Verbal Learning Deficits Research Articles

Amyloid-Negative, Neurodegeneration-Negative Amnestic Mild Cognitive Impairment.

The concept of amnestic mild cognitive impairment (aMCI) was developed to identify patients at an initial stage of Alzheimer's disease (AD). However, some patients with aMCI do not present biomarkers of amyloid pathology or neuronal injury. To know the natural history of amyloid-negative and neurodegeneration-negative patients with aMCI, namely to ascertain: 1) whether these patients remain cognitively stable or they present a slow decline in neuropsychological tests; 2) whether the memory complaints subside with the apparently benign clinical course of the disorder or if they persist along the time. Patients who fulfilled criteria for aMCI with no biomarkers of amyloid pathology or neuronal injury were selected from a large cohort of non-demented patients with cognitive complaints, and were followed with clinical and neuropsychological assessments. Twenty-one amyloid-negative and neurodegeneration-negative aMCI patients were followed for 7.1±3.7 years. At the baseline they had more pronounced deficits in verbal learning (California Verbal Learning Test) and were also impaired in Word Recall and Logical Memory. However, they did not decline in any cognitive test during follow-up. The patients maintained a high level of subjective memory complaints from baseline (9.7±4.1) to the follow-up visit (9.2±4.1, a non-significant difference), in spite of a statistically significant decrease in the depressive symptoms, with Geriatric Depression Scale (15 items) score 4.9±2.8 at baseline and 3.2±1.8 at the follow-up visit. Amyloid-negative, neurodegeneration-negative aMCI is a chronic clinical condition characterized by the long-term persistence of cognitive deficits and distressing memory complaints. Adequate strategies to treat this condition are needed.

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Sex-specific neuropsychological correlates of apathy and depression across neurodegenerative disorders.

Apathy and depression are common neuropsychiatric symptoms across neurodegenerative disorders and are associated with impairment in several cognitive domains, yet little is known about the influence of sex on these relationships. We examined the relationship between these symptoms with neuropsychological performance across a combined cohort with mild or major neurodegenerative disorders, then evaluated the impact of sex. We conducted a cohort analysis of participants in the COMPASS-ND study with mild cognitive impairment (MCI), vascular MCI, Alzheimer's disease, mixed dementia, Parkinson's disease, frontotemporal dementia, and cognitively unimpaired (CU) controls. Participants with neurodegenerative disease and CU controls were stratified by the presence (severity ≥1 on Neuropsychiatric Inventory Questionnaire) of either depressive symptoms alone, apathy symptoms alone, both symptoms, or neither. A neuropsychological battery evaluated executive function, verbal fluency, verbal learning, working memory, and visuospatial reasoning. Analysis of covariance was used to assess group differences with age, sex, and education as covariates. Groups included depressive symptoms only (n=70), apathy symptoms only (n=52), both (n=68), or neither (n=262). The apathy and depression+apathy groups performed worse than the neither group on tests of working memory (t(312) =-2.4, p=0.02 and t(328) =-3.8, p=0.001, respectively) and visuospatial reasoning (t(301) =-2.3, p=0.02 and t(321) =-2.6, p=0.01, respectively). The depression, apathy, and depression+apathy groups demonstrated a similar degree of impairment on tests of executive function, processing speed, verbal fluency, and verbal learning when compared to participants without apathy or depression. Sex-stratified analyses revealed that compared to the male neither group, the male apathy and depression+apathy groups were impaired broadly across all cognitive domains except for working memory. Females with depression alone showed deficits on tests of executive function (t(166) =2.4, p=0.01) and verbal learning (t(167) =-4.3, p=0.001) compared to the female neither group. This study demonstrated that in neurodegenerative diseases, apathy with or without depression in males was associated with broad cognitive impairments. In females, depression was associated with deficits in executive function and verbal learning. These findings highlight the importance of effectively treating apathy and depression across the spectrum of neurodegenerative disorders with the goal of optimizing neuropsychological outcomes.

