7 results
64 Neuroimaging Evidence of Neurodegenerative Disease in Former Professional American Football Players Who “Fail” Validity Testing: A Case Series
- Ranjani Shankar, Julia Culhane, Leonardo Iaccarino, Chris Nowinski, Nidhi Mundada, Karen Smith, Jeremy Tanner, Charles Windon, Yorghos Tripodis, Gustavo Mercier, Thor D Stein, Anne C McKee, Robert A Stern, Neil Kowall, Bruce L Miller, Jesse Mez, Ron Killiany, Gil D Rabinovici, Michael L Alosco, Breton M Asken
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 574-575
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Former professional American football players have a high relative risk for neurodegenerative diseases like chronic traumatic encephalopathy (CTE). Interpreting low cognitive test scores in this population occasionally is complicated by performance on validity testing. Neuroimaging biomarkers may help inform whether a neurodegenerative disease is present in these situations. We report three cases of retired professional American football players who completed comprehensive neuropsychological testing, but “failed” performance validity tests, and underwent multimodal neuroimaging (structural MRI, Aß-PET, and tau-PET).
Participants and Methods:Three cases were identified from the Focused Neuroimaging for the Neurodegenerative Disease Chronic Traumatic Encephalopathy (FIND-CTE) study, an ongoing multimodal imaging study of retired National Football League players with complaints of progressive cognitive decline conducted at Boston University and the UCSF Memory and Aging Center. Participants were relatively young (age range 55-65), had 16 or more years of education, and two identified as Black/African American. Raw neuropsychological test scores were converted to demographically-adjusted z-scores. Testing included standalone (Test of Memory Malingering; TOMM) and embedded (reliable digit span, RDS) performance validity measures. Validity cutoffs were TOMM Trial 2 < 45 and RDS < 7. Structural MRIs were interpreted by trained neurologists. Aß-PET with Florbetapir was used to quantify cortical Aß deposition as global Centiloids (0 = mean cortical signal for a young, cognitively normal, Aß negative individual in their 20s, 100 = mean cortical signal for a patient with mild-to-moderate Alzheimer’s disease dementia). Tau-PET was performed with MK-6240 and first quantified as standardized uptake value ratio (SUVR) map. The SUVR map was then converted to a w-score map representing signal intensity relative to a sample of demographically-matched healthy controls.
Results:All performed in the average range on a word reading-based estimate of premorbid intellect. Contribution of Alzheimer’s disease pathology was ruled out in each case based on Centiloids quantifications < 0. All cases scored below cutoff on TOMM Trial 2 (Case #1=43, Case #2=42, Case #3=19) and Case #3 also scored well below RDS cutoff (2). Each case had multiple cognitive scores below expectations (z < -2.0) most consistently in memory, executive function, processing speed domains. For Case #1, MRI revealed mild atrophy in dorsal fronto-parietal and medial temporal lobe (MTL) regions and mild periventricular white matter disease. Tau-PET showed MTL tau burden modestly elevated relative to controls (regional w-score=0.59, 72nd%ile). For Case #2, MRI revealed cortical atrophy, mild hippocampal atrophy, and a microhemorrhage, with no evidence of meaningful tau-PET signal. For Case #3, MRI showed cortical atrophy and severe white matter disease, and tau-PET revealed significantly elevated MTL tau burden relative to controls (w-score=1.90, 97th%ile) as well as focal high signal in the dorsal frontal lobe (overall frontal region w-score=0.64, 74th%ile).
Conclusions:Low scores on performance validity tests complicate the interpretation of the severity of cognitive deficits, but do not negate the presence of true cognitive impairment or an underlying neurodegenerative disease. In the rapidly developing era of biomarkers, neuroimaging tools can supplement neuropsychological testing to help inform whether cognitive or behavioral changes are related to a neurodegenerative disease.
54 Individuals Employing Extreme Coping Behaviors Correlated with Increased Severity of Symptoms Following mTBI
- Jessica Bove, Jacob A Fiala, oJrdan Milano, Adriana Sandino, Breton M Asken, Russell M Bauer
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 159-160
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Approximately 10-15% of patients with mild traumatic brain injury (mTBI) report persistent, chronic symptoms more than one month later. Coping behaviors after mTBI can range from fear avoidance (FA), or a reluctance to return to activity because of the fear of symptom exaggeration, to endurance (END), or an overly aggressive return to activity. We evaluated how coping strategy relates to self-reported symptoms in patients with prolonged recovery from mTBI.
