Neuropsychological Test Battery Research Articles

European cross-cultural neuropsychological test battery (CNTB) for the assessment of cognitive impairment in multiple sclerosis: Cognitive phenotyping and classification supported by machine learning techniques

BackgroundThe European Cross-Cultural Neuropsychological Test Battery (CNTB) has been proposed as a comprehensive battery for cognitive assessment, reducing the potential impact of cultural variables. In this validation study, we aimed to evaluate the diagnostic capacity of CNTB for the assessment of participants with multiple sclerosis (pwMS) compared to the Neuronorma battery (NN) according to the International Classification of Cognitive Disorders in MS criteria, and to develop machine learning (ML) algorithms to improve the diagnostic capacity of CNTB and to select the most relevant tests. MethodsSixty pwMS and 60 healthy controls (HC) with no differences in sex, age, or years of education were enrolled. All participants completed the CNTB and pwMS were also examined with NN, depression, and fatigue scales. Impaired domains and cognitive phenotypes were defined following ICCoDiMS based on CNTB scores and compared to NN, according to -1SD and -1.5SD cutoff scores. To select the most relevant tests, random forest (RF) was performed for different binary classifications. ResultsPwMS showed a lower performance compared to HC with medium-large effect sizes, in episodic memory, executive function, attention, and processing speed, in accordance with their characteristic cognitive profile. There were no differences in impaired domains or cognitive phenotypes between CNTB and NN, highlighting the role of episodic memory, executive function, attention, and processing speed tests. The most relevant tests identified by RF were consistent with inter-group comparisons and allowed a better classification than SD cutoff scores. ConclusionCNTB is a valid test for cognitive diagnosis in pwMS, including key tests for the most frequently impaired cognitive domains in MS. The use of ML techniques may also be useful to improve diagnosis, especially in some tests with lower sensitivity.

Olfaction and thyroid hormones in patients with subjective cognitive decline, non-amnestic and amnestic mild cognitive impairment.

Thyroid hormones may affect olfaction in different stages of cognitive impairment: subjective cognitive decline (SCD), non-amnestic (naMCI) and amnestic mild cognitive impairment (aMCI). Additionally, biometric parameters, depression, and neuropsychological performance are considered as possible influencing factors. Aretrospective single-center data analysis was conducted during the observation period 2001-2023, with n = 495 (52.3% female) SCD, naMCI and aMCI subjects, aged ≥50years, at the General Hospital of Vienna. The criterion olfactory function was objectively measured by Sniffin' Sticks© odor identification and subjectively through the Assessment of Self-Reported Olfactory Functioning test. Serum thyroid hormone levels, mainly thyroid-stimulating hormone, as well as T3, T4, fT3, and fT4, were used to assess thyroid function. Statistical analyses using IBM SPSS® 29.0.0 covered adjusted multiple linear regression models with hierarchical blocks to predict olfactory performance considering β‑weights. Of the study participants, 4.2% had hypothyroidism and 2.4% had hyperthyroidism. The majority exhibited normal thyroid function. One third (33.5%; 95% confidence interval, CI 29.4-37.0%) were hyposmic. The results indicate no substantial association between thyroid and olfactory functions. Increasing age (β = 0.20), lower performance in the Neuropsychological Test Battery Vienna (NTBV) dimensions verbal memory (β = -0.33) and attention (β = -0.12) appear to be risk factors for lower olfaction. Adiscrepancy between subjective and objective olfaction was found. Thyroid and olfactory functions had no substantial relationship. Higher fT4 correlated weakly with lower odor identification. Increasing age and decreased performance in two out of six NTBV dimensions are relevant prognostic factors for olfactory dysfunction.

Cognitive frailty in older adults: examining the impact of frailty criteria on neuropsychological profile, functional outcomes, activity levels, and quality of life.

