Persistent Cognitive Complaints Research Articles

3 Optimizing Cognitive Rehabilitation of the Injured Warfighter

Objective:Many individuals who experienced a mild traumatic brain injury (mTBI) have persistent cognitive complaints. Traditional cognitive rehabilitation (TCR) interventions were primarily developed for severe neurological injury which has limited effectiveness in rehabilitation of active duty military personnel who have the goal of returning to full military operational status. To remain on active duty, warfighters must have sufficient mental competency to safely and effectively function in complex environments such as combat. There is need for a cognitive rehabilitation approach that addresses demands of military personnel to expedite return to duty. The Strategic Memory Advanced Reasoning Training (SMART) program is novel alternative to TCR. SMART is an evidence-based advanced reasoning protocol that enhances cognitive domains essential to military readiness (e.g., mental agility, strategic learning, problem solving, and focus) and requires less than half of the treatment time. The objective of this study was to assess the efficacy of SMART compared to TCR in terms of overall recovery as well as change in specific cognitive domains.Participants and Methods:Participants were recruited from a military treatment facility. All patients had at least one diagnosed mTBI as well as persistent cognitive complaints. Participants completed the Rey-15 to ensure performance validity. Final sample was SMART n = 28 and SCORE n = 19. Primary dependent measure was the Global Deficit Scale (GDS). GDS was calculated from: Hopkins Verbal Learning Test-Revised (HVLT-R); Delis Kaplan Executive Functioning System Color Word (CW) and Trail Making (TM), Paced Auditory Serial Addition Test (PASAT), and the Symbol Digit Modality Test (SDMT). Demographically corrected t-scores were converted to deficit scores as follows: >40 = 0, 35-39 = 1, 30-34 = 2, 25-29 = 3, 20-24 = 4, <20 = 5. Deficit scores were averaged to calculate GDS. For each measure, Hohen’s g was analyzed for effect size comparisons pre-post treatment.Results:Average number of treatment hours was significantly lower in the SMART condition (SMART: M = 18.47 hours, SD = 2.17; TCR: M = 42.42 hours, SD = 3.79, p <.001). A repeated measures ANOVA showed a significant change on GDS post-treatment (F = 30.25, p < .001) with a large effect size (n2 = .402); however, the interventions did not differ on GDS change. Impact on cognitive domains was relatively equivalent for processing speed (SMART h = 0.67 vs TCR h = -.54) and executive function (SMART h = -0.92 vs TCR h = -.85); however, SMART had a larger impact on memory (SMART h = -0.81 vs TCR h = -.39). SMART resulted in large improvements in retention and recognition memory which were minimally impacted by TCR.Conclusions:Both TCR and SMART had comparable effectiveness in improving cognitive impairment, though SMART was completed in less than half of the treatment time. Both interventions had large effect sizes on processing speed and executive functioning; however, SMART was more effective in improving long-term memory. Memory is an integral part of military readiness. Further investigation is required to determine the relative effectiveness of these two approaches to improving cognitive readiness of the warfighter.

