Wechsler Memory Scale-Third Edition Research Articles

4 Preoperative International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) Phenotype is Associated with Postoperative Memory Decline Following Temporal Lobectomy

Objective:The International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) is a new consensus-based taxonomy that classifies patients into one of four cognitive phenotypes (i.e., cognitively intact, single-domain impairment, bi-domain impairment, generalized impairment). The IC-CoDE has been effectively applied to patients with temporal lobe epilepsy (TLE), but little is known about the relationship between pre-operative cognitive phenotype and post-operative cognitive outcome following epilepsy surgery. The purpose of this study was to examine whether the IC-CoDE classifications are related to memory decline following surgery for TLE.Participants and Methods:347 patients (ages 16-66; 57% female) with pharmacoresistant TLE completed comprehensive pre- and post-surgical neuropsychological assessments. Patients were classified into IC-CoDE phenotypes based on pre-surgical pattern of cognitive impairment using a threshold of >1.5 standard deviations (SD) below the normative mean. Change scores were calculated from delay trial scores of the following memory tests: Rey Auditory Verbal Learning Test (RAVLT), and Logical Memory (LM) and Verbal Paired Associates (VPA) subtests from the Wechsler Memory Scale - Third Edition (WMS-III). Cutoffs were applied using epilepsy-specific reliable change indices and patients were classified within the ‘decline’ group if they experienced significant decline on any of the three memory measures.Results:The distribution of IC-CoDE phenotypes in our sample were as follows: 57% intact, 29% single-domain, 10% bi-domain, and 5% generalized impairment. 108 patients (31%) demonstrated post-surgical memory decline. Patients who underwent dominant temporal lobectomy were more likely to show post-surgical memory decline compared to non-dominant temporal lobectomy. However, there was no significant difference in phenotype distribution between patients who underwent left versus right-sided resections; thus, analyses were conducted on the entire sample to increase power. Chi-square analyses revealed unique patterns of post-surgical memory decline across phenotypes, X2 = 8.79, p = .032. There was a significantly higher proportion of patients with memory decline in the single-domain phenotype (39%) and this was followed by the bi-domain phenotype (33%) and the intact phenotype (29%). In contrast, patients with generalized impairment were unlikely to show memory decline (.06%). Within the single domain impaired phenotype, there were no differences between the specific domains impaired and memory decline. Logistic regression model was also significant; after controlling for surgery side, the IC-CoDE phenotypes significantly predicted the likelihood of a patient experiencing post-surgical memory decline; X2 = 8.18, p = .043.Conclusions:In addition to the IC-CoDE providing a useful cognitive classification scheme in epilepsy, the IC-CoDE phenotypes appear helpful in identifying those at risk for post-operative memory decline. Previous literature has suggested that those with better pre-surgical cognition are generally at highest risk for cognitive decline. Our results generally follow this trend, but interestingly, patients with single domain impairment were at the highest risk of memory decline, even above those in the cognitively intact group. Future studies are important to confirm this pattern in other samples and examine additional contributing factors and underlying mechanisms that may influence risk of memory decline across these cognitive phenotypes.

Physical exercise improves memory in sedentary middle-aged adults: Are these exercise-induced benefits associated with S-Klotho and 1,25-dihydroxivitamin D? The FIT-AGEING randomized controlled trial.

We aimed to investigate the effect of three types of exercise interventions on memory (i.e., immediate memory (IM), long-term memory (LTM), and recognition). We also investigated whether exercise-induced changes in circulating S-Klotho and 1,25-dihydroxivitamin D (1,25(OH)2 D) levels were related to those observed in memory in healthy middle-aged sedentary adults. A 12-week randomized controlled trial was performed with a parallel-group design. Seventy-four participants (45-65 years old: 53% women) were randomly assigned to (1) no exercise (control) group, (2) concurrent training based on the international physical activity recommendations (PAR) group, (3) high-intensity interval training (HIIT) group, or (4) HIIT plus whole-body electromyostimulation (HIIT-EMS) group. Memory outcomes were assessed using the Wechsler Memory Scale-third edition. S-Klotho plasma levels were determined according to a solid-phase sandwich enzyme-linked immunosorbent assay kit while 1,25(OH)2 D plasma levels were measured using a DiaSorin-Liaison immunochemiluminometric analyzer. IM-Verbal Paired Associates (IM-VPA) and IM-Logical Memory (IM-LM) were improved in both the HIIT and HIIT-EMS groups compared with the control group (all p ≤ 0.045). Exercise-induced changes in S-Klotho plasma levels were positively associated with those observed in IM, LTM, and recognition (all p ≤ 0.007), whereas exercise-induced changes in 1,25(OH)2 D plasma levels were directly related to changes in IM and LTM (all p ≤ 0.048). In conclusion, a 12-week HIIT intervention with or without WB-EMS seems to be the most effective exercise program to improve IM. The significant and positive associations between exercise-induced changes in S-Klotho and 1,25(OH)2 D levels with those observed in memory outcomes suggest that these factors may be potentially related to exercise-induced improvements of memory in middle-aged adults.