Cognitive frailty (CF) is the co-existence of cognitive impairment and physical frailty without dementia, conferring greater risks of adverse clinical outcomes compared to either condition alone. However, the impact of physical frailty components on cognitive performance remains unclear. This study aims to evaluate CF by determining the neuropsychological profiles, functional outcomes, activity levels, and quality of life across the Fried Frailty Phenotype (FFP) and its components. Cross-sectional study involving 120 community-dwelling older adults without dementia, but with subjective cognitive complaints (SCC, defined as AD8 ≥ 1). Participants were stratified into three groups to assess CF: SCC-Robust, SCC-Prefrail, and SCC-Frail, and further categorized by individual FFP components. Cognitive performance was assessed by comparing neuropsychological test battery (NTB) Z-scores between CF and non-CF groups with Cohen's d for effect sizes. We performed linear regression to examine the relationships between both groups with NTB scores, Instrumental Activities of Daily Living (IADL), Frenchay Activities Index (FAI), and quality of life scores. NTB scores showed no differences between individuals with CF when classified according to FFP criteria. Individuals with SCC-slow gait speed exhibited reduced processing speed (d = 0.62) and memory (d = 0.61); SCC-fatigue was associated with decreased working memory (d = 0.55). Regression analyses, adjusted for demographic and clinical variables, identified significant associations: slow gait speed with logical memory (-0.42; 95% CI -0.79 to -0.038]) and symbol search (-0.28; 95% CI -0.56 to -0.006]); fatigue with digit span backwards (-0.66; 95% CI -1.19 to -0.14) and color trails 2 (-0.67; 95% CI, -1.15 to -0.20). SCC-slow gait speed and SCC-fatigue were associated with reduced quality of life scores, but not with IADL and FAI scores. Specific frailty components, notably slow gait speed and fatigue, influence cognitive function and quality of life. Our findings provide greater insights into characterizing CF. Further longitudinal studies are required to determine the cognitive and functional trajectories of CF.

Repeated prefrontal tDCS for improving mental health and cognitive deficits in multiple sclerosis: a randomized, double-blind, parallel-group study

BackgroundMultiple Sclerosis (MS) is an autoimmune disease associated with physical disability, psychological impairment, and cognitive dysfunctions. Consequently, the disease burden is substantial, and treatment choices are limited. In this randomized, double-blind study, we conducted repeated prefrontal electrical stimulation in 40 patients with MS to evaluate mental health variables (quality of life, sleep difficulties, psychological distress) and cognitive dysfunctions (psychomotor speed, working memory, attention/vigilance), marking it as the third largest sample size tDCS research conducted in MS to date.MethodsThe patients were randomly assigned (block randomization method) to two groups of sham (n = 20), or 1.5-mA (n = 20) transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (F3) and right frontopolar cortex (Fp2) with anodal and cathodal stimulation respectively (electrode size: 25 cm2). The treatment included 10 sessions of 20 min of stimulation delivered every other day. Outcome measures were MS quality of life, sleep quality, psychological distress, and performance on a neuropsychological test battery dedicated to cognitive dysfunctions in MS (psychomotor speed, working memory, and attention). All outcome measures were evaluated at the pre-intervention and post-intervention assessments. Both patients and technicians delivering the stimulation were unaware of the type of stimulation being used.ResultsRepeated prefrontal real tDCS significantly improved quality of life and reduced sleep difficulties and psychological distress compared to the sham group. It, furthermore, improved psychomotor speed, attention, and vigilance compared to the sham protocol. Improvement in mental health outcome variables and cognitive outperformance were interrelated and could predict each other.ConclusionsRepeated prefrontal and frontopolar tDCS ameliorates secondary clinical symptoms related to mental health and results in beneficial cognitive effects in patients with MS. These results support applying prefrontal tDCS in larger trials for improving mental health and cognitive dysfunctions in MS.Trial registrationClinicalTrials.gov Identifier: NCT06401928.

