Table 1.

Epidemiological studies of association between lead levels and cognitive impairment by different ages of exposure.

Population (Age Range)	Study Design and Subjects	Location	Lead Levels	Outcomes	Reference
Children
2–4 years	Cross-sectional study; 76 children. Gesell Developmental Scale: t-test comparisons. The Achenbach Child Behavior Checklist (CBCL): χ2 test. Scores on each behavior factor and the total behavioral score were analyzed by the rank-sum test.	Xi’an, China	Blood: 4–246 µg/L	↓ Adaptative behavior, gross motor performance, fine motor movements, language development, and individual social behavior. ↑ Depression, abnormal behavior, aggressions, social withdrawal, sleep problems, and destruction.	[11]
2–5 years	Cross-sectional study; 201 children. Child Behavior Checklist (CBCL): χ2 test and t-test comparisons. Total Behavior Problem Score (TBPS) based upon the percentile ranking of raw scores and in the clinical range (90th percentile). Multiple regression analysis for the likelihood ratio and influential factor on the TBPS was measured from the mothers using the Center for Epidemiologic Studies Depression Scale (CES-D).	Baltimore, United States	Blood: 2–30 µg/dL	Troublesome behaviors (aggression, sleep problems, and somatic problems) Increase in externalizing behaviors (motor activity, nonadaptive behaviors, conduct problems, inattentiveness, passivity, and hyperactivity)	[12]
8–9 years	Cross-sectional study; 167 children. Wechsler Intelligence Scale for Children (WISC), Göttinger Formreproduktions-Test (GFT), Bender Gestalt-Test (German version), Benton Test, Diagnostics for Cerebral Damage Test and Wiener Reaction Device. Duisburg study t tests for correlating samples. Stolberg sample associations were tested using of stepwise multiple regression analysis.	Duisburg city and Stolberg city, Germany	Baby teeth: 1.4–38.5 µg/g Blood: 6.8–34 µg/100 mL	Deterioration of visual-motor integration IQ deficits (5–7 points) Disturbance of reaction performance Deficits in verbal IQ (4–7 points)	[13]
6–12 years	100 children Wechsler Intelligence Scale for Children, 3rd edition (WISC-III) Spearman’s rank correlation, logistic and linear regressions to test independent predictors for impairment of cognitive function and the relationship between blood lead levels and cognitive function. Receiver operating characteristic (ROC) curve was used to calculate the best cut-off value of blood lead levels (based on the highest sensitivity with the lowest false-positive results) above which the majority of the children have cognitive dysfunction.	Cairo, Egypt	Blood: 3–28 µg/dL	↓ IQ in 15 points (mainly in verbal subsets, arithmetic and digit span) Poor scholastic achievement Cognitive dysfunction (flat affect, slow, and delayed responses)	[14]
Adults
50–60 years	Cross-sectional study; 53 adults. Wechsler adult intelligence scale-revised (WAIS-R), Wechsler memory scale (WMS), a test of attention and visuomotor tracking (trail making), test of verbal fluency (FAS), test of non-verbal reasoning (Raven progressive matrices), test of motor speed (finger tapping) and inventory of current mood (POMS). Wilcoxon signed ranks test, used to compare matched pairs of subjects exposed to lead and controls; and the Mann–Whitney test, used to compare entire groups. χ2 test was used to evaluate the distribution of categorical frequencies.	Boston, United States	Blood: 60–120 µg/dL	Difficulties in attention and executive functioning, reasoning, and short-term memory. Attenuation of the ability to learn new information. Problems with attention and concentration Reduced ability to do more than one activity at the same time. Impaired ability to organize information or steps in a procedure. Increased difficulty in arriving at solutions for problems.	[8]
50–70 years	Cross-sectional study; 1033 adults. A battery of 20 cognitive test results was standardized and collapsed into 7 cognitive domain scores. All 7 domain scores were standardized for direction so that a negative regression coefficient indicated worse performance. χ2 test for interaction between tibia lead, Neighborhood Psychosocial Hazards Scale (NPH). NPH scale and the 7 domains of Cognitive function in the Baltimore Memory study. Multilevel regression models were used to account for the nesting of persons within neighborhoods.	Baltimore, USA	Tibia 18.8 ± 11.6 µg/g	Affectations in language and executive function	[1]
Male workers
22 years	Case report	India	Blood: 128.3 µg/dL	Aggressiveness	[15]
39–50 years	Cross-sectional study 47 adults exposed to Pb for 11.7 ± 9 years. Modified version of the Wisconsin card sorting test, the block design test, the visual recognition test, choice reaction, simple reaction, and digit symbol substitution. One-tailed t-test for independent samples was used for the following tasks: block design and visual recognition tests, simple reaction time, and digit symbol substitution. The results of the choice reaction were analyzed by multivariate analysis of variance. Since scores of the Wisconsin test were not distributed normally, they were analyzed by one-tailed Mann– Whitney test. Because of multiple univariate testing, Bonferroni correction was applied.	Germany	Blood: 30.8 + 11.2 µg/100 mL	Neurobehavioral performance poorer than control in categories such as executive functions (visual recognition), short-time memory, and visuospatial abilities.	[16]
25–67 years	Cross-sectional study: 100 adults exposed to Pb for 1–7 years. WHO neurobehavioral core test battery. Multiple linear regression of neurobehavioral function in workers and lead exposure indices. Correlation coefficients (Pearson r) between blood lead concentration and covariates Analysis of covariance for dichotomous exposure variables.	Venezuela	Blood: 9–60 µg/dL	↓ results on Wechsler adult intelligence subtests. ↓ Simple reaction time. Mood indicative of depression. Anger hostility, fatigue, and confusion.	[17]
71 years	Case report Twins	Boston, United States	Blood: 15–125 µg/dL Patella: 119–343 µg/g Tibia: 79–189 µg/g	Verbal/language abilities and working memory/executive function lower than average (worse in twin 1) Deficits in short-term memory function (in learning and retention of new information) Bad manual motor control	[18]
Female workers
55–65 years	Cross-sectional study: 31 adults exposed to Pb for 1.4–20.7 years. N-back working memory paradigm. Mean values of continuous variables were compared using the Student’s t-test. Pearson correlation analyses between mean percentage changes of activated brain regions and working memory performance. The effects of blood lead on percent signal change by multiple regression analysis.	Korea	Blood: 0.88–13.5 µg/dL	Decreased working memory (in-back memory task). Decreased activation in the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, pre-supplementary motor areas, and inferior parietal cortex	[19]