APOE ϵ4 modifies the relationship between infectious burden and poor cognition

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Cognitive decline is a growing public health concern.
• The apolipoprotein E (APOE) ϵ4 allele is a known risk factor for Alzheimer's disease.
• Infectious agents have been implicated in cognitive impairment.

Purpose of the Study:

• To investigate if the APOE ϵ4 allele modifies the association between infectious burden and cognitive function.
• To explore the role of specific infections, like herpes simplex virus 1 (HSV-1), in this relationship.

Main Methods:

• Assessed infectious burden (IB) using a weighted index (IBI) and serology in a multiethnic cohort (Northern Manhattan Study).
• Evaluated cognition using the Mini-Mental State Examination and a comprehensive neuropsychological battery over approximately 6 years.
• Employed adjusted linear and logistic regressions, including an interaction term for APOE ϵ4 and IBI.

Main Results:

• Significant interactions were observed between IBI and APOE ϵ4 (p=0.07) and between HSV-1 and APOE ϵ4 (p=0.02) for processing speed.
• Higher IBI was linked to slower processing speed in non-APOE ϵ4 carriers, but not in carriers.
• HSV-1 positivity was associated with slower processing speed in non-APOE ϵ4 carriers, but not in carriers.

Conclusions:

• The APOE ϵ4 allele may act as an effect modifier in the relationship between infectious burden, particularly viral infections, and cognitive processing speed.
• Further research is warranted to elucidate the mechanisms underlying this interaction.
• Findings suggest a potential genetic influence on susceptibility to infection-related cognitive decline.