Linda L. Chao

Background: People living with Alzheimer's disease and related dementias constitute a substantial proportion of residents in U.S. Veterans Health Administration nursing homes (Community Living Centers, CLCs). Non-pharmacologic interventions have demonstrated positive effects for people living with dementia (PLWD) but face implementation barriers in nursing homes. The Preventing Loss of Independence through Exercise (PLIÉ) program is an evidence-based multimodal mind-body movement program that supports quality of life and function for PLWD. Objective: To identify potential facilitators and barriers that may impact implementation of PLIÉ in CLCs (PLIÉ-CLC) and inform the development of a remote staff training program. Methods: We conducted a developmental formative evaluation using qualitative methods, guided by the Consolidated Framework for Implementation Research (CFIR). Semi-structured interviews with 30 CLC staff, directors, and VA health system leaders, explored perspectives on implementing PLIÉ-CLC. Data were analyzed using a template analysis approach. Results: Key facilitators included PLIÉ's evidence base, adaptability, and alignment with person-centered care. Barriers included staffing constraints, workload demands, and limited accessible space. Participants emphasized the need for both synchronous and asynchronous training components to fit staff schedules and enhance feasibility. Conclusions: This study highlighted the importance of adaptability and evidence-based support in implementing PLIÉ in VA nursing homes. The findings suggest that a flexible, remote training program incorporating both didactic and experiential learning may facilitate the scalability of PLIÉ. Understanding barriers and facilitators can inform strategies to improve the implementation of non-pharmacologic interventions for residents with dementia, ultimately enhancing care quality and outcomes in nursing homes.

Introduction: Potentially more than 100,000 US troops were exposed to organophosphorus (OP) nerve agents when an ammunition bunker at Khamisiyah, Iraq was destroyed shortly after the end of the 1991 Gulf War (GW). We previously reported evidence of differences in brain structure and function in GW veterans with predicted exposure to the Khamisiyah plume compared to veterans without predicted exposure. Here, we investigate the effects of predicted exposure to the Khamisiyah plume on brain functional connectivity in the default mode network (DMN). Methods: Forty-one GW veterans (19 with and 22 without predicted exposure) underwent structural and resting-state magnetic resonance imaging (MRI) on a 3 Tesla scanner. Differences in DMN connectivity between veterans with and without predicted Khamisiyah exposure were examined using a left posterior cingulate cortex (PCC) seed-based analysis in AFNI. FreeSurfer was used to derive quantitative estimates of total hippocampal volume. The veterans were also assessed with the Conners Continuous Performance Test (CPT). Results: Compared to veterans without predicted exposure, those with predicted Khamisiyah exposure demonstrated weaker connectivity between the left PCC and a cluster in the caudal right anterior cingulate cortex (ACC). Veterans with predicted exposure also had smaller left hippocampal volume compared to unexposed veterans. Discussion: Although the cross-sectional nature of this study precludes conclusions about causality, the finding of decreased DMN functional connectivity in GW veterans with predicted Khamisiyah exposure warrants replication in a larger, independent sample. If confirmed, this result would add to the literature suggesting persistent differences in brain function between deployed GW veterans with and without predicted Khamisiyah exposure and argue for further investigation into the long-term effects of GW-deployment related exposures.

Objective: To assess deployed Gulf War (GW) veterans for prodromal Parkinson's Disease (PD) using the REM Sleep Behavioral Disorder (RBD) Screening Questionnaire (RBDSQ). Methods: GW veterans ( n = 165) were assessed for nonmotor PD symptoms with the RBDSQ, Non-Motor Symptoms Scale, and Scales for Outcomes in Parkinson's Disease–Autonomic. Some veterans were also assessed with the University of Pennsylvania Smell Identification Test ( n = 120), neurological examinations ( n = 41), and 3T magnetic resonance imaging ( n = 16). Results: Eighty percent of veterans with PD and 73% of veterans without PD had probable RBD (ie, RBDSQ ≥5). Exploratory analysis conducted for hypothesis-generating purposes revealed that RBDSQ scores were positively associated with GW deployment–related exposures and inversely associated with brainstem volume. Conclusions: These findings suggest that veterans with GWI and high levels of deployment-related exposures are at risk for prodromal PD, possibly through RBD as a mediator.

