Measures Of Cognitive Function Research Articles

Test conditions impact measures of visual, perceptual, and cognitive performance

Traditionally, visual, perceptual, and cognitive (VPC) testing is performed in well-lit, silent rooms, whilst seated, and with little incentive. Whilst this is a well-controlled setting, it may lack key features of ecological validity and therefore generalisations to real-world environments and tasks may be erroneous. In the present study, 60 participants completed tests of processing speed, divided attention, and selective attention under varying conditions of light, auditory demands, movement demands, and incentive. The results found that processing speed was significantly better in the incentive condition compared to the non-incentive condition; and in the seated and standing conditions compared to the stepping condition. Divided attention and selective attention were significantly worse in the silent condition compared to the music conditions. No significant differences were found between light and dark conditions. These findings demonstrate that performance on the VPC tests is affected by auditory conditions, movement conditions, and incentives, but not light conditions.

White Matter Hyperintensities and Microstructural Alterations in Contact Sport Athletes from Adolescence to Early Midlife.

Studies have demonstrated associations between cumulative concussion and repetitive head impact exposure (RHI) via contact sports with white matter (WM) alterations later in life. The course of WM changes associated with exposure earlier in the lifespan are unclear. This study investigated alterations in white matter (WM hyperintensity [WMH] volume and microstructural changes) associated with concussion and RHI exposure from adolescence to early midlife, as well as the interaction between exposure and age-cohort (i.e., adolescent/young adult compared to early midlife athlete cohorts) on WM outcomes. Participating football players included an adolescent/young adulthood cohort (n=82; Mage=18.41.7) and an early midlife cohort (37 former collegiate players approximately 15-years removed from sport; Mage=37.71.4). Years of football participation and number of prior concussions were exposures of interest. White matter outcomes included log-transformed manually segmented total WMH volume and neurite orientation dispersion and density imaging metrics of microstructure/organization (isotropic volume fraction[Viso], intra-cellular volume fraction[Vic], and orientation dispersion[OD]). Regression models were fit to test effects of concussion history, years of football participation, and age-cohort by years of football participation with WM outcomes. Spearman's correlations assessed associations between significant WM metrics and measures of cognitive and psychological function. A significant age-cohort by years of participation effect was observed for whole brain white matter OD, B=-0.002, SE=0.001, p=0.001. The interaction was driven by a negative association between years of participation and OD within the younger cohort, B=-0.001, SE=0.0004, p=0.008, whereas a positive association between participation and OD in the early midlife cohort, B=0.001, SE=0.0003, p=0.039, was observed. Follow-up ROI analyses showed significant interaction effects for OD in the body of the corpus callosum, genu of the corpus callosum, cingulum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, posterior thalamic radiation (ps<0.05). Greater concussion history was significantly associated with greater Viso in the early midlife cohort, B=0.001, SE= 0.0002, p=0.010. Years of participation and concussion history were not associated with WMH volume, ps>0.05. Performance on a measure of executive function was significantly associated with years of participation, =.34, p=.04, and a trend was observed for OD, =.28, p=.09 in the early midlife cohort only. The global characterization of white matter changes associated with years of football participation were broadly similar and stable from adolescence through early midlife (i.e., microstructural alterations, but not macroscopic lesions). An inverse association between years of participation and orientation dispersion across age-cohorts may represent a process of initial recovery/reorganization proximal to sport, followed by later reduction of white matter coherence.

Physician Antipsychotic Overprescribing Letters and Cognitive, Behavioral, and Physical Health Outcomes Among People With Dementia

