Primary progressive aphasia and amyotrophic lateral sclerosis (PPA-ALS): A longitudinal case study.

OBJECTIVE: Approximately 50% of patients with amyotrophic lateral sclerosis (ALS) experience cognitive decline, with frontotemporal dementia (FTD) accounting for up to 15% of these cases. Despite this, there is considerable delay in diagnosis, which affects patient care. METHODS: We report longitudinal results of neuropsychological evaluations in a patient diagnosed with non-fluent/agrammatic primary progressive aphasia (nfvPPA) and amyotrophic lateral sclerosis (ALS). The patient, Ms. X, presented with progressive speech difficulties starting in her late-60's. Initial diagnosis was nfvPPA. After 4-5 years of progressive swallowing difficulties, as well as facial weakness, her diagnosis was modified to PPA-ALS. RESULTS: Ms. X underwent neuropsychological evaluations three times over a period of five years. Results of evaluations were intact and stable over time, except for progressive loss of speech impacting her performance on a sentence repetition task. CONCLUSION: This case study provides valuable insight into the overlap between PPA-ALS from a neuropsychological standpoint. The results reflect preserved cognitive skills in the context of loss of speech and motor abilities. This case study also shows the length of time between onset of symptoms and clear diagnosis, which often requires an immense amount of health literacy and personal advocacy on the part of the patient.

Racial differences in positive findings on embedded performance validity tests.

INTRODUCTION: Embedded performance validity tests (PVTs) may show increased positive findings in racially diverse examinees. This study examined positive findings in an older adult sample of African American (AA) and European American (EA) individuals recruited as part of a study on aging and cognition. METHOD: The project involved secondary analysis of deidentified National Alzheimer's Coordinating Center data (N = 22,688). Exclusion criteria included diagnosis of dementia (n = 5,550), mild cognitive impairment (MCI; n = 5,160), impaired but not MCI (n = 1,126), other race (n = 864), and abnormal Mini Mental State Examination (MMSE < 25; n = 135). The initial sample included 9,853 participants (16.4% AA). Propensity score matching matched AA and EA participants on age, education, sex, and MMSE score. The final sample included 3,024 individuals with 50% of participants identifying as AA. Premorbid ability estimates were calculated based on demographics. Failure rates on five raw score and six age-adjusted scaled score PVTs were examined by race. RESULTS: Age, education, sex, MMSE, and premorbid ability estimate were not significantly different by race. Thirteen percent of AA and 3.8% of EA participants failed two or more raw score PVTs (p < .0001). On age-adjusted PVTs, 20.6% of AA and 5.9% of EA participants failed two or more (p < .0001). CONCLUSIONS: PVT failure rates were significantly higher among AA participants. Findings indicate a need for cautious interpretation of embedded PVTs with underrepresented groups. Adjustments to embedded PVT cutoffs may need to be considered to improve diagnostic accuracy.

Making a Difference: Affective Distress Explains Discrepancy Between Objective and Subjective Cognitive Functioning After Mild Traumatic Brain Injury.

OBJECTIVE: To assess the relationship between subjective cognitive symptoms and objective cognitive test scores in patients after concussion. We additionally examined factors associated with subjective and objective cognitive dysfunction, as well as their discrepancy. PARTICIPANTS: Eighty-six individuals (65.1% female; 74.4% adult) from an interdisciplinary concussion clinic. METHODS: Subjective and objective cognitive functioning was measured via the SCAT-Symptom Evaluation and the CNS Vital Signs Neurocognition Index (NCI), respectively. Cognitive discrepancy scores were derived by calculating standardized residuals (via linear regression) using subjective symptoms as the outcome and NCI score as the predictor. Hierarchical regression assessed predictors (age, education, time postinjury, attention-deficit/hyperactivity disorder, affective distress, and sleep disturbance) of cognitive discrepancy scores. Nonparametric analyses evaluated relationships between predictor variables, subjective symptoms, and NCI. RESULTS: More severe affective and sleep symptoms (large and medium effects), less time postinjury (small effect), and older age (small effect) were associated with higher subjective cognitive symptoms. Higher levels of affective distress and less time since injury were associated with higher cognitive discrepancy scores (ß = .723, P < .001; ß = -.204, P < .05, respectively). CONCLUSION: Clinical interpretation of subjective cognitive dysfunction should consider these additional variables. Evaluation of affective distress is warranted in the context of higher subjective cognitive complaints than objective test performance.

The influence of traumatic brain injury on the allocation of vertical spatial attention.