48 A Case of an Extremely Rare CNS C. Bantiana Infection with Cognitive Sequela in an Immunocompetent Patient

Objective:Central nervous system (CNS) infections with the dematiaceous fungus Cladophialophora bantiana (C. bantiana) are extremely rare, with approximately 120 confirmed cases reported as of 2016. C. bantiana is a highly neurotropic and thermotolerant fungus found in soil worldwide. The mode of entry into the CNS remains unknown, but inhalation of fungal spores or subcutaneous trauma have been suggested. Entry of fungal spores can cause cerebral phaeohyphomycosis with the main clinical manifestation of a brain abscess. Symptoms are non-specific and can include headache, fever, hemiparesis, aphasia, visual disturbances, and confusion. C. bantiana cerebral phaeohyphomycosis occurs in both immunocompetent and immunocompromised individuals, with a slightly higher prevalence in immunocompetent males for unknown reasons. Diagnosis is often delayed due to its nonspecific presentation and prevalence in individuals without pre-existing immunological disease. Prognosis is poor, with mortality rates of approximately 70% despite aggressive treatment. Treatment is not standardized but may include several anti-fungal agents and surgical intervention. Case reports documenting the variability seen with cerebral phaeohyphomycosis by C. bantiana can provide valuable insight into this emerging disease. C. bantiana’s neurotropic propensity also warrants cognitive investigation of the disease; however, there are currently limited descriptions of cognitive findings in published case reports of C. bantiana CNS infections.Participants and Methods:Here, we describe a case of a 35-year-old immunocompetent, college educated male with a CNS C. bantiana infection, presumably following a fall while biking in Costa Rica. First symptoms included left sided facial palsy, headache, and hand weakness, prompting extensive diagnostic workup, with diagnosis of C. bantiana infection confirmed 8 months after symptom onset. Initial treatment included anti-fungal agents and steroids, but his course of infection was complicated by infectious vasculitis with posterior circulation infarcts and obstructive hydrocephalus requiring ventriculoperitoneal shunt placement two years following the fungal infection diagnosis. The most recent brain MRI revealed encephalomalacia in global periventricular areas, two small masses, likely representing small fungal phlegmons, and enhancing lesions in the upper cervical spinal canal.Results:The patient reported cognitive changes following the infarcts and shunt placement including difficulties with spatial navigation, following directions, and articulating thoughts. Memory concerns and lapses in judgment were also reported. Results from a neuropsychological evaluation revealed high average baseline intellectual abilities with decrements in visuospatial processing, processing speed, executive functioning, and aspects of memory stemming from his executive dysfunction. At the time, his cognitive profile suggested parietal and frontosubcortical systems disruption meeting criteria for mild cognitive impairment. Two years later, the patient reported continuing cognitive difficulties prompting a follow-up neuropsychological evaluation. Results were similar to his first evaluation, revealing deficits in aspects of visuospatial processing, decreased verbal and visual learning, bradyphrenia and processing speed deficits, and difficulties with visual planning and organization. Minimal anxiety and depression, but increased apathy and executive dysfunction were endorsed on self-report measures.Conclusions:This case report highlights neurological sequela resulting from CNS infection with C. bantiana, -with a course complicated by subsequent strokes, hydrocephalus, and cognitive impairment-, and contributes additional insight into the relatively limited existing reports of an extremely rare but emerging disease.

A-151 Cognitive Sequelae of “Long COVID-19” in Older Adults with Cerebrovascular Risk Factors: A Case Series

Objective: Cardiovascular risk factors have been associated with increased risk for severe COVID-19 symptoms among older adults (CDC, 2021). Severe symptoms increase the likelihood of persistent symptoms following acute COVID-19 infection (i.e., “Long-COVID-19”) (Garg et al., 2021). Preliminary research has associated Long COVID-19 with psychological disorders and decline in multiple cognitive domains (Pyne & Brickman 2021). Provided the novelty of COVID-19, further research is required to substantiate findings and inform clinical application.Methods: This case series includes three Caucasian geriatric patients with cardiovascular risk factors (e.g., diabetes and hypertension) and unremarkable psychiatric histories. Each was referred for neuropsychological evaluation due to residual cognitive symptoms 6-10 months post-recovery from severe COVID-19 infection. Only Patient A was hospitalized.Results: Patient A’s (82, M) neuropsychological profile reflected deficits in executive functioning, variable processing speed, and mild depression. Patient B (86, F) demonstrated deficits in verbal learning and recall and variable attention, language, and visuospatial abilities. Patient C’s (70, F) results revealed deficits in verbal learning and recall, variable processing speed, and severe depression. All patients reported intact instrumental activities of daily living and were diagnosed with Mild Neurocognitive Disorder.Conclusion: Older adults with cardiovascular risk factors may be at higher risk for persistent changes in cognitive and psychological functioning following COVID-19 infection. Consistent with previous research, the cognitive presentation of Long COVID-19 was heterogeneous among these patients. Future studies should examine the influence of cardiovascular risk factors or neuroimaging-based cerebrovascular burden on long-term recovery from COVID-19 infection among older adults.

