Head circumference and incident Alzheimer's disease: modification by apolipoprotein E

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Alzheimer's disease (AD) clinical expression is linked to exceeding a critical threshold of "brain reserve."
• Head circumference (HC) serves as a proxy for brain reserve.
• The study investigates the association between HC, AD incidence, and APOE epsilon 4 genotype modification.

Purpose of the Study:

• To examine the relationship between head circumference (HC) and the incidence of probable Alzheimer's disease (AD).
• To assess the modifying effect of the APOE epsilon 4 genotype on the HC-AD association.
• To investigate the brain reserve hypothesis in the context of AD onset.

Main Methods:

• A cohort of 1,869 initially nondemented individuals followed for a mean of 3.8 years.
• Identified 59 incident cases of probable AD.
• Used Cox proportional hazard regression to analyze hazard ratios (HR) for HC and APOE epsilon 4, adjusting for covariates like age, education, and gender.

Main Results:

• Individuals with probable AD were older, less educated, shorter, lighter, and more likely to have APOE epsilon 4.
• The lowest tertile of HC showed a non-significant HR of 2.3 (p=0.16) after adjustments.
• APOE epsilon 4 significantly increased AD risk (HR=4.8, p=0.002).
• The combination of low HC and APOE epsilon 4 strongly predicted earlier AD onset (HR=14.1, p=0.0007).

Conclusions:

• Smaller head circumference (HC), particularly with the APOE epsilon 4 allele, accelerates the age of Alzheimer's disease (AD) onset.
• Findings support the brain reserve hypothesis, highlighting its role in AD manifestation.
• Genetic predisposition (APOE epsilon 4) interacts with brain reserve (HC) to influence clinical AD expression.