51 Impact of Blast Exposures on the Cognitive Abilities of Warfighters

Objective:There is growing evidence to indicate that blast exposure military personnel experience throughout their career can have a negative impact on their brain health. The majority of research in the area of blast related neurotrauma has been focused on traumatic brain injury (TBI); however, the blast exposure may often be independent of TBI. It is common in both active duty military and veterans to report years of blast exposure from combat and training. The objective of this study was to explore the relationship between blast exposure and cognitive functioning in military personnel seeking treatment for a mild TBI.Participants and Methods:Participants were recruited from a military hospital while enrolled in a multidisciplinary treatment program for TBI. All patients had at least one diagnosed mTBI as well as persistent cognitive complaints. Exclusion criteria included invalid performance on a performance validity test and a symptom validity test. 97 participants were included in the analysis with an average age of 34.0 (SD = 7.9) and average 4.0 combat deployments (SD = 3.6). Blast exposure history was measured by the overall score from the Blast Exposure Threshold Survey (BETS) which assessed the frequency and duration of use of various blast sources. Outcomes included the Neurobehavioral Symptom Inventory (NSI) and the Global Deficit Scale (GDS) an objective measure of cognitive deficiency. GDS was calculated from seven measures: Hopkins Verbal Learning Test-Revised Total and Delayed Recall (HVLT-TR and HVLT-DR); DKEFS System Color-Word Condition 3 Inhibition (CW3), Color-Word Condition 4 Switching (CW4) and Trail Making Condition 3 Letter Sequencing (TM3), Paced Auditory Serial Addition Test (PASAT), and the Symbol Digit Modality Test (SDMT). Demographically corrected t-scores (M=50, SD = 10) were converted to deficit scores and averaged to calculate GDS. To adjust for nonnormal distributions, non-parametric statistics were examined.Results:The BETS was not related to GDS (rho = -.055); however, there was a significant correlation between higher levels on the BETS and better performance on measures of selective attention (PASAT rho = .307) and processing speed (SDMT rho = .218). The correlation between BETS and the other neuropsychological measures were not meaningful (all rho’s <.10). Those with an impaired GDS, did not differ from others on the BETS. BETS was also not associated with neurobehavioral symptoms (rho = .125). BETS had moderate correlations with number of combat deployments (rho =.483), severity of combat exposure (rho =.556). It was not related to education (rho = .004) or pre-morbid intelligence (rho =-.029).Conclusions:The BETS was not related to GDS (rho = -.055); however, there was a significant correlation between higher levels on the BETS and better performance on measures of selective attention (PASAT rho = .307) and processing speed (SDMT rho = .218). The correlation between BETS and the other neuropsychological measures were not meaningful (all rho’s <.10). Those with an impaired GDS, did not differ from others on the BETS. BETS was also not associated with neurobehavioral symptoms (rho = .125). BETS had moderate correlations with number of combat deployments (rho =.483), severity of combat exposure (rho =.556). It was not related to education (rho = .004) or pre-morbid intelligence (rho =-.029).

A - 72 Neuropsychological Test Performance in Mild to Moderate COVID-19 Patients with and without Subjective Cognitive Complaints.

This cross-sectional study measured cognitive performance in mild-moderate COVID-19 patients with and without self-reported persistent cognitive complaints, while accounting for demographic variables, cardiovascular (CVD) risk factors, and mood symptoms. We hypothesized that individuals with persistent cognitive complaints would demonstrate lower global cognitive composite scores compared to those without. 67 adults aged 24-83 completed in-person neuropsychological testing in a hospital setting in Phoenix, Arizona. PCR-confirmed COVID-19 within 24months before evaluation and no pre-existing neurological conditions. The Long COVID (LC) group included those with persistent cognitive symptoms 4+ weeks after infection; COVID-positive Controls (CC) included those with prior infection but without persistent cognitive symptoms. Demographic information, CVD risk factors, and psychiatric history were collected. Neuropsychological evaluation included performance validity testing and validated measures of attention, language, visuospatial ability, executive function, and memory. T-scores from each domain were averaged to create a global cognitive composite score. Gender, age, race (white/non-white), mood disorder, and CVD were equivalent across groups. Education was significantly higher in the LC group, t(65) = 2.737, p = 0.008, and was included as a covariate in the model to account for differences in cognitive reserve. With this adjustment, there was not a statistically significant difference in global composite scores between groups, F(1, 64) = 0.13, p = 0.911, partial η2 = 0.000. Cognitive performance did not differ between LC and CC groups when demographics, cardiovascular risk, and mood symptoms were held constant, suggesting that other factors influence the development of persistent cognitive complaints in mild-moderate COVID-19 patients.

A - 134 The Impact of Pre-Treatment Mental Health Symptoms on the Efficacy of Cognitive Rehabilitation for Warfighters with a History Mild TBI.

