk factor for Alzheimer's dementia (AD), but findings on whether it is a risk factor for the AD prodrome, mild cognitive impairment (MCI), have been inconsistent. In a prospective longitudinal design, we investigated (a) whether transitions to MCI and other forms of neurocognitive impairment without dementia (CIND) are more frequent among normal ε4 carriers than among noncarriers and (b) whether subsequent transitions to AD from MCI and from other forms of CIND are more frequent among ε4 carriers than among noncarriers. Method: The frequency of the ε4 allele was studied in older adults (mean age 70), who had participated in two or more waves of neuropsychological testing and diagnosis in the Aging, Demographics, and Memory Study (ADAMS) of the United States Department of Health and Human Services, National Institutes of Health, National Institute on Aging's Health and Retirement Study, conducted by the University of Michigan. The association between ε4 and longitudinal transitions to specific types of CIND and dementia can be determined with this data set. Results: Epsilon 4 increased the rate of progression from normal functioning to MCI (58{\%} of new diagnoses were carriers) but not to other forms of CIND. The rate of progression to AD from MCI or from other forms of CIND was not increased by ε4. Conclusions: The results support the hypothesis that ε4 is a risk factor for transitions from normal functioning to MCI but not for subsequent transitions to AD. In the ADAMS sample, the reason ε4 is elevated in AD individuals is because it is already elevated in MCI individuals, who are the primary source of new AD diagnoses.",
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T1 - The apolipoprotein e genotype predicts longitudinal transitions to mild cognitive impairment but not to alzheimer's dementia

T2 - Findings from a nationally representative study

AU - Brainerd, C. J.

AU - Reyna, V. F.

AU - Petersen, Ronald Carl

AU - Smith, G. E.

AU - Kenney, A. E.

AU - Gross, C. J.

AU - Taub, E. S.

AU - Plassman, B. L.

AU - Fisher, G. G.

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N2 - Objective: The ε4 allele of the apolipoprotein E (APOE) genotype is the most widely accepted genetic risk factor for Alzheimer's dementia (AD), but findings on whether it is a risk factor for the AD prodrome, mild cognitive impairment (MCI), have been inconsistent. In a prospective longitudinal design, we investigated (a) whether transitions to MCI and other forms of neurocognitive impairment without dementia (CIND) are more frequent among normal ε4 carriers than among noncarriers and (b) whether subsequent transitions to AD from MCI and from other forms of CIND are more frequent among ε4 carriers than among noncarriers. Method: The frequency of the ε4 allele was studied in older adults (mean age 70), who had participated in two or more waves of neuropsychological testing and diagnosis in the Aging, Demographics, and Memory Study (ADAMS) of the United States Department of Health and Human Services, National Institutes of Health, National Institute on Aging's Health and Retirement Study, conducted by the University of Michigan. The association between ε4 and longitudinal transitions to specific types of CIND and dementia can be determined with this data set. Results: Epsilon 4 increased the rate of progression from normal functioning to MCI (58% of new diagnoses were carriers) but not to other forms of CIND. The rate of progression to AD from MCI or from other forms of CIND was not increased by ε4. Conclusions: The results support the hypothesis that ε4 is a risk factor for transitions from normal functioning to MCI but not for subsequent transitions to AD. In the ADAMS sample, the reason ε4 is elevated in AD individuals is because it is already elevated in MCI individuals, who are the primary source of new AD diagnoses.

AB - Objective: The ε4 allele of the apolipoprotein E (APOE) genotype is the most widely accepted genetic risk factor for Alzheimer's dementia (AD), but findings on whether it is a risk factor for the AD prodrome, mild cognitive impairment (MCI), have been inconsistent. In a prospective longitudinal design, we investigated (a) whether transitions to MCI and other forms of neurocognitive impairment without dementia (CIND) are more frequent among normal ε4 carriers than among noncarriers and (b) whether subsequent transitions to AD from MCI and from other forms of CIND are more frequent among ε4 carriers than among noncarriers. Method: The frequency of the ε4 allele was studied in older adults (mean age 70), who had participated in two or more waves of neuropsychological testing and diagnosis in the Aging, Demographics, and Memory Study (ADAMS) of the United States Department of Health and Human Services, National Institutes of Health, National Institute on Aging's Health and Retirement Study, conducted by the University of Michigan. The association between ε4 and longitudinal transitions to specific types of CIND and dementia can be determined with this data set. Results: Epsilon 4 increased the rate of progression from normal functioning to MCI (58% of new diagnoses were carriers) but not to other forms of CIND. The rate of progression to AD from MCI or from other forms of CIND was not increased by ε4. Conclusions: The results support the hypothesis that ε4 is a risk factor for transitions from normal functioning to MCI but not for subsequent transitions to AD. In the ADAMS sample, the reason ε4 is elevated in AD individuals is because it is already elevated in MCI individuals, who are the primary source of new AD diagnoses.

KW - Alzheimer's dementia

KW - APOE genotype

KW - Mild cognitive impairment

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