Self-reported Cognitive Symptoms Research Articles

In vivo brain estrogen receptor density by neuroendocrine aging and relationships with cognition and symptomatology

17β-estradiol, the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order cognitive function and neurobiological aging. However, our knowledge of ER expression and regulation by neuroendocrine aging in the living human brain is limited. This in vivo brain 18F-fluoroestradiol (18F-FES) Positron Emission Tomography (PET) study of healthy midlife women reveals progressively higher ER density over the menopause transition in estrogen-regulated networks. Effects were independent of age, plasma estradiol and sex hormone binding globulin, and were highly consistent, correctly classifying all women as being postmenopausal or premenopausal. Higher ER density in target regions was associated with poorer memory performance for both postmenopausal and perimenopausal groups, and predicted presence of self-reported mood and cognitive symptoms after menopause. These findings provide novel insights on brain ER density modulation by female neuroendocrine aging, with clinical implications for women’s health.

Attentional, anticipatory and spatial cognition fluctuate throughout the menstrual cycle: potential implications for female sport

Current research suggests that menstruating female athletes might be at greater risk of musculoskeletal injury in relation to hormonal changes throughout the menstrual cycle. A separate body of work suggests that spatial cognition might also fluctuate in a similar manner. Changes in spatial cognition could, in theory, be a contributing risk factor for injury, especially in fast-paced sports that require precise, millisecond accuracy in interactions with moving objects in the environment. However, existing theories surrounding causes for increased injury risk in menstruating females largely focus on biomechanical mechanisms, with little consideration of possible cognitive determinants of injury risk. Therefore, the aim of this proof-of-principle study was to explore whether menstruating females exhibit fluctuations in cognitive processes throughout their cycle on a novel sport-oriented cognitive test battery, designed to measure some of the mental processes putatively involved in these sporting situations.A total of 394 participants completed an online cognitive battery, a mood scale and a symptom questionnaire twice, 14 days apart. After exclusions, 241 eligible participants were included in the analyses (mean: 28 ± 6 years) (male = 96, female(menstruating) = 105, female(contraception) = 47). Cycle phase for menstruating females was based on self-reported information. The cognitive battery was designed to measure reaction times, attention, visuospatial functions (including 3D mental rotation) and timing anticipation. Three composite scores were generated using factor analysis with varimax rotation (Errors, Reaction Time, Intra-Individual Variability). Mixed model ANOVAs and repeated measures ANOVAs were performed to test for between and within-subject effects.There was no group difference in reaction times and accuracy between males and females (using contraception and not). However, within subject analyses revealed that regularly menstruating females performed better during menstruation compared to being in any other phase, with faster reaction times (10ms c.ca, p < .01), fewer errors (p < .05) and lower dispersion intra-individual variability (p < .05). In contrast they exhibited slower reaction times (10ms c.ca, p < .01) and poorer timing anticipation (p < .01) in the luteal phase, and more errors in the predicted ovulatory phase (p < .01). Self-reported mood, cognitive and physical symptoms were all worst during menstruation (p < .01), and a significant proportion of females felt that their symptoms were negatively affecting their cognitive performance during menstruation on testing day, which was incongruent with their actual performance.These findings suggest that visuospatial and anticipatory processes may fluctuate throughout the menstrual cycle in the general population, with better performance during the menstrual phase and poorer performance during the luteal phase. If these extend to associations between phase-specific cognitive performance and injury incidence, they would support a cognitive theory of determinants of injury risk in cycling female athletes, opening an opportunity to develop mitigation strategies where appropriate.

The Effects of a Single-Session Virtual Rumination Intervention to Enhance Cognitive Functioning in Veterans With Subjective Cognitive Symptoms: Multimethod Pilot Study.

