A meta-analysis for the neuropsychological outcomes among farmworkers and pesticide applicators (The presentation awarded one of the best three oral presentations)

Abstract

Chronic low level exposure of agricultural workers and applicators to pesticides has been found to be associated with different degrees of decrement in cognitive and psychomotor functions. The goal of this work is to use meta-analysis to (1) identify and quantify the neurobehavioral (NB) deficits among agricultural workers and pesticide applicators, and (2) analyze the potential confounders or moderators of these neurobehavioral deficits. Seventeen studies, composed of 21 independent cohort groups, were included in the meta-analysis. These studies involved 16 neuropsychological tests providing 23 different performance measures that constitute the neurobehavioral constructs. All tests and measures of the NB functions of attention, visuomotor, verbal abstraction, and perception constructs showed significant decrements for exposed participants. One out of three tests of memory, two of five tests of sustained attention, and four of eight tests of motor speed constructs also showed significant decrements. Nine out of these fifteen effect size distributions demonstrated significant heterogeneity across cohorts. A search for cohort-level variables (e.g., agricultural workers versus applicators, duration of exposure, age and percentage of male participants) to explain this heterogeneity was largely unsuccessful. However, for one test, Block Design, the duration of exposure was positively associated with performance decrements. Furthermore, it was also found that performance decrements on this test were smaller with older participants. Increasing the number of studies and using more consistent methodologies in the field studies are needed.

Full text

Dr. Ahmed Ismail
Assistant professor
Community and family Medicine Dep.
Faculty of Medicine
Jazan University
ismail@hotmail.com-aa

INTRODUCTION
Acute (high) dose OP poisoning
ACH: acetylcholine; Epi: epinephrine; NE: norepinephrine; NMJ: neuromuscular junction.

Delayed OP effects
Intermediate Syndrome; 1-4 days; muscle weakness,
respiratory failure
Organophosphate induced delayed polyneuropathy
(OPIDN); 2- 5 weeks, sensory abnormalities, muscle
cramps, weakness, and even paralysis, primarily in the
legs
Acute (high) OP exposure

Chronic exposure
Symptom Prevalence
headache, dizziness, fatigue, weakness, nausea, chest tightness, difficulty
breathing, insomnia, confusion, and difficulty concentrating
Mood and Affect
higher levels of tension, anger, and depression
Neurobehavioral Performance
Cognitive and psychomotor functions
Sensory and Motor functions
Vibration sensitivity
Visual contrast and color vision
Grip strength
Balance
Nerve conduction
Neurologic diseases
Parkinson’s disease
Amyotrophic Lateral Sclerosis (ALS)
Dementia
Alzeheimer’s disease (AD)

Neurobehavioral performance
Cognitive functions
Verbal Abilities; Similarities
Learning; Serial Digit Learning (SDL), Reversal Learning (RL)
Memory;
Recall and Recognition; Digit Span Test (DST), Object memory test
Visual; Benton Visual Retention Test (BVRT), Match-To-Sample test
(MTS)
Match to Sample test
Serial Digit Learning test

Coding and complex functions; Symbol Digit test (SDT),
Digit Symbol Test (DST)
Coordination;
Manual Dexterity; Santa Ana, Pursue Aiming; Pegboard
Tapping test (TAP)
Attention
Regular; Letter cancellation test
Divided; Trail Making A and B
Selective; Selective Attention Test (SAT)
Symbol Digit test
Tapping test
Neurobehavioral performance
Cognitive functions
Selective Attention test

Psychomotor functions
Response speed (Psychomotor speed); TAP, Reaction
Time (RT)
Motivation; Progressive Ratio test (PRT)
Spatial Relations
Visual; Block Design test (BDT), Benton Visual
Retention Test (BVRT)
Tactual; Tactual Performance test
Neurobehavioral performance
Progressive Ratio test
Block Design test

