Neuropsychological Composite Scores Research Articles

Computerized Games versus Crosswords Training in Mild Cognitive Impairment: The COG‐IT trial

AbstractBackgroundMild cognitive impairment (MCI) increases the risk of dementia. The efficacy of cognitive training in MCI is unclear.MethodIn a two‐site, single‐blinded, 78‐week trial, participants with MCI — stratified by age, severity (early/late MCI), and site — were randomly assigned to 12 weeks of intensive, home‐based, computerized training with Web‐based cognitive games or Web‐based crossword puzzles, followed by six booster sessions. In mixed‐model analyses, the primary outcome was change from baseline in the 11‐item Alzheimer’s Disease Assessment Scale‐Cognitive (ADAS‐Cog) score, adjusted for baseline. Secondary outcomes included change from baseline in neuropsychological composite score and Functional Activities Questionnaire score at 78 weeks, adjusted for baseline. Changes in hippocampal volume and cortical thickness on magnetic resonance imaging were assessed.ResultAmong 107 participants (n = 51 [games]; n = 56 [crosswords]), ADAS‐Cog11 score worsened slightly for games and improved for crosswords at week 78 (least squares [LS] means difference, 21.44; 95% CI 22.83 to 20.06; P = 0.04). From baseline to week 78, mean ADAS‐Cog score worsened for games (9.53 to 9.93) and improved for crosswords (9.59 to 8.61). The late MCI subgroup showed similar results (LS means difference, 22.45; SE, 0.89; 95% CI 24.21 to 20.70). Among secondary outcomes, the Functional Activities Questionnaire score worsened more with games than with crosswords at week 78 (LS means difference, 21.08; 95% CI 21.97 to 20.18, p = 0.02). Other secondary outcomes showed no differences. Decreases in hippocampal volume and cortical thickness were greater for games than for crosswords (LS means difference, 34.07; SE, 17.12; 95% CI 0.51 to 67.63, p < .05 [hippocampal volume]; LS means difference, 0.02; SE, 0.01; 95% CI, 0.00 to 0.04, p = .02 [cortical thickness]).ConclusionHome‐based computerized training with crosswords demonstrated superior efficacy to games at 78 weeks. Common directionality was observed in the primary outcome of ADAS‐Cog (cognition) and the secondary outcomes of FAQ (function) score and changes in MRI hippocampal volume and cortical thickness (neurodegeneration). If these effects are replicated and expanded in future trials with the inclusion of a control group that does not receive cognitive training, crossword puzzles training could become a home‐based, scalable, cognitive enhancement tool for individuals with MCI.

1 Neuropsychological Outcome After Cardiac Arrest: Results from a Sub-study of the Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) Trial

Objective:To describe cognitive impairment in out-of-hospital cardiac arrest (OHCA) survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.Participants and Methods:This was a prospective case control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. We administered an extensive neuropsychological assessment at approximately 7 months post-cardiac event, including a neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes. Z-scores of individual tests were converted to neuropsychological composite scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions). Between-group differences on the neuropsychological composite scores were investigated with linear regression. Associations between anxiety, depression, fatigue, insomnia, hypertension, diabetes, and the neuropsychological composite scores among OHCA survivors were calculated with Spearman’s rho.Results:Of 184 eligible OHCA survivors, 108 were included (mean age = 62, 88% male), with 92 MI controls enrolled (mean age = 64, 89% male). Amongst OHCA survivors, 29% performed z <-1 indicating at least borderline-mild impairment in >2 cognitive domains, and 14% performed z <-2 exhibiting major impairment in >1 cognitive domain. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = -0.37, 95% confidence intervals [-0.61, -0.12]), verbal (MD = -0.34 [-0.62, -0.07]), and visual/constructive functions (MD = -0.26 [-0.47, -0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, processing speed (MD = -0.41 [-0.74, -0.09]) and executive functions (MD = -0.69 [-1.13, -0.24]) were also worse following OHCA. Depressive symptoms were associated with worse executive functions (rs = -0.37, p <0.001) and worse processing speed (rs = -0.27, p = 0.01) post-OHCA. Anxiety symptoms (rs = -0.21, p = 0.01) and general fatigue (rs = -0.24, p = 0.01) were associated with worse executive functions. Diabetes was associated with worse processing speed (rs = -0.20, p = 0.03), visual/constructive (rs = -0.29, p <0.001) and executive functions (rs = -0.25, p = 0.02), while hypertension and insomnia were not significantly associated with neuropsychological test performance.Conclusions:Cognitive impairment is generally mild following OHCA, but most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed worse than MI controls. We suggest that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.