Antipsychotics, such as quetiapine, are frequently prescribed to people with dementia to address behavioral symptoms but can also cause harm in this population. To determine whether warning letters to high prescribers of quetiapine can successfully reduce its use among patients with dementia and to investigate the impacts on patients' health outcomes. This is a secondary analysis of a randomized clinical trial of overprescribing letters that began in April 2015 and included the highest-volume primary care physician (PCP) prescribers of quetiapine in original Medicare. Outcomes of patients with dementia were analyzed in repeated 90-day cross-sections through December 2018. Analyses were conducted from September 2021 to February 2024. PCPs were randomized to a placebo letter or 3 overprescribing warning letters stating that their prescribing of quetiapine was high and under review by Medicare. The primary outcome of this analysis was patients' total quetiapine use in days per 90-day period (the original trial primary outcome was total quetiapine prescribing by study PCPs). Prespecified secondary outcomes included measures of cognitive function and behavioral symptoms from nursing home assessments, indicators of depression from screening questionnaires in assessments and diagnoses in claims, metabolic diagnoses derived from assessments and claims, indicators of use of the hospital and other health care services, and death. Outcomes were analyzed separately for patients living in nursing homes and in the community. Of the 5055 study PCPs, 2528 were randomized to the placebo letter, and 2527 were randomized to the 3 warning letters. A total of 84 881 patients with dementia living in nursing homes and 261 288 community-dwelling patients with dementia were attributed to these PCPs. There were 92 874 baseline patients (mean [SD] age, 81.5 [10.5] years; 64 242 female [69.2%]). The intervention reduced quetiapine use among both nursing home patients (adjusted difference, -0.7 days; 95% CI, -1.3 to -0.1 days; P = .02) and community-dwelling patients (adjusted difference, -1.5 days; 95% CI, -1.8 to -1.1 days; P < .001). There were no detected adverse effects on cognitive function (cognitive function scale adjusted difference, 0.01; 95% CI, -0.01 to 0.03; P = .19), behavioral symptoms (agitated or reactive behavior adjusted difference, -0.2%; 95% CI -1.2% to 0.8% percentage points; P = .72), depression, metabolic diagnoses, or more severe outcomes, including hospitalization and death. This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia. This intervention and others like it may be useful for future efforts to promote guideline-concordant care. ClinicalTrials.gov Identifier: NCT05172687.

Examining mental health and autonomic function as putative mediators of the relationship between sleep and trajectories of cognitive function: findings from the Irish longitudinal study on ageing (TILDA)

Objectives This study investigates the mediating roles of autonomic function and mental health in the association between sleep and cognitive decline in adults aged 50 and above. Method A total of 2,697 participants with observations on sleep and mediators at baseline and repeated measures of cognitive function (MMSE) were included. Clusters of individuals with similar cognitive trajectories (high-stable, mid-stable and low-declining) were identified. Multinomial logistic regressions were used to estimate the likelihood of membership to each trajectory group based on sleep duration and disturbance. Finally, mediation analysis tested potential mediating effects of autonomic function and mental health underpinning the sleep–cognition relationship. Results Short (p = .028), long (p =.019), and disturbed sleep (p =.008) increased the likelihood of a low-declining cognitive trajectory. Mental health measures fully attenuated relationships between cognitive decline and short or disturbed sleep but not long sleep. No autonomic function mediation was observed. Conclusion Older adults with short or disturbed sleep are at risk of cognitive decline due to poor mental health. Individuals with long sleep are also at risk, however, the acting pathways remain to be identified. These outcomes have clinical implications, potentially identifying intervention strategies targeting mental health and sleep as prophylactic measures against dementia.

Global cognition, gender, and level of education predict dual-task gait speed variability metrics in older adults.

To determine if demographic variables and measures of cognitive function, functional mobility, self-reported balance self-efficacy, and self-reported physical activity can predict gait speed variability during single-task walking (STgscv), during cognitive-motor dual-tasking (DTgscv), and dual-task effect on gait speed variability (DTEgscv) in older adults. In 62 older adults, demographics were recorded and cognitive function (including the Montreal Cognitive Assessment, MoCA), functional mobility, balance self-efficacy (Activity-Specific Balance Confidence Scale, ABC), and self-reported physical activity (Physical Activity Scale for the Elderly, PASE) were assessed. Three linear regression models were used to determine whether the functional mobility tests, PASE score, ABC score, and tests of cognitive function predicted gait speed variability outcomes (STgscv, DTgscv, DTEgscv), with demographics included as covariates. MoCA score (p = 0.003), gender (p = 0.040), and years of education (p = 0.010) significantly predicted DTgscv (R^2 = 0.297, p = 0.002). MoCA score (p = 0.008) and years of education (p < 0.001) also significantly predicted DTEgscv. Despite a significant regression model (R^2 = 0.316, p = 0.001), there were no significant individual predictors of STgscv. Older adults with lower cognitive function scores, according to the MoCA, and higher levels of education demonstrate larger gait speed variability during dual-tasking and may be at increased risk of real-world mobility issues or falling.