Inconsistency among
studies

AIM OF THE STUDY
Examine and quantify the effect of chronic, low-level
pesticide exposure in agricultural workers on specific
functions of neurobehavioral performance (e.g.,
memory, attention, motor speed) through meta-
analysis.
Examine the impact of potential confounders or
modifiers of these neurobehavioral effects (e.g.,
assessment methods, demographics, job category)

METHODS
Literature Search; A Medline/PubMed search (1966 –
December 2010)
Inclusion and Exclusion Criteria
Exposure to OPs as a result of working in agriculture or applying
pesticides
The selected study needed to address chronic exposure without
previous acute symptoms or poisoning
Include common neurobehavioral tests or measures of cognitive or
motor functions that had been used in at least three studies
Coding
Age; adult and adolescents
Job category; Applicator and farmworkers
Method used to asses neurobehavioral functions (Computerized or
non-computerized)
Seven constructs; memory, attention, sustained attention, motor
speed, visuomotor, verbal ability, and perception

Meta-Analytic Procedures
Effect sizes of every measure;
Standardized mean difference,
Fixed effects model analyses; to examine effect size
centrality, homogeneity and moderation
Test centrality using Z-test
Test homogeneity using Q-test
the meta-analytic analogue to an analysis of variance test, was
used to examine the impact of categorical moderator variables
The meta-analytic analogue to regression analysis was used to
examine the impact continuous moderator variables
METHODS (continued)
pooled
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ES 21 
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211
21
2
2
21
2
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nn nsns
spooled

Publication bias
A tendency to publish research with a positive outcome
more frequently than research with a negative outcome
The fail safe N, defined as the number of studies with
non-significant results (p > 0.05) that would bring a
significant pooled analysis to non-significant levels.
Rating the quality of the included studies;
A modified scale from the Newcastle-Ottawa scale for
assessing the quality of observational studies was used.
METHODS (continued)

RESULTS

Figure 1. Fixed effect sizes of different neurobehavioral measures
Effect sizes and confidence intervals
-1.0 -0.8 -0.6 -0.4 -0.2 0.0 0.2 0.4
Measures
Match to Sample, score
Serial Digit Learning, score
Benton Visual Reaction Time
Digit Span, Forward
Digit Span, Backward
Continuous Performance , %hits
Continuous Performance, Hit latency
Selective Attention, no. of trials
Selective Attention, ISI
Selective Attention, latency
Tapping, preferred hand
Tapping, non preferred hand
Tapping, alternating
Santa Ana, preferred hand
Progressive Ratio, no. of taps
Reaction Time, latency
Pursuit Aiming, correct dots
Symbol Digit, latency
Digit Symbol, score
Trail Making, A
Trail Making, B
Similarities
Block Design, scaled score
Memory
Attention
Sustained
Attention Motor speed/
coordination
Visual-
motor
Verbal abstraction
Perception
RESULTS (continued)

Positive significant effect of study quality on the
effect sizes for three of the tests (Benton Visual
Retention Test, Reaction Time latency, and Block
Design),
Studies of poorer quality were associated with finding
weaker effects of pesticide exposure on these tests.
Exclusion of a particular cohort; in most cases, led to a
change of the mean effect size from non-significance
to significance.
Studying the quality of included studies
RESULTS (continued)
Studying the effect of individual studies

Weighted regression analysis results:
Only Block Design test was negatively affected by the
duration of exposure and positively affected by age of
the participants.
The percent of males in the exposed group is a positive
predictor for both Block Design and Finger Tapping
non-preferred hand tests. This results shows that
pesticide exposure may be less detrimental to male
agricultural workers than female workers.
RESULTS (continued)

CONCLUSIONS
Chronic low-level exposure to pesticides of agricultural
workers and pesticide applicators has a significant impact
on neurobehavioral performance as described across all
neurobehavioral constructs.
Dividing the cohorts into agricultural workers and
applicators exposed or including the duration of exposure,
age of the exposed groups, and percent of males in the
regression model largely did not assist with explaining the
differences in results across cohorts.
Increasing the number of studies and using more
consistent methodologies in the field studies are needed.

THANK YOU