Objective: Research on impairments of spatial attention has primarily investigated hemispatial neglect in brain-lesioned patients, revealing decrements in the allocation of attention to right versus left egocentric or allocentric hemispace. Whereas head trauma might injure those parts of the brain that allocate vertical attention, little is known about the influence of trauma on the allocation of visuospatial attention in vertical space. Thus, the goal of this study was to learn if chronic moderate-to-severe traumatic brain injury (m/sTBI) alters the allocation of vertical visuospatial attention as assessed by the Attention Network Task (ANT). The ANT assesses the influence of Posner-type spatial cues and distractors using an Eriksen flanker task.Methods: 12 chronic m/sTBI patients and 12 demographically-matched neurologically-healthy controls (HCs) completed a version of the ANT wherein trials were coded for cue and target locations above and below central visual fixation. Trial-wise reaction times (RT) and accuracy were subjected to mixed-model ANOVAs and planned contrasts.Results: These data were subject to secondary analyses, which revealed that across groups, median RTs were significantly faster when targets occurred above than below the central visual fixation (p < .01); however, only HCs' error rates differed as a function of target altitude. Unlike controls, m/sTBI survivors did not exhibit the anticipated upward error-rate attentional bias.Conclusions: As alteration of spatial attention can be a major cause of disability, present findings suggest that m/sTBI survivors exhibit this loss of normal upward attentional bias. Future studies are need to learn if these patients might benefit from treatment.

Exploratory study of sport-related concussion effects on peripheral micro-RNA expression.

OBJECTIVE: Explore changes in micro-RNA (miRNA) expression in blood after sport-related concussion (SRC) in collegiate athletes. METHODS: Twenty-seven collegiate athletes (~41% male, ~75% white, age 18.8 ± 0.8 years) provided both baseline and post-SRC blood samples. Serum was analyzed for expression of miR-153-3p (n = 27), miR-223-3p (n = 23), miR-26a-5p (n = 26), miR-423-3p (n = 23), and miR-let-7a-5p (n = 23) at both time points via quantitative polymerase chain reaction (qPCR). Nonparametric analyses were used to compare miRNA expression changes between baseline and SRC and to evaluate associations with clinical outcomes (symptom severity, cognition, balance, and oculomotor function, and clinical recovery time). RESULTS: Participants manifested a significant increase in miRNA expression following SRC for miR153-3p (Z = -2.180, p = .029, 59% of the participants increased post-SRC), miR223-3p (Z = -1.998, p = .046, 70% increased), and miR-let-7a-5p (Z = -2.190, p = .029, 65% increased). There were no statistically significant associations between changes in miRNA expression and clinical test scores, acute symptom severity, or clinical recovery time. CONCLUSION: MiR-153-3p, miR-223-3p, and miR-let-7a-5p were significantly upregulated acutely following SRC in male and female collegiate athletes compared to baseline levels, though several athletes demonstrated no change or a decrease in expression. The biological mechanisms and functional implications of the increased expression of these circulating miRNA are unclear and require more research, as does their relevance to clinical outcomes.

Concussion BASICS III: Serum biomarker changes following sport-related concussion.

OBJECTIVE: To evaluate changes in serum biomarker concentrations (ß-amyloid peptide 42 [Aß42], total tau, ubiquitin carboxy-terminal hydrolyzing enzyme L1, S100 calcium binding protein B [S100B], glial fibrillary acidic protein [GFAP], microtubule associated protein 2 [MAP2], and 2',3'-cyclic-nucleotide 3'-phosphodiesterase [CNPase]) after sport-related concussion (SRC) in a sample of collegiate athletes. Associations with clinical outcomes were also investigated. METHODS: Participants in this case-control study included 36 athletes (50% male, 61% white, aged 19.7 ± 1.0 years) with SRC. Twenty-nine also had baseline blood drawn, allowing for within-patient analyses of concentration changes. Between-group analyses incorporated 86 demographically matched controls (51% male, 63% white, aged 19.6 ± 1.1 years). Biomarker sensitivity/specificity for SRC vs controls and relative to standardized normative cutoffs was evaluated (receiver operating characteristics). We also analyzed associations between post-SRC clinical outcomes and both biomarker change from baseline and post-SRC concentrations. RESULTS: The majority of blood samples had concentrations of GFAP, MAP2, and CNPase below limits of quantification. Within-patient analyses indicated elevated S100B after SRC (p = 0.003, 67% of patients elevated), especially for blood samples collected <4 hours post-SRC (88% of patients). Significant between-group differences were limited to blood draws <4 hours post-SRC: Aß42 (81% of SRC > control median, area under the curve [AUC] = 0.75 [95% confidence interval 0.59-0.91]), total tau (75% SRC > control, AUC = 0.74 [0.56-0.79]), and S100B (88% SRC > control; AUC [specific to white race] = 0.82 [0.72-0.93]). Using standardized normative cutoffs (z > 1.0), specificity ranged from 79.1% to 89.3% while sensitivity was <70%. Biomarkers were not associated with clinical outcomes. CONCLUSION: For SRC, diagnostic accuracy of serum biomarkers appears best if blood is collected within a few hours. Accurate blood marker identification of SRC appears somewhat dependent on the "healthy" comparison. Additional research must evaluate whether physiologic changes in the absence of clinical changes, or vice versa, are relevant for concurrent or future neurologic health. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that certain serum biomarkers are elevated from baseline and higher than demographically matched controls after sport-related concussion.