Mild traumatic brain injury (mTBI) is common among warfighters. Most have a full recovery but some have persistent cognitive complaints. Cognitive rehabilitation is the primary treatment; however, mTBI is highly co-morbid with depression and post-traumatic stress (PTS). This study investigated if high levels of mental health symptoms negatively impacted the efficacy of cognitive rehabilitation. 82 military personnel with at least one diagnosed mTBI and persistent cognitive complaints completed 4-6weeks of cognitive rehabilitation. PTS was measured by the Post-Traumatic Checklist-5 (PCL-5) and depression was measured with the Patient Health Questionnaire 8 (PHQ8); scores were dichotomized based on published cut-offs (>33 and > 10, respectively). Outcomes included change pre-post treatment on: Neurobehavioral Scale Inventory (NSI), Key Behavior Change Index (KBCI), and Global Deficit Scale (GDS). GDS was derived from: Hopkins Verbal Learning Test-Revised, Color Word, Trail Making, Paced Auditory Serial Addition Test, and the Symbol Digit Modality Test. A MANOVA revealed PTS had no effect on the NSI, KBCI, or GDS (p = 0.659). There was a significant effect for depression (p = 0.017); however, this was specific to change in GDS (p = 0.002). The average reduction was 0.98 (SD = 0.87) in high depression and 0.43 (SD = 0.68) in low depression. Depression did not impact NSI or KBCI. In contrast to the initial hypothesis, high levels of depression or PTS did not negatively impact the efficacy of cognitive rehabilitation. In fact, warfighters with high levels of depression had greater improvements in cognitive functioning.

B - 107 Exploratory Analysis of the Relationship between Health Anxiety (HA) and Neuropsychological Performance in a Validity Controlled Sample of Patients with Post-Acute Sequelae of COVID-19 (PASC).

Since the emergence of COVID-19, research has consistently indicated cognitive difficulties as a primary complaint after infection (Altuna et al., 2021). It is unclear to what extent these cognitive deficits may be attributable to, or exacerbated by, health anxiety (HA) (Venkataramani et al., 2022). This study explored the relationship between HA and cognition in a performance validity controlled sample of patients with PASC complaints. Participants included patients referred for a focused neuropsychological evaluation for persistent cognitive complaints after COVID infection (N = 19). Participants were excluded for Test of Memory Malingering scores below standard cutoff. The sample mean age was 43years (SD = 12.9), 57.9% were female, and 47.4% were from minority racial/ethnic groups. HA was assessed using the Short Health Anxiety Inventory (SHAI). Cognitive abilities were measured using the Wechsler Adult Intelligence Scale-IV (WAIS-IV: Processing Speed Index [PSI]; Letter-Number Sequencing [LNS]) and Trail Making Test Part-A (TMT-A). Regression analyses were conducted to assess the extent to which HA predicts cognitive performance. The SHAI main subscale significantly predicted TMT-A [β= -3.93, p < 0.01] and WAIS-IV PSI [β= -4.60, p = 0.04]. The SHAI negative consequences subscale significantly predicted TMT-A [β= -4.64, p = 0.04] and WAIS-IV LNS [β= 0.49, p = 0.048]. Findings suggest that general HA predicted PSI, while fear of negative health outcomes predicted LNS. Basic attention abilities were predicted by global HA. Future studies will benefit from evaluating the moderating effect of HA on the relationship between subjective symptom severity and cognition.

Cerebral hypoperfusion in post-COVID-19 cognitively impaired subjects revealed by arterial spin labeling MRI

Cognitive impairment is one of the most prevalent symptoms of post Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) state, which is known as Long COVID. Advanced neuroimaging techniques may contribute to a better understanding of the pathophysiological brain changes and the underlying mechanisms in post-COVID-19 subjects. We aimed at investigating regional cerebral perfusion alterations in post-COVID-19 subjects who reported a subjective cognitive impairment after a mild SARS-CoV-2 infection, using a non-invasive Arterial Spin Labeling (ASL) MRI technique and analysis. Using MRI-ASL image processing, we investigated the brain perfusion alterations in 24 patients (53.0 ± 14.5 years, 15F/9M) with persistent cognitive complaints in the post COVID-19 period. Voxelwise and region-of-interest analyses were performed to identify statistically significant differences in cerebral blood flow (CBF) maps between post-COVID-19 patients, and age and sex matched healthy controls (54.8 ± 9.1 years, 13F/9M). The results showed a significant hypoperfusion in a widespread cerebral network in the post-COVID-19 group, predominantly affecting the frontal cortex, as well as the parietal and temporal cortex, as identified by a non-parametric permutation testing (p < 0.05, FWE-corrected with TFCE). The hypoperfusion areas identified in the right hemisphere regions were more extensive. These findings support the hypothesis of a large network dysfunction in post-COVID subjects with cognitive complaints. The non-invasive nature of the ASL-MRI method may play an important role in the monitoring and prognosis of post-COVID-19 subjects.