Psychosocial Factors Associated with Cognitive Function in Prostate Cancer Survivors on Hormonal Treatments: A Systematic Review.

Hormonal treatments (HT) for prostate cancer (e.g., androgen deprivation therapy) yield clinical and survival benefits, yet adverse cognitive changes may be a side effect. Since psychosocial factors are largely modifiable, interventions targeting these factors may help mitigate these adverse cognitive effects. This systematic review aimed to identify a range of psychosocial factors associated with cognitive function in individuals with prostate cancer undergoing HT and to determine whether these factors mitigate or exacerbate this effect. Applying PRISMA guidelines, a comprehensive search of relevant databases conducted in September 2023 using terms related to prostate cancer, hormone therapy, and cognitive outcomes was undertaken. The search yielded 694 unique abstracts, with 11 studies included for analysis examining the relationship between cognitive function and the following psychosocial factors: psychological distress, fatigue, insomnia, and coping processes. Findings were mixed with only two studies reporting significant associations between cognitive performance with fatigue and depression. Three studies that included measures of perceived cognitive function identified associations with depression, anxiety, fatigue, insomnia, illness threat appraisals, and coping styles. However, no studies found evidence for an association between self-reported and objective measures of cognitive functioning. Evidence regarding the association of interpersonal factors is lacking. Moreover, whether these factors mitigate or exacerbate the effect of HT on cognitive function still needs to be determined. Overall, the research exploring the association between psychosocial factors and cognitive function in prostate cancer survivors undergoing HT is still in its infancy. Further research is required to optimize the implementation of neuropsychological interventions for prostate cancer survivors.

Mitochondrial complex I density is associated with IQ and cognition in cognitively healthy adults: an in vivo [18F]BCPP-EF PET study.

Mitochondrial function plays a key role in regulating neurotransmission and may contribute to general intelligence. Mitochondrial complex I (MC-I) is the largest enzyme of the respiratory chain. Recently, it has become possible to measure MC-I distribution in vivo, using a novel positron emission tomography tracer [18F]BCPP-EF, thus, we set out to investigate the association between MC-I distribution and measures of cognitive function in the living healthy brain. Analyses were performed in a voxel-wise manner and identified significant associations between [18F]BCPP-EF DVRCS-1 in the precentral gyrus and parietal lobes and WAIS-IV predicted IQ, WAIS-IV arithmetic and WAIS-IV symbol-digit substitution scores (voxel-wise Pearson's correlation coefficients transformed to Z-scores, thresholded at Z = 2.3 family-wise cluster correction at p < 0.05, n = 16). Arithmetic scores were associated with middle frontal and post-central gyri tracer uptake, symbol-digit substitution scores were associated with precentral gyrus tracer uptake. RAVLT recognition scores were associated with [18F]BCPP-EF DVRCS-1 in the middle frontal gyrus, post-central gyrus, occipital and parietal regions (n = 20). Taken together, our findings support the theory that mitochondrial function may contribute to general intelligence and indicate that interindividual differences in MC-I should be a key consideration for research into mitochondrial dysfunction in conditions with cognitive impairment.

Comparison of cognitive performance measures in individuals with systemic lupus erythematosus

ObjectiveCognitive impairment is a common complaint in SLE, but approaches to measuring cognitive performance objectively vary. Leveraging data collected in a population-based cohort of individuals with validated SLE, we compared...

484 A Preliminary Study on the Pharmacodynamics of Oral Cannabis Ingestion in Older Adults

OBJECTIVES/GOALS: Our study explores the dose-related effects of THC on cardiovascular measures, self-reported effects, balance, and cognitive function among older adults. We also evaluate the acceptability and feasibility of study procedures, to inform future study designs employing this population. METHODS/STUDY POPULATION: Using a within-subject, double-blind, placebo-controlled design and standard behavioral pharmacology methods, reasonably healthy male and female adults aged 55-70 years undergo an eligibility screening, followed by a mock session and 3 experimental sessions (&gt;7 days apart). During experimental sessions, participants are administered cannabis-infused brownies with varying THC doses. Prior to and at multiple intervals post- consumption, subjects complete assessments including self reports and observer ratings, psychomotor and cognitive performance measures, and vital signs. Follow-up interviews regarding the experience will be conducted one day after each session. RESULTS/ANTICIPATED RESULTS: We anticipate our results to mirror those of previously reported studies conducted in adults under 45 years old in that a dose-response relationship exists for subjective drug effects and vital signs with the caveat that this relationship may be exacerbated in our population. We additionally anticipate findings that indicate THC impairs balance and coordination, potentially increasing the risk of falls and accidents among this population, and cognitive function, affecting attention, memory, and executive functions. Feedback provided during the follow-up interviews will help refine procedures for future studies, ensuring that the methodology is acceptable and feasible for this population. DISCUSSION/SIGNIFICANCE: Prior work demonstrates the safety and efficacy of THC in conditions common among older adults, however, no conclusive data regarding tolerability and safety in this population exists. The presented work is vital groundwork for future research on THC as a potential therapeutic for older adults.