Subjective cognitive concerns (SCCs) entail perceived difficulties in thinking or memory, often reported without substantial objective evidence of cognitive impairment. These concerns are prevalent among individuals with a history of brain injuries, neurological conditions, or chronic illnesses, contributing to both psychological distress and functional limitations. They are increasingly considered to be a risk factor for future objective decline. A considerable number of individuals reporting SCCs also exhibit mental health symptoms, such as a history of trauma, depression, or anxiety. Interventions that address modifiable emotional and cognitive factors related to SCC could improve functioning and quality of life. Therefore, the use of emotion regulation strategies, especially those directed at minimizing rumination, could serve as a promising focus for interventions aimed at mitigating subjective cognitive concerns in veteran populations. This pilot study explored the feasibility, acceptability, and preliminary efficacy of a brief, 1-session emotion regulation intervention called "Worry Less, Remember More." The Worry Less, Remember More intervention was designed to reduce rumination and improve subjective cognitive functioning in veterans with subjective cognitive changes (N=15). We randomized 15 veterans to either the active telehealth condition or waitlist control and completed the intervention. Participants were aged between 31 and 67 (mean 49.5, SD 10.1) years, and the sample was primarily male (12/15, 83%) and White (10/15, 67%). The most common diagnoses were posttraumatic stress disorder and depression. Following the intervention, veteran input was sought through semistructured interviews with a subset of 12 participants, examining feasibility, acceptability, and perceived efficacy. Preliminary efficacy was also measured using pre- and postintervention self-report measures. Veterans reported that this intervention was acceptable, with 92% (11/12) of the sample reporting that they benefited from the intervention and would recommend the intervention to others with similar difficulties. Semistructured interviews revealed difficulties with feasibility, including problems with the remote consenting process, forgetting appointments, and needing additional strategies to remember to consistently use the interventions. The intervention improved self-reported cognitive symptoms on quantitative measures but did not improve self-reported rumination. This pilot study establishes the preliminary feasibility, acceptability, and efficacy of the Worry Less, Remember More intervention for veterans with subjective cognitive symptoms. Future iterations of the intervention may benefit from simplifying the electronic consent process, providing reminders for appointments, and incorporating compensatory cognitive strategies to assist with using the telehealth system, as well as applying the strategies learned in the intervention. While future research is needed with larger samples, including nonveteran populations, the intervention may also be a useful clinical tool to bridge care between neuropsychology clinics and mental health treatment.

Implications of vascular depression for successful cognitive aging in HIV Disease.

Although older adults with HIV are at high risk for mild neurocognitive disorders, a subset experience successful cognitive aging (SCA). HIV is associated with an increased risk of vascular depression (VasDep), which can affect cognitive and daily functioning. The current study examined whether VasDep impedes SCA among older adults with HIV. 136 persons with HIV aged 50 years and older were classified as either SCA+ (n = 37) or SCA- (n = 99) based on a battery of demographically adjusted neurocognitive tests and self-reported cognitive symptoms. Participants were also stratified on the presence of vascular disease (e.g., hypertension) and current depression as determined by the Composite International Diagnostic Interview and the Depression/Dejection scale of the Profile of Mood States. A Cochran-Armitage test revealed a significant additive effect of vascular disease and depression on SCA in this sample of older adults with HIV (z = 4.13, p <.0001). Individuals with VasDep had the lowest frequency of SCA+ (0%), which differed significantly from the group with only vascular disease (30%, OR = 0.04, CI = 0.002,0.68)) and the group with neither vascular disease nor depression (47% OR = 0.02, CI = 0.33,0.001). Findings were not confounded by demographics, HIV disease severity, or other psychiatric and medical factors (ps > 0.05). These data suggest that presence of VasDep may be a barrier to SCA in older adults with HIV disease. Prospective, longitudinal studies with neuroimaging-based operationalizations of VasDep are needed to further clarify this risk factor's role in the maintenance of cognitive and brain health in persons with HIV disease.

A register and questionnaire study of long-term general health symptoms following SARS-CoV-2 vaccination in Denmark

Many individuals who refuse COVID-19 vaccination have concerns about long-term side effects. Here, we report findings on self-reported symptoms from a Danish survey- and register study. The study included 34,868 vaccinated primary course recipients, 95.8% of whom received mRNA vaccines, and 1,568 unvaccinated individuals. Participants had no known history of SARS-CoV-2 infection. Using g-computation on logistic regression, risk differences (RDs) for symptoms between vaccinated and unvaccinated persons were estimated with adjustments for possible confounders. Within six weeks after vaccination, higher risks were observed for physical exhaustion (RD 4.9%, 95% CI 1.1% to 8.4%), fever or chills (RD 4.4%, 95% CI 2.1% to 6.7%), and muscle/joint pain (RD 7.0%, 95% CI 3.1% to 10.7%), compared to unvaccinated individuals. Beyond twenty-six weeks, risks were higher among the vaccinated for sleeping problems (RD 3.0, 95% 0.2 to 5.8), fever or chills (RD 2.0, 95% CI 0.4 to 3.6), reduced/altered taste (RD 1.2, 95% CI 0.2 to 2.3) and shortness of breath (RD 2.6, 95% CI 0.9 to 4.0). However, when examining pre-omicron responses only, the difference for reduced/altered taste was significant. As expected, the risk of experiencing physical exhaustion, fever or chills, and muscle/joint pain was higher among persons who responded within six weeks of completing the primary course. No significant differences were observed for the 7-25-week period after vaccination. Associations for the period beyond 26 weeks must be interpreted with caution and in the context of undetected SARS-CoV-2 infection, wide confidence intervals, and multiple testing. Overall, we observe no concerning signs of long-term self-reported physical, cognitive, or fatigue symptoms after vaccination.