The diagnostic signature of Susac’s syndrome

A 48-year-old man presented with scotomatous visual disturbance described as “black spots” in his left peripheral vision. One month later he developed right ear tinnitus and encephalopathy characterized by mild deficits in verbal abstract reasoning, learning and recall of unstructured verbal material, and mild disinhibition. On examination there were no other focal neurological signs. MRI of the brain (Fig. 1A-D) revealed punctate, bi-hemispheric, white matter T2 FLAIR hyperintensities including in the corpus callosum.

Acute effects of ketamine and esketamine on cognition in healthy subjects: A meta-analysis

BackgroundImpairment in cognition is frequently associated with acute ketamine administration. However, some questions remain unanswered as to which deficits are most prominent and what variables modulate these effects. MethodsA literature search yielded 56 experimental studies of acute ketamine administration that assessed cognition in 1041 healthy volunteers. A multivariate meta-analysis was performed, and effect sizes were estimated for eleven cognitive domains: attention, executive function, response inhibition, social cognition, speed of processing, verbal / language, verbal learning, verbal memory, visual learning & memory, visuospatial abilities, and working memory. ResultsThere were small-to-moderate impairments across all cognitive domains. Deficits in verbal learning / memory were most prominent, whereas response inhibition was the least affected. Meta-regression analysis revealed that the negative effects of ketamine on cognition are dependent on infusion dose and plasma level, but unaffected by enantiomer type, route of administration, sex or age. A publication bias was observed. DiscussionAcute ketamine broadly impairs cognition across all domains among healthy individuals. Verbal learning and memory figures most prominently in cognitive impairment elicited by acute ketamine administration.

Preoperative Visual Measures of Verbal Learning and Memory and their Relations to Speech Recognition After Cochlear Implantation.

This study examined the performance of a group of adult cochlear implant (CI) candidates (CIC) on visual tasks of verbal learning and memory. Preoperative verbal learning and memory abilities of the CIC group were compared with a group of older normal-hearing (ONH) control participants. Relations between preoperative verbal learning and memory measures and speech recognition outcomes after 6 mo of CI use were also investigated for a subgroup of the CICs. A group of 80 older adult participants completed a visually presented multitrial free recall task. Measures of word recall, repetition learning, and the use of self-generated organizational strategies were collected from a group of 49 CICs, before cochlear implantation, and a group of 31 ONH controls. Speech recognition outcomes were also collected from a subgroup of 32 of the CIC participants who returned for testing 6 mo after CI activation. CICs demonstrated poorer verbal learning performance compared with the group of ONH control participants. Among the preoperative verbal learning and memory measures, repetition learning slope and measures of self-generated organizational clustering strategies were the strongest predictors of post-CI speech recognition outcomes. Older adult CI candidates present with verbal learning and memory deficits compared with older adults without hearing loss, even on visual tasks that are independent from the direct effects of audibility. Preoperative verbal learning and memory processes reflecting repetition learning and self-generated organizational strategies in free recall were associated with speech recognition outcomes 6 months after implantation. The pattern of results suggests that visual measures of verbal learning may be a useful predictor of outcomes in postlingual adult CICs.

Neurocognitive outcomes of tuberculous meningitis in a primarily HIV-positive Ugandan cohort.

Background: The toll of tuberculous meningitis (TBM) in both mortality and disability is considerable, but advancements in rehabilitation have the potential to improve the functional abilities and the quality of survivors' lives. However, the typical phenotype of neurocognitive impairment in TBM survivors remains unstudied in HIV-predominant populations in sub-Saharan Africa. Methods: We tested 36 survivors of TBM in Uganda with a comprehensive battery of neurocognitive assessments at 8 and 24 weeks after diagnosis, and compared results to a representative cohort of HIV-uninfected Ugandans. Results: While participants had a broad range of impairments at eight weeks, there was marked improvement by 24 weeks, when a phenotype of impairment including deficits in motor functioning, verbal learning and memory, processing speed, and executive function emerged. These deficits were present despite good clinician-rated functional status. The majority (23/27, 85%) had evidence of moderate to severe depression at week 8, and at week 24 (18/24, 75%). Conclusion: These findings highlight the need for more comprehensive neurocognitive assessment in the survivors of TBM, and further investment in and study of rehabilitation, including management of depression, to improve long-term outcomes in this population.

