Table 1 Main characteristics of studies included in the systematic review

1

Smith, et al. [58]

USA

Columbus, Ohio

Volunteers employed in two mercury cell chlor-alkali plants

A total of 98 workers

Mean (standard deviation) of subjects age 42.1 ± 13.4 years

Exposure to elemental mercury and urinary mercury concentration

Among the cohort of 98 elementary concentration workers, the average urinary mercury concentration stood at 0.14 ± 0.14 mg/l, while in the current group of 28 individuals, it registered slightly elevated at 0.18 mg/l ± 0.17 mg/l

Cohort

Short-term memory capacity (1: Wechsler digit span forward, 2: precise measurement of the STM

Span—the 50% threshold)

Correlation

The second measure assessed a worker’s 50% threshold for correct serial recall and revealed a significant decrease in short-term memory capacity with higher elemental mercury exposure. This was observed in a study involving 26 workers with urinary mercury levels ranging from 0–20 to 0–51 mg/1. A follow-up study with 60 different workers, despite lower urinary mercury levels (0–11 mg/1 on average), confirmed the link between urine mercury levels and reduced short-term memory capacity

2

van Wijngaarden, et al. [66]

Seychelles

Participants of the Seychelles Child Development Study

(SCDS)

533

19 years old

Prenatal methyl mercury exposure

The mean prenatal methylmercury (MeHg) exposure, quantified through maternal hair analysis, amounted to 6.89 (4.52) parts per million (ppm). Conversely, the recent postnatal MeHg exposure, evaluated through children's hair samples, exhibited a higher average of 10.29 (6.06) ppm

Cohort

The research conducted an evaluation of neurodevelopment and behavior through a variety of assessments. These included mood assessment using the Profile of Mood States—Bipolar (POMS-Bi), fine motor control examination with Finger Tapping, cognitive ability assessment using the Kaufman Brief Intelligence Test (K-BIT), evaluation of motor skills through measures of fine motor control and complex perceptual motor control, and the assessment of visual perception and sensitivity using Visual Spatial Contrast Sensitivity

Linear regression

Prenatal exposure to methylmercury (MeHg) did not exhibit any negative correlations with the evaluated endpoints. In contrast, recent postnatal MeHg exposure was linked to adverse outcomes. These included diminished Finger Tapping performance in women and lower scores on the K-BIT Matrices test for both genders, irrespective of adjustments made for polyunsaturated fatty acids (PUFA)

3

Sallon, et al. [55]

India and China

The study comprised volunteers who were fluent Tibetan speakers, spanning an age range from 18 to 65 years. The assessment of mercury (Hg) exposure drew from a prior pilot investigation (Group 1) that involved a comparison of urinary Hg levels between individuals using Hg in the form of Tsothel in Precious Pills and those utilizing other variants of traditional medicine (Group 2). Moreover, data on population-based background Hg exposure (Group 3) served as a reference point for the analysis

120

18 and 65 years

Urinary Hg levels,

Blood Hg level

Urinary Hg (µg/L):

Group 1; mean (SD):

1.5 ± 1.24

Group 2; mean (SD):

1.57 ± 0.55

Group 3; mean (SD):

NA

Blood Hg (µg/L):

Group 1; mean (SD): 0.22 ± 0.19

Group 2; mean (SD):

0.18 (± 0.11)

Group 3; mean (SD):

0.35(± 0.35)

Cross-sectional

Neurocognitive testing (Standardized Mini-Mental State Examination

(MMSE))

Mean difference

Regarding neurocognitive testing, no statistically significant distinctions were discerned among the groups concerning the Wechsler Memory Scale, Grooved Pegboard, and Visual Retention. Nevertheless, in the case of Mini-Mental, Brief Word Learning, and Verbal Fluency assessments, participants in Group 1 demonstrated superior scores, even after adjusting for potential confounding variables

4

Li, et al. [30]

USA

US adults aged 60 years or older

2068

Adults aged 60 years or older

Blood cadmium levels

The study participants exhibited a median blood cadmium concentration of 0.35 μg/L, with an interquartile range (IQR) spanning from 0.24 to 0.56 μg/L

Cross-sectional,

Cognitive function was evaluated through various assessments, encompassing the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Test, the CERAD Word List Recall Test, the Animal Fluency Test, and the Digit Symbol Substitution Test (DSST). These assessments were likely selected to appraise diverse facets of cognitive performance, including memory, verbal fluency, and processing speed