Emotional, Behavioral, and Cognitive Symptom Associations With Community Participation in Chronic Traumatic Brain Injury.

To determine the association between self-reported emotional and cognitive symptoms and participation outcomes in chronic traumatic brain injury (TBI) and to explore the relative contribution of self-reported versus performance-based cognition to participation outcomes. Community. Community-dwelling adults ( n = 135) with a lifetime history of mild to severe TBI. Secondary analysis of a cross-sectional study on neurobehavioral symptoms in chronic TBI. Behavioral Assessment Screening Tool (BAST) (Negative Affect, Fatigue, Executive Dysfunction, Impulsivity, Substance Abuse subscales) measured self-reported neurobehavioral symptoms; Participation Assessment with Recombined Tools (Productivity, Social Relations, and Out and About) measured self-reported participation outcomes; and Brief Test of Adult Cognition by Telephone (BTACT) measured performance-based cognition (Episodic Memory and Executive Function summary scores) in a subsample ( n = 40). The BAST Executive Dysfunction was significantly associated with less frequent participation and had the strongest effect on participation in all participation domains. No other BAST subscales were associated with participation, after adjusting for all subscale scores and age, with the exception of BAST Impulsivity, which was associated with more frequent Social Relationships. Exploratory analysis in the sample including the BTACT revealed that, after accounting for subjective Executive Dysfunction using the BAST, performance-based Executive Function was associated with Productivity and Working Memory was associated with Social Relations, but neither was associated with being Out and About; the BAST Executive Dysfunction remained significant in all models even after including BTACT scores. Self-reported Executive Dysfunction contributed to participation outcomes after mild to severe TBI in community-dwelling adults, whereas self-reported emotional and fatigue symptoms did not. Performance-based cognition measures may capture different variability in participation after injury.

Cognitive Symptoms of Post–COVID-19 Condition and Daily Functioning

The frequent occurrence of cognitive symptoms in post-COVID-19 condition has been described, but the nature of these symptoms and their demographic and functional factors are not well characterized in generalizable populations. To investigate the prevalence of self-reported cognitive symptoms in post-COVID-19 condition, in comparison with individuals with prior acute SARS-CoV-2 infection who did not develop post-COVID-19 condition, and their association with other individual features, including depressive symptoms and functional status. Two waves of a 50-state nonprobability population-based internet survey conducted between December 22, 2022, and May 5, 2023. Participants included survey respondents aged 18 years and older. Post-COVID-19 condition, defined as self-report of symptoms attributed to COVID-19 beyond 2 months after the initial month of illness. Seven items from the Neuro-QoL cognition battery assessing the frequency of cognitive symptoms in the past week and patient Health Questionnaire-9. The 14 767 individuals reporting test-confirmed COVID-19 illness at least 2 months before the survey had a mean (SD) age of 44.6 (16.3) years; 568 (3.8%) were Asian, 1484 (10.0%) were Black, 1408 (9.5%) were Hispanic, and 10 811 (73.2%) were White. A total of 10 037 respondents (68.0%) were women and 4730 (32.0%) were men. Of the 1683 individuals reporting post-COVID-19 condition, 955 (56.7%) reported at least 1 cognitive symptom experienced daily, compared with 3552 of 13 084 (27.1%) of those who did not report post-COVID-19 condition. More daily cognitive symptoms were associated with a greater likelihood of reporting at least moderate interference with functioning (unadjusted odds ratio [OR], 1.31 [95% CI, 1.25-1.36]; adjusted [AOR], 1.30 [95% CI, 1.25-1.36]), lesser likelihood of full-time employment (unadjusted OR, 0.95 [95% CI, 0.91-0.99]; AOR, 0.92 [95% CI, 0.88-0.96]) and greater severity of depressive symptoms (unadjusted coefficient, 1.40 [95% CI, 1.29-1.51]; adjusted coefficient 1.27 [95% CI, 1.17-1.38). After including depressive symptoms in regression models, associations were also found between cognitive symptoms and at least moderate interference with everyday functioning (AOR, 1.27 [95% CI, 1.21-1.33]) and between cognitive symptoms and lower odds of full-time employment (AOR, 0.92 [95% CI, 0.88-0.97]). The findings of this survey study of US adults suggest that cognitive symptoms are common among individuals with post-COVID-19 condition and associated with greater self-reported functional impairment, lesser likelihood of full-time employment, and greater depressive symptom severity. Screening for and addressing cognitive symptoms is an important component of the public health response to post-COVID-19 condition.

