Lecanemab and Vascular-Amyloid Deposition in Brains of People With Down Syndrome.

Importance: Anti-ß-amyloid immunotherapy using lecanemab is becoming increasingly available to patients with Alzheimer disease (AD). Individuals with Down syndrome (DS) develop AD neuropathology by age 40 years, representing a significant cohort of genetically determined AD. Objective: To investigate the binding properties of lecanemab in the brains of people with DS, in anticipation of their inclusion in clinical trials or access to antiamyloid immunotherapies. Design, Setting, Participants: The study included cases of postmortem brain tissue analysis from 15 individuals with DS aged 43 to 68 years that were acquired from Alzheimer Disease research centers at the University of California, Irvine and the University of Kentucky from 2008 to 2021. Data were analyzed from August 2023 through May 2024. Exposure: The binding properties of lecanemab were assessed in brain tissue. Main Outcome: The primary outcome was the extent of lecanemab binding to amyloid plaques and brain blood vessels. Results: Tissue from 15 people (8 were female [53%]) with DS ranging in age from 43 to 68 (mean, 56.6) years were included in the study. Lecanemab-labeled amyloid plaques appeared in all 15 DS cases studied, indicating potential target engagement. However, extensive binding of lecanemab to brain blood vessels in DS was observed, raising significant safety concerns. These findings underscore the necessity for clinical trials of lecanemab in people with DS to evaluate both safety and efficacy, particularly in individuals older than 43 years. Conclusions and Relevance: These findings suggest significant binding of lecanemab to cerebral amyloid angiopathy in DS. Lecanemab should be rigorously tested in clinical trials for AD in the DS population to determine its safety and efficacy, especially in those older than 43 years.

The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy.

INTRODUCTION: The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. METHODS: There were 81 subjects that met inclusion criteria for this study. These subjects underwent MT for ELVO, and carotid arterial blood samples acquired at time of intervention were sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), and cognitive outcomes (Montreal Cognitive Assessment; MoCA). RESULTS: No significant differences were found in demographic data or co-morbidities when comparing Appalachian to non-Appalachian subjects. However, time from stroke onset to treatment (last known normal) was significantly longer and edema volume significantly higher in patients from Appalachia. Further, when comparing Appalachian to non-Appalachian subjects, there were significant unadjusted differences in the NIHSS functional outcome. A comprehensive analysis of 184 proteins from Olink proteomic (92 Cardiometabolic and 92 Inflammation panels) showed that the association between protein expression outcomes significantly differed by Appalachian status for seven proteins for the NIHSS, two proteins for the MoCA, and three for the mRS. CONCLUSION: Our study utilizes an ELVO tissue bank and registry to investigate the intracranial/intravascular proteomic environment occurring at the time of thrombectomy. We found that patients presenting from Appalachian areas have different levels of proteomic expression at the time of MT when compared to patients presenting from non-Appalachian areas. These proteins differentially relate to stroke outcome and could be used as prognostic biomarkers, or as targets for novel therapies. The identification of a disparate proteomic response in Appalachian patients provides initial insight to the biological basis for health disparity. Nevertheless, further investigations through community-based studies are imperative to elucidate the underlying causes of this differential response.

The Association of Gabapentin Initiation with Cognitive and Behavioral Changes in Older Adults with Cognitive Impairment: A Retrospective Cohort Study.

BACKGROUND: Although gabapentin has been increasingly prescribed to older adults, the relation between gabapentin initiation and longer-term neurocognitive changes is not well understood. Thus, this study aimed to examine the association of gabapentin initiation with cognitive and motor function decline in older adult participants with cognitive impairment. METHODS: A retrospective cohort study was conducted using the National Alzheimer's Coordinating Center Uniform Data Set (2005-March 2023). Participants with cognitive impairment at the visit of gabapentin initiation (i.e., index visit) were included. Using the incidence density sampling method, up to nine non-users were randomly selected for each initiator. Cognitive decline over 1 year was defined as any increase in Clinical Dementia Rating global score (CDR®GLOB) or a 1-point increase in CDR® sum of boxes (CDR®SB). Functional status decline over 1 year was defined as at least a 3-point increase in the Functional Activities Questionnaire (FAQ) sum or a 0.3-point increase of mean of FAQ. Motoric decline over 1 year was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, joint stabilized inverse probability of treatment weights and censoring weights were used. Analyses compared index with index + 1 and index + 2 visits. RESULTS: For the study of cognitive and functional status decline, we included 505 initiators (mean age [SD] 78.8 [7.4]; male = 45%) and 4545 non-users (79.2 [7.6]; 50.1%). For the study of motor decline, we included 353 initiators (78.3 [7.2]; 42.8%) and 3177 non-users (78.5 [7.4]; 48.1%). Gabapentin initiation was not statistically associated with decline on CDR®GLOB, CDR®SB, FAQ sum, or mean FAQ at the index + 1 or index + 2 visits. However, gabapentin initiation was significantly associated with increased odds of new falls at the index + 2 visit (odds ratio [95% confidence interval] 2.5 [1.3, 4.6]). CONCLUSIONS: Over 1 or 2 years of follow-up, gabapentin initiation was not associated with decline in cognitive or functional status but was associated with increased odds of falling among research participants with cognitive impairment.