56 TBI Severity Moderates the Association between Subjective and Objective Attention in Older Veterans

Objective:Prior work on associations between self-reported cognition and objective cognitive performance in Veterans has yielded mixed findings, with some evidence indicating that mild traumatic brain injury (TBI) may not impact the associations between subjective and objective cognition. However, few studies have examined these relationships in both mild and moderate-to-severe TBI, in older Veterans, and within specific cognitive domains. Therefore, we assessed the moderating effect of TBI severity on subjective and objective cognition across multiple cognitive domains.Participants and Methods:This study included 246 predominately male Vietnam-Era Veterans (age M=69.61, SD=4.18, Range = 60.87 – 85.16) who completed neuropsychological testing and symptom questionnaires as part of the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI). Participants were classified as having history of no TBI (n=81), mild TBI (n=80), or moderate-tosevere TBI (n=85). Neuropsychological composite scores in the domains of memory, attention/executive functioning, and language were included as the outcome variables. The Everyday Cognition (ECog) measure was used to capture subjective cognition and, specifically, the ECog domain scores of memory, divided attention, and language were chosen as independent variables to mirror the objective cognitive domains. General linear models, adjusting for age, education, apolipoprotein E ε4 carrier status, pulse pressure, depressive symptom severity, and PTSD symptom severity, tested whether TBI severity moderated the associations of domain-specific subjective and objective cognition.Results:Across the sample, subjective memory was associated with objective memory (β=-.205, 95% CI [-.332, -.078], p=.002) and subjective language was associated with objective language (β=-.267, 95% CI [-.399, -.134], p<.001). However, the main effect of subjective divided attention was not associated with objective attention/executive functioning (p=.124). The main effect of TBI severity was not associated with any of the objective cognitive domain scores after adjusting for the other variables in the model. The TBI severity x subjective cognition interaction was significant for attention/executive functioning [F(2,234)=5.18, p=.006]. Specifically, relative to Veterans without a TBI, participants with mild TBI (β=-.311, 95% CI [-.620, -.002], p=.048) and moderate-to-severe TBI (β=-.499, 95% CI [-.806, -.193], p=.002) showed stronger negative associations between subjective divided attention and objective attention/executive functioning. TBI severity did not moderate the associations between subjective and objective cognition for memory or language domains. The pattern of results did not change when the total number of TBIs was included in the models.Conclusions:In this DoD-ADNI sample, stronger associations between subjective and objective attention were evident among individuals with mild and moderate-to-severe TBI compared to Veterans without a TBI history. Attention/executive functioning measures (Trails A and B) may be particularly sensitive to detecting subtle cognitive difficulties related to TBI and/or comorbid psychiatric symptoms, which may contribute to these attention-specific findings. The strongest associations were among those with moderate-to-severe TBI, potentially because the extent to which their attention difficulties are affecting their daily lives are more apparent despite no significant differences in objective attention performance by TBI group. This study highlights the importance of assessing both subjective and objective cognition in older Veterans and the particular relevance of the attention domain within the context of TBI.

History of traumatic brain injury does not alter course of neurocognitive decline in older adults with and without cognitive impairment.