Learning to forget: Hippocampal-amygdala connectivity partially mediates the effect of sexual trauma severity on verbal recall in older women undiagnosed with posttraumatic stress disorder.

Verbal learning deficits are common among sexually traumatized women who have not been formally diagnosed with posttraumatic stress disorder (PTSD). Aberrant resting-state functional connectivity (rsFC) of the amygdala and hippocampus are implicated in PTSD and verbal memory impairment. We tested rsFC between bilateral dentate gyrus (DG) and both centromedial (CM) and basolateral (BL) nuclei of the amygdala as statistical mediators for the effect of sexual trauma-related symptom severity on delayed verbal recall performance in 63 older women (age: 60-85 years) undiagnosed with PTSD. Participant data were drawn from the NKI-Rockland Study. Individuals completed a 10-min resting-state scan, Rey Auditory Verbal Learning Test (RAVLT), and the Sexual Abuse Trauma Index (SATI) from the Trauma Symptom Checklist. Z-scores indicating rsFC of DG with BL and CM amygdala seeds were evaluated in two separate mediation models. Higher SATI scores were associated with lower RAVLT after controlling for age, β=-.23, 95% CI [.48, .03], p=.039. This effect was negated upon adding a negative path from SATI to rsFC of left DG and right CM, β=-.29, 95% CI [-.52, -.02], p=.022, and a positive path from that seed pair to RAVLT List A recall, β=.28, 95% CI [.03, 0.48], p=.015. Chi-square fit indices supported partial mediation by this seed pair, p=.762. In the absence of PTSD sexual trauma symptoms partially relate to verbal learning deficits as a function of aberrant rsFC between left hippocampus DG and right amygdala CM nuclei.

Dissociable impairments of verbal learning differentiate childhood risk profiles for schizophrenia

Poor verbal learning and memory function is well-documented among individuals with schizophrenia and those at clinical high-risk for psychosis. This study aimed to identify these impairments among children aged 9–12 years with different schizophrenia risk profiles (family history or antecedents of schizophrenia, each of higher[H] or lower[L] risk load) relative to typically developing peers. These three groups were recruited via community-screening, and differentiated for analysis into: typically developing children (TD = 45); children who had 1 first- or ≥2 second-degree affected relatives (FHxH = 16) or one second-degree relative (FHxL = 15); and children presenting multiple replicated antecedents of schizophrenia whose clinical symptoms persisted at 2- and/or 4-year follow-up (ASzH = 16) or remitted during follow-up (ASzL = 16). Verbal learning/memory measures assessed at baseline (age 9–12 years) included: (i) total recall; (ii) trial 1 recall; (iii) learning score; (iv) intrusions; (v) total words lost; and (vi) serial position patterns. Analyses of variance indicated that FHxH and ASzH youth demonstrated impaired total recall compared to TD and ASzL children and lost significantly more words between trials than TD and FHxL children. Learning score was impaired among both FHxH and FHxL relative to TD and ASzL children. Thus, among putatively at-risk children, total words recalled and lost distinguished those with higher risk load (by family history or persistent antecedent symptomology), whereas learning score indexed familial vulnerability. Follow-up of the sample is needed to determine the capacity of verbal learning deficits to predict later illness and provide a potential avenue for early remediation to improve clinical or functional outcomes.

Loosening of Associations in Chronic Schizophrenia: Intersectionality of Verbal Learning, Negative Symptoms, and Brain Structure.