Performance Validity Testing on the NIH Toolbox Cognition Battery: Base Rates of Failed Embedded Validity Indicators in the Adult Normative Sample.

OBJECTIVE: The goal of this study was to determine the base rates of failing proposed embedded validity indicators (EVIs) for the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB) in the normative sample. METHOD: Participants included adults in the NIHTB-CB normative sample with data to calculate age-adjusted standard scores (n = 855; ages: M(SD) = 46.9(17.3), range: 18-85; 65.0% women; education: M(SD) = 14.1(2.5) years) or demographically adjusted T-scores (n = 803; ages: M(SD) = 47.3(17.3), range: 18-85; 65.3% women; education: M(SD) = 14.2(2.5) years) for all tests. The NIHTB-CB includes two tests of crystallized cognition and five tests of fluid cognition. Individual norm-referenced test performances were categorized as falling above or below liberal and conservative cutoffs based on proposed univariate EVIs. The number of univariate EVI failures was summed to compute multivariable EVIs. EVI failure rates above 10% were considered high false-positive rates, indicating specificity < .90. Using chi-square analyses, the frequencies of EVI failures were compared based on gender, race/ethnicity, education, and crystallized composite. RESULTS: The multivariable EVIs had predominantly low false-positive rates in the normative sample. EVI failure rates were most common among participants with low crystallized composites. Using age-adjusted standard scores, EVI failure rates varied by education, race/ethnicity, and estimated premorbid intelligence. These differences were mostly eliminated when using demographically adjusted T-scores. CONCLUSIONS: Multivariable EVIs requiring ≥ 4 failures using liberal cutoffs or ≥ 3 failures using conservative cutoffs had acceptable false-positive rates (i.e., < 10%) using both age-adjusted standard scores and demographically adjusted T-scores. These multivariable EVIs could be applied to large data sets with NIHTB-CB data to screen for potentially invalid test performances.

Alzheimer's disease and inflammatory biomarkers positively correlate in plasma in the UK-ADRC cohort.

INTRODUCTION: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia. METHODS: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer's Disease Research Center cohort. We evaluated six Alzheimer's disease (AD)- and neurodegeneration-related (Aß40, Aß42, Aß42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform. Statistics were performed to assess correlations. RESULTS: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD-inflammatory biomarker correlations showed significant associations between AD and inflammatory biomarkers suggesting peripheral inflammatory interactions with increasing AD pathology. Biomarker associations parsed out by clinical diagnosis (normal, MCI, and dementia) reveal changes in strength of the correlations across the cognitive continuum. DISCUSSION: Unique AD-inflammatory biomarker correlations in a community-based cohort reveal a new avenue for utilizing plasma-based biomarkers in the assessment of AD and related dementias. HIGHLIGHTS: Large community cohorts studying sex, age, and APOE genotype effects on biomarkers are few. It is unknown how biomarker-biomarker associations vary through aging and dementia. Six AD (Aß40, Aß42, Aß42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNFα, IL6, IL8, IL10, and GFAP) were used to examine associations between biomarkers. Plasma biomarkers suggesting increasing cerebral AD pathology corresponded to increases in peripheral inflammatory markers, both pro-inflammatory and anti-inflammatory. Strength of correlations, between pairs of classic AD and inflammatory plasma biomarker, changes throughout cognitive progression to dementia.

