16 Longitudinal Cognitive Functioning in Gulf War veterans with and without Gulf War Illness: Data Mining from the BBRAIN Repository

Abstract

Objective:

Veterans from the 1991 Gulf War (GW) experienced several neurotoxicant exposures, including chemical weapons, pesticide sprays and creams, oil well fires and pyridostigmine bromide anti-nerve gas pills during the war. Research has shown these exposures to affect cognition and mood. Moreover, MR diffusion imaging has shown microstructural changes in the white matter that may be related to psychomotor slowing. Over a third of all GW veterans suffer from a chronic multi-symptom disorder called Gulf War Illness (GWI). The Kansas Criteria for GWI consists of six distinct criteria including symptoms of fatigue/sleep problems, pain symptoms, neurologic/cognitive/mood symptoms, gastrointestinal symptoms, respiratory symptoms, and skin symptoms. The Boston Gulf War Illness Consortium (GWIC) was a multi-site study designed to assess symptoms of GWI. After the conclusion of the GWIC study, the Boston Biorepository Recruitment and Integrative Network for Gulf War Illness (BBRAIN) was developed to harmonize retrospectively collected GW Veteran data while simultaneously collecting Time 2 data and samples from GW veterans who participated in the original study. This analysis includes the first 58 participants who have completed the GWIC study and the BBRAIN study.

Participants and Methods:

We conducted a longitudinal analysis of cognitive outcomes from the BBRAIN data repository. Verbal learning, memory, attention, and executive functioning were assessed using neuropsychological tests including the Continuous Performance Test (CPT3), Trail Making Test A, Delis-Kaplan Executive Function System (DKEFS), California Verbal Learning Test (CVLT-II). A total of 58 participants were re-evaluated from the original GWIC cohort with a total of 47 cases and 11 controls. Paired t-tests for the cognitive measures were completed separately for GWI cases and healthy GW veteran controls for each of the neuropsychological test measures. Average time between assessments was four years.

Results:

The overall sample was on average 56 years old, 84% male and 75% White. The average level of education was 15 years. GWI cases showed significantly more commission errors and slower reaction times on the CPT3 at Time 2 compared to Time 1 (p < 0.05). Cases also showed a slowing in time to completion on Trails A at the second time point (p<0.05). On the other hand, controls only showed significantly slower reaction times on the CPT3 at Time 2 (p<0.05).

Conclusions:

These results showed that veterans with GWI are showing more decline over time in cognitive functioning particularly on psychomotor slowing and impulsivity than control veterans. It is important to document illness trajectories for veterans with GWI in order to devise strategies for interventions and treatments. The importance of studying longitudinal cohorts is to document changes in the same individuals over time. The next steps are to assess if this accelerated aging develops into neurodegenerative conditions by using brain imaging and other biomarkers in addition to cognitive evaluations. This could identify individuals who should be the focus of targeted treatment strategies while there is still time to intervene.