Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study

Area of Science:

• Neuroscience
• Genetics
• Cognitive Psychology

Background:

• Previous cross-sectional study indicated steeper age-related memory decline in apolipoprotein E (apoE)-e4/4 homozygotes.
• Initial findings were limited by statistical issues of multiple comparisons.
• Replication in a new cohort was necessary to validate these preliminary results.

Purpose of the Study:

• To replicate and validate findings on age-related cognitive decline in asymptomatic individuals based on apolipoprotein E (apoE) genotype.
• To investigate memory performance differences between apoE-e4/4 homozygotes, e3/4 heterozygotes, and e4 noncarriers.

Main Methods:

• Recruited 80 asymptomatic participants (1998-2000) matched for age, gender, and education.
• Groups included 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers.
• Administered a battery of neuropsychological tests, including Wechsler adult intelligence scale-revised (WAIS-R) digit span and complex figure test.

Main Results:

• Complex figure test recall was lower in e3/4 heterozygotes compared to noncarriers; no significant difference was found for e4/4 homozygotes.
• Wechsler adult intelligence scale-revised (WAIS-R) digit span showed a significant negative correlation with age in apoE-e4/4 homozygotes relative to e4 noncarriers (p=0.008).
• This negative correlation between WAIS-R digit span and age in apoE-e4/4 homozygotes was consistent across two independent cohorts.

Conclusions:

• A significant age-related decline in Wechsler adult intelligence scale-revised (WAIS-R) digit span was observed in apolipoprotein E (apoE)-e4/4 homozygotes compared to e4 noncarriers.
• These findings suggest a potential age-related effect on frontal lobe function specifically in the apoE-e4/4 genetic subgroup.
• The replication strengthens the evidence for an association between the apoE ε4 allele and cognitive aging patterns.