A blunted TH17 cytokine signature in women with mild cognitive impairment: insights from inflammatory profiling of a community-based cohort of older adults.

People with dementia have an increase in brain inflammation, caused in part by innate and adaptive immune cells. However, it remains unknown whether dementia-associated diseases alter neuro-immune reflex arcs to impact the systemic immune system. We examined peripheral immune cells from a community-based cohort of older adults to test if systemic inflammatory cytokine signatures associated with early stages of cognitive impairment. Human peripheral blood mononuclear cells were cultured with monocyte or T-cell-targeted stimuli, and multiplex assays quantitated cytokines in the conditioned media. Following T-cell-targeted stimulation, cells from women with cognitive impairment produced lower amounts of TH17 cytokines compared with cells from cognitively healthy women, while myeloid-targeted stimuli elicited similar amounts of cytokines from cells of both groups. This TH17 signature correlated with the proportion of circulating CD4+ and CD8+ T cells and plasma glial fibrillary acidic protein and neurofilament light concentrations. These results suggest that decreases in TH17 cytokines could be an early systemic change in women at risk for developing dementia. Amelioration of TH17s cytokines in early cognitive impairment could, in part, explain the compromised ability of older adults to respond to vaccines or defend against infection.

Inflammatory-associated proteomic predictors of cognitive outcome in subjects with ELVO treated by mechanical thrombectomy.

BACKGROUND: Emergent Large Vessel Occlusion (ELVO) stroke causes devastating vascular events which can lead to significant cognitive decline and dementia. In the subset of ELVO subjects treated with mechanical thrombectomy (MT) at our institution, we aimed to identify systemic and intracranial proteins predictive of cognitive function at time of discharge and at 90-days. These proteomic biomarkers may serve as prognostic indicators of recovery, as well as potential targets for novel/existing therapeutics to be delivered during the subacute stage of stroke recovery. METHODS: At the University of Kentucky Center for Advanced Translational Stroke Sciences, the BACTRAC tissue registry (clinicaltrials.gov; NCT03153683) of human biospecimens acquired during ELVO stroke by MT is utilized for research. Clinical data are collected on each enrolled subject who meets inclusion criteria. Blood samples obtained during thrombectomy were sent to Olink Proteomics for proteomic expression values. Montreal Cognitive Assessments (MoCA) were evaluated with categorical variables using ANOVA and t-tests, and continuous variables using Pearson correlations. RESULTS: There were n = 52 subjects with discharge MoCA scores and n = 28 subjects with 90-day MoCA scores. Several systemic and intracranial proteins were identified as having significant correlations to discharge MoCA scores as well as 90-day MoCA scores. Highlighted proteins included s-DPP4, CCL11, IGFBP3, DNER, NRP1, MCP1, and COMP. CONCLUSION: We set out to identify proteomic predictors and potential therapeutic targets related to cognitive outcomes in ELVO subjects undergoing MT. Here, we identify several proteins which predicted MoCA after MT, which may serve as therapeutic targets to lessen post-stroke cognitive decline.

Examining the Effects of Formal Education Level on the Montreal Cognitive Assessment.

BACKGROUND: Brief, global assessments such as the Montreal Cognitive Assessment (MoCA) are widely used in primary care for assessing cognition in older adults. Like other neuropsychological instruments, lower formal education can influence MoCA interpretation. METHODS: Data from 2 large studies of cognitive aging were used-Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Alzheimer's Coordinating Center (NACC). Both use comprehensive examinations to determine cognitive status and have brain amyloid status for many participants. Mixed models were used to account for random variation due to data source. RESULTS: Cognitively intact participants with lower education (≤12 years) were more likely than those with higher education (>12 years) to be classified as potentially impaired using the MoCA cutoff of <26 (P < .01). Backwards selection revealed 4 MoCA items significantly associated with education (cube copy, serial subtraction, phonemic fluency, abstraction). Subtracting these items scores yielded an alternative MoCA score with a maximum of 24 and a cutoff of ≤19 for classifying participants with mild cognitive impairment. Using the alternative MoCA score and cutoff, among cognitively intact participants, both education groups were similarly likely to be classified as potentially impaired (P > .67). CONCLUSIONS: The alternative MoCA score neutralized the effects of formal education. Although further research is needed, this alternative score offers a simple procedure for interpreting MoCAs administered to older adults with ≤12 years education. These educational effects also highlight that the MoCA is part of the assessment process-not a singular diagnostic test-and a comprehensive workup is necessary to accurately diagnose cognitive impairments.

