APOE and mild cognitive impairment: the Framingham Heart Study

Area of Science:

• Neuroscience
• Genetics
• Gerontology

Background:

• The apolipoprotein E-4 (APOE4) genotype is a known risk factor for cognitive decline.
• The association between APOE4 and mild cognitive impairment (MCI) may differ based on diagnostic criteria.
• Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia.

Purpose of the Study:

• To investigate the association between APOE4 and prevalent amnestic MCI.
• To examine how different neuropsychological definitions of MCI affect the APOE4 association.
• To explore age-related differences in the APOE4 risk for MCI.

Main Methods:

• A community-based cohort study of 2,239 participants from the Framingham Offspring Cohort.
• APOE genotyping, clinical, and neuropsychological assessments were performed.
• Amnestic MCI was defined using two criteria: age/education adjustment and age/Wide Range Achievement Test-3 Reading (WRAT-3 Reading) adjustment.

Main Results:

• APOE4 was significantly associated with amnestic MCI when defined by age and WRAT-3 Reading (OR=1.7, P=0.002).
• No significant association was found using the age and education definition (OR=1.0, P=0.90).
• In participants aged 65 and older, APOE4 was associated with amnestic MCI by both definitions (ORs 2.4 and 1.7, P<0.001 and P=0.04, respectively).

Conclusions:

• The risk of APOE4 for prevalent amnestic MCI is definition-dependent.
• The association is more pronounced in older adults (≥65 years).
• Findings highlight the need for refined neuropsychological assessment methods for MCI.