Long-term Cognitive Functioning Research Articles

Enhancing cognitive recovery in chronic traumatic brain injury through simultaneous allosteric modulation of α7 nicotinic acetylcholine and α5 GABAA receptors

Traumatic brain injury (TBI) leads to changes in the neural circuitry of the hippocampus that result in chronic learning and memory deficits. However, effective therapeutic strategies to ameliorate these chronic learning and memory impairments after TBI are limited. Two pharmacological targets for enhancing cognition are nicotinic acetylcholine receptors (nAChRs) and GABAA receptors (GABAARs), both of which regulate hippocampal network activity to form declarative memories. A promising compound, 522–054, both allosterically enhances α7 nAChRs and inhibits α5 subunit-containing GABAARs. Administration of 522–054 enhances long-term potentiation (LTP) and cognitive functioning in non-injured animals. In this study, we assessed the effects of 522–054 on hippocampal synaptic plasticity and learning and memory deficits in the chronic post-TBI recovery period. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury or sham surgery. At 12 wk after injury, we assessed basal synaptic transmission and LTP at the Schaffer collateral-CA1 synapse of the hippocampus. Bath application of 522–054 to hippocampal slices reduced deficits in basal synaptic transmission and recovered TBI-induced impairments in LTP. Moreover, treatment of animals with 522–054 at 12 wk post-TBI improved cue and contextual fear memory and water maze acquisition and retention without a measurable effect on cortical or hippocampal atrophy. These results suggest that dual allosteric modulation of α7 nAChR and α5 GABAAR signaling may be a potential therapy for treating cognitive deficits during chronic recovery from TBI.

Resting state EEG relates to short- and long-term cognitive functioning after cardiac arrest

BackgroundApproximately half of cardiac arrest survivors have persistent cognitive impairment. Guidelines recommend early screening to identify patients at risk for cognitive impairment, but there is no consensus on the best screening method. We aimed to identify quantitative EEG measures relating with short- and long-term cognitive function after cardiac arrest for potential to cognitive outcome prediction. MethodsWe analyzed data from a prospective longitudinal multicenter cohort study designed to develop a prediction model for cognitive outcome after cardiac arrest. For the current analysis, we used twenty-minute EEG registrations from 80 patients around one week after cardiac arrest. We calculated power spectral density, normalized alpha-to-theta ratio (nATR), peak frequency, and center of gravity (CoG) of this peak frequency. We related these with global cognitive functioning (scores on the Montreal Cognitive Assessment (MoCA)) at one week, three and twelve months follow-up with multivariate mixed effect models, and with performance on standard neuropsychological examination at twelve months using Pearson correlation coefficients. ResultsEach individual EEG parameter related to MoCA at one week (βnATR = 7.36; P < 0.01; βpeak frequency = 1.73, P < 0.01; βCoG = -9.88, P < 0.01). The nATR also related with the MoCA at three months ((βnATR = 2.49; P 0.01). No EEG metrics significantly related to the MoCA score at twelve months. nATR and peak frequency related with memory performance at twelve months. Results were consistent in sensitivity analyses. ConclusionEarly resting-state EEG parameters relate with short-term global cognitive functioning and with memory function at one year after cardiac arrest. Additional predictive values in multimodal prediction models need further study.

Late cognitive and adaptive outcomes of patients with neuroblastoma-associated opsoclonus-myoclonus-ataxia-syndrome: A report from the Children's Oncology Group.

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare autoimmune disorder of the nervous system presenting with abnormal eye and limb movements, altered gait, and increased irritability. Two to four percent of children diagnosed with neuroblastoma have neuroblastoma-associated OMAS (NA-OMAS). These children typically present with non-high-risk neuroblastoma that is cured with surgery, with or without chemotherapy. Despite excellent overall survival, patients with NA-OMAS can have significant persistent neurological and developmental issues. This study aimed to describe long-term neurocognitive and adaptive functioning of patients with NA-OMAS treated with multimodal therapy, including intravenous immunoglobulin (IVIG) on Children's Oncology Group (COG) protocol ANBL00P3. Of 53 children enrolled on ANBL00P3, 25 submitted evaluable neurocognitive data at diagnosis and at least one additional time point within 2years and were included in the analyses. Adaptive development was assessed via the Vineland Adaptive Behavior Scale, and validated, age-appropriate measures of intellectual function were also administered. Twenty-one of the 25 patients in this cohort ultimately received IVIG. Descriptive spaghetti plots suggest that this cohort demonstrated stable long-term cognitive functioning and adaptive development over time. This cohort also demonstrated decreased OMAS scores over time consistent with improved OMAS symptoms. While statistical significance is limited by small sample size and loss to follow-up over 10years, findings suggest stable long-term cognitive and adaptive functioning over time in this treated cohort.