Examining the Effects of Formal Education Level on the Montreal Cognitive Assessment.

BACKGROUND: Brief, global assessments such as the Montreal Cognitive Assessment (MoCA) are widely used in primary care for assessing cognition in older adults. Like other neuropsychological instruments, lower formal education can influence MoCA interpretation. METHODS: Data from 2 large studies of cognitive aging were used-Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Alzheimer's Coordinating Center (NACC). Both use comprehensive examinations to determine cognitive status and have brain amyloid status for many participants. Mixed models were used to account for random variation due to data source. RESULTS: Cognitively intact participants with lower education (≤12 years) were more likely than those with higher education (>12 years) to be classified as potentially impaired using the MoCA cutoff of <26 (P < .01). Backwards selection revealed 4 MoCA items significantly associated with education (cube copy, serial subtraction, phonemic fluency, abstraction). Subtracting these items scores yielded an alternative MoCA score with a maximum of 24 and a cutoff of ≤19 for classifying participants with mild cognitive impairment. Using the alternative MoCA score and cutoff, among cognitively intact participants, both education groups were similarly likely to be classified as potentially impaired (P > .67). CONCLUSIONS: The alternative MoCA score neutralized the effects of formal education. Although further research is needed, this alternative score offers a simple procedure for interpreting MoCAs administered to older adults with ≤12 years education. These educational effects also highlight that the MoCA is part of the assessment process-not a singular diagnostic test-and a comprehensive workup is necessary to accurately diagnose cognitive impairments.

Amyloid-PET Levels in the Precuneus and Posterior Cingulate Cortices Are Associated with Executive Function Scores in Preclinical Alzheimer's Disease Prior to Overt Global Amyloid Positivity.

BACKGROUND: Global amyloid-ß (Aß) deposition in the brain can be quantified by Aß-PET scans to support or refute a diagnosis of preclinical Alzheimer's disease (pAD). Yet, Aß-PET scans enable quantitative evaluation of regional Aß elevations in pAD, potentially allowing even earlier detection of pAD, long before global positivity is achieved. It remains unclear as to whether such regional changes are clinically meaningful. OBJECTIVE: Test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in pAD. METHODS: Global and regional standardized uptake value ratios (SUVr) from 18F-florbetapir PET/CT scanning were determined using the Siemens Syngo.via® Neurology software package across a sample of 99 clinically normal participants with Montreal Cognitive Assessment (MoCA) scores≥23. Relationships between regional SUVr and cognitive test scores were analyzed using linear regression models adjusted for age, sex, and education. Participants were divided into two groups based on SUVr in the posterior cingulate and precuneus gyri (SUVR≥1.17). Between group differences in cognitive test scores were analyzed using ANCOVA models. RESULTS: Executive function performance was associated with increased regional SUVr in the precuneus and posterior cingulate regions only (p < 0.05). There were no significant associations between memory and Aß-PET SUVr in any regions of the brain. CONCLUSION: These data demonstrate that increased Aß deposition in the precuneus and posterior cingulate (the earliest brain regions affected with Aß pathology) is associated with changes in executive function that may precede memory decline in pAD.

Influence of BMI on adenosine deaminase and stroke outcomes in mechanical thrombectomy subjects.