Background: Although some recent studies have examined the health of female Gulf War (GW) deployed and non-deployed GW era veterans, these all relied on self-report, which can be inaccurate and subject to recall bias. This study investigated the current health of GW deployed and non-deployed GW era female and male veterans using Veterans Health Administration (VHA) electronic health records (EHR). Methods: We performed a cohort study of deployed GW and non-deployed GW era veterans, identified from a list from the Defense Manpower Data Center (DMDC). We used the VA-Frailty Index (VA-FI), calculated with VHA administrative claims and EHR, as a proxy measure of current health. Results: We identified 402,869 veterans (351,496 GW deployed; 51,3373 non-deployed GW era; 38,555 female) in VHA databases. Deployed female veterans had the highest VA-FI (i.e., were frailest) despite being younger than deployed and non-deployed male veterans and non-deployed female veterans. Compared with deployed male veterans, deployed females were more likely to be pre-frail, mildly, and moderately frail. Health differences between deployed and non-deployed female veterans were more prominent among older (60+ years) than younger (GW era and deployed male GW veterans. Because deployed female GW veterans appear to have additional health care needs, this may warrant increased outreach from women’s clinics at VA hospitals.

Background: Deployment-related neurotoxicant exposures are implicated in the etiology of Gulf War illness (GWI), the multisymptom condition associated with military service in the 1990–1991 Gulf War (GW). A Q/R polymorphism at position 192 of the paraoxonase (PON)-1 enzyme produce PON1₁₉₂ variants with different capacities for neutralizing specific chemicals, including certain acetylcholinesterase inhibitors. Methods: We evaluated PON1₁₉₂ status and GW exposures in 295 GWI cases and 103 GW veteran controls. Multivariable logistic regression determined independent associations of GWI with GW exposures overall and in PON1₁₉₂ subgroups. Exact logistic regression explored effects of exposure combinations in PON1₁₉₂ subgroups. Results: Hearing chemical alarms (proxy for possible nerve agent exposure) was associated with GWI only among RR status veterans (OR = 8.60, p = 0.014). Deployment-related skin pesticide use was associated with GWI only among QQ (OR = 3.30, p = 0.010) and QR (OR = 4.22, p < 0.001) status veterans. Exploratory assessments indicated that chemical alarms were associated with GWI in the subgroup of RR status veterans who took pyridostigmine bromide (PB) (exact OR = 19.02, p = 0.009) but not RR veterans who did not take PB (exact OR = 0.97, p = 1.00). Similarly, skin pesticide use was associated with GWI among QQ status veterans who took PB (exact OR = 6.34, p = 0.001) but not QQ veterans who did not take PB (exact OR = 0.59, p = 0.782). Conclusion: Study results suggest a complex pattern of PON1₁₉₂ exposures and exposure–exposure interactions in the development of GWI.

Background: Gulf War illness (GWI)/Chronic Multisymptom Illness (CMI) is a disorder related to military service in the 1991 Gulf War (GW). Prominent symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. Although anosmia is not a typical GWI/CMI symptom, anecdotally some GW veterans have reported losing their sense smell shortly after the war. Because olfactory deficit is a prodromal symptom of neurodegenerative diseases like Parkinson’s and Alzheimer’s disease, and because we previously reported suggestive evidence that deployed GW veterans may be at increased risk for Mild Cognitive Impairment (MCI) and dementia, the current study examined the relationship between olfactory and cognitive function in deployed GW veterans. Methods: Eighty deployed GW veterans (mean age: 59.9 ±7.0; 4 female) were tested remotely with the University of Pennsylvania Smell Identification Test (UPSIT) and the Montreal Cognitive Assessment (MoCA). Veterans also completed self-report questionnaires about their health and deployment-related exposures and experiences. UPSIT and MoCA data from healthy control (HC) participants from the Parkinson’s Progression Markers Initiative (PPMI) study were downloaded for comparison. Results: GW veterans had a mean UPSIT score of 27.8 ± 6.3 (range 9–37) and a mean MoCA score of 25.3 ± 2.8 (range 19–30). According to age- and sex-specific normative data, 31% of GW veterans (vs. 8% PPMI HCs) had UPSIT scores below the 10th percentile. Nearly half (45%) of GW veterans (vs. 8% PPMI HCs) had MoCA scores below the cut-off for identifying MCI. Among GW veterans, but not PPMI HCs, there was a positive correlation between UPSIT and MoCA scores (Spearman’s ρ = 0.39, p < 0.001). There were no significant differences in UPSIT or MoCA scores between GW veterans with and without history of COVID or between those with and without Kansas GWI exclusionary conditions. Conclusions: We found evidence of olfactory and cognitive deficits and a significant correlation between UPSIT and MoCA scores in a cohort of 80 deployed GW veterans, 99% of whom had CMI. Because impaired olfactory function has been associated with increased risk for MCI and dementia, it may be prudent to screen aging, deployed GW veterans with smell identification tests so that hypo- and anosmic veterans can be followed longitudinally and offered targeted neuroprotective therapies as they become available.