Participants and Methods:Participants were 72 individuals (age 37.8 + 18.4, 65% female) who sustained a mTBI at least one month prior to assessment (median (IQR) = 5.5 (2.0-11.3) months). Participants completed the Brain Injury Recovery Disposition Scale (BIRDS) to assess FA and END behaviors, and Sport Concussion Assessment Tool (SCAT5) Symptom Inventory. A BIRDS spectrum score was calculated as the difference between FA and END scores to determine individual coping behavior on a spectrum from extreme FA (more negative) to extreme END (more positive). SCAT5 symptoms were separated into four domain scores: somatic, cognitive, sleep, and emotion. Regressions were performed for each outcome examining their potential linear and quadratic associations to coping behavior (i.e., BIRDS spectrum score). Follow-up regressions were performed covarying for age and sex to explore the potential influence of these variables on each outcome.
Results:The linear and quadratic components of the BIRDS spectrum score were not significantly related to total number of persisting concussive symptoms. For overall total symptom severity, the quadratic component of the relationship was significant (B = .24, p = 0.04). Visualization of the overall trend line suggested that symptom severity was highest on the extreme FA side of the BIRDS spectrum (highly negative BIRDS spectrum score), decreased as coping behavior become more balanced (BIRDS spectrum score surrounding “0"), plateaued, then increased abruptly on the extreme END side (highly positive BIRDS spectrum score). For cognitive symptoms, the linear component of the BIRDS spectrum score was significant (B = -.28, p = 0.02) and the quadratic component was marginally significant (B = .22, p = 0.06). The quadratic (but not linear) component was significantly related to both the severity of sleep (B = .31, p = 0.01) and emotion symptoms (B = .25, p = 0.03). Finally, neither the linear nor quadratic components were significantly related to the somatic symptom severity. After covarying for age and sex, the quadratic component remained significant for total symptom severity (p = 0.05) as well as the linear component for cognitive severity (p = 0.02).
Conclusions:Both extreme “fear avoidance” and “endurance” coping styles may be related to more severe chronic mTBI symptoms, especially in domains of sleep and emotion symptoms. Patients with balance of both fear avoidance and endurance behaviors may be more likely to experience less severe symptoms even among mTBI patients with persistent complaints. Identifying coping behavior styles early after mTBI could improve prognostication and help with developing personalized treatment plans to improve patient recovery. Future research with larger sample sizes should further examine the influence of age and sex on the relationship between coping behavior and symptom severity.
57 Traumatic Brain Injury and Concussion in Patients with Frontotemporal Dementia Spectrum Diagnoses
- Jessica Bove, Marguerite Knudtson, Michelle You, Michael L Alosco, Jesse Mez, Bruce L Miller, Howie J Rosen, Maria Luisa Gorno-Tempini, William W Seeley, Joel H Kramer, Russell M Bauer, Breton M Asken
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 568-569
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Traumatic brain injury (TBI) and concussion are associated with increased dementia risk. Accurate TBI/concussion exposure estimates are relatively unknown for less common neurodegenerative conditions like frontotemporal dementia (FTD). We evaluated lifetime TBI and concussion frequency in patients diagnosed with a range of FTD spectrum conditions and related prior head trauma to cavum septum pellucidum (CSP) characteristics observable on MRI.
Participants and Methods:We administered the Ohio State University TBI Identification and Boston University Head Impact Exposure Assessment to 108 patients (age 69.5 ± 8.0, 35% female, 93% white or unknown race) diagnosed at the UCSF Memory and Aging Center with one of the following FTD or related conditions: behavioral variant frontotemporal dementia (N=39), semantic variant primary progressive aphasia (N=16), nonfluent variant PPA (N=23), corticobasal syndrome (N=14), or progressive supranuclear palsy (N=16). Data were also obtained from 217 controls (“HC”; age 76.8 ± 8.0, 53% female, 91% white or unknown race). CSP characteristics were defined based on width or “grade” (0-1 vs. 2+) and length of anterior-posterior separation (millimeters). We first describe frequency of any and multiple (2+) prior TBI based on different but commonly used definitions: TBI with loss of consciousness (LOC), TBI with LOC or posttraumatic amnesia (LOC/PTA), TBI with LOC/PTA or other symptoms like dizziness, nausea, “seeing stars,” etc. (“concussion”). TBI/concussion frequency was then compared between FTD and HC using chi-square. Associations between TBI/concussion and CSP characteristics were analyzed with chi-square (CSP grade) and Mann-Whitney U tests (CSP length). We explored sex differences due to typically higher rates of TBI among males.
Results:History of any TBI with LOC (FTD=20.0%, HC=19.2%), TBI with LOC/PTA (FTD:32.2%, HC=31.5%), and concussion (FTD: 50.0%, HC=44.3%) was common but not different between study groups (p’s>.4). In both FTD and HC, prior TBI/concussion was nominally more frequent in males but not significantly greater than females. Frequency of repeat TBI/concussion (2+) also did not differ significantly between FTD and HC (repeat TBI with LOC: 6.7% vs. 3.3%, TBI with LOC/PTA: 12.2% vs. 10.3%, concussion: 30.2% vs. 28.7%; p’s>.2). Prior TBI/concussion was not significantly related to CSP grade or length in the total sample or within the FTD or HC groups.