Screening for brain fog: Is the montreal cognitive assessment an effective screening tool for neurocognitive complaints post-COVID-19?

BackgroundCognitive complaints are one of the most frequent symptoms reported in post-acute sequelae of COVID-19 (PASC). The Montreal Cognitive Assessment (MoCA) has been used to estimate prevalence of cognitive impairment in many studies of PASC, and is commonly employed as a screening test in this population, however, its validity has not been established. ObjectiveTo determine the utility of the MoCA to screen for cognitive impairment in PASC. MethodsSixty participants underwent neuropsychological, psychiatric, and medical assessments, as well as the Montreal Cognitive Assessment, 6–8 months after acute COVID-19 infection. ResultsThe overall sample had a mean score of 26.1 on the MoCA, with approximately one third screening below the cutoff score of 26, similar to the rate of extremely low NP test performance. MoCA score was inversely correlated with fatigue and depression measures and ethnic minority participants scored on average lower, despite similar education and estimated premorbid function. The MoCA had an accuracy of 63.3% at detecting any degree of diminished NP performance, and an accuracy of 73.3% at detecting extremely low NP performance. Discussion/ConclusionThe MoCA may not be accurate for detecting neither mild nor more severe degrees of diminished NP test performance in PASC. Therefore, patients with persistent cognitive complaints in the setting of PASC who score in the normal range on the MoCA should be referred for formal NP assessment.

Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19.

ObjectiveA subset of individuals with coronavirus disease 2019 (COVID-19) appears to develop persisting cognitive and medical symptoms. Research in the acute stages of illness, generally utilizing cognitive screening measures or case reports, suggests presence of deficits in attention and executive function. This observational study investigated cognitive functioning among individuals with persistent cognitive complaints about 5.5 months after COVID-19 infection.MethodsPatients with polymerase chain reaction confirmed COVID-19 and persistent cognitive complaints underwent comprehensive in-person neuropsychological evaluations. Patients with prior neurological disorders were excluded. When diagnosed, 40% required hospitalization, 15% were in an intensive care unit, 10% needed mechanical ventilation, and 10% experienced delirium.ResultsThis sample was predominately women (90%), White non-Hispanic (70%), with average education of 15 years. Mild cognitive deficits were seen on tests involving attention and processing speed or executive function. Seventy percent of patients were diagnosed with a mood disorder prior to COVID-19 infection. At the time of testing, 35%–40% endorsed moderate to severe mood symptoms and 85% noted significant fatigue as measured by the Fatigue Severity Scale.ConclusionsThe pattern of cognitive deficits, although mild, is consistent with prior research at the acute stage of the illness. These findings suggest that psychological factors and other persisting symptoms (e.g., sleep, fatigue) may play a significant role in subjective cognitive complaints in patients with persisting complaints post COVID-19 who did not require intensive treatment. These patients would likely benefit from resources to manage persisting or new mood symptoms and compensatory strategies for the cognitive inefficiencies they experience.

A-117 Strategic Memory and Advanced Reasoning Training for Rehabilitation of Warfighters with Mild Traumatic Brain Injury

Abstract Background Military personnel require a level of cognitive readiness that ensures they function safely and effectively in high-stress situations. Warfighters who experienced a mild traumatic brain injury (mTBI) often complain of persistent cognitive issues that may impact those abilities. This study presents preliminary data on the efficacy of a 4-week Strategic Memory Advanced Reasoning Training (SMART) for warfighter rehabilitation. SMART improves executive functioning in order to enhance overall cognitive abilities. Methods This is part of a randomized clinical trial (Validation of Cognitive Enhancement Therapy for mTBI). 22 Marines with prior mTBI and current cognitive complaints; 7 of whom completed SMART and were included in the analysis. Cognitive tests of interest included the Delis-Kaplan Executive Function System Color Word (CW) and Trail Making (TM). Results Improvements were observed on TM Number Sequencing (Pre: M = 9.71, SD = 2.06; Post: M = 11.86, SD = 1.35, p = 0.011, d = 1.37) and approached significance on Letter Sequencing (Pre: M = 10.29, SD = 1.81; Post: M = 12.57, SD = 1.13, p = 0.066, d = 1.26). Though non-significant, a large clinically-relevant effect size was found for Number-Letter Switching (Pre: M = 8.14, SD = 1.95; Post: M = 9.57, SD = 2.15, p = 0.106, d = 0.72). CW performance improved on Inhibition (Pre: M = 5.29, SD = 3.86; Post: M = 8.86, SD = 2.34, p = 0.034, d = 1.03) and Inhibition/Switching (Pre: M = 4.86, SD = 4.06; Post: M = 8.43, SD = 4.12, p = 0.015, d = 1.26). Conclusions The SMART program resulted in large improvements in the executive functioning of a small sample of warfighters with persistent cognitive complaints following a mTBI. The results support further examination of the efficacy of SMART for warfighter rehabilitation.

