TABLE 4.

Neurotoxicants and Neuropsychological Performance.

References	Group (N)	Neuropsychological Tests	Strengths	Limitations	Key Findings and Conclusions
White et al., 2001	193 GWV, 47 Germany deployed veterans	WAIS-R CPT Trail Making Test PASAT WCST Digit Span CVLT∗ WMS-R∗ Finger Tapping Purdue Pegboard POMS∗ TOMM	– Compared deployed and non-deployed veterans – Detailed account of toxicant exposure – Stratified Random sample	– TOMM scores evidenced possible poor effort in some participants – Multiple comparisons	– Pesticide exposure by self-report was associated with worse mood functioning on all POMS subscales. – Chemical weapons exposure by self-report was associated with worse mood functioning on the POMS subscales of tension and confusion as well as poorer – performance on attention/executive functioning, memory and mood measures.
Sullivan et al., 2003	207 treatment seeking GWV (120 referred for neuropsych evaluation), 53 treatment seeking non-deployed veterans	WAIS-R Information WAIS-R Digit Span Trail Making Test NES CPT Stroop Test Paced Auditory Serial Addition Test Wisconsin Card Sort Test∗ CVLT WMS-R Paired Associate Learning WMS-R Visual Reproductions Hooper Visual Organization Test WAIS-R Block Design Finger tapping Purdue Pegboard POMS TOMM	– Investigated deployment, treatment seeking, use of pyridostigmine bromide (PB) and PTSD on cognitive functioning – Matched by control group that was also treatment seeking	– Self-report of exposure – Sample size small for exposure comparisons	– PB use in GWVs showed worse performance on an executive system task. – GWVs with PTSD versus those without PTSD showed no significant differences – There were no significant interaction effects of PB and PTSD on cognitive functioning.
Vasterling et al., 2003	72 GWVs deployed and 33 non-deployed GWVs	WAIS-R Digit Span WCST AVLT CVMT Purdue Pegboard WAIS-R Information	– Selection of a non-treatment seeking group of GWVs – Comparison of deployed GWVs to a group of GWVs mobilized but not deployed – Use of olfactory and neurocognitive measures with demonstrated sensitivity to neurotoxic exposures but not to organophosphates	– Sample was regionally recruited	– No evidence that performance on olfactory or neurocognitive measures were related to self-reported exposure to GW toxicants – GWVs reporting more significant exposures reported greater severity of health symptoms and more severe cognitive symptoms, than those reporting less significant exposures – Symptoms of emotional distress were positively correlated with self-report of health and cognitive complaints
Proctor et al., 2006	140 Army GWV with modeled estimates of nerve agent exposure	CPT Trail Making Test WAIS-R Digit Span WCST Finger Tapping Purdue Pegboard∗ WAIS-R Block Design∗ CVLT WMS-R verbal paired associate learning WMS visual reproduction	– Stratified random sampling strategy – Examined performance by exposure to sarin and cyclosarin by DOD modeling – Sample was unaware of sarin and cyclosarin components, analyses were conducted prior to exposure knowledge	– Etiology undetermined given the risk of another illness between exposure and measurement (i.e., no baseline health information) – Limited objective information about exposures – Plume estimates only by unit	– Exposure associated with poor fine psychomotor dexterity (d = 0.44) and visuospatial abilities (d = 0.43) in a dose-response manner – The difference on the motor task was equivalent to the performance effect of being approximately 20 years older and for the block design task, being 15 years older. – Higher exposure was not significantly related to mood state.
Toomey et al., 2009	1061 deployed GWV and 1128 non-deployed GWV	WAIS-III Digit Span Trail Making Test∗ PASAT CPT WCST CVLT∗ RCFT∗ Finger Tapping∗ Purdue Pegboard∗ TOMM WRAT-III	– Investigated differences in deployment, toxicant exposure, and GWI status – Large sample size, stratified random sampling method – Use of factor analysis – Use of Khamisiyah exposure data	– Low study participation rates from overall larger sample – Cross-sectional design – Neuropsychology raters were not blind to condition – Self-reported PB, pesticide, oil well fire, vaccine exposure	– Those with Khamisiyah exposure modeled sarin exposure showed poor motor speed after controlling for mood – Those reporting proximity to SCUD missiles had lower motor speed – Those reporting CARC paint exposure had worse visual memory – Khamisiyah exposure was associated with poorer verbal memory, beyond emotional distress and demographic variables
