The Apolipoprotein E ϵ4 Allele and Decline in Different Cognitive Systems During a 6-Year Period

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Abstract
POSSESSION OF 1 or more copies of the apolipoprotein E (APOE) ϵ4 allele is associated with an increased risk of Alzheimer disease (AD)1,2 but the mechanism underlying this association is unclear. Since a defining feature of AD is progressive loss of episodic memory, several researchers have hypothesized that the ϵ4 allele is selectively associated with episodic memory decline in older persons.3-5 Support for this hypothesis has been mixed, however. The ϵ4 allele has been associated with episodic memory impairment in some cross-sectional studies3,6,7 and with more global cognitive impairment in others.8-10 Although several longitudinal studies have examined the relationship of the ϵ4 allele to cognitive decline,4,11-20 few have assessed multiple cognitive systems4,13,14,17-19 and most of these have been based on only 2 observations during periods of 3 years or less and have conducted analyses on individual tests, which are subject to floor and ceiling effects. In addition, no previous longitudinal study has directly tested whether the association of ϵ4 with change in measures of episodic memory differs from its association with change in other cognitive measures.