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Original Investigation
July 14, 2021

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

Author Affiliations
  • 1Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
JAMA Psychiatry. Published online July 14, 2021. doi:10.1001/jamapsychiatry.2021.1590
Key Points

Question  Is Toxoplasma gondii seropositivity in otherwise healthy people associated with alterations in cognitive function?

Findings  In this systematic review and meta-analysis of 13 studies comprising 13 289 healthy individuals, a modest but significant association was observed between T gondii seropositivity and impaired performance on cognitive tests in all analyzed domains (processing speed, working memory, short-term verbal memory, and executive functioning).

Meaning  This study’s findings suggest that, given the high global prevalence of T gondii infection, the consequences of these associated cognitive impairments for global mental health could be substantial.


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.

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