Impact of sleep disruption on cognitive function in patients with postacute sequelae of SARS-CoV-2 infection: initial findings from a Neuro-COVID-19 clinic.

Fatigue, brain fog, and sleep disturbance are among the most common symptoms of postacute sequelae of SARS-CoV-2 infection (PASC). We sought to determine the impact of sleep disruption on cognition and quality of life in patients with neurologic manifestations of PASC (Neuro-PASC). Thirty-nine patients were recruited from Neuro-COVID-19 clinic. Mean age was 48.1 years, 71.8% were female, and 82% were never hospitalized for COVID-19. Patients were evaluated via clinical assessment, quality-of-life measures in domains of cognitive function, fatigue, sleep disturbance, anxiety, and depression, NIH Toolbox cognitive tests, and 7 days of wrist actigraphy. The median number of neurologic symptoms attributed to PASC was 6, with brain fog being the most common in 89.7%. Regarding non-neurologic symptoms, 94.9% complained of fatigue and 74.4% of insomnia. Patients reported significant impairment in all quality-of-life domains and performed worse in a task of attention compared to a normative US population. Actigraphy showed Neuro-PASC patients had lower sleep efficiency, longer sleep latency (both p < 0.001), and later sleep midpoint (p = 0.039) compared to 71 age-matched healthy controls with no PASC history. Self-reported cognitive symptoms correlated with the severity of fatigue (p < 0.001), anxiety (p = 0.05), and depression (p < 0.01). Objective evidence of sleep disruption measured by wakefulness after sleep onset, sleep efficiency, and latency were associated with decreased performance in attention and processing speed. Prospective studies including larger populations of patients are needed to fully determine the interplay of sleep disruption on the cognitive function and quality of life of patients with PASC.

Subjective cognitive complaints and objective cognitive functioning in combat veterans: Effects of PTSD and deployment mild TBI

Objectives (1) Examine the relationship between subjective cognitive complaints and objective cognitive functioning in combat veterans; and (2) evaluate conditional effects of posttraumatic stress disorder (PTSD) and deployment-related mild traumatic brain injury (TBI) within that relationship. Method Combat veterans (N = 225, 86.22% male) completed a lifetime TBI interview, a structured interview assessing PTSD symptoms, a neuropsychological assessment battery, and a self-report measure of cognitive symptoms. Results All correlations between subjective cognitive complaints and objective cognitive measures were not statistically significant. Hierarchical linear regression indicated that cognitive performance was not significantly related to cognitive complaints, but both PTSD diagnosis and history of deployment mild TBI explained a significant amount of unique variance in self-reported cognitive symptoms. Interactions between the studied variables were not significant. Conclusions PTSD and history of deployment mild TBI were uniquely related to cognitive complaints, but cognitive test performance was not. No confounding effects of PTSD or deployment mild TBI were observed in the relationship between cognitive performance and cognitive complaints. This provides support that symptom distress may be a better explanatory factor for perception of lower cognitive functioning than actual cognitive performance.

Trajectory of post-COVID brain fog, memory loss, and concentration loss in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP multicenter study.