In 1908, Bleuler proposed a unitary theory of schizophrenia, hypothesizing a “loosening of associations” as the central mechanism underlying disturbances in thinking, motivation, and affective expression. Here, we test Bleuler’s model in an archival sample of 79 healthy controls and 76 patients with chronic schizophrenia who had completed neuropsychological tests, including a measure of learning of novel word pairs, which was specifically selected to probe the structure and formation of new verbal associations. The patients also had positive and negative symptoms ratings, including measures of flat affect, anhedonia, and thought disorder. A subset of patients and controls (n = 39) had available prior archival 3-T magnetic resonance imaging (MRI) measures of prefrontal cortex (PFC) gray matter volumes. In relation to controls, patients showed evidence of a selective impairment in associative learning, independent of their overall reduced neuropsychological functioning. This neuropsychological impairment, in turn, correlated significantly with overall levels of negative but not positive symptoms, with the data showing an especially strong contribution of flattened emotional expression to verbal associate learning deficits in this patient sample. Moreover, the archival MRI data were consistent with prior research pointing to an important role of the PFC in supporting verbal associate learning and memory in patients and controls. Taken together, the current results provided evidence of a selective impairment in schizophrenia on a PFC-supported verbal associate learning and memory task, which was accompanied by negative symptoms in general, and flattened emotional expression, in particular.

Working Memory and Language Contribution to Verbal Learning and Memory in Drug-Resistant Unilateral Focal Temporal Lobe Epilepsy.

We aimed to investigate the working memory (WM) and language separate contributions to verbal learning and memory in patients with unilateral drug-resistant temporal lobe epilepsy (drTLE); additionally, we explored the mediating role of WM on the relationship between the number of antiepileptic drugs (AEDs) and short-term verbal memory. We retrospectively enrolled 70 patients with left (LTLE; n = 44) and right (RTLE; n = 26) drTLE. About 40 similar (age and education) healthy controls were used to determine impairments of groups at WM, language (naming and verbal fluency), and verbal learning and memory (five trials list-learning, story memory—immediate recall). To disentangle the effect of learning from the short-term memory, we separately analyzed performances at the first trial, last trial, and delayed-recall list-learning measures, in addition to the total learning capacity (the sum of the five trials). Correlation and regression analyses were used to assess the contribution of potential predictors while controlling for main clinical and demographic variables, and ascertain the mediating role of WM. All patients were impaired at WM and story memory, whereas only LTLE showed language and verbal learning deficits. In RTLE, language was the unique predictor for the most verbal learning performances, whereas WM predicted the results at story memory. In LTLE, WM was the sole predictor for short-term verbal learning (list-learning capacity; trial 1) and mediated the interaction between AED number and the performance at these measures, whereas language predicted the delayed-recall. Finally, WM confounded the performance at short-term memory in both groups, although at different measures. WM is impaired in drTLE and contributes to verbal memory and learning deficits in addition to language, mediating the relationship between AED number and short-term verbal memory in LTLE. Clinicians should consider this overlap when interpreting poor performance at verbal learning and memory in drTLE.

Neurocognitive outcomes of tuberculous meningitis in a primarily HIV-positive Ugandan cohort

Background: The toll of tuberculous meningitis (TBM) in both mortality and disability is considerable, but advancements in rehabilitation have the potential to improve the functional abilities and the quality of survivors’ lives. However, the typical phenotype of neurocognitive impairment in TBM survivors remains unstudied in HIV-predominant populations in sub-Saharan Africa. Methods: We tested 36 survivors of TBM in Uganda with a comprehensive battery of neurocognitive assessments at 8 and 24 weeks after diagnosis, and compared results to a representative cohort of HIV-uninfected Ugandans. Results: While participants had a broad range of impairments at eight weeks, there was marked improvement by 24 weeks, when a phenotype of impairment including deficits in motor functioning, verbal learning and memory, processing speed, and executive function emerged. These deficits were present despite good clinician-rated functional status. The majority (23/27, 85%) had evidence of moderate to severe depression at week 8, and at week 24 (18/24, 75%). Conclusion: These findings highlight the need for more comprehensive neurocognitive assessment in the survivors of TBM, and further investment in and study of rehabilitation, including management of depression, to improve long-term outcomes in this population.

Neurocognitive outcomes of HIV-associated tuberculous meningitis

Background: The toll of tuberculous meningitis (TBM) in both mortality and disability is considerable, but advancements in rehabilitation have the potential to improve the functional abilities and the quality of survivors’ lives. However, the typical phenotype of neurocognitive impairment in TBM survivors remains unstudied in HIV-predominant populations in sub-Saharan Africa. Methods: We tested 36 survivors of TBM in Uganda with a comprehensive battery of neurocognitive assessments at 8 and 24 weeks after diagnosis, and compared results to a representative cohort of HIV-uninfected Ugandans. Results: While participants had a broad range of impairments at eight weeks, there was marked improvement by 24 weeks, when a phenotype of impairment including deficits in motor functioning, verbal learning and memory, processing speed, and executive function emerged. These deficits were present despite good clinician-rated functional status. The majority (23/27, 85%) had evidence of moderate to severe depression at week 8, and at week 24 (18/24, 75%). Conclusion: These findings highlight the need for more comprehensive neurocognitive assessment in the survivors of TBM, and further investment in and study of rehabilitation, including management of depression, to improve long-term outcomes in this population.