Chao et al., 2010	40 GWV with a history of DOD notified sarin cyclosarin exposure risk and 40 non-exposed matched GW veteran controls	CPT Trail Making Test∗ WAIS-III Digit Span Short Category Test COWAT∗ Grooved Pegboard∗ WAIS-III Digit Symbol, matching WAIS-III Block Design∗ WAIS-III Verbal Comprehension Index∗ CVLT-II WMS-III Logical Memory BVMT-R TOMM	– Use of DOD modeled Khamisiyah data for sarin/cyclosarin exposure – Demographically matched groups	– Lack of information regarding the unit and rank of veterans – Lack of information regarding symptom severity (i.e., CMI, smoking status, head injuries) – Lack of cumulative exposure for all GW veterans – Plume estimates only by unit	– No differences in cognitive measures after controlling for poor effort (i.e., failure of TOMM). – No correlation between unit-level dose-estimates and neuropsychological data in the exposed veterans. – In exposed veterans, hippocampal volume correlate positively with verbal comprehension scores, while total GM volume correlated positively with performance on verbal fluency and visuospatial ability and negatively with time to complete the Trail Making Test and time to place all pegs in the pegboard with the non-dominant hand. – In exposed veterans, total WM volume correlated positively with verbal fluency, and visuospatial function.
Chao et al., 2011	64 sarin and cyclosarin exposed GWVs and 64 “matched” unexposed GWVs	CPT∗ WAIS-III Digit Span∗ Trail Making Test Short Category Test CVLT-II∗ Grooved Pegboard TOMM	– Used matched controls to compare structural and functional differences in veterans with suspected neurotoxicant exposure – Use of more sensitive MRI (4T) – Use of sensitive tests for neuropsychological and mood outcomes	– Lack of information regarding veteran’s unit, severity of GWI symptoms, smoking status, or history of head injury – Neurotoxicant exposure measured at unit over individual level	– Reduced gray matter and white matter in exposed veterans which was linked to sarin/cyclosarin exposure, over and above confounding demographic, clinical, and psychosocial variables. – Exposed veterans made more omission errors and had slower response times on CPT; omission errors was also linked to sarin neurotoxicant exposure – Positive correlation between GM and WM volume, on CVLT performance and digit span backward in the exposed veterans.
Chao et al., 2016	136 GWVs: 106 who reported hearing chemical alarms sound	WAIS III Block Design∗ Digit Span∗ CVLT		– Had to rely on self-reports of deployment-related exposures – Lack of pre-GW measurements of brain structure and function – Didn’t measure experience and exposure that took place after the GW – Small sample size – Lack of a non-deployed GW-era veteran control group	– Self-reported frequency of hearing chemical alarms was inversely associated with and significantly predicted performance on the Block Design visuospatial task. – This effect was partially mediated by the relationship between hearing chemical alarms and lateral occipital cortex volume. – Volumes of the lateral occipital cortex, right inferior frontal cortex, and right supramarginal gyrus were positively correlated with Block design raw scores. – Volumes of lateral occipital cortex, right supramarginal gyrus and right precuneus were negatively correlated with the frequency of hearing chemical alarms. – No dose-effect relationship between Khamisiyah exposures and Block Design raw scores – Frequency of hearing chemical alarms sound was inversely correlated with Backward Digit Span raw scores but not with raw scores on CVLT learning trial 2 or with CVLT short-delay free recall.
Sullivan et al., 2018	159 GW-deployed preventative medicine personnel who had varying levels of pesticide exposure	WAIS-III information subtest Boston Naming Test Trail Making Test∗ CPT∗ WCST Finger Tapping Grooved Pegboard HVOT RCFT∗ Stanford-Binet Copying Test CVLT II POMS∗ TOMM	– Grouped veterans by exposure (low/high) to PB and pesticides – Sample had sophisticated knowledge of exposure as they were part of the medical team	– Multiple analyses – Exposures of PB and pesticide may be correlated – Classifications of groups based on self-report	– High pesticide/high PB had worse information processing speed, attention (i.e., errors), visual memory, and increased mood complaints, after controlling for either CMI, PTSD, or depression. – High pesticides/low PB group was the worst performing in terms of visual memory recall while the low pesticides/low PB and low pesticides/high PB group performed significantly better. – Dichlorvos (pest strips) exposure was the best predictor of poorer performance in the attention and psychomotor domains. Methomyl (fly bait) exposure and lindane (delouser) were the best predictors of affective complaints in the mood domain. Bendiocarb and lindane were the best predictors for the visuospatial domain.

See original journal articles in first column for test references. ^∗Denotes significance of p < 0.05.