Perceived Cognitive Impairment in Breast Cancer Survivors and Its Relationships with Psychological Factors

Simple SummaryCognitive complaints are common adverse effects for breast cancer survivors, with potential negative impacts on quality of life or return to work. Identifying subjects at risk could allow to reduce cognitive disorders or to set up appropriate care. In this study we explored current cognitive complaints reported by breast cancer survivors, using the Functional Assessment of Cancer Therapy-Cognition (FACT-Cog) questionnaire and examined the relationships between current cognitive complaints and current psychological symptoms (especially post-traumatic stress symptoms). This large survey showed that about half of breast cancer survivors reported cognitive complaints after cancer treatments. These complaints were mainly associated with chemotherapy, age, self-reported sleep difficulties, the frequency of psychotropic treatments and psychological factors including post-traumatic stress symptoms or. Some modifiable risk factors should be detected early to reduce persistent cognitive complaints after cancer, including sleep difficulties and post-traumatic stress symptoms.Cognitive complaints are common adverse effects in cancer patients. Identifying subjects at risk could make it possible to limit their impact. We aimed to explore the relationship between current cognitive complaints and demographic and psychological factors in a group of breast cancer survivors. Through an online survey, cancer survivors reported current cognitive complaints using the FACT-Cog questionnaire (Perceived Cognitive Impairment) and answered questions about their demographics, lifestyle and cancer-related characteristics. Anxiety, depression, fatigue and post-traumatic stress symptoms were also assessed. We used multivariable logistic regression models to explore the relationships between current cognitive complaints and social and psychological factors. Among the 1393 breast cancer survivors, 47.2% (n = 657) reported current cognitive complaints. Chemotherapy (OR = 2.26, 95%CI = 1.67–3.05), age (OR21-44 vs. >65 = 0.14, 95%CI = 0.07–0.27), sleep difficulties (ORnever vs. often = 2.41, 95%CI = 1.47–3.95), frequency of psychotropic treatments (ORnever vs. >1/week = 1.70, 95%CI = 1.23–2.36), post-traumatic stress symptoms (OR = 2.05, 95%CI = 1.57–2.69) and employment status (ORfull-time or part-time vs. sick leave = 1.64, 95%CI = 1.08–2.49) were strongly associated with current cognitive complaints. In this large study, about half of breast cancer survivors reported cognitive complaints, particularly after chemotherapy. Some risk factors should be detected early to reduce persistent cognitive complaints after cancer: mainly sleep difficulties, post-traumatic stress symptoms and psychotropic medications.