Traumatic brain injury (TBI) history is associated with dementia risk, but it is unclear whether TBI history significantly hastens neurocognitive decline in older adults. Data were derived from the National Alzheimer's Coordinating Center (NACC) data set. Participants with a history of TBI (TBI +; n = 1,467) were matched to individuals without a history of TBI (TBI-; n = 1,467) based on age (50-97, M = 71.61, SD = 8.40), sex, education, race, ethnicity, cognitive diagnosis, functional decline, number of Apolipoprotein ε4 (APOE ε4) alleles, and number of annual visits (3-6). Mixed linear models were used to assess longitudinal neuropsychological test composite scores of executive functioning/attention/speed, language, and memory in TBI + and TBI- participants. Interactions between TBI and demographics, APOE ε4 status, and cognitive diagnosis were also examined. Longitudinal neuropsychological functioning did not differ between TBI groups (p's > .001). There was a significant three-way interaction (age, TBI history, time) in language (F[20, 5750.1] = 3.133, p < .001) and memory performance (F[20, 6580.8] = 3.386, p < .001), but post hoc analyses revealed TBI history was not driving this relationship (all p's > .096). No significant interactions were observed between TBI history and sex, education, race/ethnicity, number of APOE ε4 alleles, or cognitive diagnosis (p's > .001). Findings suggest TBI history, regardless of demographic factors, APOE ε4 status, or cognitive diagnosis, does not alter the course of neurocognitive functioning later-in-life in older adults with or without cognitive impairment. Future clinicopathological longitudinal studies that well-characterize head injuries and the associated clinical course are needed to help clarify the mechanism in which TBI may increase dementia risk. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A - 19 Cognitive Test Score Dispersion VS. Traditional Memory Composite Scores: Predicting Mild Cognitive Impairment (MCI) & Dementia among Cognitively Impaired, Not MCI Patients.

To compare mild cognitive impairment (MCI) and dementia conversion rates between global neuropsychological dispersion (GD) and traditional memory neuropsychological composite score (MComp) in participants with baseline evidence of cognitive decline but no diagnosis of MCI or dementia. Data from the National Alzheimer's Coordinating Center (NACC) for 364 participants with a CDR of 0.5, no initial diagnosis of MCI or dementia, and five visits were analyzed. GD was the intraindividual standard deviation across baseline normative (NACC norms) neuropsychological performance. MComp was the mean of the four verbal and visual memory normed scores. Multinomial logistic regression models fit statistics compared GD and MComp as predictors of conversion to MCI/dementia, adjusting for age, sex, race, ethnicity, ApoE4 status, and stratified by suspected etiology (Alzheimer's disease [ad] or no-ad). Lower Akaike Information Criteria (AIC) values indicate better model fit and predictions. 37% progressed to MCI, and 47% to dementia by visit 5. 53% of these were suspected to have ad etiology, and 47% non-ad. MComp showed a better fit with significant predictions of MCI and dementia progression in both suspected ad (AIC: 351.77, p < 0.001) or non-ad etiology (AIC: 215.02, p < 0.004), versus GD was only significant for non-ad etiology (AIC: 385.74, p < 0.003). Better memory performance predicted a lower likelihood of conversion to non-ad MCI (B = -0.65, p = 0.003) and non-ad dementia (B = -1.33, p < 0.001). GD predicted eventual progression to non-ad dementia (B = 2.311, p = 0.004), but not non-ad MCI. Traditional memory composite score may be a better predictor of MCI and dementia conversion than cognitive dispersion in individuals with early cognitive decline who do not yet meet MCI criteria.

Cognitive and psychiatric outcomes in the GALAXY trial: effect of anaesthesia in deep brain stimulation

BackgroundThis study aims: (1) To compare cognitive and psychiatric outcomes after bilateral awake versus asleep subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson’s disease (PD). (2) To explore...

Neuropsychological Function in Traumatic Brain Injury and the Influence of Chronic Pain.

Cognitive dysfunction, pain, and psychological morbidity all present unique challenges to those living with traumatic brain injury (TBI). In this study we examined (a) the impact of pain across domains of attention, memory, and executive function, and (b) the relationships between pain and depression, anxiety, and post-traumatic stress disorder (PTSD) in persons with chronic TBI. Our sample included 86 participants with a TBI and chronic pain (n = 26), patients with TBI and no chronic pain (n = 23), and a pain-free control group without TBI (n = 37). Participants visited the laboratory and completed a comprehensive battery of neuropsychological tests as part of a structured interview. Multivariate analysis of covariance using education as a covariate, failed to detect a significant group difference for neuropsychological composite scores of attention, memory, and executive function (p = .165). A follow-up analysis using multiple one-way analysis of variance (ANOVA) was conducted for individual measures of executive function. Post-hoc testing indicated that those in both TBI groups preformed significantly worse on measures of semantic fluency when compared to controls (p < 0.001, ηρ2 = .16). Additionally, multiple ANOVAs indicated that those with TBI and pain scored significantly worse across all psychological assessments (p < .001). We also found significant associations between measures of pain and most psychological symptoms. A follow-up stepwise linear regression among those in the TBI pain group indicated that post concussive complaints, pain severity, and neuropathic pain symptoms differentially contributed to symptoms of depression, anxiety, and PTSD. These findings suggest deficits in verbal fluency among those living with chronic TBI, with results also reinforcing the multidimensional nature of pain and its psychological significance in this population.