Long-term neurocognitive function and quality of life after multimodal therapy in adult glioma patients: a prospective long-term follow-up.

Multimodal therapies have significantly improved prognosis in glioma. However, in particular radiotherapy may induce long-term neurotoxicity compromising patients' neurocognition and quality of life. The present prospective multicenter study aimed to evaluate associations of multimodal treatment with neurocognition with a particular focus on hippocampal irradiation. Seventy-one glioma patients (WHO grade 1-4) were serially evaluated with neurocognitive testing and quality of life questionnaires. Prior to (baseline) and following further treatment (median 7.1years [range 4.6-11.0] after baseline) a standardized computerized neurocognitive test battery (NeuroCog FX) was applied to gauge psychomotor speed and inhibition, verbal short-term memory, working memory, verbal and non-verbal memory as well as verbal fluency. Mean ipsilateral hippocampal radiation dose was determined in a subgroup of 27 patients who received radiotherapy according to radiotherapy plans to evaluate its association with neurocognition. Between baseline and follow-up mean performance in none of the cognitive domains significantly declined in any treatment modality (radiotherapy, chemotherapy, combined radio-chemotherapy, watchful-waiting), except for selective attention in patients receiving chemotherapy alone. Apart from one subtest (inhibition), mean ipsilateral hippocampal radiation dose > 50Gy (Dmean) as compared to < 10Gy showed no associations with long-term cognitive functioning. However, patients with Dmean < 10Gy showed stable or improved performance in all cognitive domains, while patients with > 50Gy numerically deteriorated in 4/8 domains. Multimodal glioma therapy seems to affect neurocognition less than generally assumed. Even patients with unilateral hippocampal irradiation with > 50Gy showed no profound cognitive decline in this series.

Early predictors of neurodevelopment after perinatal arterial ischemic stroke: a systematic review and meta-analysis.

Perinatal arterial ischemic stroke (PAIS) often has lifelong neurodevelopmental consequences. We aimed to review early predictors (<4 months of age) of long-term outcome. We carried out a systematic literature search (PubMed and Embase), and included articles describing term-born infants with PAIS that underwent a diagnostic procedure within four months of age, and had any reported outcome parameter ≥12 months of age. Two independent reviewers included studies and performed risk of bias analysis. We included 41 articles reporting on 1395 infants, whereof 1255 (90%) infants underwent follow-up at a median of 4 years. A meta-analysis was performed for the development of cerebral palsy (n = 23 studies); the best predictor was the qualitative or quantitative assessment of the corticospinal tracts on MRI, followed by standardized motor assessments. For long-term cognitive functioning, bedside techniques including (a)EEG and NIRS might be valuable. Injury to the optic radiation on DTI correctly predicted visual field defects. No predictors could be identified for behavior, language, and post-neonatal epilepsy. Corticospinal tract assessment on MRI and standardized motor assessments are best to predict cerebral palsy after PAIS. Future research should be focused on improving outcome prediction for non-motor outcomes. We present a systematic review of early predictors for various long-term outcome categories after perinatal arterial ischemic stroke (PAIS), including a meta-analysis for the outcome unilateral spastic cerebral palsy. Corticospinal tract assessment on MRI and standardized motor assessments are best to predict cerebral palsy after PAIS, while bedside techniques such as (a)EEG and NIRS might improve cognitive outcome prediction. Future research should be focused on improving outcome prediction for non-motor outcomes.

Long-term cognitive performance and its relation to anti-inflammatory therapy in a cohort of survivors of severe COVID-19