Evaluation of Neighborhood-Level Disadvantage and Cognition in Mexican American and Non-Hispanic White Adults 50 Years and Older in the US

Understanding how socioeconomic factors are associated with cognitive aging is important for addressing health disparities in Alzheimer disease. To examine the association of neighborhood disadvantage with cognition among a multiethnic cohort of older adults. In this cross-sectional study, data were collected between September 1, 2017, and May 31, 2022. Participants were from the Health and Aging Brain Study-Health Disparities, which is a community-based single-center study in the Dallas/Fort Worth area of Texas. A total of 1614 Mexican American and non-Hispanic White adults 50 years and older were included. Neighborhood disadvantage for participants' current residence was measured by the validated Area Deprivation Index (ADI); ADI Texas state deciles were converted to quintiles, with quintile 1 representing the least disadvantaged area and quintile 5 the most disadvantaged area. Covariates included age, sex, and educational level. Performance on cognitive tests assessing memory, language, attention, processing speed, and executive functioning; measures included the Spanish-English Verbal Learning Test (SEVLT) Learning and Delayed Recall subscales; Wechsler Memory Scale, third edition (WMS-III) Digit Span Forward, Digit Span Backward, and Logical Memory 1 and 2 subscales; Trail Making Test (TMT) parts A and B; Digit Symbol Substitution Test (DSST); Letter Fluency; and Animal Naming. Raw scores were used for analyses. Associations between neighborhood disadvantage and neuropsychological performance were examined via demographically adjusted linear regression models stratified by ethnic group. Among 1614 older adults (mean [SD] age, 66.3 [8.7] years; 980 women [60.7%]), 853 were Mexican American (mean [SD] age, 63.9 [7.9] years; 566 women [66.4%]), and 761 were non-Hispanic White (mean [SD] age, 69.1 [8.7] years; 414 women [54.4%]). Older Mexican American adults were more likely to reside in the most disadvantaged areas (ADI quintiles 3-5), with 280 individuals (32.8%) living in ADI quintile 5, whereas a large proportion of older non-Hispanic White adults resided in ADI quintile 1 (296 individuals [38.9%]). Mexican American individuals living in more disadvantaged areas had worse performance than those living in ADI quintile 1 on 7 of 11 cognitive tests, including SEVLT Learning (ADI quintile 5: β = -2.50; 95% CI, -4.46 to -0.54), SEVLT Delayed Recall (eg, ADI quintile 3: β = -1.11; 95% CI, -1.97 to -0.24), WMS-III Digit Span Forward (eg, ADI quintile 4: β = -1.14; 95% CI, -1.60 to -0.67), TMT part A (ADI quintile 5: β = 7.85; 95% CI, 1.28-14.42), TMT part B (eg, ADI quintile 5: β = 31.5; 95% CI, 12.16-51.35), Letter Fluency (ADI quintile 4: β = -2.91; 95% CI, -5.39 to -0.43), and DSST (eg, ADI quintile 5: β = -4.45; 95% CI, -6.77 to -2.14). In contrast, only non-Hispanic White individuals living in ADI quintile 4 had worse performance than those living in ADI quintile 1 on 4 of 11 cognitive tests, including SEVLT Learning (β = -2.35; 95% CI, -4.40 to -0.30), SEVLT Delayed Recall (β = -0.95; 95% CI, -1.73 to -0.17), TMT part B (β = 15.95; 95% CI, 2.47-29.44), and DSST (β = -3.96; 95% CI, -6.49 to -1.43). In this cross-sectional study, aging in a disadvantaged area was associated with worse cognitive functioning, particularly for older Mexican American adults. Future studies examining the implications of exposure to neighborhood disadvantage across the life span will be important for improving cognitive outcomes in diverse populations.

