Neuropsychological measures in normal individuals that predict subsequent cognitive decline.
OBJECTIVE
To examine neuropsychological measures among normal individuals that predict time to subsequent cognitive decline.


METHODS
Cognitive performance, as measured by 6 neuropsychological tests, was examined at baseline. Participants were followed up for approximately 5 years. Cox proportional hazards models were used to evaluate the neuropsychological measures at baseline that predicted time to progression from normal cognition to mild impairment. Comparable data also examined time to progression from mild impairment to a diagnosis of Alzheimer disease.


METHODS
Community volunteer-based sample examined at a medical institution.


METHODS
One hundred and seven individuals who were cognitively normal and 235 individuals with mild cognitive impairment at baseline.


METHODS
Time to progression from normal cognition to mild impairment and time to progression from mild impairment to a diagnosis of Alzheimer disease.


RESULTS
The risk of progressing from normal to mild impairment was considerably greater among those with lower scores on tests of episodic memory (eg, hazard ratio for a 1-SD decrease in the California Verbal Learning Test, 0.55; P<.001). Normal individuals who carried at least 1 copy of the apolipoprotein E epsilon2 allele were less likely to develop cognitive impairments over time than individuals with no epsilon2 allele (hazard ratio for presence of allele, 0.13; P = .006). Measures of both episodic memory and executive function were significant predictors of time to progression from mild impairment to a clinical diagnosis of Alzheimer disease (eg, hazard ratio for a 1-SD decrease in California Verbal Learning Test score, 0.67; P = .005; hazard ratio for a 1-SD increase in the time to complete part B of the Trail Making test, 1.40; P = .007). Among individuals with mild impairments, the apolipoprotein E epsilon4 allele increased risk for Alzheimer disease in a dose-dependent manner; however, this effect was not significant within the context of multivariable models.


CONCLUSIONS
Episodic memory performance among normal individuals predicts time to progression to mild impairment while apolipoprotein E epsilon2 status is associated with lower risk of cognitive decline among normal individuals. Tests of both episodic memory and executive function are predictors of time to progression from mild impairment to a clinical diagnosis of Alzheimer disease.
Blacker
Deborah
D
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Lee
Hang
H
Muzikansky
Alona
A
Martin
Emily C
EC
Tanzi
Rudolph
R
McArdle
John J
JJ
Moss
Mark
M
Albert
Marilyn
M
D000368:Aged; D000483:Alleles; D053329:Apolipoprotein E2 / Q000097:blood; D053327:Apolipoprotein E4 / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D018628:Gene Dosage; D006579:Heterozygote; D006801:Humans; D008297:Male; D011939:Mental Recall; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012016:Reference Values; D018570:Risk Assessment; D013997:Time Factors
D053329:Apolipoprotein E2; D053327:Apolipoprotein E4