Background and objectivesLong-term cognitive performance data in former critically ill COVID-19 patients are sparse. Current evidence suggests that cognitive decline is related to neuroinflammation, which might be attenuated by COVID-19 related anti-inflammatory therapies. The objective of this prospective cohort study was to study long term cognitive outcomes following severe COVID-19 and the relation to anti-inflammatory therapies. MethodsProspective observational cohort of patients that survived an intensive care unit (ICU) admission due to severe COVID-19. Six months after hospital discharge, we extensively assessed both objective cognitive functioning and subjective cognitive complaints. Furthermore, patients were stratified in cohorts according to their anti-inflammatory treatment (i.e. no immunomodulatory therapy, dexamethasone, or both dexamethasone and interleukin-6 receptor antagonist tocilizumab). Results96 patients were included (March 2020–June 2021, median [IQR] age 61 [55–69] years). 91% received invasive mechanical ventilation, and mean ± SD severity-of-disease APACHE–II–score at admission was 15.8 ± 4.1. After 6.5 ± 1.3 months, 27% of patients scored cognitively impaired. Patients that did or did not develop cognitive impairments were similar in ICU-admission parameters, clinical course and delirium incidence. Patients with subjective cognitive complaints (20%) were more likely women (61% vs 26%), and had a shorter ICU stay (median [IQR] 8 [5–15] vs 18 [9–31], p = 0.002). Objective cognitive dysfunction did not correlate with subjective cognitive dysfunction. 27% of the participants received dexamethasone during intensive care admission, 44% received additional tocilizumab and 29% received neither. Overall occurrence and severity of cognitive dysfunction were not affected by anti-inflammatory therapy, although patients treated with both dexamethasone and tocilizumab had worse executive functioning scores (Trail Making Test interference) than patients without anti-inflammatory treatment (T-score 40.3 ± 13.5 vs 49.1 ± 9.3, p = 0.007). DiscussionA relevant proportion of critically ill COVID-19 patients shows deficits in long-term cognitive functioning. Apart from more pronounced executive dysfunction, overall, anti-inflammatory therapy appeared not to affect long-term cognitive performance. Our findings provide insight in long-term cognitive outcomes in patients who survived COVID-19, that may facilitate health-care providers counseling patients and their caregivers.

Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study

BackgroundCognitive impairment has emerged as a common post-acute sequela of coronavirus disease 2019 (COVID-19). We hypothesised that cognitive impairment exists in patients after COVID-19 and that it is most severe in patients admitted to the intensive care unit (ICU).MethodsThis prospective controlled cohort study of 213 participants performed at the Helsinki University Hospital and the University of Helsinki, Finland, comprised three groups of patients—ICU-treated (n = 72), ward-treated (n = 49), and home-isolated (n = 44)—with confirmed COVID-19 between March 13 and December 31, 2020, participating in a comprehensive neuropsychological evaluation six months after the acute phase. Our study included a control group with no history of COVID-19 (n = 48). Medical and demographic data were collected from electronic patient records and interviews carried out four months after the acute phase. Questionnaires filled six months after the acute phase provided information about change in cognitive functioning observed by a close informant, as well as the presence of self-reported depressive and post-traumatic symptoms.ResultsThe groups differed (effect size η2p = 0.065, p = 0.004) in the total cognitive score, calculated from neuropsychological measures in three domains (attention, executive functions, and memory). Both ICU-treated (p = 0.011) and ward-treated patients (p = 0.005) performed worse than home-isolated patients. Among those with more than 12 years of education, ICU-treated patients performed worse in the attention domain than ward-treated patients (p = 0.021) or non-COVID controls (p = 0.045); ICU-treated male patients, in particular, were impaired in executive functions (p = 0.037).ConclusionsICU-treated COVID-19 patients, compared to patients with less severe acute COVID-19 or non-COVID controls, showed more severe long-term cognitive impairment. Among those with more than 12 years of education, impairment existed particularly in the domains of attention and for men, of executive functions.Trial registration number: ClinicalTrials.gov NCT04864938, retrospectively registered February 9, 2021

High-density EEG sleep correlates of cognitive and affective impairment at 12-month follow-up after COVID-19

ObjectiveTo disentangle the pathophysiology of cognitive/affective impairment in Coronavirus Disease-2019 (COVID-19), we studied long-term cognitive and affective sequelae and sleep high-density electroencephalography (EEG) at 12-month follow-up in people with a previous hospital admission for acute COVID-19. MethodsPeople discharged from an intensive care unit (ICU) and a sub-intensive ward (nonICU) between March and May 2020 were contacted between March and June 2021. Participants underwent cognitive, psychological, and sleep assessment. High-density EEG recording was acquired during a nap. Slow and fast spindles density/amplitude/frequency and source reconstruction in brain gray matter were extracted. The relationship between psychological and cognitive findings was explored with Pearson correlation. ResultsWe enrolled 33 participants ( 17 nonICU) and 12 controls. We observed a lower Physical Quality of Life index, higher post-traumatic stress disorder (PTSD) score, and a worse executive function performance in nonICU participants. Higher PTSD and Beck Depression Inventory scores correlated with lower executive performance. The same group showed a reorganization of spindle cortical generators. ConclusionsOur results show executive and psycho-affective deficits and spindle alterations in COVID-19 survivors – especially in nonICU participants – after 12 months from discharge. SignificanceThese findings may be suggestive of a crucial contribution of stress experienced during hospital admission on long-term cognitive functioning.