B - 36 Investigating High-Definition Transcranial Direct Current Stimulation for Remediating Word Finding Difficulty in Civilians with a History of Chronic Traumatic Brain Injury: a Pilot Study

Abstract Objective Verbal-retrieval deficits often occur after traumatic brain injury (TBI), but no effective treatment is available. In this study, High-Definition Transcranial Direct Current Stimulation (HD-tDCS) was applied to examine its potential effects on cognitive, especially verbal-retrieval, performance in individuals with chronic TBI. Method Four adults (mean age 48 years; 3 females) with self-reported word-finding difficulty confirmed by objective measures following mild to moderate non-military TBIs sustained over a year ago underwent a double-blind, cross-over, randomized, sham-controlled trial. Each participant received 10 sessions of active HD-tDCS and sham stimulation over the superior medial frontal cortex. A battery of neuropsychological tests was administered including verbal-retrieval measures (i. e. letter fluency, category fluency, Boston Naming Test/BNT) at baseline, immediately, and 8 weeks post-treatment. Post-treatment performance was compared to baseline using 2-tailed paired t-tests. Results Improvements on letter fluency were observed between baseline and immediate assessments post active HD-tDCS, approaching statistical significance (p = 0.076, Cohen’s d = 0.957, 7.5 ± 5.7 more items). No immediate effects with sham HD-tDCS (p > 0.10, 1.5 ± 3.5 more items) and no sustained effects (8 weeks after) were found with either active or sham HD-tDCS (ps > 0.10). Additionally, no significant changes were observed for category fluency or BNT (all ps > 0.10). Conclusion While our pilot study suggests a potential benefit for improved letter fluency immediately following active HD-tDCS compared to sham, the lack of sustained improvement after 8 weeks and the observed variability across different tests acknowledges the need for future larger-scale investigation across multiple cognitive domains.

B - 137 Analyzing Completion Time on a Created Forced Choice Trial of the Hopkins Verbal Learning Test – Revised (HVLT-R) to Measure Engagement in a Mixed Clinical Sample

Abstract Objective We created a forced choice recognition trial (FCR) for the HVLT-R, including recording completion time (FCompT), to evaluate the utility of combining completion time with accuracy scores when using performance validity tests (PVTs). Method Participants included 29 clinically referred patients at a large medical center who completed the HVLT-R in addition to multiple free-standing and embedded PVTs including the TOMM, Word Choice Test (WCT), Reliable Digit Span (RDS), and the Dot Counting Test (DCT) as part of a larger battery of neuropsychological tests in an outpatient setting. Data from the sample (M age = 64.79, SD = 13.86; M education = 15.65, SD = 2.47; 62.1% females) were analyzed using correlation and linear regression. Results The HVLT-R FCR trial correlated with the TOMM-10, r(19) = 0.75, p = <0.001, TOMM trial 1, r(17) = 0.75, p = <0.01, the DCT r(12) = −0.71, p = <0.01, and the FCompT, r(29) = −0.72, p = <0.001. The FCompT was correlated with RDS, r(28) = −0.46, p = 0.03, TOMM-10, r(19) = −0.64, p = <0.01, and TOMM trial 1, r(17) = −0.61, p = <0.01. FCompT significantly predicted FCR accuracy b = −0.72, t(29) = −5.41, p < 0.001. Conclusions The HVLT-R FC and FCompT strongly correlated with free-standing and embedded PVTs. Data demonstrates that a longer completion time predicts poorer performance on FCR. Results demonstrate the value of measuring completion time for specific PVTs, in addition to providing support for the addition of a FCR trial to the HVLT-R.