Poor oral health predicts cognitive impairment in elders

AbstractBackgroundTooth loss, periodontal disease, dementia, and Alzheimer’s disease share several risk factors in older adults. Several previous studies have reported positive associations between these dental problems and global cognitive defects. However, limited is known about the relationships among multiple dental/periodontal statuses and different cognitive domains.MethodThis six‐year (2011‐2017) cohort study includes 515 older adults (65+). Global cognition was assessed by Montreal cognitive assessment‐Taiwan version (MoCA‐T). For cognitive domains, we used logical memory tests (immediate and delayed theme and free recall) in Wechsler Memory Scale‐Third Edition (WMS‐III) to assess memory. Trail Making Test A and B was used to assess attention and executive function, respectively. Digit span‐forward and backward was used to evaluate attention and working memory/short‐term memory, respectively. Verbal fluency tests were used to assess category/semantic fluency. A Z‐score was calculated for each cognitive domain‐specific test according to baseline mean and standard deviation. Oral health status includes tooth defect (dental caries, tooth wear, cervical abrasion, retained root or crown fracture), periodontal health (disease severity from healthy periodontal status, gingivitis to periodontitis), and arch integrity (no tooth loss nor retained root or crown fracture). Generalized linear mixed models were used to assess the associations above adjust important covariates.ResultAt baseline, periodontitis was associated with poor performance in executive function [Trail Making Test A: b = ‐0.14, 95% confidence interval (CI) = ‐0.27 to ‐0.01]. The association between baseline severity of tooth defect and poor memory decreased (logical memory‐immediate theme recall: b = ‐0.05, 95% CI = ‐0.10 to ‐0.01); similarly finding was found for attention domain (digit span‐forward: b = ‐0.04, 95% CI = ‐0.07 to ‐0.001). At baseline, loss of arch integrity was associated with a better working memory/short‐term memory (digit span‐backward: β = 0.18, 95% CI = 0.01 to 0.36); as follow‐up time increased, this association decreased over six years (β = ‐0.04, 95% CI = ‐0.07 to ‐0.003).ConclusionPeriodontitis, tooth defects, or arch integrity was associated with poor performance of cognitive domains (memory, attention, and executive function) over time. A oral health evaluation may serve as predictors of the preclinical phase of dementia in its upcoming years.

Effects of comorbid alcohol use disorder on bipolar disorder: Focusing on neurocognitive function and inflammatory markers

BackgroundAlcohol use disorder (AUD) is a highly prevalent comorbid disorder in patients with bipolar disorder (BD). Both BD and AUD were found to be associated with inflammation and cognitive deficits, but few study has been done on BD comorbid with AUD (BD+AUD). We aimed to investigate the impacts of comorbid AUD and BD on cognitive function, inflammatory and neurotrophic markers. MethodWe recruited 641 BD patients, 150 patients with BD+AUD, and 185 healthy controls (HC). Neuropsychological tests [Wisconsin card sorting test (WCST), continuous performance test (CPT), and Wechsler memory scale - third edition (WMS-III)] and cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1), and brain-derived neurotrophic factor (BDNF)] were assessed. ResultsBD+AUD patients had worse cognitive performance than those without AUD. There was a significant difference in the plasma levels of TNF-α, IL-8, and BDNF (P < 0.001, <0.001, and 0.01, respectively) between the patients and the HC groups. Post hoc analysis showed that BD+AUD patients had higher levels of TNF-α and IL-8 than BD-only patients (P < 0.001). Additionally, plasma IL-8 levels were negatively associated with number of completed categories in WCST (P = 0.02), and TNF-α levels were negatively associated with visual immediate index in WMS-III (P = 0.05). ConclusionOur results suggest that comorbid AUD and BD might worsen cognitive impairments and inflammatory processes. Further longitudinal studies on BD+AUD may be needed.

Association of Concurrent Olfactory Dysfunction and Probable Rapid Eye Movement Sleep Behavior Disorder with Early Parkinson's Disease Progression.

ABSTRACTBackgroundParkinson's disease (PD), with either rapid eye movement sleep behavior disorder (RBD) or olfactory dysfunction (OD), has been associated with disease progression. However, there is currently heterogeneity in predicting prognosis.ObjectivesTo identify whether the concurrent presence of OD and probable RBD (pRBD) in PD (Dual hit in PD, PD‐DH) is associated with disease progression.MethodsWe included 420 patients with de novo PD from the Parkinson's Progression Markers Initiative: 180 PD only (PD), 82 PD with OD (PD‐OD), 94 PD with pRBD (PD‐pRBD), and 64 PD with both OD and pRBD (PD‐DH). Participants underwent motor and nonmotor evaluations, dopamine transporter imaging, and cerebrospinal fluid (CSF) assessment. Data were analyzed with generalized estimating equations and Cox proportional hazards analysis.ResultsThe PD‐DH subtype was associated with higher scores and faster progression rates in Movement Disorder Society–Unified PD Rating Scale (MDS‐UPDRS) Parts II and III. Also, patients in PD‐DH group had faster deterioration in nonmotor symptoms, including MDS‐UPDRS Part I score, Montreal Cognitive Assessment, Hopkins Verbal Learning Test–Revised, Wechsler Memory Scale‐Third edition (WMS‐III) Letter Number Sequencing score, Symbol Digit Modalities Test, and Scales for Outcomes in PD–Autonomic scores, with all P values <0.002. Moreover, the PD‐DH subtype had a higher mild cognitive impairment risk (hazard ratio = 1.756, 95% confidence interval [CI] = 1.132–2.722; P = 0.012), faster decline in caudate standard uptake values (β = −0.03, 95% CI = −0.06 to −0.008, P = 0.012), and CSF α‐synuclein levels (β = −77, 95% CI = −149 to −5, P = 0.034) than the PD group.ConclusionCoexisting pRBD and OD in patients with PD may be associated with faster progressions in motor measurements and in cognitive and autonomic symptoms, indicating PD‐DH as a more aggressive subtype for PD.