Multidisciplinary early intervention in Down syndrome: a retrospective study.

Scientific community agrees on the importance of early, global multidisciplinary family-based care in the neuropsychological development of children with disabilities, including those with Down Syndrome (DS). This study aim to assess whether a structured, multidisciplinary early intervention carried out at the outpatient service of Stella Maris I.R.C.C.S. can lead to better outcomes in children with DS, in development and cognitive functioning, compared to conventional care provided by the local health centres (ASL). We included in the study 20 children with DS. The experimental group received early treatment (0-36 months), while the control group only underwent cognitive assessments. In order to examine the outcome of long-term cognitive functioning, our study evaluated assessments of the children at 5 years of age, by administering the WPPSI-III scale. In our result we can confirm the typical profile of children with Down Syndrome described in the literature. Comparing the results obtained in both groups, we see that the mean scores obtained by the experimental group, in all three of the quotients examined, are higher than the mean scores obtained by the control group. This study makes it clear that early, structured, multidisciplinary interventions play a fundamental role in modifying neurocognitive outcomes in children with Down Syndrome. The results of this study thus confirm the usefulness of the outpatient service in the early management of individuals with DS, following a multidisciplinary, structured pathway focused on the child and his/her family.

Younger and Older Adults’ Cognitive and Physical Functioning in a Virtual Reality Age Manipulation

Objectives: Age group stereotypes (AGS), especially those targeting old age, affect an individual’s behavior and long-term cognitive and physiological functioning. Conventional paradigms investigating the related mechanisms lack validity and stability. Our novel approach for the activation of self-relevant AGS uses a virtual reality (VR) ageing experience, measuring relevant effects on performance parameters. Methods: In a between-subjects experimental design, young participants embodied either a younger or older avatar in a 3D virtual environment to capture the effects on physical (Study 1; N = 68) and cognitive performance (Study 2; N = 45). In Study 3 (N = 117), the paradigm was applied to older participants. Results: For the younger participants, embodying older avatars was associated with declines in memory and physical performance when compared to the younger avatar age group. Furthermore, the manipulations’ main effects were moderated by negative explicit AGS that matched the respective performance domains. For the older participants, we found no significant performance differences in the two domains investigated. Discussion: The experimental manipulation demonstrated an impact on relevant performance parameters on a motivational and strategic level, especially for strong performance-related AS, but for young participants only. Possible reasons and mechanisms for the differences in younger and older samples’ results are discussed.

Long-term Cognitive Outcomes and Socioprofessional Attainment in People With Multiple Sclerosis With Childhood Onset.

Patients with pediatric-onset multiple sclerosis (MS) can be especially vulnerable to cognitive impairment (CI) due to the onset of MS during a critical period for CNS development and maturation. The objective of this longitudinal study was to assess long-term cognitive functioning and socioprofessional attainment in the Italian pediatric MS cohort, previously assessed at baseline and 2 and 5 years. The 48 patients evaluated at the 5-year assessment were screened for inclusion. All participants were assessed with a cognitive test battery exploring 4 different cognitive abilities. Depression, fatigue, and socioprofessional attainment were also assessed. Mean cognitive z scores were calculated for the whole cohort, and their evolution over time was analyzed with an analysis of variance for repeated measurements test. Predictors of cognitive worsening or improvement were assessed with a linear mixed-model analysis. Thirty-three participants were included (mean follow-up 12.8 ± 0.8 years). The global cognitive performance worsened at year 2 and improved at year 5, although the z score remained significantly lower than at baseline (-0.9 ± 1.2 vs -0.3 ± 0.9, p = 0.002). There was no significant variation between years 5 and 12 (-0.7 ± 1.1, p = 0.452). Higher IQ (>90) at baseline (effect 0.3, 95% CI 0.1-0.5, p = 0.017) and lower number of relapses in the 2 years before baseline (effect -0.1, 95% CI -0.1 to 0.1, p = 0.025) predicted better cognitive performances. Eighteen (54.5%) patients failed at least 2 tests compared with healthy controls and were defined as cognitively impaired. The presence of CI predicted worse socioprofessional attainment (β = 4.8, 95% CI 1.4-8.2, p = 0.008). The longitudinal cognitive trajectory in pediatric-onset MS has a heterogeneous course over time, with a decline in the first years followed by a partial recovery over the long term. However, at the last follow-up evaluation, the proportion of impaired patients was more than double compared with baseline, with a negative impact on the individual's socioprofessional attainment in adulthood. This study underscores how cognitive reserve may partially mitigate the negative effects of brain damage, highlighting the critical importance of intellectual enrichment early during the disease course.