BACKGROUND: Emergent Large Vessel Occlusion (ELVO) strokes are ischemic vascular events for which novel biomarkers and therapies are needed. The purpose of this study is to investigate the role of Body Mass Index (BMI) on protein expression and signaling at the time of ELVO intervention. Additionally, we highlight the protein adenosine deaminase (ADA), which is a deaminating enzyme that degrades adenosine, which has been shown to be neuroprotective in ischemia. We investigate the relationship between ADA and BMI, stroke outcomes, and associated proteomic networks which might aid in personalizing prognosis and future treatment of ELVO stroke. METHODS: The Blood And Clot Thrombectomy And Collaboration (BACTRAC) study is a continually enrolling tissue bank (clinicaltrials.gov NCT03153683) and registry from stroke patients undergoing mechanical thrombectomy (MT). N â€‹= â€‹61 human carotid plasma samples were analyzed for inflammatory and cardiometabolic protein expression by Olink Proteomics. Statistical analyses used t-tests, linear, logistic, and robust regressions, to assess the relationship between BMI, proteomic expression, and stroke-related outcomes. RESULTS: The 61 subjects studied were broken into three categories: normal weight (BMI 18.5-24.9) which contained 19 subjects, overweight (BMI 25-30) which contained 25 subjects, and obese (BMI ≥30) which contained 17 subjects. Normal BMI group was a significantly older population (mean 76 years) when compared to overweight (mean 66 years) and obese (mean 61 years) with significance of p â€‹= â€‹0.041 and p â€‹= â€‹0.005, respectively. When compared to normal weight and overweight categories, the obese category had significantly higher levels of adenosine deaminase (ADA) expression (p â€‹= â€‹0.01 and p â€‹= â€‹0.039, respectively). Elevated levels of ADA were found to have a significant positive correlation with both infarct volume and edema volume (p â€‹= â€‹0.013 and p â€‹= â€‹0.041, respectively), and were associated with a more severe stroke (NIHSS on discharge) and greater stroke related disability (mRS on discharge) with significance of p â€‹= â€‹0.053 and p â€‹= â€‹0.032, respectively. CONCLUSIONS: When examined according to BMI, subjects undergoing MT for ELVO demonstrate significant differences in the expression of certain plasma proteins, including ADA. Levels of ADA were found to be significantly higher in the obese population when compared to normal or overweight groups. Increased levels of ADA in the obese group were predictive of increased infarct volume, edema volume, and worse NIHSS scores and mRS at discharge. These data provide novel biomarker candidates as well as treatment targets while increasing the personalization of stroke prognosis and treatment.

Cognitive and Behavioral Domains That Reliably Differentiate Normal Aging and Dementia in Down Syndrome.

Primary care integration of Down syndrome (DS)-specific dementia screening is strongly advised. The current study employed principal components analysis (PCA) and classification and regression tree (CART) analyses to identify an abbreviated battery for dementia classification. Scale- and subscale-level scores from 141 participants (no dementia n = 68; probable Alzheimer's disease n = 73), for the Severe Impairment Battery (SIB), Dementia Scale for People with Learning Disabilities (DLD), and Vineland Adaptive Behavior Scales-Second Edition (Vineland-II) were analyzed. Two principle components (PC1, PC2) were identified with the odds of a probable dementia diagnosis increasing 2.54 times per PC1 unit increase and by 3.73 times per PC2 unit increase. CART analysis identified that the DLD sum of cognitive scores (SCS < 35 raw) and Vineland-II community subdomain (<36 raw) scores best classified dementia. No significant difference in the PCA versus CART area under the curve (AUC) was noted (D(65.196) = -0.57683; p = 0.57; PCA AUC = 0.87; CART AUC = 0.91). The PCA sensitivity was 80% and specificity was 70%; CART was 100% and specificity was 81%. These results support an abbreviated dementia screening battery to identify at-risk individuals with DS in primary care settings to guide specialized diagnostic referral.

Four Common Late-Life Cognitive Trajectories Patterns Associate with Replicable Underlying Neuropathologies.

BACKGROUND: Late-life cognitive function is heterogeneous, ranging from no decline to severe dementia. Prior studies of cognitive trajectories have tended to focus on a single measure of global cognition or individual tests scores, rather than considering longitudinal performance on multiple tests simultaneously. OBJECTIVE: The current study aimed to examine cognitive trajectories from two independent datasets to assess whether similar patterns might describe longitudinal cognition in the decade preceding death, as well as what participant characteristics were associated with trajectory membership. METHODS: Data were drawn from autopsied longitudinally followed participants of two cohorts (total N = 1,346), community-based cohort at the University of Kentucky Alzheimer's Disease Research Center (n = 365) and National Alzheimer's Coordinating Center (n = 981). We used group-based multi-trajectory models (GBMTM) to identify cognitive trajectories over the decade before death using Mini-Mental State Exam, Logical Memory-Immediate, and Animal Naming performance. Multinomial logistic and Random Forest analyses assessed characteristics associated with trajectory groups. RESULTS: GBMTM identified four similar cognitive trajectories in each dataset. In multinomial models, death age, Braak neurofibrillary tangles (NFT) stage, TDP-43, and α-synuclein were associated with declining trajectories. Random Forest results suggested the most important trajectory predictors were Braak NFT stage, cerebral atrophy, death age, and brain weight. Multiple pathologies were most common in trajectories with moderate or accelerated decline. CONCLUSION: Cognitive trajectories associated strongly with neuropathology, particularly Braak NFT stage. High frequency of multiple pathologies in trajectories with cognitive decline suggests dementia treatment and prevention efforts must consider multiple diseases simultaneously.