Clinical, Neuropsychological, and Neuroimaging Characteristics of Amyloid- positive vs. Amyloid-negative Patients with Clinically Diagnosed Alzheimer's Disease and Amnestic Mild Cognitive Impairment.

A significant proportion of patients with clinically diagnosed Alzheimer's Disease (AD) and an even higher proportion of patients with amnestic mild cognitive impairment (aMCI) do not show evidence of amyloid deposition on Positron Emission Tomography (PET) with amyloid-binding tracers such as 11C-labeled Pittsburgh Compound B (PiB). This study aimed to identify clinical, neuropsychological and neuroimaging factors that might suggest amyloid neuropathology in patients with clinically suspected AD or aMCI. Forty patients with mild to moderate AD and 23 patients with aMCI who were clinically diagnosed in our memory clinic and had PiB PET scans were included. Clinical, neuropsychological, and imaging characteristics, such as Medial Temporal lobe Atrophy (MTA) and White Matter Hyperintensities (WMH) on MRI and metabolic pattern on 18F-labeled fluorodeoxyglucose (FDG) PET, were compared between patients with PiB positive and negative PET results for AD, aMCI, and all subjects combined, respectively. Compared with PiB positive patients, PiB negative patients had a higher prevalence of hypertension history, better performance on the Mini-Mental State Examination, the Rey Auditory Verbal Learning Test, and the Judgement of Line Orientation, lower score of MTA, and were less likely to have temporoparietal-predominant hypometabolism on FDG PET. Affective symptoms were less common in PiB negative patients diagnosed with AD, and the Animal Fluency Test score was higher in PiB negative patients diagnosed with aMCI. In patients with clinically diagnosed AD or aMCI, absence of a history of hypertension, deficits in verbal learning and memory, visuospatial function, semantic verbal fluency, presence of affective symptoms, MTA on MRI, and temporoparietal hypometabolism on FDG PET suggested amyloid deposition in the brain.

Neuropsychological functioning in long-term survivors of pediatric acute lymphoblastic leukemia: A prospective cross-sectional study

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Given the improvement in the survival of patients with ALL over the last few decades, the adverse effects of treatment and disease on survivors have become a major concern. Neuropsychological functioning has been reported to be affected in long-term survivors of ALL and can impact their quality of life. Objective: The objective of the study was to assess the neuropsychological functioning of long-term survivors of pediatric ALL. Materials and Methods: This prospective cross-sectional study was conducted at the Cancer Institute, Chennai, India, between March and August 2014. Pediatric patients with ALL who had survived at least 2 years after treatment and were in remission were included in the study. Various neuropsychological domains such as sustained attention, focused attention, verbal working memory, immediate memory, verbal learning, immediate recall, delayed recall, visuoconstructive ability, and visuomotor speed were assessed using age-appropriate tests. Data were analyzed using descriptive statistics and nonparametric tests such as the Mann–Whitney U and Kruskal–Wallis H-tests. P Results: Of the 51 participants, there were 30 male and 21 female survivors. Their median ages at diagnosis and assessment were 8.6 years and 18.3 years, respectively. Adult survivors (n = 31) were found to have deficits in immediate memory, verbal learning, immediate recall, visuoconstructive ability, and visuomotor speed. Adolescent survivors (n = 20) were found to have deficits in immediate memory and verbal working memory. Survivors aged 8 years or more at diagnosis had better focused attention and verbal working memory, while those diagnosed at age Conclusions: Long-term survivors of pediatric ALL experience deficits in various neuropsychological functions. Adult survivors have deficits in immediate memory, visuoconstructive ability, verbal learning, immediate recall, and visuomotor speed, whereas adolescent survivors have deficits in immediate memory and verbal working memory.

The Impact of Amyloid Burden and APOE on Rates of Cognitive Impairment in Late Life Depression.