Memory and executive functioning outcomes of selective amygdalohippocampectomy in patients with hippocampal sclerosis: A preliminary study in a developing country.

Background: Selective amygdalohippocampectomy (SA) is an effective treatment for drug-resistant cases of epilepsy due to hippocampal sclerosis (HS). However, its neurocognitive outcomes are inconsistent across the previous studies, pointing to potential location-specific confounders. Here, we investigated the neurocognitive outcomes of SA in an Iranian center recently adopting this approach.Methods: Thirty adults (53.3% of females, age 31.4 ± 6.2 years) with drug-resistant epilepsy due to HS were included in the study. Patients were stratified into surgical (n = 15) and medical (n = 15) treatment groups based on their preferences. Neurocognitive function was assessed before and 6 months after intervention using Wisconsin Card Sorting Test (WCST), Wechsler Adult Intelligence Scale-Revised, and Wechsler Memory Scale- Third Edition (WMS-III). Postintervention performance changes were compared between the two groups, and predictors of worse postoperative outcomes were investigated.Results: Longitudinal changes of performance in WMS-III and WCST were significantly different between the surgically and medically treated patients. Postoperative WMS-III performance showed an average 25% decline (mean ∆T2-T1 = –25.1%, T = –6.6, P < 0.001), and WCST performance improved by an average of 49% (mean ∆T2-T1 = +49.1%, T = 4.6, P < 0.001). The decline in memory performance was more severe in the left-sided surgery and in patients with higher baseline education (mean ∆T2-T1 = –31.1%, T = –8.9, P < 0.001).Conclusion: In our center, executive functioning improved or remained stable after SA, but memory functions declined moderately. The left-sided SA and higher education were associated with more severe decline in memory functions, highlighting the need for special considerations for these groups.

What's in Your Nomogram? Personalized Prognostication of Verbal Memory Decline after Temporal Lobe Resection in Adults With Epilepsy.

ObjectiveThis study aims to develop and externally validate models to predict the probability of postoperative verbal memory decline in adults following temporal lobe resection (TLR) for epilepsy using easily accessible preoperative clinical predictors.MethodsMultivariable models were developed to predict delayed verbal memory outcome on 3 commonly used measures: Rey Auditory Verbal Learning Test (RAVLT), and Logical Memory (LM), and Verbal Paired Associates (VPA) subtests from Wechsler Memory Scale-Third Edition. Using Harrell’s step-down procedure for variable selection, models were developed in 359 adults who underwent TLR at Cleveland Clinic and validated in 290 adults at 1 of 5 epilepsy surgery centers in the United States or Canada.ResultsTwenty-nine percent of the development cohort and 26% of the validation cohort demonstrated significant decline on at least 1 verbal memory measure. Initial models had good-to-excellent predictive accuracy (calibration (c) statistic range = .77–.80) in identifying patients with memory decline; however, models slightly underestimated decline in the validation cohort. Model coefficients were updated using data from both cohorts to improve stability. The model for RAVLT included surgery side, baseline memory score, and hippocampal resection. The models for LM and VPA included surgery side, baseline score, and education. Updated model performance was good to excellent (RAVLT c = .81, LM c = .76, VPA c = .78). Model calibration was very good, indicating no systematic over- or under-estimation of risk.ConclusionsNomograms are provided in 2 easy-to-use formats to assist clinicians in estimating the probability of verbal memory decline in adults considering TLR for treatment of epilepsy.

Clinical efficacy of aerobic exercise combined with computer-based cognitive training in stroke: a multicenter randomized controlled trial

ABSTRACT Purpose The objectives are to evaluate the effects of a sequential combination of aerobic exercise and cognitive training, compared with exercise or cognitive training alone, on cognitive function, physical function, daily function, quality of life, and social participation in stroke survivors with cognitive impairment. Methods This is a single-blind, parallel, randomized controlled trial. Stroke patients with mild cognitive impairment (n = 56) were randomly assigned to aerobic exercise training (n = 18), computerized cognitive training (n = 18), and the sequential combination of aerobic exercise and computerized cognitive training (n = 20) group. All groups underwent training 60 min/day, 3 days/week, for a total of 12 weeks. The primary outcomes included Montreal Cognitive Assessment (MoCA), Wechsler Memory Scale-Third Edition, and the Stroop color-word test. Secondary outcomes were the Timed Up and Go test, 6-Minute Walk Test, Functional Independence Measure, Lawton Instrumental Activities of Daily Living Scale, Community Integration Questionnaire, and Stroke Impact Scale. Results 56 participants completed the trial. Compared with a single type of aerobic exercise or cognitive training, the combined training group showed significant improvement in MoCA (P < .05, η2 = 0.13), and two sub-tests in WMS-III (both P’s < 0.05) following the intervention. However, no between-group differences were observed for physical functions, daily function, quality of life, and social participation measures. Conclusions The findings provide evidence for the potential synergistic intervention in stroke survivors. Future studies investigating the transfer effects and the optimal training parameters with a larger sample is needed.