The effects of symptom information coaching on the feigning of adult ADHD.

College students without ADHD may feign symptoms of ADHD to gain access to stimulant medications and academic accommodations. Unfortunately, research has shown that it can be difficult to discriminate malingered from genuine ADHD symptomatology, especially when evaluations are based only on self-report questionnaires. The present study investigated whether nonclinical college students given no additional information could feign ADHD as successfully as those who were coached on symptoms of the disorder. Similar to Jasinski et al. (2011) and other research on feigned ADHD, a battery of neuropsychological, performance validity, and self-report tests was administered. Undergraduates with no history of ADHD or other psychiatric disorders were randomly assigned to 1 of 2 simulator groups: a coached group that was given information about ADHD symptoms, or a noncoached group that was given no such information. Both simulator groups were asked to feign ADHD. Their performance was compared to a genuine ADHD group and a nonclinical group asked to respond honestly. Self-report, neuropsychological, and performance validity test data are discussed in the context of the effect of coaching and its implications for ADHD evaluations. Symptom coaching did not have a significant effect on feigning success. Performance validity tests were moderately effective at detecting feigned ADHD. (PsycINFO Database Record

The Effects of Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Combined Mild Traumatic Brain Injury/Post-Traumatic Stress Disorder on Returning Veterans.

United States veterans of the Iraqi (Operation Iraqi Freedom [OIF]) and Afghanistan (Operation Enduring Freedom [OEF]) conflicts have frequently returned from deployment after sustaining mild traumatic brain injury (mTBI) and enduring stressful events resulting in post-traumatic stress disorder (PTSD). A large number of returning service members have been diagnosed with both a history of mTBI and current PTSD. Substantial literature exists on the neuropsychological factors associated with mTBI and PTSD occurring separately; far less research has explored the combined effects of PTSD and mTBI. The current study employed neuropsychological and psychological measures in a sample of 251 OIF/OEF veterans to determine whether participants with a history of mTBI and current PTSD (mTBI+PTSD) have poorer cognitive and psychological outcomes than participants with mTBI only (mTBI-o), PTSD only (PTSD-o), or veteran controls (VC), when groups are comparable on intelligence quotient, education, and age. The mTBI+PTSD group performed more poorly than VC, mTBI-o, and PTSD-o groups on several neuropsychological measures. Effect size comparisons suggest small deleterious effects for mTBI-o on measures of processing speed and visual attention and small effects for PTSD-o on measures of verbal memory, with moderate effects for mTBI+PTSD on the same variables. Additionally, the mTBI+PTSD group was significantly more psychologically distressed than the PTSD-o group, and PTSD-o group was more distressed than VC and mTBI-o groups. These findings suggest that veterans with mTBI+PTSD perform significantly lower on neuropsychological and psychiatric measures than veterans with mTBI-o or PTSD-o. The results also raise the possibility of mild but persisting cognitive changes following mTBI sustained during deployment.

Discriminating among ADHD alone, ADHD with a comorbid psychological disorder, and feigned ADHD in a college sample.

Since the early 2000s concern has increased that college students might feign ADHD in pursuit of academic accommodations and stimulant medication. In response, several studies have validated tests for use in differentiating feigned from genuine ADHD. Although results have generally been positive, relatively few publications have addressed the possible impact of the presence of psychological disorders comorbid with ADHD. Because ADHD is thought to have accompanying conditions at rates of 50% and higher, it is important to determine if the additional psychological disorders might compromise the accuracy of feigning detection measures. The present study extended the findings of Jasinski et al. (2011) to examine the efficacy of various measures in the context of feigned versus genuine ADHD with comorbid psychological disorders in undergraduate students. Two clinical groups (ADHD only and ADHD + comorbid psychological disorder) were contrasted with two non-clinical groups (normal controls answering honestly and normal participants feigning ADHD). Extending previous research to individuals with ADHD and either an anxiety or learning disorder, performance validity tests such as the Test of Memory Malingering (TOMM), the Letter Memory Test (LMT), and the Nonverbal Medical Symptom Validity Test (NV-MSVT) were effective in differentiating both ADHD groups from normal participants feigning ADHD. However, the Digit Memory Test (DMT) underperformed in this study, as did embedded validity indices from the Wechsler Adult Intelligence Scale-IV (WAIS-IV) and Woodcock Johnson Tests of Achievement-III (WJ-III).