This study aimed to apply Sankey plots and exponential bar plots for visualizing the trajectory of post-COVID brain fog, memory loss, and concentration loss in a cohort of previously hospitalized COVID-19 survivors. A sample of 1,266 previously hospitalized patients due to COVID-19 during the first wave of the pandemic were assessed at 8.4 (T1), 13.2 (T2), and 18.3 (T3) months after hospital discharge. They were asked about the presence of the following self-reported cognitive symptoms: brain fog (defined as self-perception of sluggish or fuzzy thinking), memory loss (defined as self-perception of unusual forgetfulness), and concentration loss (defined as self-perception of not being able to maintain attention). We asked about symptoms that individuals had not experienced previously, and they attributed them to the acute infection. Clinical and hospitalization data were collected from hospital medical records. The Sankey plots revealed that the prevalence of post-COVID brain fog was 8.37% (n = 106) at T1, 4.7% (n = 60) at T2, and 5.1% (n = 65) at T3, whereas the prevalence of post-COVID memory loss was 14.9% (n = 189) at T1, 11.4% (n = 145) at T2, and 12.12% (n = 154) at T3. Finally, the prevalence of post-COVID concentration loss decreased from 6.86% (n = 87) at T1, to 4.78% (n = 60) at T2, and to 2.63% (n = 33) at T3. The recovery exponential curves show a decreasing trend, indicating that these post-COVID cognitive symptoms recovered in the following years after discharge. The regression models did not reveal any medical record data associated with post-COVID brain fog, memory loss, or concentration loss in the long term. The use of Sankey plots shows a fluctuating evolution of post-COVID brain fog, memory loss, or concentration loss during the first years after the infection. In addition, exponential bar plots revealed a decrease in the prevalence of these symptoms during the first years after hospital discharge. No risk factors were identified in this cohort.

Multidisciplinary interventions increase weekly working hours and quality of life in persons with post-concussion syndrome

ABSTRACT Objectives To improve labor market attachment, general health and quality of life in persons suffering from post-concussion syndrome. Labor market attachment often changes after mTBI, and especially in persons suffering from post-concussion syndrome, and constitutes a huge societal burden. Methods Eighty-two adults with persistent post-concussion syndrome participated in this single-center and uncontrolled interventional efficacy open-label investigation. The primary endpoint was to increase weekly working hours. Outcome measures ranged from self-reported cognitive symptoms to objective performance testing. Multidisciplinary interventions were used to reduce symptoms of fatigue, stress, pain, oculomotor malfunction, and sensitivity to both sound and light. Results Workhours improved from median 0 to 6 hours (p = 0.00002). Several significant improvements were observed in quality of life measured by the SF-36. General fatigue measured by the MFI-20 was reduced (p < 0.0001), and symptoms of depression were reduced (p < 0.0001). The COPM results were improved for task completion satisfaction and for ability to perform a task (p < 0.0001). Reading speed, and performances in the Groffman Visual Tracing Test and the King-Devick Test, all improved (p < 0.01). The intervention did not reduce perception of pain intensity (p = 0.11). Conclusion After the intervention, participants increased weekly workhours and improved in many aspects of life – including quality of life, performance in everyday activities, fatigue and depression. Perception of pain intensity was not improved.

Preliminary efficacy and predictors of response to a remotely-delivered symptom self-management program for persistent symptoms after concussion

ABSTRACT Background More than a quarter of adults with concussion endure prolonged symptoms of >3 months. We developed the Concussion Education Self-Management program to help people manage persisting symptoms. Here, we assess feasibility, preliminary efficacy, and correlates of response. Methods N = 80 adults participated in the program; ages ranged from 18 to 65 years and time post-injury ranged from 6 months to 18 years. Weekly sessions, delivered remotely and in groups, comprised education and strategies for management of cognitive, emotional, and physical symptoms. Primary outcome: Confidence to self-manage symptoms. Secondary outcomes: Quality of life; mood/anxiety/stress. Predictors of response: Self-reported cognitive, emotional and physical symptoms at intake. Results Pre- to post-program improvements were observed in confidence to self-manage, p < 0.03; quality of life, p < 0.001; depression, p < 0.001; anxiety, p < 0.001; and stress, p < 0.001. Considering confidence to self-manage, those with fewer cognitive and physical symptoms benefitted more (p’s < 0.0005 and p < 0.01, respectively). Discussion This program shows promise for improving self-management of prolonged symptoms. Those with high symptom burden may need extra sessions to benefit. This is a cost-effective and scalable program that can reach people regardless of geographic location or impediments to travel.

Neuropsychological measures of post-COVID-19 cognitive status.