Computerized Cognitive Rehabilitation verses Clinician Directed Therapy in mTBI

Abstract Background Cognitive problems following mTBI are common and typically managed with one-on-one clinician directed treatment (CDT); however, this is time and labor intensive. Computerized cognitive rehabilitation (CCR) programs overcome these limitation but the comparable efficacy is not well understood in mTBI. Method A randomized controlled trial included 13 active duty service members with a history of mTBI and persistent cognitive complaints. Participants received either CCR (N = 6) or CDT (N = 7) during the initial phase of this study. Treatments were one hour, 3 times a week for 4 weeks. Average age was 32.77 (SD = 7.96). Average intelligence estimated by word reading was average (WTAR M = 107.46, SD = 9.32). Specific measures for attention included Symbol Digit Modality Test (SDMT), Paced Auditory Serial Addition Test (PASAT), Conners Continuous Performance Test (CPT-3), as well as Digit Forward (DF), Digit Backward, and Driving from the Neuropsychological Assessment Battery (NAB). Standard scores corrected for age were analyzed. Change scores were computed between pre and post intervention. Results There was a significant difference for SDMT (p = 0.034, d = 1.342) and DF (p = 0.0015, d = 2.33), where those who received CDT showed greater improvement. The groups did not differ on Driving, PASAT, CPT-3, and DB (p’s &gt; 0.62). Conclusions Preliminary analysis of data suggests that clinician directed treatment was superior to a computerized intervention matched for time and intensity in treating patients with persistent cognitive complaints following mTBI. Large effects were observed on measures of processing speed and focused attention. This may suggest computerized treatment alone is less effective though further data is needed.

Cognitive functioning and quality of life following chemotherapy in pre- and peri-menopausal women with breast cancer.

The purpose of the study was to prospectively examine changes in subjective and objective cognitive functions and quality of life (QOL) for pre- and peri-menopausal women receiving chemotherapy for breast cancer and to explore potential predictors of cognitive changes. Participants were assessed as follows: prior to chemotherapy (T1), after cycle 3 (T2), within 2-3weeks of completing adjuvant chemotherapy (T3) (N=20), and 8+ years later (T4; n=18). Objective cognitive function was measured with the High Sensitivity Cognitive Screen (T1, T3, T4). Subjective measures for cognitive function, depressive symptoms, fatigue, and mental and physical QOL were assessed at all time points. Estradiol levels were measured at T1, T2, and T3. The Functional Assessment of Cancer Therapy-Cognition and the MD Anderson Cancer Symptom Inventory item for neuropathy were administered at T4. No significant changes in objective cognitive function were found. However, participants reported decreased cognitive function over the course of treatment accompanied by depressive symptoms and fatigue. Depression and fatigue returned to near-baseline levels at T4, but over half of the participants continued to report mild to moderate depression. Estradiol levels were not associated with cognitive function. Neuropathy and higher body mass index (BMI) were associated with persistent cognitive complaints at T4 (adjusted R 2=0.712, p=0.001). Higher QOL was correlated with better subjective cognitive function (r=0.705, p=0.002) and lower body mass index (r=- 0.502, p=0.017) at T4. Further investigation of BMI, neuropathy, and depressive symptoms as predictors of persistent cognitive dysfunction following chemotherapy for breast cancer is warranted.

Measuring cognitive complaints in breast cancer survivors: psychometric properties of the patient's assessment of own functioning inventory.

Cognitive complaints are a concern for breast cancer survivors. Among various published measures for cognitive complaints, the Patient's Assessment of Own Functioning Inventory (PAOFI) is one of the few assessing a spectrum of cognitive abilities, including those most commonly reported by breast cancer survivors. This study aimed to examine the psychometric properties of the PAOFI in breast cancer survivors. An exploratory factor analysis was conducted with a sample of breast cancer survivors (n = 189) who had completed all primary cancer treatments. Construct validity was examined by correlating factor scores with valid measures of cognitive complaints, fatigue, and quality of life. Reliability was measured by internal consistency of the items in each factor within this sample, a separate sample of breast cancer survivors with high persistent cognitive complaints (n = 72), and healthy controls (n = 63). Factor scores were compared across the three samples. A five-factor structure similar to the PAOFI standardization study was found, with factors related to executive functioning (accounting for most of the variance), two aspects of memory functioning, language, and motor/sensory-perceptual abilities. Factor scores highly correlated with measures of cognitive complaints, fatigue, and quality of life. Executive functioning and memory-related factors achieved adequate reliability across samples. Scores were significantly different across the three samples as expected. The PAOFI is a reliable and valid tool for measuring cognitive complaints in breast cancer survivors.

Cognitive dysfunction and symptom burden in women treated for breast cancer: a prospective behavioral and fMRI analysis.