Subjective Concerns Regarding the Effects of Sport-Related Concussion on Long-Term Brain Health among Former NFL Players: An NFL-LONG Study.

Potential links between a history of sport-related concussions and later-life neurobiological and psychological brain health have been studied in former collision-sport athletes. However, empirical studies of how former athletes perceive the future of their brain health as a result of these injuries are missing. We aimed to (1) identify the extent to which former National Football League players currently have concerns about their long-term psychological and cognitive functioning as a result of concussions sustained while playing football; (2) examine whether current concerns are different than concerns they had while playing football; (3) examine the relationship between current brain health concerns and self-reported concussion history (SR-CHx); and (4) explore other important factors associated with these concerns. In this cross-sectional study, former National Football League players with a SR-CHx of one or more concussions (n = 1514; aged mean [standard deviation] = 52.3 [15.7] years) completed a general health questionnaire. Participants reported their lifetime concussion history, as well as both their current concerns and concerns while playing football (i.e., retrospective concerns) regarding the long-term effects of concussions on their memory, thinking skills, and risk of developing chronic traumatic encephalopathy. Current and retrospective concerns were self-reported on a five-point Likert scale. Four concussion history categories were created based on SR-CHx: 1-2 (n = 309); 3-5 (n = 413); 6-9 (n = 356); and 10 + (n = 436) lifetime concussions. Proportions of participants reporting each level of current and retrospective concerns were examined to identify whether concerns presently exist in these former players, and whether their current concerns are different than retrospective concerns. Next, we explored associations between current concerns and SR-CHx. More than one-third of participants reported being currently "extremely concerned" about memory problems (36.9%), thinking skills (37.8%), and developing chronic traumatic encephalopathy (39.5%). In contrast, when asked about concerns while playing, most reported being "not at all concerned" regarding memory = 61.2%, thinking skills = 56.1%, and developing chronic traumatic encephalopathy = 71.2%. Of those who retrospectively endorsed being "not at all" or "slightly" concerned regarding memory (n = 1159/1514), thinking skills (n = 1080/1514), and developing chronic traumatic encephalopathy (n = 1219/1514), approximately half reported being currently "moderately" or "extremely" concerned about those same issues (n = 586/1159; n = 534/1080; n = 619/1219, respectively). Current concerns regarding memory (χ216 = 316.61; p < 0.001; V = 0.264), thinking skills (χ216 = 333.17; p < 0.001; V = 0.271), and developing chronic traumatic encephalopathy (χ216 = 280.85; p < 0.001; V = 0.249) were significantly related to SR-CHx, with more concussions being associated with greater current concerns. Former National Football League players reported significant concerns regarding the potential effects of their prior concussions on long-term brain health, and these concerns are more prevalent now than when they were playing football. Cognitive and mental health concerns are readily identifiable targets for clinical intervention. Clinicians working with former players may wish to explore the extent to which individual players experience these concerns, the nature and depth of these concerns, and the impact of these concerns on the player's functioning and well-being.

Longitudinal course of cognition in schizophrenia: Does treatment resistance play a role?

Treatment-resistant schizophrenia (TRS) represents a main clinical issue, associated with worse functional outcome and higher healthcare costs. Clozapine is the most effective antipsychotic for TRS, although 40% of resistant patients, defined as ultra-treatment resistant (UTR), are clozapine-refractory. Previous literature suggests that TRS is characterized by worse cognitive functioning and a more disrupted neurobiological substrate, but only few studies focused on UTR schizophrenia. Moreover, despite this evidence and the central role of cognition, to date no study has investigated long-term cognitive outcome in TRS.Based on these premises, this study aims to analyze cross-sectional and long-term cognitive functioning of patients with schizophrenia, stratified according to antipsychotic response: first-line responders (FLRs), clozapine responders (CRs) and UTRs.We analyzed cross-sectional and retrospective cognitive evaluations of 93 patients with schizophrenia (32 FLRs, 42 CRs, 19 UTRs) over a mean follow-up period of 9 years, also taking into account possible influencing factors such as clinical severity and antipsychotic load.Analyses showed that UTR is associated with overall impaired cognitive functioning and represents the main predictor of long-term cognitive decline. We observed no significant differences between FLR and CR patients, which showed moderate cognitive improvement over time.This is the first study to report an association of treatment resistance with longitudinal cognitive course in schizophrenia, indicating that UTR is correlated with cognitive decline over time. This decline may either be a consequence of the persistence of psychotic symptoms or depend on a distinct and more disrupted neurobiological substrate affecting both cognition and antipsychotic response.