COVID-19 may result in persistent symptoms in the post-acute phase, including cognitive and neurological ones. The aim of this study is to investigate the cognitive and neurological features of patients with a confirmed diagnosis of COVID-19 evaluated in the post-acute phase through a direct neuropsychological evaluation. Individuals recovering from COVID-19 were assessed in an out-patient practice with a complete neurological evaluation and neuropsychological tests (Mini-Mental State Examination; Rey Auditory Verbal Test, Multiple Feature Target Cancellation Test, Trial Making Test, Digit Span Forward and Backward, and Frontal Assessment Battery). Pre- and post-COVID-19 global and mental health status was assessed along with the history of the acute phase of infection. Post-COVID-19 cognitive status was modeled by combining persistent self-reported COVID-related cognitive symptoms and pathologic neuropsychological tests. A total of 406 individuals (average age 54.5 ± 15.1 years, 45.1% women) were assessed on average at 97.8 ± 48.0 days since symptom onset. Persistent self-reported neurological symptoms were found in the areas of sleep (32%), attention (31%), and memory (22%). The MMSE mean score was 28.6. In total, 84 subjects (20.7%) achieved pathologic neuropsychological test results. A high prevalence of failed tests was found in digit span backward (18.7%), trail making (26.6%), and frontal assessment battery (10.9%). Cognitive status was associated with a number of factors including cardiovascular disease history, persistent fatigue, female sex, age, anxiety, and mental health stress. COVID-19 is capable of eliciting persistent measurable neurocognitive alterations particularly relevant in the areas of attention and working memory. These neurocognitive disorders have been associated with some potentially treatable factors and others that may stratify risk at an early stage.

Associations between health-related behaviors and self-reported cognitive symptoms in U.S. military personnel injured on deployment

Health behaviors may be core contributors to cognition and mental health following mild traumatic brain injury (TBI). The aims of the present study examined: (1) whether health behaviors including sleep duration, alcohol use, and physical activity differed in injured military personnel with and without deployment-related mild TBI history and (2) the relative contributions of health behaviors and deployment-related mild TBI history to self-reported cognitive, posttraumatic stress disorder (PTSD), and depressive symptoms. Participants included 3076 military personnel injured on deployment participating in the Wounded Warrior Recovery Project, an ongoing web-based study. Military personnel with deployment-related mild TBI history reported similar rates of physical activity and levels of alcohol problems as those without, but were less likely to report receiving the recommended duration of sleep. When adjusting for demographic and injury variables, all three health behaviors were associated with cognitive, PTSD, and depressive symptoms. Alcohol problems demonstrated significant but small effects across all outcomes measures (ηp2=.01) whereas physical activity was associated with slightly larger effects albeit still within the small range (ηp2=.02-0.04). Duration of sleep bordered a medium effect for cognitive symptoms (ηp2=.05) and was in the medium range for PTSD and depressive symptoms (ηp2=.06). Although deployment-related mild TBI history was significant in all models, effect sizes were small (ηp2=.01). Findings from the present study provide support that health behaviors have stronger effects with regard to cognitive, PTSD, and depressive symptoms compared to deployment-related mild TBI history in military personnel and, given their modifiable nature, may represent treatment targets in this population.

Improvement in self-reported cognitive functioning but not in rumination following online working memory training in a two-year follow-up study of remitted major depressive disorder.

Self-reported subjective cognitive difficulties (subjective deficits) and rumination are central residual cognitive symptoms following major depressive disorder (MDD). These are risk factors for more a severe course of illness, and despite the considerable relapse risk of MDD, few interventions target the remitted phase, a high-risk period for developing new episodes. Online distribution of interventions could help close this gap. Computerized working memory training (CWMT) shows promising results, but findings are inconclusive regarding which symptoms improve following this intervention, and its long-term effects. This study reports results from a longitudinal open-label two-year follow-up pilot-study of self-reported cognitive residual symptoms following 25 sessions (40 min), five times a week of a digitally delivered CWMT intervention. Ten of 29 patients remitted from MDD completed two-year follow-up assessment. Significant large improvements in self-reported cognitive functioning on the behavior rating inventory of executive function-adult version appeared after two-years (d = 0.98), but no significant improvements were found in rumination (d < 0.308) measured by the ruminative responses scale. The former showed moderate non-significant associations to improvement in CWMT both post-intervention (r = 0.575) and at two-year follow-up (r = 0.308). Strengths in the study included a comprehensive intervention and long follow-up time. Limitations were small sample and no control group. No significant differences between completers and drop-outs were found, however, attrition effects cannot be ruled out and demand characteristics could influence findings. Results suggested lasting improvements in self-reported cognitive functioning following online CWMT. Controlled studies with larger samples should replicate these promising preliminary findings.