Classification and prediction of cognitive trajectories of cognitively unimpaired individuals.

Efforts to prevent Alzheimer's disease (AD) would benefit from identifying cognitively unimpaired (CU) individuals who are liable to progress to cognitive impairment. Therefore, we aimed to develop a model to predict cognitive decline among CU individuals in two independent cohorts. A total of 407 CU individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and 285 CU individuals from the Samsung Medical Center (SMC) were recruited in this study. We assessed cognitive outcomes by using neuropsychological composite scores in the ADNI and SMC cohorts. We performed latent growth mixture modeling and developed the predictive model. Growth mixture modeling identified 13.8 and 13.0% of CU individuals in the ADNI and SMC cohorts, respectively, as the "declining group." In the ADNI cohort, multivariable logistic regression modeling showed that increased amyloid-β (Aβ) uptake (β [SE]: 4.852 [0.862], p < 0.001), low baseline cognitive composite scores (β [SE]: -0.274 [0.070], p < 0.001), and reduced hippocampal volume (β [SE]: -0.952 [0.302], p = 0.002) were predictive of cognitive decline. In the SMC cohort, increased Aβ uptake (β [SE]: 2.007 [0.549], p < 0.001) and low baseline cognitive composite scores (β [SE]: -4.464 [0.758], p < 0.001) predicted cognitive decline. Finally, predictive models of cognitive decline showed good to excellent discrimination and calibration capabilities (C-statistic = 0.85 for the ADNI model and 0.94 for the SMC model). Our study provides novel insights into the cognitive trajectories of CU individuals. Furthermore, the predictive model can facilitate the classification of CU individuals in future primary prevention trials.

Cognitive trajectories diverge by genetic risk in a preclinical longitudinal cohort.

We sought to characterize the timing of changes in cognitive trajectories related to genetic risk using the apolipoprotein E (APOE) score, a continuous measure of Alzheimer's disease (AD) risk. We also aimed to determine whether that timing was different when genetic risk was measured using an AD polygenic risk score (PRS) that contains APOE. We analyzed trajectories (N ≈1135) for four neuropsychological composite scores using mixed effects regression for longitudinal change across APOE scores and PRS of participants in the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of adults aged 40 to 70 at baseline, with a median participant follow-up time of 7.8 years. We found a significant non-linear age-by-APOE score interaction in predicting cognitive decline. Cognitive trajectories diverged by APOE score at approximately 65 years of age. A 0.5 standard deviation difference in cognition between extreme percentiles of the PRS was predicted to occur 1 to 2 years before that of the APOE score. Cognitive decline differs across time and APOE score. Estimates did not substantially shift with the AD PRS. The apolipoprotein E (APOE) score, a continuous measure, accounts for non-linear genetic risk of Alzheimer's disease. Non-linear age interacts with the APOE score to affect cognition. Cognitive decline starts to differ by APOE score levels at approximately age 65. Cognitive decline timing by polygenic risk (including APOE) is similar to APOE alone.

¹⁸F-fluorodeoxyglucose-positron emission tomography findings are not related to cognitive functioning in service members with remote history of mild traumatic brain injury.

Determine whether glucose uptake as measured by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is associated with cognitive performance and cognitive deficits in active duty service members with a history of mild traumatic brain injury (mTBI). 287 patients with a history of mTBI underwent FDG-PET scans at rest and neuropsychological testing at the National Intrepid Center of Excellence at Walter Reed National Military Medical Center. Glucose uptake in the bilateral frontal, parietal, occipital, and temporal lobes, and 58 cortical/cerebellar regions were correlated with seven neuropsychological composite scores, with and without relevant covariates. Perceptual reasoning correlated with bilateral hippocampi glucose uptake (rs = .141-.165, p < .03), processing speed was inversely related to glucose uptake in the left temporal lobe (r = -.134, p = .034), and working memory was related to glucose uptake in the left parietal, temporal, and occipital lobes (rs = .128-.140, p < .05); however, these findings did not survive correction for multiple comparisons. Partial correlations between cognition and the 56 cortical/cerebellar regions of interests were not significant after correction for multiple comparisons. Glucose uptake in the left hippocampus was inversely related to the likelihood of cognitive deficits (OR = .745, p = .041); however, this did not survive correction for multiple comparisons. After correction for multiple comparisons, there was no significant relationship between regional glucose uptake and neurocognitive performance or cognitive deficits. Glucose uptake as measured by FDG-PET is not indicative of cognitive performance in active duty service members with a remote history of mTBI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

No association between age beginning tackle football, or years played and neurocognitive performance later-in-life among older National Football League retirees.