Plasma metabolomic markers underlying skeletal muscle mitochondrial function relationships with cognition and motor function.

Lower skeletal muscle mitochondrial function is associated with future cognitive impairment and mobility decline, but the biological underpinnings for these associations are unclear. We examined metabolomic markers underlying skeletal muscle mitochondrial function, cognition and motor function. We analysed data from 560 participants from the Baltimore Longitudinal Study of Aging (mean age: 68.4years, 56% women, 28% Black) who had data on skeletal muscle oxidative capacity (post-exercise recovery rate of phosphocreatine, kPCr) via 31P magnetic resonance spectroscopy and targeted plasma metabolomics using LASSO model. We then examined which kPCr-related markers were also associated with cognition and motor function in a larger sample (n = 918, mean age: 69.4, 55% women, 27% Black). The LASSO model revealed 24 metabolites significantly predicting kPCr, with the top 5 being asymmetric dimethylarginine, lactic acid, lysophosphatidylcholine a C18:1, indoleacetic acid and triacylglyceride (17:1_34:3), also significant in multivariable linear regression. The kPCr metabolite score was associated with cognitive or motor function, with 2.5-minute usual gait speed showing the strongest association (r = 0.182). Five lipids (lysophosphatidylcholine a C18:1, phosphatidylcholine ae C42:3, cholesteryl ester 18:1, sphingomyelin C26:0, octadecenoic acid) and 2 amino acids (leucine, cystine) were associated with both cognitive and motor function measures. Our findings add evidence to the hypothesis that mitochondrial function is implicated in the pathogenesis of cognitive and physical decline with aging and suggest that targeting specific metabolites may prevent cognitive and mobility decline through their effects on mitochondria. Future omics studies are warranted to confirm these findings and explore mechanisms underlying mitochondrial dysfunction in aging phenotypes.

What happens at home stays at home: the Vegas rule for work depends on working memory

ABSTRACT Family problems, although separate from the work sphere, can impact one’s experience of work even when away from home. We propose that challenges arising from the home and family domain affect individuals’ experience of work because they act as distractions. If so, working memory, an ability relevant to managing distractions, should attenuate the effects that one’s family problems have on experienced job demands. Using a nationally representative dataset (N = 2591) with both concrete measures of family problems and cognitive performance measures, we show that family problems predict experiencing one’s job as more demanding and stressful. However, increasing working memory ability attenuates this relationship. Results suggest that although family problems impinge on one’s work, increased working memory ability to manage distractions may reduce their consequences. We connect our findings and their implications to relevant theoretical frameworks that inform the linkage between family and work.

Improving Neuroplasticity through Robotic Verticalization Training in Patients with Minimally Conscious State: A Retrospective Study.

In disorders of consciousness, verticalization is considered an effective type of treatment to improve motor and cognitive recovery. Our purpose is to investigate neurophysiological effects of robotic verticalization training (RVT) in patients with minimally conscious state (MCS). Thirty subjects affected by MCS due to traumatic or vascular brain injury, attending the intensive Neurorehabilitation Unit of the IRCCS Neurolesi (Messina, Italy), were included in this retrospective study. They were equally divided into two groups: the control group (CG) received traditional verticalization with a static bed and the experimental group (EG) received advanced robotic verticalization using the Erigo device. Each patient was evaluated using both clinical scales, including Levels of Cognitive Functioning (LCF) and Functional Independence Measure (FIM), and quantitative EEG pre (T0) and post each treatment (T1). The treatment lasted for eight consecutive weeks, and sessions were held three times a week, in addition to standard neurorehabilitation. In addition to a notable improvement in clinical parameters, such as functional (FIM) (p < 0.01) and cognitive (LCF) (p < 0.01) outcomes, our findings showed a significant modification in alpha and beta bands post-intervention, underscoring the promising effect of the Erigo device to influence neural plasticity and indicating a noteworthy difference between pre-post intervention. This was not observed in the CG. The observed changes in alpha and beta bands underscore the potential of the Erigo device to induce neural plasticity. The device's custom features and programming, tailored to individual patient needs, may contribute to its unique impact on brain responses.