Neuropsychological Profiles of Patients with Progressive Apraxia of Speech and Aphasia.

To characterize and compare the neuropsychological profiles of patients with primary progressive apraxia of speech (PPAOS) and apraxia of speech with progressive agrammatic aphasia (AOS-PAA). Thirty-nine patients with PPAOS and 49 patients with AOS-PAA underwent formal neurological, speech, language, and neuropsychological evaluations. Cognitive domains assessed included immediate and delayed episodic memory (Wechsler Memory Scale-Third edition; Logical Memory; Visual Reproduction; Rey Auditory Verbal Learning Test), processing speed (Trail Making Test A), executive functioning (Trail Making Test B; Delis-Kaplan Executive Functioning Scale - Sorting), and visuospatial ability (Rey-Osterrieth Complex Figure copy). The PPAOS patients were cognitively average or higher in the domains of immediate and delayed episodic memory, processing speed, executive functioning, and visuospatial ability. Patients with AOS-PAA performed more poorly on tests of immediate and delayed episodic memory and executive functioning compared to those with PPAOS. For every 1 unit increase in aphasia severity (e.g. mild to moderate), performance declined by 1/3 to 1/2 a standard deviation depending on cognitive domain. The degree of decline was stronger within the more verbally mediated domains, but was also notable in less verbally mediated domains. The study provides neuropsychological evidence further supporting the distinction of PPAOS from primary progressive aphasia and should be used to inform future diagnostic criteria. More immediately, it informs prognostication and treatment planning.

Hydrolyzed Chicken Extract (ProBeptigen®) on Cognitive Function in Healthy Middle-Aged People: A Randomized Double-Blind Trial.

Cognitive decline is an important issue of global public health. Cognitive aging might begin at middle adulthood, the period particularly vulnerable to stress in lifespan. Essence of chicken (EOC) has consistently demonstrated its beneficial effects on various cognitive domains as nutritional supplementation. This study primarily aimed to examine the cognitive enhancement effects of ProBeptigen® (previously named CMI-168), hydrolyzed peptides extracted from EOC, in healthy middle-aged people under mild stress. Ninety healthy subjects were randomly assigned into the ProBeptigen® or placebo group for eight weeks. Neurocognitive assessment, event-related potentials (ERPs), and blood tests were conducted before, during, and after the treatment. The ProBeptigen® group outperformed placebo group on Logical Memory subtests of Wechsler Memory Scale-third edition (WMS-III) and Spatial Working Memory task in the Cambridge Neuropsychological Test Automated Battery (CANTAB). The anti-inflammatory effects of ProBeptigen® in humans were also confirmed, with progressively declining high-sensitivity C-reactive protein (hs-CRP) levels. Regular dietary supplementation of ProBeptigen® is suggested to improve verbal short- and long-term memory as well as spatial working memory, and reduce inflammation in middle-aged healthy individuals with stress. The effects of ProBeptigen® on cognition warrant further investigation. (NCT03612752)

Prediction of Memory Impairment in Epilepsy Surgery by White Matter Diffusion

To analyze the relationship between cognitive performance and white matter integrity in patients with temporal lobe epilepsy (TLE) to establish radiologic criteria to help with patient selection for surgery. The study included 19 adults with temporal lobe epilepsy. A tractography analysis of fractional anisotropy and mean diffusivity (MD) of the following fascicles was performed: arcuate fascicle, cingulum, fornix, inferior fronto-occipital fascicle, inferior longitudinal fascicle, parahippocampal fibers of the cingulum, and uncinate fascicle. The Wechsler Memory Scale-Third Edition neuropsychological test was performed to evaluate short- and long-term verbal (Logical Memory I and II subtests) and nonverbal (Visual Reproduction I and II subtests) memory. Relationships between memory scores and diffusion were calculated. Lower Logical Memory I subtest scores were correlated with lower MD of the right inferior fronto-occipital fascicle, while lower Logical Memory II subtest scores were related to higher values of fractional anisotropy in bilateral cingulum, right uncinate, and right parahippocampal fibers of the cingulum and lower MD in left cingulum fascicle. Finally, lower values in Visual Reproduction I subtest scores were associated with lower values in MD in right cingulum and inferior fronto-occipital fascicles. Structural changes of some white matter tracts were associated with deterioration of both short- and long-term memory. These alterations were more associated with verbal memory than with nonverbal memory. These changes mainly consist of an increase in fractional anisotropy and a decrease in MD, which could be interpreted as reorganization phenomena. Diffusion tensor imaging could be a useful tool for cognitive assessment in surgical candidates with temporal lobe epilepsy who are not suitable for neuropsychological testing or in whom their results do not lead to definitive conclusions.

