@article {8605, title = {The apolipoprotein E genotype predicts longitudinal transitions to mild cognitive impairment but not to Alzheimer{\textquoteright}s dementia: findings from a nationally representative study.}, journal = {Neuropsychology}, volume = {27}, year = {2013}, month = {2013 Jan}, pages = {86-94}, abstract = {

OBJECTIVE: The ε4 allele of the apolipoprotein E (APOE) genotype is the most widely accepted genetic risk factor for Alzheimer{\textquoteright}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{\textquoteright}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.

}, keywords = {Aged, Aged, 80 and over, Alzheimer disease, Apolipoproteins E, Cognitive Dysfunction, disease progression, Female, Genetic Predisposition to Disease, Genetic Testing, Genotype, Humans, Logistic Models, Longitudinal Studies, Male, National Institutes of Health (U.S.), Neuropsychological tests, Risk Factors, United States}, issn = {1931-1559}, doi = {10.1037/a0030855}, url = {http://psycnet.apa.org/journals/neu/27/1/86/}, author = {Brainerd, C. J. and V. F. Reyna and Ronald C Petersen and Glenn E Smith and Kenney, A. E. and C. J. Gross and Taub, E. S. and Brenda L Plassman and Gwenith G Fisher} } @article {7671, title = {Is the apolipoprotein e genotype a biomarker for mild cognitive impairment? Findings from a nationally representative study.}, journal = {Neuropsychology}, volume = {25}, year = {2011}, note = {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.}, month = {2011 Nov}, pages = {679-89}, publisher = {25}, abstract = {

OBJECTIVE: Although the ε4 allele of the apolipoprotein E (APOE) genotype is a known risk factor for Alzheimer{\textquoteright}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{\textquoteright}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.

}, keywords = {Aged, 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}, issn = {1931-1559}, doi = {10.1037/a0024483}, author = {Brainerd, Charles J and V. F. Reyna and Ronald C Petersen and Glenn E Smith and Taub, Emily S} }