The Effect of Psychological Resilience on Cognitive Decline in Community-Dwelling Older Adults: The Korean Frailty and Aging Cohort Study.

Chronic stress is associated with an increased risk of cognitive impairment and Alzheimer's disease. This study aimed to assess whether better coping with stress, as assessed using the Brief Resilience Scale (BRS), is associated with slower cognitive decline in community-dwelling older adults. This study used 2018/2019 data and 2-year follow-up data from the Korean Frailty and Aging Cohort Study. Of the 3,014 total participants, we included 1,826 participants (mean age, 77.6±3.7 years, 51.9% female) who completed BRS and Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Battery and the Korean version of the Frontal Assessment Battery (FAB). Higher BRS score at baseline was associated with a lesser decline in the Mini-Mental State Examination score over 2 years after adjusting for age, sex, years of education, smoking status, hypertension, diabetes, and depression (B, 0.175; 95% confidence interval, 0.025-0.325) for 2 years, which represents global cognitive function. Other cognitive function measurements (Word List Memory, Word List Recall, Word List Recognition, Digit Span, Trail Making Test-A, and FAB) did not change significantly with the BRS score at baseline. These findings suggest that better stress-coping ability, meaning faster termination of the stress response, may limit the decline in cognitive function.

Does acute cannabidiol (CBD) use impair performance? A meta-analysis and comparison with placebo and delta-9-tetrahydrocannabinol (THC).

Cannabidiol (CBD) is widely used and believed to be non-intoxicating, lacking acute performance effects (e.g., non-impairing). However, a synthesis of data has not evaluated this. This meta-analysis synthesized data from controlled human laboratory studies that evaluated if acute CBD use impairs performance. Performance on objective and subjective measures of cognitive and psychomotor function were used as markers for potential performance changes and impairment. Studies were identified through systematic database searches. Adult clinical trials measuring acute CBD effects (within 0-8 h of administration) were included. The primary outcome was the peak mean difference in performance measures between CBD and placebo. A secondary analysis utilizing delta-9-tetrahydrocannabinol (Δ9-THC) as a positive control for comparison to CBD was completed. Pooled Hedges' g estimates were calculated using robust variance estimation (RVE) meta-regression. The omnibus RVE meta-analysis indicated a statistically significant, but small effect size (Hedge's g < 0.2) for impaired performance following acute CBD consumption compared to placebo (N = 16 trials, Hedges' g = 0.122, 95% CI: 0.023-0.221, p = 0.019). Measure type was a significant moderator with larger mean differences between CBD and placebo when subjective measures, specifically self-reported sedation, were used versus objective performance tasks (Hedges' gSubjective = 0.288 versus Hedges' gObjective = 0.048). Δ9-THC had a significantly greater magnitude of impairment compared to CBD (N = 8, Hedges' g = 0.416, 95% CI: 0.017-0.816, p = 0.043). In summary, acute CBD consumption was associated with a small increase in subjective ratings of sedation, but no difference from placebo was observed across multiple domains of objectively assessed cognitive or psychomotor performance. These findings suggest that acute CBD alone is unlikely to significantly impair daily functioning or workplace performance.

Epigenetic scores of blood-based proteins as biomarkers of general cognitive function and brain health