Association between polymorphism of the NEDD4 gene and cognitive dysfunction of schizophrenia patients in Chinese Han population

BackgroundSchizophrenia is a complex psychiatric disorder with unknown etiology. A number of recent studies have shown that the polymorphism of the neural precursor cell expressed developmentally down-regulated 4 (NEDD4) gene is associated with a variety of neuropsychiatric disorders, such as schizophrenia, and may also be associated with cognitive dysfunction in these diseases.MethodsA case-control study was carried out, the alleles and genotypes distributions of five loci (rs3088077, rs2303579, rs7162435, rs11550869, rs62043855) of the NEDD4 gene from 296 schizophrenia patients and 320 healthy controls were detected by using Taqman single-nucleotide polymorphism (SNP) genotyping technology. The clinical data of case and control group members were collected by self-made questionnaire and the psychotic symptoms of case group members were assessed by the Positive and Negative Syndrome Scale (PANSS). The Matrics Consensus Cognitive Battery (MCCB) was used to test the cognitive function of case group members.ResultsThe alleles and genotypes frequency of two loci (rs3088077, rs2303579) between case and control group showed significant differences (P < 0.05). There was no significant difference in MCCB scores of patients with different genotypes at rs3088077, rs11550869 and rs7162435 loci in case group. The study of rs2303579 locus showed that, patients’ scores with CT genotype were significantly lower than those with CC and TT genotypes (P < 0.05) in the test of Wechsler Memory Scale-Third Edition (WMS-III): Spatial Span, the scores of patients with TT genotype were significantly higher than those with CT genotype (P < 0.05) in the test of Hopkins Verbal Learning Test-Revised (HVLT-R). The study of rs62043855 locus showed that patients with TG genotype had significantly lower scores than those with GG genotype (P < 0.05) in the test of Neuropsychological Assessment Battery (NAB): Mazes.ConclusionsOur study showed that in schizophrenia patients of Chinese Han population, the polymorphisms of rs3088077 and rs2303579 loci were related to the pathogenesis of schizophrenia, while the polymorphisms of rs2303579 and rs62043855 loci were associated with cognitive dysfunction.

Faulty Executive Attention and Memory Interactions in Schizophrenia: Prefrontal Gray Matter Volume and Neuropsychological Impairment.

We hypothesized that neuropsychological disturbance in schizophrenia (SZ) may reflect faulty interactions of executive attention and episodic memory, emanating, in part, from reduced prefrontal cortex (PFC) gray matter volume. Participants with SZ (n = 84) and age-matched (n = 77) controls completed both the Wisconsin Card Sorting Test (WCST) and the Wechsler Memory Scale-Third Edition (WMS-III), used, respectively, as measures of executive attention and episodic memory. A subset of SZ (n = 27) and control (n = 17) groups also had available 3-T magnetic resonance imaging (MRI) studies of the PFC. For SZ, but not control groups, neuropsychological results indicated that executive attention interacted significantly with episodic memory, with failures of executive attention, as reflected by increased WCST perseverative errors, directly linked to poor performance on the WMS-III measure of delayed visual recall of action scenes. MRI results indicated reduced left PFC gray matter volume for SZ group, which in turn correlated significantly with their deficits in visual memory but not in executive attention. Results showed that 61% of the variance in neuropsychological performance in the SZ group was attributed to gray matter volume of left inferior prefrontal gyrus gray matter volume. PFC-mediated failure of executive attention-episodic memory interactions may represent an important mechanism in neuropsychological disturbance in SZ.

The Effects of Radiation and Sex Differences on Adaptive Functioning in Adult Survivors of Pediatric Posterior Fossa Brain Tumors.

Radiation therapy (RT) improves rates of survival of patients with childhood brain tumors but increases deficits in cognition and independent living skills. Previous literature has studied difficulties in basic cognitive processes, but few explore impairment in higher-order skills such as adaptive functioning. Some studies identify females as at risk for cognitive deficits due to RT, but few investigate sex differences in adaptive functioning. It was hypothesized that females would exhibit poorer long-term independent living skills and core cognitive skills relative to males following RT. Forty-five adult survivors of posterior fossa childhood brain tumors (24 females) completed the Wechsler Abbreviated Scale of Intelligence (WASI-II), Wechsler Memory Scale, Third Edition (WMS-III) Digit Span Forward (DSF) and Backward (DSB), and Oral Symbol Digit Modalities Test (OSDMT). Informants completed the Scales of Independent Behavior-Revised (SIB-R). DSF and OSDMT were positively correlated with all five SIB-R domains, full-scale IQ (FSIQ) was positively correlated with four SIB-R domains, and DSB was positively correlated with three SIB-R domains. There was an interaction between sex and RT for OSDMT and community living skills with trend level interactions for personal living skills and broad independent living skills, where females without RT had higher scores than females with RT. Female survivors were more affected by RT than males across the community living skills domain of adaptive functioning as well as processing speed. Processing speed deficits may have a cascading impact on daily living skills. Future studies should investigate how clinical and biological factors may contribute to personalized treatment plans between sexes. (JINS, 2019, 25, 729-739).