In a retrospective cohort, we evaluated whether age beginning tackle football (ABTF) and more total years of playing football (TYPF) were associated with worse later-in-life neuropsychological change among older retired National Football League (NFL) players. Participants were 19 older NFL retirees aged 54-79, including 12 who returned for follow-up evaluation 15-51months later. Mixed-linear models evaluated the association between ABTF/TYFP and baseline neuropsychological composite scores (executive functioning/attention/speed, language, memory), and neuropsychological composites over time. ABTF and TYPF were not significantly associated with neuropsychological composites at baseline or over time (all p's > .05). There were no significant differences in neuropsychological performance between those ABTF <12 and ≥ 12years old (all p's ≥ .475) or between those with TYPF <19 or ≥ 19years played (median split; all p's ≥ .208). Preliminary findings suggest that ABTF and TYPF does not worsen neurocognitive decline later-in-life among older NFL retirees.

Computerized Games versus Crosswords Training in Mild Cognitive Impairment

BackgroundMild cognitive impairment (MCI) increases the risk of dementia. The efficacy of cognitive training in patients with MCI is unclear.MethodsIn a two-site, single-blinded, 78-week trial, participants with MCI — stratified by age, severity (early/late MCI), and site — were randomly assigned to 12 weeks of intensive, home-based, computerized training with Web-based cognitive games or Web-based crossword puzzles, followed by six booster sessions. In mixed-model analyses, the primary outcome was change from baseline in the 11-item Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) score, a 70 point scale in which higher scores indicate greater cognitive impairment at 78 weeks, adjusted for baseline. Secondary outcomes included change from baseline in neuropsychological composite score, University of California San Diego Performance-Based Skills Assessment (functional outcome) score, and Functional Activities Questionnaire (functional outcome) score at 78 weeks, adjusted for baseline. Changes in hippocampal volume and cortical thickness on magnetic resonance imaging were assessed.ResultsAmong 107 participants (n=51 [games]; n=56 [crosswords]), ADAS-Cog score worsened slightly for games and improved for crosswords at week 78 (least squares [LS] means difference, −1.44; 95% confidence interval [CI], −2.83 to −0.06; P=0.04). From baseline to week 78, mean ADAS-Cog score worsened for games (9.53 to 9.93) and improved for crosswords (9.59 to 8.61). The late MCI subgroup showed similar results (LS means difference, −2.45; SE, 0.89; 95% CI, −4.21 to −0.70). Among secondary outcomes, the Functional Activities Questionnaire score worsened more with games than with crosswords at week 78 (LS means difference, −1.08; 95% CI, −1.97 to −0.18). Other secondary outcomes showed no differences. Decreases in hippocampal volume and cortical thickness were greater for games than for crosswords (LS means difference, 34.07; SE, 17.12; 95% CI, 0.51 to 67.63 [hippocampal volume]; LS means difference, 0.02; SE, 0.01; 95% CI, 0.00 to 0.04 [cortical thickness]).ConclusionsHome-based computerized training with crosswords demonstrated superior efficacy to games for the primary outcome of baseline-adjusted change in ADAS-Cog score over 78 weeks. (Supported by the National Institutes of Health, National Institute on Aging; ClinicalTrials.gov number, NCT03205709.)

