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Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease

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APOE genotype and cognitive functioning in a large age-stratified population sample.

Anthony F Jorm¹, Karen A Mather, Peter Butterworth

¹ORYGEN Research Centre, University of Melbourne, Parkville, VIC, Australia. ajorm@unimelb.edu.au

Neuropsychology

|January 5, 2007

Summary

The apolipoprotein E (APOE) *E4 allele does not appear to affect cognitive functions early in life. Cognitive decline observed between ages 20-64 is not linked to preclinical Alzheimer's disease.

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Area of Science:

Neuroscience
Genetics
Cognitive Psychology

Background:

Alzheimer's disease (AD) cognitive symptoms can manifest decades before diagnosis.
The apolipoprotein E (APOE) *E4 allele is a known genetic risk factor for late-onset AD.
Early-life cognitive effects of APOE *E4 are hypothesized but not well-established.

Purpose of the Study:

To investigate the association between the APOE *E4 allele and cognitive functioning across different adult age groups.
To determine if APOE *E4 influences cognitive performance in early to mid-adulthood.
To assess if preclinical AD-related cognitive changes are detectable via APOE *E4 status.

Main Methods:

Analysis of cognitive test data from a large Caucasian population sample (N=6,560).
Inclusion of participants across three age strata: 20-24, 40-44, and 60-64 years.
Assessment of episodic memory, working memory, mental speed, reaction time, and vocabulary, stratified by APOE *E4 genotype.

Main Results:

Cognitive performance, excluding vocabulary, declined significantly with increasing age across all groups.
No statistically significant effect of the APOE *E4 allele on any cognitive measure was found at any age.
The APOE *E4 genotype did not differentiate cognitive performance in young, middle-aged, or older adults.

Conclusions:

The APOE *E4 allele does not exert a detectable influence on core cognitive functions from early adulthood through older age.
Observed cognitive aging between ages 20 and 64 is unlikely to be a manifestation of preclinical Alzheimer's disease.
Future research should explore other genetic or environmental factors contributing to cognitive aging and AD risk.