Memory Impairment and Plasma BDNF Correlates of the BDNF Val66Met Polymorphism in Patients With Bipolar II Disorder

Studies suggest that a functional polymorphism of brain-derived neurotrophic factor (BDNF), polymorphism BDNF Val66Met affects cognitive functions, however, the effect is unclear in bipolar II (BD-II) disorder. We used the Wechsler Memory Scale-third edition (WMS-III), the presence of the BDNF Val66Met polymorphism, and plasma concentrations of BDNF to investigate the association between memory impairment and BDNF in BD-II disorder. We assessed the memory functions of 228 BD-II patients and 135 healthy controls (HCs). BD-II patients had significantly lower scores on five of the eight WMS-III subscales. In addition to education, the BDNF polymorphism were associated with the following subscales of WMS-III, auditory delayed memory, auditory delayed recognition memory and general memory scores in BD-II patients, but not in HC. Moreover, BD-II patients with the Val-homozygote scored significantly higher on the visual immediate memory subscale than did those with the Met/Met and Val/Met polymorphisms. The significantly positive effect of the Val-homozygote did not have a significantly positive effect on memory in the HC group, however. We found no significant association between BDNF polymorphisms and plasma concentrations of BDNF. The plasma BDNF was more likely to be associated with clinical characteristics than it was with memory indices in the BD-II group. The impaired memory function in BD-II patients might be dependent upon the association between the BDNF Val66Met polymorphism and peripheral BDNF levels.

Beyond depression: The impact of executive functioning on quality of life in patients with temporal lobe epilepsy

ObjectiveIndividuals with temporal lobe epilepsy (TLE) often experience diminished quality of life (QoL). Although comorbid depression is one of the most recognized predictors of poor QoL in TLE, impairments in verbal memory (VM) and executive functioning (EF), have also been identified as risk factors, independent of other biological and psychosocial factors. In this study, we examine the contribution of depression, VM, and EF to QoL in 52 well-characterized medically-refractory TLE patients. MethodsQuality of life was assessed with the Quality of Life in Epilepsy (QOLIE-31) questionnaire and depression symptomatology was evaluated with the Beck Depression Inventory-II (BDI-II). Tests of VM included the California Verbal Learning Test-Second Edition and the Wechsler Memory Scale-Third Edition, Logical Memory and Verbal Paired Associates subtests. Tests of EF included the D-KEFS Category Switching and Color Word Interference Tests, and the Trail Making Test. Using these measures, a principal component (PC) was derived for VM and for EF. Hierarchical multiple linear regression analysis was used to evaluate the unique contributions of BDI-II Score, VM PC, and EF PC to the QOLIE-31 Total Score, while controlling for important clinical and demographic variables. Post-hoc analyses were also performed to examine the contribution of each variable to specific QOLIE subscales. ResultsOf the clinical variables, only number of antiepileptic drugs contributed to QOLIE scores. As expected, severity of depressive symptoms was the most significant predictor of QOLIE Total Score, explaining 43.4% of the variance in total QoL. The VM PC did not contribute to the QOLIE Total Score. Rather, our EF PC emerged as an important predictor of QoL, explaining an additional 5% of the variance, after controlling for clinical variables, depression severity, and VM performance. SignificanceThese findings suggest that a combination of clinical, affective, and cognitive factors influence QoL in patients with TLE. Designing interventions with careful attention to depression and EF may be needed to optimize QoL in patients with refractory TLE and potentially other epilepsy syndromes.

Left Hippocampal Dosimetry Correlates With Visual and Verbal Memory Outcomes in Pediatric Brain Tumor Survivors

