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Comparing neuropsychological, typical, and ADNI criteria for the diagnosis of mild cognitive impairment in Vietnam-era veterans
- Monica T. Ly, Jennifer Adler, Adan F. Ton Loy, Emily C. Edmonds, Mark W. Bondi, Lisa Delano-Wood, for the Department of Defense Alzheimer’s Disease Neuroimaging Initiative
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- Journal:
- Journal of the International Neuropsychological Society / Volume 30 / Issue 5 / June 2024
- Published online by Cambridge University Press:
- 24 January 2024, pp. 439-447
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Objective:
Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer’s disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD.
Method:267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] p-tau181, t-tau, and Aβ42) by diagnostic criteria. Logistic regressions adjusting for age and education assessed the effects of TBI severity and PTSD symptom severity simultaneously on MCI classification by each criteria.
Results:Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF p-tau181 and t-tau. Typical and ADNI criteria were not associated with CSF biomarkers. PTSD symptom severity predicted MCI diagnosis by neuropsychological and ADNI criteria. History of moderate/severe TBI predicted MCI by typical and ADNI criteria.
Conclusions:MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.
40 APOE x BDNF Genetic Interaction is Associated with Poorer Cognitive Outcomes in Veterans with Histories of mTBI
- Adan F. Ton-Loy, Victoria C. Merritt, Erin D Ozturk, Monica Ly, Alin Alshaheri, Scott F. Sorg, Lisa Delano-Wood
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 147-148
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Objective:
Many Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans have sustained a mild traumatic brain injury (mTBI) during their military service and a substantial “miserable minority” frequently report significant cognitive complaints long after injury. Although existing studies have shown associations between genetic factors (e.g., apolipoprotein E [APOE] and brain-derived neurotrophic factor [BDNF]) and cognitive performance in this vulnerable population, the TBI-genetics literature has generally been varied and inconsistent. Although past findings suggest that individuals who possess APOE £4 and BDNF Met alleles have worse cognitive outcomes after mTBI, this has not been consistently reported. Additionally, the influence of any gene-by-gene interactions on cognition has not been sufficiently explored and therefore remains a critical area of interest. Thus, we examined relationships between APOE and BDNF genotypes on neuropsychological function in a well-characterized sample of younger Veterans with mTBI histories.
Participants and Methods:Participants included Veterans with a history of mTBI who adequately completed performance validity testing. In total, 78 Veterans (84.6% male; age: M=32.95, SD=7.00; race/ethnicity: 51.3% White, 28.2% Hispanic/Latino, and 20.5% Another Race/Ethnicity) completed a structured clinical interview to collect detailed information on TBI history and underwent a comprehensive neuropsychological exam. A buccal swab was also collected to determine APOE and BDNF allele status for each participant. Three cognitive composite scores were computed reflecting memory (8 items), attention/processing speed (7 items), and executive functioning (10 items). Two-way analyses of covariance (ANCOVAs) adjusting for age, sex, and race/ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning (ε4+/Met-: n=12, ε4+/Met+: n=8, £4-/Met-: n=35, and ε4-/Met+: n=23).
Results:ANCOVAs revealed no significant main effects for APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE x BDNF genotype interaction for all three cognitive composites (memory: p=.026, np2=.068; attention/processing speed: p=.045, np2=.055; and executive functioning: p=.031, np2=.064). Specifically, the interaction was such that Veterans in the ε4+/Met+ group demonstrated the poorest cognitive functioning relative to all other allele group combinations (ε4+/Met-, ε4-/Met+, ε4-/Met-).
Conclusions:The results of this preliminary study demonstrate that, compared to the other genetic subgroups in the TBI sample, Veterans with APOE £4 and BDNF Met alleles demonstrated the poorest cognitive functioning across several domains known to be negatively affected in the context of head injury (i.e., memory, attention/processing speed, and executive functioning). These findings are the first to show an APOE x BDNF interaction in Veterans with histories of mTBI. Further
research is necessary to replicate and extend this study in larger samples. Moreover, future work should incorporate neuroimaging variables to better interrogate structural and functional correlates of these observed genetic polymorphism associations in Veterans with mTBI histories.
48 Elevated Postconcussive Symptoms are Associated with Increased Anterior Cerebral Blood Flow and Not Cortical Thickness in Veterans with a History of Remote mTBI
- Erin D Ozturk, Victoria C Merritt, Monica T Ly, Alexandra L Clark, Katherine J Bangen, Adan F. Ton-Loy, Lisa Delano-Wood
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 154-155
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Objective:
Veterans with a history of mild traumatic brain injury (mTBI) often endorse enduring postconcussive symptoms (PCS) including cognitive and neuropsychiatric complaints. However, although several studies have shown associations between these complaints and brain structure and cerebrovascular function, few studies have examined relationships between structural and functional brain alterations and PCS in the context of remote mTBI. We therefore examined whether PCS were associated with cortical thickness and cerebral blood flow (CBF) in a well-characterized sample of Veterans with a history of mTBI.
Participants and Methods:116 Veterans underwent structural neuroimaging and a clinical interview to obtain detailed TBI history and injury-related information. Participants also completed the following self-report measures: the Neurobehavioral Symptom Inventory (NSI) for ratings of cognitive, emotional, somatic-sensory, and vestibular symptoms, and the Posttraumatic Stress Disorder (PTSD) Checklist for PTSD symptom severity. Regional brain thickness was indexed using FreeSurfer-derived cortical parcellations of frontal and temporal regions of interest (ROIs) including the superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), medial temporal lobe (MTL), and lateral temporal lobe (LTL). A subset of Veterans (n=50) also underwent multi-phase pseudo-continuous arterial spin labeling (MPPCASL) to obtain resting CBF. T1-weighted structural and MPPCASL scans were co-registered and CBF estimates were extracted from the 7 bilateral parcellations of ROIs. To assess the relationship between NSI total and subscale scores and ROI thickness and CBF, multiple regression analyses were conducted adjusting for age, sex, and PTSD symptom severity. False Discovery Rate was used to correct for multiple comparisons.
Results:NSI total and subscale scores were not associated with cortical thickness of any ROI. However, higher NSI scores were associated with increased ROI CBF of the SFG (q=.014) and MFG CBF (q=.014). With respect to symptom subscales, higher affective subscale scores were associated with increased SFG (q=.001), MFG (q=.001), IFG (q=.039), ACC (q=.026), and LTL CBF (q=.026); higher cognitive subscale scores were associated with increased SFG (q=.014) and MFG CBF (q=.032); and higher vestibular subscale scores were associated with increased ACC CBF (q=.021). NSI somatic-sensory subscale scores were not associated with ROI CBF.
Conclusions:Results demonstrate that in TBI-susceptible anterior ROIs, alterations in CBF but not cortical thickness are associated with postconcussive symptomatology in Veterans with a history of mTBI. Specifically, postconcussive total symptoms as well as affective, cognitive, and vestibular subscale symptoms were strongly linked primarily to CBF of frontal regions. Remarkably, these results indicate that enduring symptoms in generally younger samples of Veterans with head injury histories may be closely tied to cerebrovascular function rather than brain structure changes. These findings may provide a neurological basis for negative clinical outcomes (e.g., enduring PCS and poor quality of life) that is frequently reported by many individuals following mTBI. Future work is needed to examine unique effects of blast exposure as well as associations with repeated injury on brain-behavior relationships.