Conclusions:TBI/concussion rates depend heavily on the symptom definition used for classifying prior injury. Lifetime symptomatic TBI/concussion is common but has an unclear impact on risk for FTD-related diagnoses. Larger samples are needed to appropriately evaluate sex differences, to evaluate whether TBI/concussion rates differ between specific FTD phenotypes, and to understand the rates and effects of more extensive repetitive head trauma (symptomatic and asymptomatic) in patients with FTD.
Lower White Matter Volume and Worse Executive Functioning Reflected in Higher Levels of Plasma GFAP among Older Adults with and Without Cognitive Impairment
- Breton M. Asken, Lawren VandeVrede, Julio C. Rojas, Corrina Fonseca, Adam M. Staffaroni, Fanny M. Elahi, Cutter A. Lindbergh, Alexandra C. Apple, Michelle You, Sophia Weiner-Light, Nivetha Brathaban, Nicole Fernandes, Adam L. Boxer, Bruce L. Miller, Howie J. Rosen, Joel H. Kramer, Kaitlin B. Casaletto
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 28 / Issue 6 / July 2022
- Published online by Cambridge University Press:
- 22 June 2021, pp. 588-599
-
- Article
- Export citation
-
Objective:
There are minimal data directly comparing plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in aging and neurodegenerative disease research. We evaluated associations of plasma NfL and plasma GFAP with brain volume and cognition in two independent cohorts of older adults diagnosed as clinically normal (CN), mild cognitive impairment (MCI), or Alzheimer’s dementia.
Methods:We studied 121 total participants (Cohort 1: n = 50, age 71.6 ± 6.9 years, 78% CN, 22% MCI; Cohort 2: n = 71, age 72.2 ± 9.2 years, 45% CN, 25% MCI, 30% dementia). Gray and white matter volumes were obtained for total brain and broad subregions of interest (ROIs). Neuropsychological testing evaluated memory, executive functioning, language, and visuospatial abilities. Plasma samples were analyzed in duplicate for NfL and GFAP using single molecule array assays (Quanterix Simoa). Linear regression models with structural MRI and cognitive outcomes included plasma NfL and GFAP simultaneously along with relevant covariates.
Results:Higher plasma GFAP was associated with lower white matter volume in both cohorts for temporal (Cohort 1: β = −0.33, p = .002; Cohort 2: β = −0.36, p = .03) and parietal ROIs (Cohort 1: β = −0.31, p = .01; Cohort 2: β = −0.35, p = .04). No consistent findings emerged for gray matter volumes. Higher plasma GFAP was associated with lower executive function scores (Cohort 1: β = −0.38, p = .01; Cohort 2: β = −0.36, p = .007). Plasma NfL was not associated with gray or white matter volumes, or cognition after adjusting for plasma GFAP.
Conclusions:Plasma GFAP may be more sensitive to white matter and cognitive changes than plasma NfL. Biomarkers reflecting astroglial pathophysiology may capture complex dynamics of aging and neurodegenerative disease.
Worth the Wait: Delayed Recall after 1 Week Predicts Cognitive and Medial Temporal Lobe Trajectories in Older Adults
- Cutter A. Lindbergh, Nicole Walker, Renaud La Joie, Sophia Weiner-Light, Adam M. Staffaroni, Kaitlin B. Casaletto, Fanny Elahi, Samantha M. Walters, Michelle You, Devyn Cotter, Breton Asken, Alexandra C. Apple, Elena Tsoy, John Neuhaus, Corrina Fonseca, Amy Wolf, Yann Cobigo, Howie Rosen, Joel H. Kramer, the Hillblom Aging Network
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 27 / Issue 4 / April 2021
- Published online by Cambridge University Press:
- 14 October 2020, pp. 382-388
-
- Article
- Export citation
-
Objective: We evaluated whether memory recall following an extended (1 week) delay predicts cognitive and brain structural trajectories in older adultsMethod:
Clinically normal older adults (52–92 years old) were followed longitudinally for up to 8 years after completing a memory paradigm at baseline [Story Recall Test (SRT)] that assessed delayed recall at 30 min and 1 week. Subsets of the cohort underwent neuroimaging (N = 134, mean age = 75) and neuropsychological testing (N = 178–207, mean ages = 74–76) at annual study visits occurring approximately 15–18 months apart. Mixed-effects regression models evaluated if baseline SRT performance predicted longitudinal changes in gray matter volumes and cognitive composite scores, controlling for demographics.
Results:Worse SRT 1-week recall was associated with more precipitous rates of longitudinal decline in medial temporal lobe volumes (p = .037), episodic memory (p = .003), and executive functioning (p = .011), but not occipital lobe or total gray matter volumes (demonstrating neuroanatomical specificity; p > .58). By contrast, SRT 30-min recall was only associated with longitudinal decline in executive functioning (p = .044).