The late neurocognitive effects of radiation therapy in the pediatric brain tumor population are well known. Here, we specifically investigate outcomes of verbal and visual memory in a cohort treated with proton radiotherapy (RT), as well as potential clinical and regional dosimetric predictors of these outcomes. We hypothesize that increased RT dose to the hippocampi will amount to decline in memory scores. Seventy pediatric brain tumor patients (median age at RT = 12.1, range = 5.0–22.5) treated with proton RT between 2002 and 2013 were identified as having baseline and follow-up evaluations of visual and verbal memory (Children’s Memory Scale [CMS] and/or Wechsler Memory Scale-third edition [WMS-III]) conducted at our institution, as well as available dosimetry plans. Hippocampi, temporal lobes, and whole brain contours were manually delineated for calculation of multiple dosimetric indices using MimVista 6.6.5. Univariate analysis was performed to determine clinical predictors of score decline or improvement, and multivariate linear regression using dosimetric indices and other clinical covariates (age, gender, baseline score, presence or absence of baseline neurologic symptoms, and time elapsed since RT) allowed calculation of models to predict follow-up memory scores. The median neurocognitive follow-up time was 3.0 years (range = 1.1 – 11.4 years), and 140 cognitive assessments—70 baseline and 70 latest follow-up—were included in the analysis. On histogram analysis, Delayed Verbal memory scores showed a statistically significant decline in the overall cohort (P = 0.01), but Immediate Verbal memory and both measures of visual memory did not. On univariate analysis, higher baseline scores (P < 0.001) and female gender (P = 0.034) were significant predictors of Delayed Verbal memory score decline at follow-up. On multivariate analysis, increased left hippocampal dosimetry was correlated with decline in all four measures, with the individual dosimetric components (left hippocampal V20GyE) of the Immediate Verbal and Delayed Visual memory models being statistically significant (P = 0.027 and P = 0.016, respectively). Additionally, male gender predicted higher Delayed Verbal memory scores (P = 0.035). Of the four memory subtests evaluated here, only Delayed Verbal memory declined, while others were relatively stable between baseline and patients’ most recent follow-up assessments. Given a correlation of hippocampal dosimetry and memory outcomes after RT and a modest effect size of RT dose in these multivariate models, hippocampal-sparing RT plans may assist pediatric brain tumor patients in preserving memory functions.

Smaller hippocampal subfield volumes predict verbal associative memory in pediatric brain tumor survivors.

The developing hippocampus is highly sensitive to chemotherapy and cranial radiation treatments for pediatric cancers, yet little is known about the effects that cancer treatents have on specific hippocampal subfields. Here, we examined hippocampal subfield volumes in 29 pediatric brain tumor survivors treated with cranial radiation and chemotherapy, and 30 healthy developing children and adolescents. We also examined associations between hippocampal subfield volumes and short-term verbal memory. Hippocampal subfields (Cornus Ammonis (CA) 1, CA2-3, dentate gyrus (DG)-CA4, stratum radiatum-lacunosum-moleculare, and subiculum) were segmented using the Multiple Automatically Generated Templates for Different Brains automated segmentation algorithm. Neuropsychological assessment of short-term verbal associative memory was performed in a subset of brain tumor survivors (N = 11) and typically developing children (N = 16), using the Children's Memory Scale or Wechsler's Memory Scale-third edition. Repeated measures analysis of variance showed that pediatric brain tumor survivors had significantly smaller DG-CA4, CA1, CA2-3, and stratum radiatum-lacunosum-moleculare volumes compared with typically developing children. Verbal memory performance was positively related to DG-CA4, CA1, and stratum radiatum-lacunosum-moleculare volumes in pediatric brain tumor survivors. Unlike the brain tumor survivors, there were no associations between subfield volumes and memory in typically developing children and adolescents. These data suggest that specific subfields of the hippocampus may be vulnerable to brain cancer treatments, and may contribute to impaired episodic memory following brain cancer treatment in childhood.

Arbitrary and semantic associations insubjective memory impairment and amnestic mild cognitive impairment among Taiwanese individuals: A cross-sectional study.

Researchers have recently proposed a preclinical stage of dementia of Alzheimer's type (DAT), referred to as subjective memory impairment (SMI), with the aim of developing methods for the early detection of DAT and subsequent intervention. It has been proposed that the objective memory functions of individuals with SMI are normal; however, arbitrary and semantic associations are both used to describe the processes of memory. No previous studies have investigated these processes among individuals with SMI. Cross-sectional analysis was used to compare the memory function of individuals with SMI, amnestic mild cognitive impairment (aMCI), or DAT. One hundred and eighty-three participants were recruited from the Memory Clinic of National Taiwan University Hospital and communities in northern Taiwan, including individuals with no memory complaints (HC, n=30) and individuals with SMI (n=61), aMCI-single domain (n=24), aMCI-multiple domain (n=33), or DAT (n=35). The Word Sequence Learning Test (WSLT) was used to assess the formation of arbitrary associations and the Logical Memory subtest of the Wechsler Memory Scale-Third Edition was used to assess the formation of semantic associations. Compared to the HC group, the SMI group performed poorly only on the WSLT, whereas the other groups performed poorly on both of the memory tasks. This study demonstrated that SMI individuals tend to perform poorly in the formation of arbitrary associations. Our findings suggest that tasks requiring arbitrary associations may provide greater sensitivity in the detection cognitive changes associated with preclinical DAT.