A-178 18F-Fluorodeoxyglucose Positron Emission Tomography Findings Are Not Related to Cognitive Functioning in Service Members with Remote History of Traumatic Brain Injury

Abstract Objective: Determine whether glucose uptake as measured by 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is associated with cognitive performance and mild neurocognitive disorder (MNCD) in active-duty service members with a history of mild traumatic brain injury (mTBI). Method: 287 patients with a history of mTBI underwent FDG-PET scans at rest and neuropsychological testing at the National Intrepid Center of Excellence at Walter Reed National Military Medical Center. Glucose uptake in bilateral frontal, parietal, occipital, and temporal lobes, and 58 cortical/cerebellar regions were correlated with seven neuropsychological composite scores, with and without relevant covariates. Results: Prior to correction for multiple comparisons, perceptual reasoning correlated with bilateral hippocampi glucose uptake (rs:.141-.165, ps&amp;lt;.03), processing speed was inversely related to glucose uptake in the left temporal lobe (r=-.134, p=.034), working memory was related to glucose uptake in the left parietal, temporal, and occipital lobes (rs:.128-.140, ps&amp;lt;.05). Partial correlations between cognition and the 56 cortical/cerebellar regions of interest (ROIs) were not significant after correction for multiple comparisons. Increased glucose uptake in the bilateral pericalcarine, left superior temporal, and right occipital, superior parietal, transverse temporal, precuneus, and lingual cortices was related to increased likelihood of MNCD (ORs:41.02-2263.7, ps&amp;lt;.05); however, did not survive correction for multiple comparisons. Conclusions: After correction for multiple comparisons, there was no significant relationship between regional glucose uptake and neurocognitive performance or MNCD. Glucose uptake as measured by FDG-PET is not related to cognitive performance in active-duty service members with a remote history of mTBI and may have limited clinical utility for these individuals.

Association of Depressive Symptoms and Cognition in Older Adults Without Dementia Across Different Biomarker Profiles.

Depression is a late-life risk factor for cognitive decline. Evidence suggests an association between Alzheimer's disease (AD) associated pathologic changes and depressive symptoms. To investigate the influence of AT(N) biomarker profile (amyloid-β [A], p-tau [T], and neurodegeneration [N]) and gender on cross-sectional associations between subclinical depressive symptoms and cognitive function among older adults without dementia. Participants included 868 individuals without dementia from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Depressive symptoms were measured using the Geriatric Depression Scale (GDS). ADNI neuropsychological composite scores assessed memory and executive function (EF). PET, cerebrospinal fluid, and MRI modalities classified the study sample into biomarker profiles: normal biomarkers (A-T-N-), AD continuum (A+T±N±), and suspect non-AD pathology (SNAP; A-T±N-or A-T-N±). Multivariate regression models were used to investigate associations between GDS and cognitive domains. GDS was negatively associated with memory (β= -0.156, p < 0.001) and EF (β= -0.147, p < 0.001) in the whole sample. When classified by biomarker profile, GDS was negatively associated with memory and EF in AD continuum (memory: β= -0.174, p < 0.001; EF: β= -0.129 p = 0.003) and SNAP (memory: β= -0.172, p = 0.005; EF: β= -0.197, p = 0.001) subgroups. When stratified by sex, GDS was negatively associated with memory (β= -0.227, p < 0.001) and EF (β= -0.205, p < 0.001) in men only. The association between subclinical depressive symptoms and cognitive function is highly influenced by the AT(N) biomarker profile.

Post-Traumatic Stress Disorder Symptoms Are Related to Cognition after Complicated Mild and Moderate Traumatic Brain Injury but Not Severe and Penetrating Traumatic Brain Injury.

Although post-traumatic stress disorder (PTSD) has been associated with worse cognitive outcomes after mild traumatic brain injury (TBI), its impact has not been evaluated after more severe TBI. This study aimed to determine whether PTSD symptoms are related to cognition after complicated mild, moderate, severe, and penetrating TBI. Service members (n = 137) with a history of complicated mild/moderate TBI (n = 64) or severe/penetrating TBI (n = 73) were prospectively enrolled from United States Military Treatment Facilities. Participants completed a neuropsychological assessment one year or more post-injury. Six neuropsychological composite scores and an overall test battery mean (OTBM) were considered. Participants were excluded if there was evidence of invalid responding. Hierarchical linear regressions were conducted evaluating neuropsychological performance. The interaction between TBI severity and PTSD Checklist-Civilian version total score was significant for processing speed (β = 0.208, p = 0.034) and delayed memory (β = 0.239, p = 0.021) and trended toward significance for immediate memory (β = 0.190, p = 0.057) and the OTBM (β = 0.181, p = 0.063). For each of these composite scores, the relationship between PTSD symptoms and cognition was stronger in the complicated mild/moderate TBI group than the severe/penetrating TBI group. Within the severe/penetrating TBI group, PTSD symptoms were unrelated to cognitive performance. In contrast, within the complicated mild/moderate TBI group, PTSD symptoms were significantly related to processing speed (R2Δ = 0.077, β = -0.280, p = 0.019), immediate memory (R2Δ = 0.197, β = -0.448, p < 0.001), delayed memory (R2Δ = 0.176, β = -0.423, p < 0.001), executive functioning (R2Δ = 0.100, β = -0.317, p = 0.008), and the OTBM (R2Δ = 0.162, β = -0.405, p < 0.001). The potential impact of PTSD symptoms on cognition, over and above the impact of brain injury alone, should be considered with service members and veterans with a history of complicated mild/moderate TBI. In addition, in research comparing cognitive outcomes between patients with histories of complicated-mild, moderate, severe, and/or penetrating TBI, it will be important to account for PTSD symptoms.

