Is Toxoplasma gondii a potential risk factor for Alzheimer's disease? A systematic review and meta-analysis.

Toxoplasmosis is a major public health concern due to neurotropic nature and role in the development of mental and behavioral disorders. Alzheimer's disease (AD) is an important nervous disease that results in the reduction of the amount of beta-amyloid plaque deposition and irreversible loss of neurons in the brain. Although a few studies evaluated the association between AD and toxoplasmosis, the present study as a systematic review and meta-analysis of published studies investigated the possible association between Toxoplasma gondii (T. gondii) and AD. A systematic literature search was conducted using seven electronic databases from the inception to 25th of November 2018 with no restriction of language that looked at toxoplasmosis (as an exposure) and AD (as a disease). The random effect model was used to determine the total odds ratio (OR) and total p-value. Generally, eight studies containing 3239 subjects (360 patients and 2879 controls) met the eligibility criteria. Then, eight articles were used for meta-analysis with respect to inclusion and exclusion criteria. The results of the meta-analysis (random effect model) showed a common OR of 1.53 (95% CI: 1.07-2.18). Despite the fact that there was no evidence of publication bias (P = 0.079) using formal statistical test, the visual inspection of the funnel graph suggested that the observed effect was fueled mainly by three studies with large effects (and large standard errors). Moreover, the file-drawer effect (i.e. publishing mainly studies with positive results) might play a role in the phenomenon. Results of this meta-analytic study suggested that T. gondii can be considered a risk factor for the development of AD and exacerbation of its symptoms. However, the number of published relevant studies is still relatively low, and the risk of the presence of publication bias is relatively high. Therefore, the investigation of the clinically important question of the possible association between toxoplasmosis and AD definitively deserves further attention.