Neural dysfunction and cognitive complaints are associated with chemotherapy for breast cancer although trajectory and contributory factors remain unclear. We prospectively examined neurocognition using fMRI and self-reported cognitive, physical and psychological symptoms in women treated with adjuvant chemotherapy over one year. Patients treated with (n=28) or without (n=34) chemotherapy for localized breast cancer and healthy controls (n=30) performed a Verbal Working Memory Task (VWMT) during fMRI and provided self-reports at baseline (pre-adjuvant treatment), five- (M5) and 12-months (M12). Repeated measures ANOVA and multivariable regression determined change over time and possible predictors (e.g., hemoglobin, physical symptoms, worry) of VWMT performance, fMRI activity in the frontoparietal executive network, and cognitive complaints at M12. Trajectories of change in VWMT performance for chemotherapy and healthy control groups differed significantly with the chemotherapy group performing worse at M12. Chemotherapy patients had persistently higher spatial variance (neural inefficiency) in executive network fMRI-activation than both other groups from baseline to M12. Cognitive complaints were similar among groups over time. At M12, VWMT performance and executive network spatial variance were each independently predicted by chemotherapy treatment and their respective baseline values, while cognitive complaints were predicted by baseline level, physical symptoms and worry. Executive network inefficiency and neurocognitive performance deficits pre-adjuvant treatment predict cognitive dysfunction one-year post-baseline, particularly in chemotherapy-treated patients. Persistent cognitive complaints are linked with physical symptom severity and worry regardless of treatment. Pre-chemotherapy interventions should target both neurocognitive deficits and symptom burden to improve cognitive outcomes for breast cancer survivors.

Neuropsychological performance in treatment-seeking Operation Enduring Freedom/Operation Iraqi Freedom Veterans with a history of mild traumatic brain injury

Introduction: Clinical neuropsychological presentation of treatment-seeking Veterans with a remote history of mild traumatic brain injury (mTBI) is widely variable. This manuscript seeks to better characterize cognitive concerns in the post-acute phase following mTBI and to identify the neuropsychological profiles of a large sample of clinically referred Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) Veterans with a history of mTBI and current cognitive complaints. We hypothesized that a minority of cases would exhibit valid and widespread neuropsychological deficits. Method: Retrospective chart reviews of neuropsychological testing and mental health symptoms and diagnoses were conducted on 411 clinically referred OEF/OIF/OND Veterans with a history of mTBI. Groups were created based on scores on performance validity measures and based on overall neuropsychological performance. Results: A total of 29.9% of the sample performed below normative expectations on at least one performance validity test (PVT). Of those Veterans performing adequately on PVTs, 60% performed within normal limits on virtually all neuropsychological measures administered, leaving only 40% performing below expectations on two or more measures. Mood and neurobehavioral symptoms were significantly elevated in Veterans performing below cutoff on PVTs compared to Veterans who performed within normative expectations or those with valid deficits. Neurobehavioral symptoms were significantly correlated with mental health symptom reports but not with injury variables. Conclusions: In summary, in a large sample of clinically referred Veterans with persistent cognitive complaints after mild TBI, a third demonstrated invalid clinical neuropsychological testing, and, of those performing at or above cutoff on PVTs, over half performed within normative expectations across most neuropsychological tests administered. Results highlight the importance of objective assessment of cognitive functioning in this population as subjective reports do not correspond to objective assessment in the majority of cases.

An investigation of attention, executive, and psychomotor aspects of cognitive fatigability

Objective: Self-perceived mental fatigue is a common presenting symptom in many neurological diseases. Discriminating objective fatigability from self-perceived mental fatigue might facilitate neuropsychological diagnosis and treatment programs. However clinically valid neuropsychological instruments suitable for assessment of fatigability are still lacking. The prime aim of the study was to investigate aspects of cognitive fatigability and to identify properties of neuropsychological tests suitable to assess fatigability in patients with persistent cognitive complaints after mild brain injury. Another aim was to investigate whether cognitive fatigability captured by neuropsychological measures is influenced by depression or sleep disturbances. Method: Twenty-four patients with persistent cognitive symptoms after mild traumatic brain injury (mTBI), (aged 18–51 years) and 31 healthy controls (aged 20–49 years) underwent neuropsychological testing measuring three cognitive fatigability domains: Attention fatigability was assessed using the Ruff 2 & 7 Selective Attention Test, executive fatigability using the Color Word Test (Stroop), and psychomotor fatigability using the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale–Third Edition (WAIS–III). Subjective fatigue was measured using the Fatigue Severity Scale and a questionnaire of everyday consequences of fatigue. Depression was screened using the Hospital Anxiety and Depression Scale and sleep disturbances using the Pittsburgh Sleep Quality Index. Results: The patients reported significantly more mental fatigue and performed worse on tests of psychomotor and executive fatigability than the healthy controls. Furthermore, the cognitive fatigability measures were not influenced by depression or sleep disturbances, as was the case in self-reported fatigue. Conclusion: Tests demanding executive or simultaneous processing of several neuropsychological functions seem most sensitive in order to capture cognitive fatigability. Clinical tests that can capture fatigability enable a deeper understanding of how fatigability might contribute to cognitive complaints and problems in maintaining daily activities.