Cognitive impairment (CI) is a key feature of late life depression (LLD), but the contribution of underlying neurodegenerative pathology remains unclear. To evaluate cognitive dysfunction in LLD relative to a sample of nondepressed (ND) older adults with matched levels of memory impairment and amyloid-β (Aβ) burden. Participants included 120 LLD and 240 ND older adults matched on age, education, sex, Mini-Mental State Exam, mild cognitive impairment diagnosis, and PET Aβ burden. LLD showed higher rates of impairment relative to ND with 54.6% of the LLD sample demonstrating impairment in at least one cognitive domain compared to 42.9% of controls (H = 7.13, p = 0.008). LLD had poorer performance and higher rates of impairment on Rey Auditory Verbal Learning Test learning and memory compared to controls. In the overall sample, Aβ positivity was associated with worse performance on Logical Memory I (p = 0.044), Logical Memory II (p = 0.011), and Trail Making Test -B (p = 0.032), and APOEɛ4 genotype was associated with worse performance on Logical Memory I (p = 0.022); these relationships did not differ between LLD and ND. LLD showed higher rates of CI driven by focal deficits in verbal learning and memory. Alzheimer's disease (AD) biomarkers were associated with worse performance on timed set-shifting and story learning and memory, and these relationships were not impacted by depression status. These findings suggest that AD may account for a portion of previously reported multi-domain CI in LLD and highlight the potential for AD to confound studies of cognition in LLD.

Role of cognitive reserve in cognitive variability in euthymic individuals with bipolar disorder: cross-sectional cluster analysis.

People with bipolar disorder have moderate cognitive difficulties that tend to be more pronounced during mood episodes but persist after clinical remission and affect recovery. Recent evidence suggests heterogeneity in these difficulties, but the factors underlying cognitive heterogeneity are unclear. To examine whether distinct cognitive profiles can be identified in a sample of euthymic individuals with bipolar disorder and examine potential differences between subgroups. Cognitive performance was assessed across four domains (i.e. processing speed, verbal learning/memory, working memory, executive functioning) in 80 participants. We conducted a hierarchical cluster analysis and a discriminant function analysis to identify cognitive profiles and considered differences in cognitive reserve, estimated cognitive decline from premorbid cognitive functioning, and clinical characteristics among subgroups. Four discrete cognitive profiles were identified: cognitively intact (n = 25; 31.3%); selective deficits in verbal learning and memory (n = 15; 18.8%); intermediate deficits across all cognitive domains (n = 30; 37.5%); and severe deficits across all domains (n = 10; 12.5%). Cognitive decline after illness onset was greater for the intermediate and severe subgroups. Cognitive reserve scores were increasingly lower for subgroups with greater impairments. A smaller proportion of cognitively intact participants were using antipsychotic medications compared with all other subgroups. Our findings suggest that individuals with cognitively impaired profiles demonstrate more cognitive decline after illness onset. Cognitive reserve may be one of the factors underlying cognitive variability across people with bipolar disorder. Patients in the intermediate and severe subgroups may be in greater need of interventions targeting cognitive difficulties.

Distinct Functional Connectivity Signatures of Impaired Social Cognition in Multiple Sclerosis

Objective: Multiple sclerosis (MS) is characterized by impairments in basic cognitive functions such as information processing speed as well as in more complex, higher-order domains such as social cognition. However, as these deficits often co-occur, it has remained challenging to determine whether they have a specific pathological basis or are driven by shared biology.Methods: To identify neural signatures of social cognition deficits in MS, data were analyzed from n = 29 patients with relapsing–remitting MS and n = 29 healthy controls matched for age, sex, and education. We used neuropsychological assessments of information processing speed, attention, learning, working memory, and relevant aspects of social cognition (theory of mind, emotion recognition (ER), empathy) and employed neuroimaging of CNS networks using resting-state functional connectivity.Results: MS patients showed significant deficits in verbal learning and memory, as well as implicit ER. Performance in these domains was uncorrelated. Functional connectivity analysis identified a distinct network characterized by significant associations between poorer ER and lower connectivity of the fusiform gyrus (FFG) with the right lateral occipital cortex, which also showed lower connectivity in patients compared to controls. Moreover, while ER was correlated with MS symptoms such as fatigue and motor/sensory functioning on a behavioral level, FFG connectivity signatures of social cognition deficits showed no overlap with these symptoms.Conclusions: Our analyses identify distinct functional connectivity signatures of social cognition deficits in MS, indicating that these alterations may occur independently from those in other neuropsychological functions.