BackgroundEpigenetic Scores (EpiScores) for blood protein levels have been associated with disease outcomes and measures of brain health, highlighting their potential usefulness as clinical biomarkers. They are typically derived via penalised regression, whereby a linear weighted sum of DNA methylation (DNAm) levels at CpG sites are predictive of protein levels. Here, we examine 84 previously published protein EpiScores as possible biomarkers of cross-sectional and longitudinal measures of general cognitive function and brain health, and incident dementia across three independent cohorts.ResultsUsing 84 protein EpiScores as candidate biomarkers, associations with general cognitive function (both cross-sectionally and longitudinally) were tested in three independent cohorts: Generation Scotland (GS), and the Lothian Birth Cohorts of 1921 and 1936 (LBC1921 and LBC1936, respectively). A meta-analysis of general cognitive functioning results in all three cohorts identified 18 EpiScore associations (absolute meta-analytic standardised estimates ranged from 0.03 to 0.14, median of 0.04, PFDR < 0.05). Several associations were also observed between EpiScores and global brain volumetric measures in the LBC1936. An EpiScore for the S100A9 protein (a known Alzheimer disease biomarker) was associated with general cognitive functioning (meta-analytic standardised beta: − 0.06, P = 1.3 × 10−9), and with time-to-dementia in GS (Hazard ratio 1.24, 95% confidence interval 1.08–1.44, P = 0.003), but not in LBC1936 (Hazard ratio 1.11, P = 0.32).ConclusionsEpiScores might make a contribution to the risk profile of poor general cognitive function and global brain health, and risk of dementia, however these scores require replication in further studies.

The effect of breaking sitting time with physical activity breaks on cognitive performance in young people with cerebral palsy: an exposure response cross-over feasibility design

Abstract Objectives To assess the feasibility of methods and estimate the potential effect of interrupting sedentary behaviour, with intermittent or continuous physical activity breaks, on cognitive performance in young people with Cerebral Palsy. Methods A randomised three-arm exposure response cross-over design with process evaluation. Participants were recruited throughout the Thames Valley, UK between 01/11/2018 to 31/03/2020. The three 2 h activity exposure visits included: (i) sitting only (controls), (ii) sitting plus 20 min of moderate-to-vigorous activity burst, or (iii) 4×5 min of moderate-to-vigorous activity bursts, during a 2.5 h sedentary session. Measures of feasibility were sought. Cognitive performance outcomes (using the Eriksen Flanker task and Forward and Backward Digit Span) were delivered before and after the 2 h testing period. Results 36 participants were randomised (age 13.2±2.7, Gross-Motor Functional Classification System 1–3). Study retention was 83 % across all three interventions and overall missing data for measures was 4 %. A small intervention effect was found in reaction time in the 4×5 min physical activity exposure session compared to the sedentary control condition (0.42; 95 % CI 0.40 to 0.79). There were two research-related minor adverse effects, an allergic reaction to the FreeStyle Libre and feeling faint and vomiting after consumption of glucose solution. Both events were resolved and participants continued with the study. Conclusions The study design and intervention implementing short bursts of physical activity was feasible and indicated a potential effect on reaction time as a measure of cognitive performance in young people with cerebral palsy.

Abstract 7453: Psychometric analysis of Neuro-QoL Perceived Cognitive Function tool in primary brain tumor patients

Abstract Cognitive dysfunction is commonly reported but variable in course and severity in the primary brain tumor (PBT) population. Brief, reliable, and sensitive measures of patient-reported outcomes (PRO) of cognitive symptoms on function are needed for clinical care and research. This study aims to assess the reliability and validity of the Neuro-QoL Perceived Cognitive Function tool (NQC) and explore associations with symptoms and objective testing of cognitive dysfunction in a cohort of PBT patients enrolled in a natural history study (NCT02851706: PI T. Armstrong). Patient sample characteristics and PROs, including NQC (&amp;lt;40 = moderate/severe (MS) dysfunction), a symptom burden measure (MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT), scores ≥5 = MS) and the Montreal Cognitive Assessment ((MoCA), scores ≤ 25 indicating cognitive impairment (range: 0-30)) were collected. Descriptive statistics and a psychometric analysis consisting of bivariate correlations, Cronbach’s alpha, and factor analyses using principal axis factoring with nonorthogonal rotation were performed. Cohen’s kappa and correlation were used to assess agreement between objective and subjective measures of cognitive function. The cohort included 327 patients who completed the NQC at study entry [median age: 47 years (range: 18-85), primarily white (78%) males (55%) with high-grade tumors (73%), 65% with a Karnofsky Performance Status (KPS) ≥ 90 (good), and 29% reporting MS cognitive dysfunction]. Factor analysis of the NQC identified two underlying factor groupings: concentration/focus and executive function with Cronbach’s alphas of 0.92 and 0.91 that are interpretable and provided adequate fit for the data. While the NQC was moderately correlated with several MDASI-BT symptom factors, it was highly associated with the cognitive factor (r = -.646). To assess agreement, a subset of patients also completed the MoCA (n=172). These were primarily male (58%), white (79%), had high-grade tumors (67%), and a good KPS score (67%). In this subset, 24% had MS cognitive dysfunction as measured by the NQC while 44% were cognitively impaired using the MoCA resulting in a kappa agreement of 0.07. The correlation between the MoCA score and NQC T-score was -0.292. Understanding the impact and prevalence of cognitive symptoms, objective cognitive testing, and perceived impact is essential for PBT patient care and identifying supportive care interventions. Select NQC psychometric properties demonstrate reliability and validity in this population, with strong agreement with self-report of cognitive symptoms but weaker correlation with objective testing, highlighting the variability in perceived impact. Future research in cognitive function will explore the use of objective testing and perceived impact, its predictors in select populations (i.e., IDH-mutant tumors), and examine its association with biomarkers. Citation Format: Morgan L. Johnson, Elizabeth Vera, Kimberly Reinhart, Hope Miller, Anna Choi, Tricia Kunst, Bennett McIver, Ewa Grajkowska, Michelle L. Wright, Terri S. Armstrong, Tito Mendoza. Psychometric analysis of Neuro-QoL Perceived Cognitive Function tool in primary brain tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7453.

