Pattern and progression of cognitive decline in Alzheimer's disease: role of premorbid intelligence and ApoE genotype.
OBJECTIVE
Because of controversial results across studies, we evaluated the predictive value of premorbid intelligence and the apolipoprotein E (ApoE) genotype on baseline and progression of cognitive performance in Alzheimer's disease (AD).


METHODS
Eighty-five mild AD cases, ApoE genotyped and included in a longitudinal cliniconeuropsychological-genetic study, underwent a premorbid intelligence test and up to 11 (average 5) neuropsychological assessments. We applied linear- and logistic-regression models for cross-sectional data and mixed models for longitudinal ones.


RESULTS
Higher premorbid intelligence was associated with higher global, executive and memory performance, while the ApoE epsilon 4 allele was specifically related to poorer memory performance. The premorbid intelligence-ApoE epsilon 4/epsilon 4 interaction was significant, with higher premorbid intelligence scores reducing the detrimental effect of ApoE epsilon 4 homozygosity on memory performance. Higher premorbid intelligence, but not the ApoE epsilon 4 allele, was related to faster memory deficit progression.


CONCLUSIONS
The association of higher premorbid intelligence with better baseline cognitive performance and faster memory decline, as well as its interaction with the ApoE genotype, strengthens the role of cognitive reserve in shaping the disease's clinical expression. Our findings confirm that the epsilon 4 allele affects memory deficit at baseline but does not exert any influence on the rate of cognitive decline.
Bracco
Laura
L
Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy. bracco@unifi.it
Piccini
Carolina
C
Baccini
Michela
M
Bessi
Valentina
V
Biancucci
Federica
F
Nacmias
Benedetta
B
Bagnoli
Silvia
S
Sorbi
Sandro
S
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007360:Intelligence; D008297:Male; D009483:Neuropsychological Tests; D012720:Severity of Illness Index
D053327:Apolipoprotein E4