Long-Term Gender-Affirming Hormone Therapy and Cognitive Functioning in Older Transgender Women Compared With Cisgender Women and Men

Long-term gender-affirming hormone therapy (GHT) in older transgender individuals could have beneficial effects on cognitive functioning. Cardiovascular risk factors and psychological factors are known determinants of cognition. Despite the rising number of older transgender individuals, only few studies have examined cognitive functioning in this population. We aimed to assess differences in cognitive functioning between transgender women, and non-transgender (cisgender) women and men, and investigated the contribution of cardiovascular risk factors and psychological factors on these differences. In this study, 37 transgender women (age range 55 to 69) receiving GHT for at least ten years (range 10.2 to 41.6) were examined, and their cognitive functioning was compared to an age and education level matched cohort consisting of 222 cisgender women and men from the Longitudinal Aging Study Amsterdam. Linear regression analyses were performed. Cognitive functioning was assessed by neuropsychological tests including Mini-Mental State Examination (MMSE), Category Fluency animals, Letter Fluency D, 15-Word test (15WT) immediate and delayed recall. Additionally, cardiovascular risk factors and psychological factors such as cardiovascular disease, hypertension, antihypertensive use, statin use, diabetes mellitus, overweight, smoking, alcohol consumption, psychopharmaceutical use, anxiety and depression symptoms were collected. Transgender women had higher MMSE scores compared with cisgender women (+0.9, 95% CI 0.4 to 1.5), and cisgender men (+1.1, 95% CI 0.4 to 1.8). On all other tests transgender women performed similar to cisgender men. Transgender women performed at a lower level than cisgender women on 15WT immediate recall, -5.5, 95% CI -7.6 to -3.4, and 15WT delayed recall, -2.7, 95% CI -3.7 to -1.7, and equal to cisgender women on Fluency animals and Fluency D. Cardiovascular and psychological factors (i.e., cardiovascular disease and depression symptoms) partly explained differences on MMSE score between transgender women and cisgender-control groups. The results of this study do not indicate a need for tailored hormone treatment strategies for older transgender women, based on cognitive aspects after long-term GHT. As one of the first studies, this study compared older transgender women to a large cohort of cisgender men and women regarding cognitive functioning and took into account numerous potential influencing factors. Limitations include difference in test procedures and the cross-sectional design of the study. Cognitive differences between transgender women and cisgender women and men were small, albeit significant. This may suggest that long-term GHT effects on cognitive functioning in older transgender women are minimal.

Abstract P121: Twenty-two-year Cognitive Decline Was Significantly Associated With Vascular And Neurodegenerative Brain Changes In The Aric Neurocognitive Study