Conclusions:Memory paradigms that capture longer-term recall may be particularly sensitive to age-related medial temporal lobe changes and neurodegenerative disease trajectories. (JINS, 2020, xx, xx-xx)
Discrepancy-Based Evidence for Loss of Thinking Abilities (DELTA): Development and Validation of a Novel Approach to Identifying Cognitive Changes
- Breton M. Asken, Kelsey R. Thomas, Athene Lee, Jennifer D. Davis, Paul F. Malloy, Stephen P. Salloway, Stephen Correia
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 26 / Issue 5 / May 2020
- Published online by Cambridge University Press:
- 11 December 2019, pp. 464-479
-
- Article
- Export citation
-
Objective:
To develop and validate the Discrepancy-based Evidence for Loss of Thinking Abilities (DELTA) score. The DELTA score characterizes the strength of evidence for cognitive decline on a continuous spectrum using well-established psychometric principles for improving detection of cognitive changes.
Methods:DELTA score development used neuropsychological test scores from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (two tests each from Memory, Executive Function, and Language domains). We derived regression-based normative reference scores using age, gender, years of education, and word-reading ability from robust cognitively normal ADNI participants. Discrepancies between predicted and observed scores were used for calculating the DELTA score (range 0–15). We validated DELTA scores primarily against longitudinal Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Functional Activities Questionnaire (FAQ) scores (baseline assessment through Year 3) using linear mixed models and secondarily against cross-sectional Alzheimer’s biomarkers.
Results:There were 1359 ADNI participants with calculable baseline DELTA scores (age 73.7 ± 7.1 years, 55.4% female, 100% white/Caucasian). Higher baseline DELTA scores (stronger evidence of cognitive decline) predicted higher baseline CDR-SOB (ΔR2 = .318) and faster rates of CDR-SOB increase over time (ΔR2 = .209). Longitudinal changes in DELTA scores tracked closely and in the same direction as CDR-SOB scores (fixed and random effects of mean + mean-centered DELTA, ΔR2 > .7). Results were similar for FAQ scores. High DELTA scores predicted higher PET-Aβ SUVr (ρ = 324), higher CSF-pTau/CSF-Aβ ratio (ρ = .460), and demonstrated PPV > .9 for positive Alzheimer’s disease biomarker classification.
Conclusions:Data support initial development and validation of the DELTA score through its associations with longitudinal functional changes and Alzheimer’s biomarkers. We provide several considerations for future research and include an automated scoring program for clinical use.
Multivariate Base Rates of Low Scores and Reliable Decline on ImPACT in Healthy Collegiate Athletes Using CARE Consortium Norms
- Zac M. Houck, Breton M. Asken, Russell M. Bauer, Anthony P. Kontos, Michael A. McCrea, Thomas W. McAllister, Steven P. Broglio, James R. Clugston, Care Consortium Investigators
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 25 / Issue 9 / October 2019
- Published online by Cambridge University Press:
- 05 July 2019, pp. 961-971
-
- Article
- Export citation
-
Objectives: To describe multivariate base rates (MBRs) of low scores and reliable change (decline) scores on Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) in college athletes at baseline, as well as to assess MBR differences among demographic and medical history subpopulations. Methods: Data were reported on 15,909 participants (46.5% female) from the NCAA/DoD CARE Consortium. MBRs of ImPACT composite scores were derived using published CARE normative data and reliability metrics. MBRs of sex-corrected low scores were reported at <25th percentile (Low Average), <10th percentile (Borderline), and ≤2nd percentile (Impaired). MBRs of reliable decline scores were reported at the 75%, 90%, 95%, and 99% confidence intervals. We analyzed subgroups by sex, race, attention-deficit/hyperactivity disorder and/or learning disability (ADHD/LD), anxiety/depression, and concussion history using chi-square analyses. Results: Base rates of low scores and reliable decline scores on individual composites approximated the normative distribution. Athletes obtained ≥1 low score with frequencies of 63.4% (Low Average), 32.0% (Borderline), and 9.1% (Impaired). Athletes obtained ≥1 reliable decline score with frequencies of 66.8%, 32.2%, 18%, and 3.8%, respectively. Comparatively few athletes had low scores or reliable decline on ≥2 composite scores. Black/African American athletes and athletes with ADHD/LD had higher rates of low scores, while greater concussion history was associated with lower MBRs (p < .01). MBRs of reliable decline were not associated with demographic or medical factors. Conclusions: Clinical interpretation of low scores and reliable decline on ImPACT depends on the strictness of the low score cutoff, the reliable change criterion, and the number of scores exceeding these cutoffs. Race and ADHD influence the frequency of low scores at all cutoffs cross-sectionally.