Multiple linear regression models

Blood cadmium levels, when considered as a continuous variable, displayed an inverse association with the composite z-score (μg/L, β =  − 0.11, 95% CI − 0.20 to − 0.03). Similarly, when blood cadmium levels were categorized into quartiles, a significant association was evident. Participants in the upper quartile of exposure (blood cadmium ≥ 0.63 μg/L) exhibited somewhat lower composite z-scores compared to those in the lower quartile of exposure (blood cadmium < 0.25 μg/L) (μg/L, β =  − 0.14, 95% CI − 0.25 to –0.03), and this pattern demonstrated a statistically significant trend across the quartiles of blood cadmium levels (P < 0.0001)

5

Geier, et al. [21]

USA

The study examined a total of 1,821,663 individuals aged between 60 and 80 years old, whose blood samples from the 2011–2012 National Health and Nutrition Examination Survey revealed detectable levels of blood ethylmercury (ethyl-Hg)

1,821,663

Ages of 60 and 80 years

Blood ethyl-Hg levels

Blood mercury levels (µg/L)

Mean Ethylmercury ± std (range) = 0.3 ± 0.2 (0.16–1.0)

Mean Methylmercury ± std (range) = 4.0 ± 5.3 (0.08–23.2)

Mean Inorganic mercury ± std (range) = 0.4 ± 0.3 (0.2–2.8)

Cross-sectional,

Cognitive function scores were determined using the following assessments:

Consortium to Establish a Registry for Alzheimer’s Disease–Word List Learning (CERADW-L) delayed recall test

Animal Fluency Test

Digit Symbol Substitution Test

Logistic regression modeling/odds ratios

A notably higher risk for reduced scores on the Animal Fluency Test (odds ratio (OR) = 13.652, p = 0.0029) and the CERAD W-L delayed recall test (OR = 6.401, p = 0.0433) was observed among individuals in the higher ethylmercury (ethyl-Hg) exposure group when compared to those in the lower ethyl-Hg exposure group

6

Mao, et al. [34]

USA

The study involved a total of 3,231 participants from the CARDIA (Coronary Artery Risk Development in Young Adults) study

3231

18–30 years of age

Toenail mercury and selenium levels

Toenail selenium at exam Y2 (ppm): 0.86 ± 0.15

Toenail mercury at exam Y2 (ppm): 0.32 ± 0.37

Cohort

Cognitive function was assessed using the Rey Auditory Verbal Learning Test (RAVLT), the Digit Symbol Substitution Test (DSST), and the Stroop test

The general linear regression model

The research aimed to explore the isolated impacts of toenail selenium (Se) and mercury (Hg) levels on cognitive function tests; however, no significant associations were detected after accounting for potential confounding factors. Furthermore, the study investigated whether the interaction between toenail Se and Hg levels affected cognitive function, especially concerning LCv-3 PUFA (long-chain omega-3 polyunsaturated fatty acids) intake. It is worth noting that this interaction did not attain statistical significance

7

Peng, et al. [48]

China

375 older men aged 60–74 years in Guangxi, China

375

Aged 60–74 years (mean age: 66.0 years)

Urinary Cd concentrations

The median urinary Cd concentration of all participants was 1.58 mg/g creatinine

Cross-sectional

Cognitive function was evaluated through the utilization of the Chinese version of the Mini-Mental State Examination (MMSE). Cognitive impairment was identified based on education-specific cutoff points established for MMSE scores

General linear regression and logistic regression models

Urinary cadmium (Cd) levels exhibited an inverse association with MMSE scores, with a beta-coefficient of − 0.76 and a 95% confidence interval (CI) ranging from − 1.28 to − 0.23 for a twofold increase in urinary Cd. Moreover, a twofold rise in urinary Cd was linked to an elevated risk of cognitive impairment, as indicated by an adjusted odds ratio (OR) of 1.46 and a 95% CI ranging from 1.14 to 1.86

8

Silman, et al. [57]

Upper Amazonian, Peru

Matsigenka communities residing within the Manu National Park (MNP) along the Manu River include Maizal, Cacaotal, and Yomibato

38

Average years (SD) 29 (13.8)

Samples of blood and hair. Mercury Exposure/Word Span

Hg (ppm): mean (SD) = 7.05 (2.40)

Cross-sectional

The study encompassed the customization of working memory tasks to align with the Matsigenka culture and language. This adaptation included evaluations for verbal storage (Word Span), visuospatial storage (Corsi Block Task), and the assessment of executive functions through the Self-Ordered Pointing Task (SOPT). Furthermore, a modified iteration of the Trail Making Tests A & B (TMT A & B) was subjected to a pilot test to explore its potential as a measure of executive function

Ordinary least squares

multiple linear regression

Word Span Accuracy: − 0.01 (− 0.03, 0.01)

Corsi Block Accuracy: − 0.04 (− 0.06, − 0.01)

SOPT Errors: 0.23 (0.05, 0.42)