Introduction: Studies have found that smaller brain volumes, cerebral infarcts, and white matter abnormalities are associated with dementia and mild cognitive impairment. However, these studies have been limited by short follow-up precluding a strong establishment of temporality. Therefore, it is unknown whether brain imaging findings are preceded by long-term changes in cognition. We sought to address this gap by examining brain imaging and two decades of cognitive changes in and a large, representative population-based cohort of older adults of black and white race. Hypothesis: We hypothesized that 22-year declines in global cognitive factor scores (GCFS) would be associated with a pattern of smaller total brain and temporal lobe meta region of interest (likely to be affected by Alzheimer’s disease) volumes, larger white matter hyperintensity volumes, and greater odds of ≥1 lacunar infarct and elevated brain β-amyloid deposition. Methods: ARIC participants with brain imaging data, complete cognitive factor score, and not missing key covariates were included. GCFS were collected at three visits across 22 years (1990-2013), and brain MRI and florbetapir PET imaging were collected in 2011-13; PET in subset of n=327. Mixed effects models with random intercepts and slopes predicted individual change in GCFS. Outcomes of interest were total brain volume (cc), temporal lobe meta region volume, log 2 (white matter hyperintensity volume), ≥1 lacunar infarct, and elevated brain β-amyloid deposition (SUVR &gt;1.2). Multivariable linear and logistic regression was used to relate outcomes to GCFS slopes after adjusting for confounders, including vascular risk factors. As appropriate, models were also adjusted for total intracranial volume. Results: Among 1957 with complete brain MRI imaging, 1830 were included in the study, 60% (n=1096) women and 26% (n=480) black. At the first visit, the mean (SD) baseline age was 55 (5.2) yrs. The mean (SD) observed GCFS at the three visits were 0.16 (0.79), 0.05 (0.75), and -0.78 (0.86). After adjustment, a 1-SD larger decline in GCFS was significantly associated with a smaller brain volume by 1.6% [95%CI: 1.3, 1.8] relative to mean brain volume, a smaller temporal lobe meta region volume by 2.4% [2.1, 2.8] relative to the mean volume, a 15% [11, 19] larger volume of white matter hyperintensities, 1.3-fold [1.2, 1.4] higher odds of having ≥1 lacune, and 1.8-fold [1.4, 2.4] higher odds of elevated brain β-amyloid deposition. Associations remained significant after further adjustment for first or last GCFS. Conclusions: Greater declines in long-term cognitive functioning were significantly associated with smaller brain volumes and dementia-related brain characteristics and were independent of last visit GCFS. This suggests long-term changes in cognition may precede late-life brain morphology and outperform cross-sectional cognitive measures.

Long-Term Benzodiazepine Prescription During Maintenance Therapy of Individuals With Psychosis Spectrum Disorders-Associations With Cognition and Global Functioning.

BackgroundCognitive difficulties have a significant impact on life functioning and overall well-being in patients with psychosis spectrum disorders (PSDs). There are indications that continuous use of benzodiazepines (BZDs) in various patient groups has a detrimental effect on cognition. Our aim was to explore the association between long-term BZD prescription, global functioning, and cognitive functioning in persons with PSD.MethodsThis exploratory study included 55 PSD patients, recruited from 2 outpatient services in Serbia. Patients were grouped into BZD long-term prescription group and BZD-other group. Brief Psychiatric Rating Scale was used for symptom assessment, functioning was measured by Global Assessment and Functioning Scale, and cognition was assessed by the Global Assessment of Functioning–Cognition in Schizophrenia Scale.ResultsThe sample comprised 52.7% patients who were prescribed with BZD for 6 months or more continually (29/55), with a mean daily dose of 3.16 ± 0.66 mg lorazepam equivalents. There were no differences between study groups in any of the sociodemographic characteristics, duration of illness, or antipsychotic daily dosages. The BZD long-term prescription group had lower global (P < 0.01) and cognitive functioning (P < 0.01), higher Brief Psychiatric Rating Scale scores (1.86 vs 1.58, respectively, P < 0.01), and more psychotropic drugs prescribed on a daily basis than the other group (median: 4 vs 2, respectively, P < 0.01).ConclusionsThe study explored a topic that continues to be underresearched, especially in the Balkans. Prospective studies and comprehensive cognitive batteries are needed to further elucidate the associations between polypharmacy, long-term BZD use, cognitive functioning, and global functioning during maintenance therapy of individuals with PSD.

Cognitive change after electroconvulsive therapy in mood disorders measured with the Montreal Cognitive Assessment.

The Montreal Cognitive Assessment (MoCA) is a sensitive and clinically practical test but its usefulness in measuring long-term cognitive effects of ECT is unclear. Using the MoCA, we investigated short- and long-term global cognitive change in ECT-treated patients with a Major Depressive Episode (MDE). We included 65 consecutive ECT-treated patients with MDE, in whom global cognitive functioning was assessed at baseline (T0); during ECT (before the third session; T1); and 1week (T2), 3months (T3), and 6months (T4) after completion of the index course. Changes in MoCA (sub)scores were analyzed using linear mixed models and reliable change indices were computed to investigate individual changes in MoCA total scores. There was a significant effect of time on MoCA scores (F(4, 230.5)=4.14, P=0.003), with an improvement in global cognitive functioning from T3 compared to T1 and T2. At the individual level, 26% (n=17) of patients showed a significantly worse cognitive functioning at T2 and 12% (n=8) an improved cognitive functioning compared to T0. For T4, these percentages ameliorated to 8% and 18% respectively. No persistent global cognitive impairment induced by ECT was found at the group level using the MoCA. At the individual level, however, there was clear heterogeneity in the effects of ECT on cognitive functioning. The MoCA is a suitable tool to monitor short- and long-term global cognitive functioning in ECT-treated patients with MDE but in younger patients, potential ceiling effects must be taken into account.