Impact of Traumatic Microbleeds on Neuropsychological Outcomes in Patients with a Traumatic Brain Injury

<h3>Research Objectives</h3> Exam the relationship between TMB and neuropsychological outcomes in patients who have sustained a TBI. <h3>Design</h3> Prospective cohort study of participants with a history of non-penetrating brain injury. Participants were evaluated with neuropsychological and magnetic resonance imaging (MRI) as early as 30 days and up to 5 years post injury. TMB were identified by a board-certified neuroradiologist. <h3>Setting</h3> The National Institutes of Health. <h3>Participants</h3> Participants with a history of mild, moderate, or severe TBI. <h3>Interventions</h3> Participants underwent 3T MRI of the brain. <h3>Main Outcome Measures</h3> TMB in relation to neuropsychological outcomes. Neuropsychological composite scores were developed to assess various domains of cognition: Processing Speed, Delayed Memory, Executive Functioning, Language, Motor, Spatial, General Fund of Knowledge, Attention/Working Memory, Overall, and Timed Test. <h3>Results</h3> Eighty-one participants age 18-86, (53, 65% male vs. 28 female 35%) with a history of TBI (34 mild, 31 moderate, 16 severe) were enrolled. At baseline 44 participants (54%) had TMB, with an average age of 45 (median 44, IQR 28) and predominantly male (20, 65% male vs. 11 female 35%). Longitudinally, 42 participants (52%) had persistent TMB, ranging from persisting less than a year up to persisting 5 years. Cross-sectionally, there were no significant differences in the neuropsychological composite scores between those with TMB versus those without. Additionally, adjusting for sex, age and TBI severity cross-sectionally did not yield any significant differences in neuropsychological composite scores between participants with and without TMBs. Longitudinally, the presence of TMBs at baseline were not associated with significant changes in neuropsychological composites scores. <h3>Conclusions</h3> Participants with TMBs showed no significant difference in neuropsychological functioning compared to participants without TMBs cross-sectionally or longitudinally. <h3>Author(s) Disclosures</h3> Nothing to disclose.

A-15 PTSD Symptoms Are Related to Cognition Following Complicated Mild and Moderate TBI, but Not Severe and Penetrating TBI

Abstract Objective Despite the strong evidence suggesting post-traumatic stress disorder (PTSD) symptoms negatively impact cognition following mild traumatic brain injury (TBI), little is known about this relationship in more severe TBI. This study investigates the relationship between PTSD symptoms and cognitive performance following complicated mild, moderate, severe, and penetrating TBI. Methods Participants were 137 U.S. military service members and veterans (SMVs) with a history of complicated mild or more severe TBI prospectively enrolled in the Defense and Veterans Brain Injury Center (DVBIC)/Traumatic Brain Injury Center of Excellence (TBICoE) 15-Year Longitudinal TBI Study. Participants were divided into two groups: complicated mild/moderate TBI (n = 64) and severe/penetrating TBI (n = 73). Participants completed a neuropsychological assessment, including the PTSD Checklist-Civilian Version one year or more post-injury. Six neuropsychological composite scores and an overall test battery mean (OTBM) were considered. Participants who failed symptom validity tests were excluded. Hierarchical linear regressions were conducted evaluating neuropsychological performance. Results TBI severity (βs:-0.163 to −0.253, ps &amp;lt; 0.04) and PTSD symptoms (βs:-0.189 to −0.212), ps &amp;lt; 0.03) were related to neuropsychological performance in the overall sample. Within the severe/penetrating TBI group, PTSD symptoms were unrelated to cognitive performance. Within the complicated mild/moderate TBI group, PTSD symptoms were significantly related to processing speed (R2Δ = 0.080, β = −0.284, p = 0.016), immediate memory (R2Δ = 0.204, β = −0.453, p &amp;lt; 0.001), delayed memory (R2Δ = 0.180, β = −0.426, p &amp;lt; 0.001), executive functioning (R2Δ = 0.102, β = −0.319, p = 0.007), and the OTBM (R2Δ = 0.170, β = −0.413, p &amp;lt; 0.001). Discussion PTSD symptom severity was significantly related to neuropsychological performance in SMVs with complicated mild/moderate TBI. PTSD symptoms should be considered when evaluating patients with a history of complicated mild to moderate TBI.

