Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele.
OBJECTIVE
To determine whether memory loss is detectable before the symptomatic presentation of mild cognitive impairment (MCI) in those at greater genetic risk for Alzheimer disease (AD) based upon presence or absence of the e4 allele of APOE.


METHODS
Participants were age 50 years or older who responded to newspaper advertisements. A total of 212 cognitively normal individuals of known APOE genotype were initially enrolled in a match paradigm that included e4 homozygotes, e3/4 heterozygotes, and e4 noncarriers in a 1:1:2 ratio (53 sets). Of the original 212 individually matched participants, 180 completed at least two epochs of testing including 45 APOE e4/4 homozygotes, 42 APOE e3/4 heterozygotes, and 93 APOE e4 noncarriers, mean age 60 (+/-6.2) years. Of these, four developed MCI or AD during the follow-up period and were excluded from analysis. Longitudinal neuropsychological study included two verbal (Auditory Verbal Learning Test [AVLT], Selective Reminding Test [SRT]) and two visual (Complex Figure Test [CFT], Visual Retention Test) memory tests.


RESULTS
Multiple measures on both verbal memory tests showed poorer performance over a mean interval of 33 months in e4 carriers than noncarriers: AVLT total learning, long term delayed recall; SRT free and cued recall. Among those age 50 to 59 years, AVLT long term delayed recall, SRT free and cued recall, and CFT recall declined more in APOE e4 carriers. No differences were found in the domains of language, spatial skills, or executive function.


CONCLUSIONS
Memory declined in APOE e4 carriers before the symptomatic presentation of MCI in a cohort whose mean age was 60 years over a median period of 33 months. The decline began prior to age 60.
Caselli
R J
RJ
Department of Neurology, Mayo Clinic Scottsdale, Scottsdale, AZ 85259, USA. Caselli.Richard@Mayo.edu
Reiman
E M
EM
Osborne
D
D
Hentz
J G
JG
Baxter
L C
LC
Hernandez
J L
JL
Alexander
G G
GG
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D001130:Arizona / Q000453:epidemiology; D015982:Bias; D003071:Cognition; D015331:Cohort Studies; D003863:Depression / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007807:Language Tests; D008137:Longitudinal Studies; D008297:Male; D008569:Memory Disorders / Q000453:epidemiology / Q000235:genetics; D011939:Mental Recall; D008875:Middle Aged; D009483:Neuropsychological Tests
D053327:Apolipoprotein E4; D001057:Apolipoproteins E