Brain Drain: Common Infections Linked to Cognitive Decline Neuroscience News

Summary: Common infections, including the chickenpox virus and herpes simplex virus type 1, can worsen cognitive performance and increase the risk of developing Alzheimer’s disease in middle-aged and older adults, a new study reports. The findings add to the growing body of evidence linking common infections to poor brain health associated with aging.

Source: Johns Hopkins medicine

A new study by a team led by researchers at the Johns Hopkins Bloomberg School of Public Health found that signs of common infections in a sample of middle-aged and older adults were associated with lower performance on a test of global cognitive function.

The findings add to a growing body of evidence suggesting that infections in middle and later life can worsen cognitive performance and may increase the risk of Alzheimer’s disease and other dementias.

For their analysis, the researchers looked at the levels of antibodies against five common pathogens in 575 adults, aged 41 to 97 years. The adults were recruited from East Baltimore in 1981, as part of the Epidemiologic Catchment Area Study initiated that year by the National Institute of Mental Health Participants in the Baltimore study donated blood for testing and took cognitive tests during the same study period.

Antibody tests were conducted for pathogens, including four herpes viruses, herpes simplex virus type 1, cytomegalovirus, varicella and shingles viruses, Epstein-Barr virus, and the parasiteToxoplasma gondii. The latter is often spread to humans from cat feces or the consumption of undercooked meat.

The research team compared the participants’ blood test results with their performance on the Mini-Mental State Examination, a comprehensive cognitive test that assesses things like orientation, attention, verbal comprehension, memory and perception. vision and on a word recall task, which tested memory for a list of words after a 20-minute delay.

The researchers found that elevated antibodies to either herpes simplex virus type 1 or cytomegalovirus were individually associated with worse performance on the global cognitive test. Additionally, participants with a greater number of positive antibody tests tended to miss a greater number of items on the global cognition test.

The study was published online April 7 in the journalAlzheimer’s and dementia.

The idea that common infections may contribute to cognitive decline and possibly Alzheimer’s disease risk was once fringed and remains controversial, but because of findings like these in this study, it’s starting to receive more public attention. says senior author Adam Spira, PhD. , a professor in the Bloomberg Schools Department of Mental Health and a core faculty member of the Johns Hopkins Center on Aging and Health.

After accounting for participants’ age, gender, race, and largest genetic risk factor for Alzheimer’s disease, our study data showed that more positive antibody tests related to five different infections were associated with lower cognitive performance. To our knowledge, this type of additive effect of multiple infections on performance on a cognitive test has not been demonstrated before.

The cause of Alzheimer’s disease remains unclear. Previous research has established the link to infections, including studies linking herpes simplex virus type 1 and cytomegalovirus to increased risk of Alzheimer’s. There is also evidence that the amyloid-beta protein fragment, which forms insoluble plaques in the brains of people with Alzheimer’s, functions as an antimicrobial peptide and is secreted at higher levels by brain cells in response to infection.

Since the 2003-2004 wave, ECA study researchers at Johns Hopkins have conducted periodic follow-up interviews in Baltimore, including standard cognitive tests and blood sampling. The most recent two waves of the study, funded by the National Institute on Aging, focused on Alzheimer’s disease and related findings.

Pathogens evaluated in the study are often encountered in childhood and are shed or transformed into latent, suppressed infections. Therefore, the researchers considered significant levels of antibodies against them in middle-aged and elderly study participants as likely indicators of their reactivation due to weakening of the immune system with age.

The first author of the studies, Alexandra Wennberg, PhD, who completed her doctoral training in the Spiras research group, is currently a postdoctoral researcher at Swedens Karolinska Institutet. Co-authors include faculty at the Johns Hopkins School of Medicine and collaborating scientists at the National Institute of Intramural Aging Research Program.

Coauthor Brion Maher, PhD, a geneticist and professor in the Bloomberg Schools Department of Mental Health, also analyzed the results for participants who had a common risk factor for Alzheimer’s disease, apolipoprotein-E gene variant 4. (ApoE). The link between positive antibody counts and cognition was present in both the 4 and non-4 groups, but was stronger in the non-4 group.

It was a surprise to find a weakest link in Group 4, says Maher. It is something that should be followed up by larger studies.

Spira, Maher, and their team, with funding from the National Institute on Aging, are following up on analyzes of data from the Baltimore ECA from 2016 to 2022. The researchers will also collect another round of data from this cohort.

Association of Common Infections with Cognitive Performance in the Baltimore Epidemiologic Catchment Area Study Follow-Up was co-authored by Alexandra Wennberg, Brion Maher, Jill Rabinowitz, Calliope Holingue, Ross Felder, Jonathan Wells, Cynthia Munro, Constantine Lyketsos, William Eaton, Keenan Walker, Nan-ping Weng, Luigi Ferrucci, Robert Yolken and Adam P. Spira.

Funding was provided by the National Institute on Aging (R01AG075996, U01AG052445), the National Institute of Mental Health (MH 47447), and the Stanley Medical Research Institute.

Author Disclosure: Wennberg is compensated by Janssen Pharmaceutica NV for a separate collaboration. Spira has received a fee for serving as a consultant for Merck and has received a fee from Springer Nature Switzerland AG for guest editing special issues ofCurrent reports on sleep medicine.

About this neurological research news

Author: Kristine Henry
Source: Johns Hopkins medicine
Contact: Kristine Henry Johns Hopkins Medicine
Image: Image is public domain

Original research: Free access.
Association of common infections with cognitive performance in the follow-up Baltimore Epidemiological Catchment Study by Adam Spira et al. Alzheimer’s and dementia

Abstract

Association of common infections with cognitive performance in the follow-up of the Baltimore Epidemiological Catchment Study

introduction

Mounting evidence suggests that some common infections are causally associated with cognitive impairment; however, less is known about the burden of multiple infections.

Methods

We investigated the cross-sectional association of positive antibody tests for herpes simplex virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) andToxoplasma gondii(TOX) with Mini-Mental State Examination (MMSE) and verbal recall delayed performance in 575 adults aged 4197 years from the Baltimore Epidemiologic Catchment Area Study.

Results

In multivariate-adjusted zero-inflated poisson (ZIP) regression models, positive antibody tests for CMV (P=.011) and herpes simplex virus (P=.018) were individually associated with lower MMSE performance (P=.011). A higher number of positive antibody tests among the five tested was associated with worse MMSE performance (P=.001).

Discussion

CMV, herpes simplex virus, and global burden of multiple common infections were independently associated with lower cognitive performance. Further research investigating whether global infection burden predicts cognitive decline and changes in Alzheimer’s disease biomarkers is needed to confirm these findings.