Introduction: Gulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.g., ≥70 years). The current study sought to replicate and extend this finding.Methods: We used the actuarial neuropsychological criteria and the Montreal Cognitive Assessment (MoCA) to assess the cognitive status of 952 GW veterans. We also examined regional brain volumes in a subset of GW veterans (n = 368) who had three Tesla magnetic resonance images (MRIs).Results: We replicated our previous finding of a greater than 10% rate of MCI in four additional cohorts of GW veterans. In the combined sample of 952 GW veterans (median age 51 years at time of cognitive testing), 17% met criteria for MCI. Veterans classified as MCI were more likely to have CMI, history of depression, and prolonged (≥31 days) deployment-related exposures to smoke from oil well fires and chemical nerve agents compared to veterans with unimpaired and intermediate cognitive status. We also replicated our previous finding of hippocampal atrophy in veterans with MCI, and found significant group differences in lateral ventricle volumes.Discussion: Because MCI increases the risk for late-life dementia and impacts quality of life, it may be prudent to counsel GW veterans with cognitive dysfunction, CMI, history of depression, and high levels of exposures to deployment-related toxicants to adopt lifestyle habits that have been associated with lowering dementia risk. With the Food and Drug Administration’s recent approval of and the VA’s decision to cover the cost for anti-amyloid β (Aβ) therapies, a logical next step for this research is to determine if GW veterans with MCI have elevated Aβ in their brains.

Background Prominent symptoms of Gulf War illness (GWI), the disorder related to military service in the 1991 Gulf War (GW), include fatigue, pain, and cognitive dysfunction. Although anosmia is not a typical GWI symptom, anecdotally some veterans reported losing their sense smell shortly after the war. Because olfactory deficit is a prodromal symptom of neurodegenerative diseases like Parkinson’s and Alzheimer’s disease, and because we previously reported suggestive evidence that deployed GW veterans may be at increased risk for Mild Cognitive Impairment (MCI) and dementia, the current study examined the relationship between olfactory and cognitive function in deployed GW veterans. Methods Eighty deployed GW veterans (mean age: 59.9 ± 7.0; 4 female) were tested remotely with the University of Pennsylvania Smell Identification Test (UPSIT) and the Montreal Cognitive Assessment (MoCA). Veterans also completed self-report questionnaires about their health and deployment-related exposures and experiences. UPSIT and MoCA data from age-matched healthy controls (HC) were downloaded from the Parkinson’s Progression Markers Initiative (PPMI) study for comparison. Results GW veterans had a mean UPSIT score of 27.8 ± 6.3 (range 9–37) and a mean MoCA score of 25.3 ± 2.8 (range 19–30). According to age- and sex-specific normative data, 31% of GW veterans (vs. 8% PPMI HCs) had UPSIT scores below the 10th percentile. Nearly half (45%) of GW veterans (vs. 8% PPMI HCs) had MoCA scores below the cut-off for identifying MCI. Among GW veterans, but not PPMI HCs, there was a positive correlation between UPSIT and MoCA scores (Spearman’s ρ = 0.39, p < 0.001). There was no significant difference in UPSIT or MoCA scores between GW veterans with and without history of COVID and with and without Kansas GWI exclusionary conditions. Conclusions We found evidence of olfactory and cognitive deficits and a significant correlation between UPSIT and MoCA scores in a cohort of 80 deployed GW veterans. Because impaired olfactory function has been associated with increased risk for MCI and dementia, it may be prudent to screen aging, deployed GW veterans with smell identification tests so that hypo- and anosmic veterans can be followed longitudinally and offered targeted neuroprotective therapies as they become available.

Background: During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of deficit emerge with more power to detect such differences. A group of researchers and clinicians with expertise in the area of GWI have identified common data elements (CDE) for use in research samples to compare data sets. At the same time, a subgroup of researchers created a new repository to share these cognitive data and biospecimens within the GWI research community. Methods: The present study aimed to compare cognitive measures of attention, executive functioning, and verbal memory in a large sample of GWI cases and healthy GW veteran controls using neuropsychological tests recommended in the CDEs. We additionally subdivided samples based on the specific neurotoxicant exposures related to cognitive deficits and compared exposed versus non-exposed veterans regardless of case criteria status. The total sample utilized cognitive testing outcomes from the newly collated Boston, Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI. Results: Participants included 411 GW veterans, 312 GWI (cases) and 99 healthy veterans (controls). Veterans with GWI showed significantly poorer attention, executive functioning, learning, and short-and-long term verbal memory than those without GWI. Further, GW veterans with exposures to acetylcholinesterase inhibiting pesticides and nerve gas agents, had worse performance on executive function tasks. Veterans with exposure to oil well fires had worse performance on verbal memory and those with pyridostigmine bromide anti-nerve gas pill exposures had better verbal memory and worse performance on an attention task compared to unexposed veterans. Conclusions: This study replicates prior results regarding the utility of the currently recommended CDEs in determining impairments in cognitive functioning in veterans with GWI in a new widely-available repository cohort and provides further evidence of cognitive decrements in GW veterans related to war-related neurotoxicant exposures.