Longitudinal volumetric analysis of gray matter atrophy in metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disorder characterized by arylsulfatase A (ASA) deficiency, leading to sulfatide accumulation and myelin degeneration in the central nervous system. While primarily considered a white matter (WM) disease, gray matter (GM) is also affected in MLD, and hematopoietic stem cell transplantation (HSCT) may have limited effect on GM atrophy. We cross-sectionally and longitudinally studied GM volumes using volumetric MRI in a cohort of 36 (late-infantile, juvenile and adult type) MLD patients containing untreated and HSCT treated subjects. Cerebrum, cortical GM, (total) CSF, cerebellum, deep gray matter (DGM) (excluding thalamus) and thalamus volumes were analyzed. Longitudinal correlations with measures of cognitive and motor functioning were assessed. Cross-sectionally, juvenile and adult type patients (infantiles excluded based on limited numbers) were compared with controls at earliest scan, before possible treatment. Patients had lower cerebrum, cortical GM, DGM and thalamus volumes. Differences were most pronounced for adult type patients. Longitudinal analyses showed substantial and progressive atrophy of all regions and increase of CSF in untreated patients. Similar, albeit less pronounced, effects were seen in treated patients for cerebrum, cortical GM, CSF and thalamus volumes. Deterioration in motor performance (all patients) was related to atrophy, and increase of CSF, in all regions. Cognitive functioning (data available for treated patients) was related to cerebral, cortical GM and thalamus atrophy; and to CSF increase. Our findings illustrate the importance of recognizing GM pathology as a potentially substantial, clinically relevant part of MLD, apparently less amenable to treatment.

Synaptic density patterns in early Alzheimer's disease assessed by independent component analysis.