Measures of Stress Exposure for Hospitalized Preterm Infants.

Extended hospitalization in neonatal intensive care units subjects preterm infants to multiple stress exposures that affect long-term cognitive functioning, motor development, and stress reactivity. Measurement of stress exposure is challenging with multiple measures of stress exposure in use, including counts of skin-breaking or invasive procedures or counts of noxious sensory exposures. The purpose of this analysis was to compare measures of stress exposure commonly used by researchers and to determine the predictive validity of these measures for early neurobehavior. We accomplished this objective through the following specific aims: (a) describe the stress exposures of preterm infants in the first 2 weeks of life, (b) determine the correlations among measures of stress exposure, and (c) compare the predictive validity of measures of stress exposure for early neurobehavior. Very preterm infants born between 28 and 31 weeks postmenstrual age were enrolled from four neonatal intensive care units in a large Midwest city. We measured stress exposure over the first 14 days of life for each infant as a count of skin-breaking procedures, a count of invasive procedures, and cumulative scores derived from the Neonatal Infant Stressor Scale. Neurobehavior was assessed at 35 weeks postmenstrual age using the motor development and vigor and alertness/orientation subscales from the Neurobehavioral Assessment of the Preterm Infant. We used Spearman's rho to determine correlations among the measures of stress exposure and multiple linear regression to determine the predictive validity of each stress exposure measure for neurobehavioral outcomes. Seventy-one preterm infants were included in the analysis. We found marked variance across individuals in all measures of stress exposure. There were moderate-high correlations among the measures of stress exposure. No measure of stress exposure was associated with early neurobehavior. The stress experiences of hospitalized preterm infants vary. This variance is reflected in all measures of stress exposure. Because measures of stress exposure are highly correlated, the most objective measure requiring the least interpretation should be used. However, the currently available measures of stress exposure used in this analysis may not reflect the infant's physiological stress responses and fail to associate with early neurobehavior.

Treatment Adherence in Youth with First-Episode Psychosis: Impact of Family Support and Telehealth Delivery

Mental health-care delivery to young people with first-episode schizophrenia presents significant challenges especially in underserved areas. This chart review reveals the importance of family support as a predictor for medication and treatment adherence with this vulnerable group. An unexpected disengagement rate of 47% was discovered. It was further discovered that receiving care with telehealth delivery was a significant predictor of lost to follow-up or treatment nonadherence. Recommendations include psychoeducation for families during the initial crisis, initiation of long-acting injectable antipsychotics early in care, a hybrid telehealth intervention with in-home medication delivery, and collaboration with educational, vocational county agencies for employment support. A system of care must be developed to support young people with this severe illness for optimum outcome and protection of long-term cognitive functioning.

Cognitive performance and structural brain correlates in long-term anabolic-androgenic steroid exposed and nonexposed weightlifters.

To test for associations between long-term anabolic-androgenic steroid (AAS) use and cognitive functioning, and establish a candidate neuronal basis by assessing the associations between cognitive performance and brain morphology both in users and nonusers. Eighty four previous or current AAS-users and 69 non-AAS-using male weightlifters aged 19-75 years (mean 32.6, SD 8.8) underwent MRI of the brain and a comprehensive neuropsychological test battery. Performance on fine motor speed, speed of processing, learning and memory, working memory, executive functioning, and problem solving was compared between the groups, and between AAS users with short versus long AAS exposure. Associations between cognitive scores and regional cortical thickness and arealization defined using FreeSurfer were tested using linear models. Relative to nonexposed, AAS-exposed weightlifters performed significantly worse on several cognitive domains, independent of age, education, verbal IQ, and exposure to classical drugs of abuse. Strongest effects were observed for speed of processing (ηp2 = .07), working memory (ηp2 = .08) and problem solving (ηp2 = .09). Longer duration of AAS-use was associated with poorer memory function (ηp2 = .11). Within AAS users, individuals with better memory and working memory performance had with thicker frontoparietal cortex and larger medial frontal surface area, respectively. Prolonged high-dose AAS use is associated with poorer cognitive function across multiple domains, and the observed regional associations between cortical brain morphometry and memory and working memory performance may suggest differential brain-based mechanisms. The public, health care professionals, and policymakers should be aware that use of AAS in large doses potentially could lead to poorer brain health and cognition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).