Effects of interactive metronome therapy on cognitive functioning after blast-related brain injury: A randomized controlled pilot trial.

We report preliminary findings on the efficacy of interactive metronome (IM) therapy for the remediation of cognitive difficulties in soldiers with persisting cognitive complaints following blast-related mild-to-moderate traumatic brain injury (TBI). Forty-six of a planned sample of 50 active duty soldiers with persistent cognitive complaints following a documented history of blast-related TBI of mild-to-moderate severity were randomly assigned to receive either standard rehabilitation care (SRC) or SRC plus a 15-session standardized course of IM therapy. Primary outcome measures were Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Index Scores. Secondary outcome measures included selected subtests from the Delis-Kaplan Executive Functioning System (Trail Making Test and Color-Word Interference) and the Wechsler Adult Intelligence Scale-Fourth Edition (Symbol Search, Digit-Symbol Coding, Digit Span, and Letter-Number Sequencing) as well as the Integrated Visual and Auditory Continuous Performance Test. Significant group differences (SRC vs. IM) were observed for RBANS Attention (p = .044), Immediate Memory (p = .019), and Delayed Memory (p = .031) indices in unadjusted analyses, with the IM group showing significantly greater improvement at Time 2 than the SRC group, with effect sizes in the medium-to-large range in the adjusted analyses for each outcome (Cohen's d = 0.511, 0.768, and 0.527, respectively). Though not all were statistically significant, effects in 21 of 26 cognitive outcome measures were consistently in favor of the IM treatment group (binomial probability = .00098). The addition of IM therapy to SRC appears to have a positive effect on neuropsychological outcomes for soldiers who have sustained mild-to-moderate TBI and have persistent cognitive complaints after the period for expected recovery has passed.

Postoperative cognitive dysfunction versus complaints: a discrepancy in long-term findings.

This review describes the discrepancy in findings between postoperative cognitive performance and postoperative cognitive complaints long time after an operation under general anesthesia. Shortly (from 6 hr to 1 week) after an operation a decline in cognitive performance is reported in most studies. However, long time (from 3 weeks to 1-2 years) after an operation this is rarely found although some patients are still reporting cognitive complaints. In general this kind of research is suffering from severe methodological problems (use of insensitive tests, lack of control groups, lack of parallel tests, different definitions of cognitive decline). However, these problems cannot totally explain the discrepancy in findings in the long term. Thus, there are patients who have persistent cognitive complaints long time after an operation, that cannot be measured with cognitive tests. More psychological factors such as fixation on short-term cognitive dysfunction, mood, coping style, and personality are possible explanations for these cognitive complaints in the long term. As a consequence, these factors should be a topic in future research elucidating the persistence of these cognitive complaints long time after an operation under general anesthesia.

Adenomas and a family history of colorectal cancer.

This review examines the clinical and neuroradiological features of traumatic brain injury that are most frequently associated with persistent cognitive complaints. Neuropsychological outcomes do not depend solely on brain injury severity but result from a complex interplay between premorbid factors, the extent and nature of the underlying structural damage, the person’s neuropsychological reserve and the impact of non-neurological factors in the recovery process. Brain injury severity is only one of these factors and has limited prognostic significance with respect to neuropsychological outcome. We examine the preinjury and postinjury factors that interact with the severity of a traumatic brain injury to shape outcome trajectories. We aim to provide a practical base on which to build discussions with the patient and their family about what to expect following injury and also to plan appropriate neurorehabilitation.