Blood Biomarkers Relate to Cognitive Performance Years after Traumatic Brain Injury in Service Members and Veterans.

This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI). Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted. Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R2Δ = .065-.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R2Δ = .052-.071, ps < .05), and NFL was related to executive functioning (R2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = .029). Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.

PTSD, but not history of mTBI, is associated with altered myelin in combat-exposed Iraq and Afghanistan Veterans

Objective To investigate the biological, cognitive, and psychological presentations of combat-exposed Veterans with a history of mild traumatic brain injury (mTBI) and/or posttraumatic stress disorder (PTSD) using a novel white matter imaging technique and comprehensive neuropsychological assessment. Method 74 Iraq and Afghanistan Veterans (mean age 33.89, 90.5% male) with history of mTBI (average 7.25 years since injury), PTSD, both, or neither underwent magnetic resonance imaging (MRI) exams including acquisition of a novel imaging technique, multicomponent-driven equilibrium single-pulse observation of T1/T2 (mcDESPOT) to quantify myelin water fraction (MWF), a surrogate measure of myelin content. Participants also underwent comprehensive neuropsychological assessment and three cognitive composite scores (memory, working memory/processing speed, and executive functioning) were created. Results There were no significant group differences on the neuropsychological composite scores. ANCOVAs revealed a main effect of PTSD across all a priori regions of interest (ROI) in which PTSD was associated with higher MWF. There was no main effect of mTBI history or TBI by PTSD interaction on any ROI. Significant positive associations were observed between myelin and PTSD symptoms, but no significant associations were found between myelin and neurobehavioral symptoms. No significant associations were found between myelin in the a priori ROIs and the cognitive composite scores. Conclusion This study did not find neuropsychological or MWF differences in combat Veterans with a remote history of mTBI but did find myelin alterations related to PTSD. Psychological trauma should be a primary target for intervention in Veterans with comorbid PTSD and mTBI reporting subjective complaints, given its salience.

Prevalence and determinants of subjective cognitive decline in a representative Greek elderly population.

We studied the prevalence of subjective cognitive decline (SCD) and its determinants in a sample of 1456 cognitively normal Greek adults ≥65years old. Subjects were evaluated by a multidisciplinary team on their neurological, medical, neuropsychological, and lifestyle profile to reach consensus diagnoses. We investigated various types of SCD, including single-question, general memory decline, specific subjective memory decline based on a list of questions and three types of subjective naming, orientation, and calculation decline. In a single general question about memory decline, 28.0% responded positively. The percentage of our sample that reported at least one complaint related to subjective memory decline was 76.6%. Naming difficulties were also fairly common (26.0%), while specific deficits in orientation (5.4%) and calculations/currency handling (2.6%) were rare. The majority (84.2%) of the population reported subjective deficits in at least one cognitive domain. Genetic predisposition to dementia increased the odds for general memory decline by more than 1.7 times. For each one-unit reduction in the neuropsychological composite score (a mean of memory, executive, language, visuospatial, and attention-speed composite scores), the odds for decline in orientation increased by 40.3%. Depression/anxiety and increased cerebrovascular risk were risk factors for almost all SCD types. SCD regarding memory is more frequent than non-memory decline in the cognitively normal Greek elderly population. Genetic predisposition to dementia, lower cognitive performance, affective symptoms, and increased cerebrovascular risk are associated with prevalent SCD. Further prospective research is needed to improve understanding of the evolution of SCD over time.