Is the apolipoprotein e genotype a biomarker for mild cognitive impairment? Findings from a nationally representative study.

TitleIs the apolipoprotein e genotype a biomarker for mild cognitive impairment? Findings from a nationally representative study.
Publication TypeJournal Article
Year of Publication2011
AuthorsBrainerd, CJ, Reyna, VF, Petersen, RC, Smith, GE, Taub, ES
Date Published2011 Nov
ISSN Number1931-1559
KeywordsAged, Aged, 80 and over, Aging, Analysis of Variance, Apolipoprotein E4, Cognitive Dysfunction, Dementia, Female, Gene Frequency, Genetic Markers, Genetic Testing, Genotype, Humans, Male, National Institute on Aging (U.S.), Neuropsychological tests, Reference Values, Reproducibility of Results, Risk Factors, United States

OBJECTIVE: Although the ε4 allele of the apolipoprotein E (APOE) genotype is a known risk factor for Alzheimer's dementia (AD), prior findings on whether it is also a risk factor for mild cognitive impairment (MCI) have been inconsistent. We tested two contrasting explanations: (a) an ε4-AD specificity hypothesis, and (b) a measurement insensitivity hypothesis.

METHOD: The frequency of the ε4 allele was investigated in older adults (mean age > 70) with various types of cognitive impairment (including MCI) and various types of dementia (including AD) with the aging, demographics, and memory study (ADAMS) of the National Institute on Aging's Health and Retirement Study (HRS). The ADAMS controls sources of Type I and Type II error that are posited in the ε4-AD specificity hypothesis and the measurement insensitivity hypothesis, and it is the only nationally representative data set on aging and cognitive impairment.

RESULTS: ε4 was a reliable predictor of MCI, with a frequency of 32% in MCI subjects versus 20% in healthy control subjects. This link was specific to MCI because ε4 was not a risk factor for other forms of cognitive impairment without dementia.

CONCLUSIONS: The results support the measurement insensitivity hypothesis rather than the ε4-AD specificity hypothesis and are consistent with recent research showing modest reductions in cognitive performance among normal functioning ε4 carriers.


Brainerd, Charles J Reyna, Valerie F Petersen, Ronald C Smith, Glenn E Taub, Emily S 1RC1AG036915-01/AG/NIA NIH HHS/United States U01AG009740/AG/NIA NIH HHS/United States Research Support, N.I.H., Extramural United States Neuropsychology. 2011 Nov;25(6):679-89.

User Guide Notes

Endnote Keywords

Aging/Analysis of Variance/Apolipoprotein E4/genetics/genetics/Dementia/Gene Frequency/Genetic Markers/Genetic Testing/Genotype/Mild Cognitive Impairment/Neuropsychological Tests/Reference Values/Reproducibility of Results/Risk Factors/Alzheimer disease/epsilon4 allele

Endnote ID


Alternate JournalNeuropsychology
Citation Key7671
PubMed ID21728427
Grant List1RC1AG036915-01 / AG / NIA NIH HHS / United States
U01AG009740 / AG / NIA NIH HHS / United States