Association of Toxoplasma gondii Seropositivity With Cognitive Function in Healthy People: A Systematic Review and Meta-analysis

Abstract

Importance: The parasite Toxoplasma gondii has been associated with behavioral alterations and psychiatric disorders. Studies investigating neurocognition in people with T gondii infection have reported varying results. To systematically analyze these findings, a meta-analysis evaluating cognitive function in healthy people with and without T gondii seropositivity is needed.

Objective: To assess whether and to what extent T gondii seropositivity is associated with cognitive function in otherwise healthy people.

Data sources: A systematic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. A systematic search of PubMed, MEDLINE, Web of Science, PsycInfo, and Embase was performed to identify studies from database inception to June 7, 2019, that analyzed cognitive function among healthy participants with available data on T gondii seropositivity. Search terms included toxoplasmosis, neurotoxoplasmosis, Toxoplasma gondii, cognition disorder, neuropsychological, and psychomotor performance.

Study selection: Studies that performed cognitive assessment and analyzed T gondii seroprevalence among otherwise healthy participants were included.

Data extraction and synthesis: Two researchers independently extracted data from published articles; if needed, authors were contacted to provide additional data. Quantitative syntheses were performed in predefined cognitive domains when 4 independent data sets per domain were available. Study quality, heterogeneity, and publication bias were assessed.

Main outcomes and measures: Performance on neuropsychological tests measuring cognitive function.

Results: The systematic search yielded 1954 records. After removal of 533 duplicates, an additional 1363 records were excluded based on a review of titles and abstracts. A total of 58 full-text articles were assessed for eligibility (including reference list screening); 45 articles were excluded because they lacked important data or did not meet study inclusion or reference list criteria. The remaining 13 studies comprising 13 289 healthy participants (mean [SD] age, 46.7 [16.0] years; 6586 men [49.6%]) with and without T gondii seropositivity were included in the meta-analysis. Participants without T gondii seropositivity had favorable functioning in 4 cognitive domains: processing speed (standardized mean difference [SMD], 0.12; 95% CI, 0.05-0.19; P = .001), working memory (SMD, 0.16; 95% CI, 0.06-0.26; P = .002), short-term verbal memory (SMD, 0.18; 95% CI, 0.09-0.27; P < .001), and executive functioning (SMD, 0.15; 95% CI, 0.01-0.28; P = .03). A meta-regression analysis found a significant association between older age and executive functioning (Q = 6.17; P = .01). Little suggestion of publication bias was detected.

Conclusions and relevance: The study's findings suggested that T gondii seropositivity was associated with mild cognitive impairment in several cognitive domains. Although effect sizes were small, given the ubiquitous prevalence of this infection globally, the association with cognitive impairment could imply a considerable adverse effect at the population level. Further research is warranted to investigate the underlying mechanisms of this association.

Figure 1.. Flow Diagram of Study Selection Process

Partial data from the unpublished study were published as a conference abstract in a journal supplement. The authors provided additional (raw) data and written permission to use these data in the meta-analysis (D. Cobia, PhD, written communication, April 9, 2020).

Figure 2.. Forest Plot of Processing Speed

A random-effects model was used. Data markers represent standardized mean differences (SMDs), and horizontal lines represent 95% CIs. The diamond represents the pooled summary estimate, and the horizontal extremes of the diamond represent its 95% CI. The arrows pointing right on the forest plot represent the upper limit of the 95% CI exceeding 1.0. Data on overall heterogeneity are available in eTable 5A in the Supplement. Unpublished (raw) data were requested from the authors of several studies because the available published results were not usable for meta-analysis; these data were used in the calculations with written permission from the authors of the following studies: Cobia et al (D. Cobia, PhD, April 9, 2020), El-Hadidy et al (M. A. El-Hadidy, MD, written communication, May 11, 2020), Gajewski et al (P. D. Gajewski, PhD, written communication, April 3, 2020), Guenter et al (W. Guenter, PhD, written communication, April 30, 2020), and Torniainen-Holm et al (M. Torniainen-Holm, PhD, written communication, May 8, 2020).

Figure 3.. Forest Plot of Working Memory

A random-effects model was used. Data markers represent standardized mean differences (SMDs), and horizontal lines represent 95% CIs. The diamond represents the pooled summary estimate, and the horizontal extremes of the diamond represent its 95% CI. The arrow pointing right on the forest plot represents the upper limit of the 95% CI exceeding 1.0. Data on overall heterogeneity are available in eTable 5B in the Supplement. Unpublished (raw) data were requested from the authors of several studies because the available published results were not usable for meta-analysis; these data were used in the calculations with written permission from the authors of the following studies: Cobia et al (D. Cobia, PhD, written communication, April 9, 2020), Gajewski et al (P. D. Gajewski, PhD, April 3, 2020), and Guenter et al (W. Guenter, PhD, written communication, April 30, 2020).

Figure 4.. Forest Plot of Executive Functioning

A random-effects model was used. Data markers represent standardized mean differences (SMDs), and horizontal lines represent 95% CIs. The diamond represents the pooled summary estimate, and the horizontal extremes of the diamond represent its 95% CI. The arrow pointing right on the forest plot represents the upper limit of the 95% CI exceeding 1.0. Data on overall heterogeneity are available in eTable 5D in the Supplement. Unpublished (raw) data were requested from the authors of several studies because the available published results were not usable for meta-analysis; these data were used in the calculations with written permission from the authors of the following studies: Cobia et al (D. Cobia, PhD, written communication, April 9, 2020), El-Hadidy et al (M. A. El-Hadidy, MD, written communication, May 11, 2020), Gajewski et al (P. D. Gajewski, PhD, written communication, April 3, 2020), Guenter et al (W. Guenter, PhD, written communication, April 30, 2020), Nimgaonkar et al (V. J. Nimgaonkar, MD, PhD, written communication, May 12, 2020), and Torniainen-Holm et al (M. Torniainen-Holm, PhD, written communication, May 8, 2020).