0301 Associations between sleep and cognitive function in patients with Neurological post-acute sequelae of SARS-CoV-2 infection

Abstract Introduction Fatigue and sleep disturbance are among the most common neurological post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). We tested the hypothesis that impaired sleep and disrupted rest-activity rhythms are associated with impaired cognitive performance and greater burden of self-reported Neuro-PASC symptoms. Methods Forty adults (mean age 45 years, 69% female, 15% hospitalized post COVID) recruited from the Neuro-COVID-19 Clinic at Northwestern Memorial Hospital. Patients were evaluated via clinical assessment/history, chart review, patient reported outcomes for symptom severity (PROMIS cognitive function, fatigue, sleep disturbance, anxiety, depression), cognitive performance tests (NIH Toolbox modules for processing speed, attention, executive function, working memory), and 7 days of wrist actigraphy with a sleep log. We tested associations between objective and subjective measures using Pearson’s correlation and difference from population normative data using Student’s t test. Results 39 participants provided sufficient data for analysis. The median number of discrete neurologic symptoms attributed to PASC was 6 with 87% reporting ≥4 neurologic symptoms. Fatigue, insomnia, and depression were common (~70% reporting each). Participants reported significant symptom burden in all PROMIS domains, and had measurably worse attention function along with borderline executive function, compared to population normative data (all p&amp;lt; 0.001 except executive cognition p=0.056). Actigraphy showed Neuro-PASC patients had lower sleep efficiency and greater sleep latency (both p&amp;lt; 0.001) but similar wakefulness after sleep onset (WASO) compared to age-matched population controls. Self-reported cognitive symptoms were correlated with severity of fatigue (p&amp;lt; 0.001), anxiety (p=0.05), and depression (p&amp;lt; 0.01), but not subjective sleep disturbance. There were no associations between actigraphy-measured sleep or rest-activity characteristics and self-reported symptoms. Patients with abnormal sleep characteristics (WASO, sleep efficiency, sleep latency) demonstrated impaired objective attention and executive function. Conclusion Neuro-PASC patients presenting to a post-COVID clinic have a significant burden of subjective mental health, sleep, fatigue and cognitive impairment symptoms, along with objectively abnormal cognitive performance and sleep, compared to population controls. Interventions to improve sleep could benefit cognitive performance. Prospective studies including larger populations of patients are needed to fully determine the interplay of sleep/circadian rhythm disruption on the cognitive function and quality of life in patients with PASC. Support (if any) Center for Circadian and Sleep Medicine

Establishing General Working Population Norms for the Cognitive Symptom Checklist-Work.

The Cognitive Symptom Checklist-Work (CSC-W) is a self-report measure to assess cognitive symptoms (i.e., memory and executive function) in working adults with cancer. To date, general working population norm data are lacking worldwide. We established CSC-W norm values in the general working population, and assessed associations of CSC-W scores with work and health-related factors. This cross-sectional study consisted of 1,000 Dutch working adults, of whom data was collected through an online respondent panel. The sample was stratified for sex and age, and data were weighted. Summary scores of the CSC-W total scale, and memory and executive function symptoms subscales, were determined (e.g., means, percentiles). Z- and T-scores were calculated, and analysis of (co)variance has been applied. Cognitive symptom scores were relatively stable across age groups, but 18-39-year-old respondents reported lower memory and executive function than respondents in other age groups. Symptom scores of memory function (mean 29.1; SD = 16.7) were higher for all age groups and in both sexes compared to executive function (mean 22.1; SD = 16.8). No sex differences in memory and executive function were observed. Higher symptom scores were associated with performing non-manual work only, manual work only, self-reported long-term illness, and higher levels of depressive symptoms and fatigue. The CSC-W norms may enhance the interpretation and facilitate the analysis of self-reported cognitive symptoms in patients with cancer at work. Our findings may support health care professionals in identifying working adults with cancer with cognitive symptoms and in developing personalized treatment.

Assessing cancer-related cognitive function in the context of everyday life using ecological mobile cognitive testing: A protocol for a prospective quantitative study.