Pb neurotoxicity: neuropsychological effects of lead toxicity.

Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored.

Accuracy of MMPI-2-RF validity scales for identifying feigned PTSD symptoms, random responding, and genuine PTSD.

The Minnesota Multiphasic Personality Inventory-2-RF (MMPI-2-RF) validity scales were evaluated to determine accuracy when differentiating honest responding, random responding, genuine posttraumatic stress disorder (PTSD), and feigned PTSD. Undergraduate students (n = 109), screened for PTSD, were randomly assigned to 1 of 4 instructional groups: honest, feign PTSD, half random, and full random. Archival data provided clinical MMPI-2-RF profiles consisting of 31 veterans diagnosed with PTSD. Veterans were diagnosed with PTSD using a structured interview and had passed a structured interview for malingering. Validity scales working as a group had correct classification rates of honest (96.6%), full random (88.9%), genuine PTSD (80.7%), fake PTSD (73.1%), and half random (44.4%). Results were fairly supportive of the scales' ability to discriminate feigning and full random responding from honest responding of normal students as well as veterans with PTSD. However, the RF validity scales do not appear to be as effective in detecting partially random responding.

Neuropsychological effects of self-reported deployment-related mild TBI and current PTSD in OIF/OEF veterans.

Current combat veterans are exposed to many incidents that may result in mild traumatic brain injury (mTBI) and/or posttraumatic stress disorder (PTSD). While there is literature on the neuropsychological consequences of PTSD only (PTSD-o) and mTBI alone (mTBI-o), less has been done to explore their combined (mTBI+PTSD) effect. The goal of this study was to determine whether Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veterans with mTBI+PTSD have poorer cognitive and psychological outcomes than veterans with PTSD-o, mTBI-o, or combat exposure-only. The final sample included 20 OIF/OEF veterans with histories of self-reported deployment mTBI (mTBI-o), 19 with current PTSD (PTSD-o), 21 with PTSD and self-reported mTBI (mTBI+PTSD), and 21 combat controls (CC) (no PTSD and no reported mTBI). Groups were formed using structured interviews for mTBI and PTSD. All participants underwent comprehensive neuropsychological testing, including neurocognitive and psychiatric feigning tests. Results of cognitive tests revealed significant differences in performance in the mTBI+PTSD and PTSD-o groups relative to mTBI-o and CC. Consistent with previous PTSD literature, significant differences were found on executive (switching) tasks, verbal fluency, and verbal memory. Effect sizes tended to be large in both groups with PTSD. Thus, PTSD seems to be an important variable affecting neuropsychological profiles in the post-deployment time period. Consistent with literature on civilian mTBI, the current study did not find evidence that combat-related mTBI in and of itself contributes to objective cognitive impairment in the late stage of injury.

Using symptom validity tests to detect malingered ADHD in college students.

Recently there has been growing concern that college students may feign symptoms of ADHD in order to obtain academic accommodations and stimulant medication. Unfortunately research has only begun to validate detection tools for malingered ADHD. The present study cross-validated the results of Sollman, Ranseen, and Berry (2010) on the efficacy of several symptom validity tests for detection of simulated ADHD among college students. Undergraduates with a history of diagnosed ADHD were randomly assigned either to respond honestly or exaggerate symptoms, and were compared to undergraduates with no history of ADHD or other psychiatric disorders who were also randomly assigned to respond honestly or feign symptoms of ADHD. Similar to Sollman et al. (2010) and other recent research on feigned ADHD, several symptom validity tests, including the Test of Memory Malingering (TOMM), Letter Memory Test (LMT), Digit Memory Test (DMT), Nonverbal Medical Symptom Validity Test (NV-MSVT), and the b Test were reasonably successful at discriminating feigned and genuine ADHD. When considered as a group, the criterion of failure of 2 or more of these SVTs had a sensitivity of. 475 and a specificity of 1.00.