Synaptic loss is a primary pathology in Alzheimer's disease and correlates best with cognitive impairment as found in post-mortem studies. Previously, we observed in vivo reductions of synaptic density with [11C]UCB-J PET (radiotracer for synaptic vesicle protein 2A) throughout the neocortex and medial temporal brain regions in early Alzheimer's disease. In this study, we applied independent component analysis to synaptic vesicle protein 2A-PET data to identify brain networks associated with cognitive deficits in Alzheimer's disease in a blinded data-driven manner. [11C]UCB-J binding to synaptic vesicle protein 2A was measured in 38 Alzheimer's disease (24 mild Alzheimer's disease dementia and 14 mild cognitive impairment) and 19 cognitively normal participants. [11C]UCB-J distribution volume ratio values were calculated with a whole cerebellum reference region. Principal components analysis was first used to extract 18 independent components to which independent component analysis was then applied. Subject loading weights per pattern were compared between groups using Kruskal-Wallis tests. Spearman's rank correlations were used to assess relationships between loading weights and measures of cognitive and functional performance: Logical Memory II, Rey Auditory Verbal Learning Test-long delay, Clinical Dementia Rating sum of boxes and Mini-Mental State Examination. We observed significant differences in loading weights among cognitively normal, mild cognitive impairment and mild Alzheimer's disease dementia groups in 5 of the 18 independent components, as determined by Kruskal-Wallis tests. Only Patterns 1 and 2 demonstrated significant differences in group loading weights after correction for multiple comparisons. Excluding the cognitively normal group, we observed significant correlations between the loading weights for Pattern 1 (left temporal cortex and the cingulate gyrus) and Clinical Dementia Rating sum of boxes (r = -0.54, P = 0.0019), Mini-Mental State Examination (r = 0.48, P = 0.0055) and Logical Memory II score (r = 0.44, P = 0.013). For Pattern 2 (temporal cortices), significant associations were demonstrated between its loading weights and Logical Memory II score (r = 0.34, P = 0.0384). Following false discovery rate correction, only the relationship between the Pattern 1 loading weights with Clinical Dementia Rating sum of boxes (r = -0.54, P = 0.0019) and Mini-Mental State Examination (r = 0.48, P = 0.0055) remained statistically significant. We demonstrated that independent component analysis could define coherent spatial patterns of synaptic density. Furthermore, commonly used measures of cognitive performance correlated significantly with loading weights for two patterns within only the mild cognitive impairment/mild Alzheimer's disease dementia group. This study leverages data-centric approaches to augment the conventional region-of-interest-based methods, revealing distinct patterns that differentiate between mild cognitive impairment and mild Alzheimer's disease dementia, marking a significant advancement in the field.

Early-life cumulative exposure to excess bodyweight and midlife cognitive function: longitudinal analysis in three British birth cohorts

Excess bodyweight (BMI >25 kg/m2) in midlife (age 40-65 years) has been linked to future cognitive decline and an increased risk of dementia. Whether chronic exposure to excess bodyweight in the early decades of life (<40 years) is associated with compromised cognitive function by midlife, however, remains unclear. This study therefore aimed to test potential bidirectional direct and indirect pathways linking cumulative exposure to excess bodyweight and cognitive function in the early decades of life. In this longitudinal analysis, harmonised measures of BMI and cognitive function were available in 19 742 participants aged 47-53 years recruited to the 1946 National Survey of Health and Development (n=2131), the 1958 National Child Development Study (n=9385), and the 1970 British Cohort Study (n=8226). Individual BMI trajectories spanning three decades from age 10-40 years were created for each participant and excess bodyweight duration, BMI change between ages, and cumulative excess bodyweight exposure were calculated. Harmonised measures of verbal and non-verbal ability, mathematical ability, and reading ability were used to create a latent factor for childhood cognitive function, and immediate and delayed recall, animal naming, and letter-search speed tests were used for midlife cognitive function. Multivariable linear regression and structural equation models (SEM) were used to test for potential bidirectional relationships between cognition and excess bodyweight in both individual cohorts and pooled datasets while accounting for other potential early-life confounders. Increases in BMI during adolescence and greater cumulative exposure to excess bodyweight across early life were associated with lower midlife cognitive function in all cohorts (eg, pooled difference in cognitive function per 10 years excess bodyweight duration -0·10; 95% CI -0·12 to -0·08; p<0·001). Further adjustment for childhood cognitive function attenuated many of these associations towards the null (eg, pooled difference in cognitive function per 10 years excess bodyweight duration -0·04; 95% CI -0·06 to -0·02; p=0·001), however, with any remaining associations then fully attenuating once further adjusted for other early-life factors (eg, pooled difference in cognitive function per 10 years excess bodyweight duration 0, -0·03 to 0·01; p=0·38). In the reverse direction, low childhood cognition was associated with greater cumulative exposure to excess bodyweight over the next four decades, although much of this relationship was found to probably be explained via other potentially modifiable upstream early-life factors such as childhood disadvantage. SEM in all cohorts suggested the presence of modest direct and indirect pathways connecting earlier cognitive function to later excess bodyweight, but scarce evidence for an effect of early-life excess bodyweight on cognitive function by midlife. The association between cumulative exposure to excess bodyweight in early life and lower cognitive function in midlife is probably confounded by a persistently lower cognitive function from childhood. Initiatives to improve early-life factors such as childhood disadvantage and education, however, might exert dual but independent benefits on both of these factors before old age. Alzheimer's Research UK, Diabetes Research and Wellness Foundation, Diabetes UK, British Heart Foundation, and Medical Research Council.