Millions of cancer survivors are at risk for cancer-related cognitive impairment (CRCI), yet accurate and accessible assessments of cognitive functioning remain limited. Ecological mobile cognitive testing (EMCT) could offer a solution. This paper presents the protocol for a study that aims to (1) establish the reliability and validity of EMCT to assess CRCI in breast cancer survivors, and (2) prospectively evaluate within-person processes (and interactions) among context, mood, and behavior that explain cognitive variability, everyday functioning, and quality of life of cancer survivors. Participants will include breast cancer survivors (>21 years old) who are within 5 years of completing chemotherapy treatment. Participants will complete two virtual visits (baseline, follow-up) 2 months apart to assess self-reported cognitive symptoms and cognitive performance, sociodemographic characteristics, clinical history, everyday functioning, and quality of life. Between virtual visits, EMCT will be used to sample cognitive functioning every other day (28 times total). We will use linear mixed-effect regressions and single-level multiple regression models to analyze the data. We anticipate a minimum of 124 breast cancer survivors enrolling and completing data collection. Study results will be published in peer-reviewed scientific journals. Our findings will have broad implications for assessing CRCI in an ecologically valid and person-centered way using EMCT. We aim to provide this protocol to aid researchers who would like to apply this approach to their studies.

Self-reported cognitive and psychiatric symptoms at 3 months predict single-item measures of fatigue and daytime sleep 12 months after ischemic stroke.

Post-stroke fatigue and increased need for daytime sleep are multidimensional and insufficiently understood sequelae. Our aim was to study the relationships of self-reported cognitive and psychiatric symptoms at 3 months with fatigue and daytime sleep at 12 months post-stroke. Ischemic stroke patients without reported history of dementia or depression completed postal surveys 3- and 12-months post-stroke. At 3 months, psychiatric symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS), and self-reported changes in cognitive symptoms (concentration and memory) compared to pre-stroke were assessed using single-item measures. At 12 months, single-item questions about changes in self-reported difficulties sleeping at night, fatigue and daytime sleep were included. First, we studied whether self-reported cognitive and/or psychiatric symptoms at 3 months were associated with daytime sleep and fatigue at 12 months using multiple logistic regression. Second, we fitted 2 structural equation models (SEMs) predicting fatigue and 2 models predicting daytime sleep. We compared a model where only age, sex, stroke severity (National Institutes of Health Stroke Scale; NIHSS), and difficulties sleeping at night predicted fatigue and daytime sleep at 12 months to a model where mental distress (i.e., a latent variable built of cognitive and psychiatric symptoms) was included as an additional predictor of fatigue and daytime sleep at 12 months. Of 156 patients (NIHSS within 24 hours after admission (mean ± SD) = 3.6 ± 4.3, age = 73.0 ± 10.8, 41% female) 37.9% reported increased daytime sleep and 50.0% fatigue at 12 months. Increased psychiatric symptoms and worsened cognitive symptoms were associated with fatigue and daytime sleep at 12 months, after controlling for NIHSS, age, sex, and difficulties sleeping at night. SEM models including mental distress as predictor showed adequate model fit across 3 fit measures (highest RMSEA = 0.063, lowest CFI and TLI, both 0.975). Models without mental distress were not supported. Self-reported cognitive and psychiatric symptoms at 3 months predict increased daytime sleep and fatigue at 12 months. This highlights the relevance of monitoring cognitive and psychiatric symptoms in the subacute phase post-stroke. However, future research using validated measures of self-reported symptoms are needed to further explore these relationships.

Impacts of breast cancer and chemotherapy on gut microbiome, cognitive functioning, and mood relative to healthy controls

Women diagnosed with breast cancer undergoing chemotherapy experience cognitive impairment, symptoms of anxiety and depression, and physical side effects including disruption in the diversity and community composition of the gut microbiome. To date, there is limited research exploring the associations among these specific challenges. The present cross-sectional study explored the associations of self-reported cognitive functioning, depression, and anxiety symptoms, and gut microbiome diversity and community composition in women who were diagnosed with and undergoing chemotherapy treatment for breast cancer (BC) compared to cancer-free healthy controls (HC). The BC group displayed higher rates of cognitive dysfunction (p < 0.001) and depressive symptoms (p < 0.05) relative to HC. There was a significant difference in microbiome community composition between BC and HC, particularly characterized by a decreased relative abundance of the mucin-degrading genus Akkermansia in BC compared to HC (p < 0.05). Association models identified significant associations among group, cognitive, depression, and microbiome variables (p < 0.001). Overall, the study identified that BC participants experienced significant differences in self-reported cognitive functioning, self-reported depression symptoms, microbiome community composition, and mucin-degrading bacteria of the gut-mucosal barrier, relative to HC. The present study is consistent with the hypothesis that gut microbiome community composition impacts a woman’s experience with breast cancer and treatment suggesting that microbiome-based interventions have potential for improving quality of life outcomes in individuals with breast cancer.