Positive Antibody Tests for Common Infections Associated With Reduced Cognition in Older Adults

A greater number of positive antibody tests for common infections—cytomegalovirus (CMV), herpes simplex virus (HSV-1), Toxoplasma gondii (TOX), varicella zoster virus (VZV), and Epstein-Barr virus (EBV)—is associated with worse cognitive performance in older adults, a recent study published in Alzheimer’s & Dementia found.

No evidence was found of effect modification by sex, age, or race. However, there was a potential interaction by APOE ε4 genotype, with a stronger association between a higher number of infections and worse Modified Mini-Mental State Examination (MMSE) performance among ε4 non-carriers than among carriers.

“To our knowledge, APOE ε4 status has not previously been explored as an effect modifier in the association between infections other than HSV-1 (e.g., CMV, EBV, VZV, TOX) and cognitive outcomes. Thus, the findings in this study are novel,” lead author Alexandra Wennberg, postdoctoral researcher, Karolinska Institutet, Stockholm, and co-authors said in the study. 

This cohort study utilized data from the Baltimore site of the Epidemiologic Catchment Area (ECA) comprising of 1071 participants enrolled in the ECA study in 1981 in East Baltimore. Researchers conducted 4 follow-up assessments, with this analysis using data from Wave 4, which included cognitive test data and infection measurements.

Of the 1071 total participants, 888 agreed to donate blood or buccal samples for infection measurement. Antibodies to 5 common infections (CMV, HSV-1, EBV, VZV, and TOX) were measured in the collected samples. The presence of antibodies indicates past infection, and the levels of antibodies reflect the antigenic load.

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Cognitive performance was assessed using the MMSE and a word-list learning and memory task. Positive antibody tests for CMV and HSV-1 were associated with more errors on the MMSE and lower scores on the delayed recall test, indicating worse cognitive performance.

Most participants had positive antibodies for EBV (79.3%), followed by VZV (70.2%), HSV-1 (68.5%), CMV (67.5%), and TOX (24.7%), the study found. The number of positive antibody tests differed by sex, race, age, and educational attainment, with a greater proportion of women, non-White participants, older individuals, and those with lower education having a higher number of positive tests.

“Additional research that investigates whether the global burden of infection predicts cognitive decline and Alzheimer disease biomarker changes is needed to confirm these findings,” researchers concluded. More specifically, how “larger samples of how APOE may act as an effect modifier in the association between infection and cognition, perhaps based on the number of viruses present” could prove advantageous for clinicians treating this population.

Reference

Wennberg AM, Maher BS, Rabinowitz JA, et al. Association of common infections with cognitive performance in the Baltimore Epidemiologic Catchment Area study follow-up [published online ahead of print, 2023 Apr 7]. Alzheimers Dement. 2023;10.1002/alz.13070. doi:10.1002/alz.13070