B - 31 Factor Analysis of Neuropsychological Attention Measures with Mild Traumatic Brain Injury Patients

Abstract Objective Mild traumatic brain injury (mTBI) often leads to attentional deficits, yet the neuropsychological tests traditionally used may not adequately reflect the cognitive impairments these patients experience. This study aimed to critically evaluate the construct validity and factor structure of attention-related neuropsychological tests in mTBI patients to better understand and diagnose attentional deficits. Method The research utilized a battery of neuropsychological tests used to assess attention among a sample of 269 adults with mTBI including the NAB Numbers & Letters Test, PASAT, Trail Making Test, and WAIS Digit Span, Coding, and Arithmetic subtests. Exploratory factor analysis was employed to investigate the factor structure of the test battery and to test the hypothesis concerning the dimensionality of attention constructs. Results The analysis revealed that attentional measures did not converge on a single latent factor but instead reflected four distinct factors. These factors were identified as 1) Visual Attention/Psychomotor Speed, 2) Auditory Working Memory, 3) Visuospatial Scanning/Search, and 4) Disruption. Conclusions This exploratory factor analysis unveiled a distinction between auditory and visual attention mechanisms within this population. This separation suggests that attentional processes are not monolithic but rather encompass distinct auditory and visual domains and corroborates the existing literature, including Mirsky’s (1991) model of attention, which posits multiple components of attention, albeit with a focus on differentiating processes rather than sensory modalities. The study highlights the complexity of attentional impairments in mTBI and underscores the need for a nuanced approach to the neuropsychological assessment of attention among mTBI patients.

B - 110 Exploring the Relationship between Subjective Cognitive Complaints, Psychiatric Symptom Reporting, and Neurocognitive Test Performance in a Post-SARS-CoV-2 Clinical Sample

Abstract Objective This study evaluated the relationship between subjective cognitive complaints, objective cognitive performance, and psychological outcomes among clinical patients referred for persisting cognitive concerns following SARS-CoV-2 infection. Method The sample consisted of 49 patients (69.4% female; 38.8% Black, 36.7% White, 18.4% Hispanic, 6.0% Other; Mage = 45.27, SD = 12.08; Meducation = 15.49; SD = 3.0) referred for neuropsychological evaluation to assess for long-term post-SARS-CoV-2 cognitive changes. All patients were administered a uniform neuropsychological test battery that included measures of working memory, processing speed, and verbal learning/memory, as well as measures of anxiety, depression, and perceived stress. Degree of subjective cognitive concerns was established using the Neurobehavioral Symptom Inventory (NSI) cognitive subscale. Linear regression models were conducted between the NSI cognitive subscale and each cognitive and psychological outcome. Results NSI cognitive scale predicted all psychological (depression [F = 31.37, p < 0.001(R2 = 0.41)]; anxiety [F = 6.71, p = 0.01(R2 = 0.13); perceived stress [F = 4.40, p = 0.04(R2 = 0.10)]) variables. The NSI cognitive scale also significantly predicted working memory [F = 4.624, p = 0.04(R2 = 0.09)]; however, no individual scores fell below the low average range upon further analysis. Cognitive complaints did not significantly predict any other cognitive (processing speed [F = 0.002, p = 0.97(R2 = 0.00)], total learning [F = 0.14, p = 0.71(R2 = 0.00)], and delayed recall [F = 1.03, p = 0.32(R2 = 0.02)]) variable. Conclusions Subjective cognitive complaints significantly predicted self-reported psychological symptoms including depression, anxiety, and perceived stress, while working memory was the only cognitive performance with a similarly meaningful relationship. These preliminary findings suggest that the psychological effects of persistent symptoms following SARS-CoV-2 infection, rather than objective cognitive changes, may better explain subjective cognitive concerns reported by this population.

B - 96 Relationships between Self-Reported Cognitive Dysfunction, Functional Activities, and Intraindividual Cognitive Variability in Persons with Multiple Sclerosis (Pwms)

Abstract Objective To examine the relationships between intraindividual cognitive variability (IIV) and self-reported cognitive and functional difficulties in persons with multiple sclerosis (pwMS). We hypothesized higher perceived cognitive and functional difficulties would be associated with higher IIV. Method Participants (n = 35) were pwMS from a prospective memory intervention study. During the baseline evaluation, participants completed an objective neuropsychological test battery and a self-report measure of cognitive functioning (Perceived Deficits Questionnaire; PDQ Total). Participants were asked if they had problems in eight different functional areas due to their memory, with the number of endorsed problems summed. Two measures of IIV, an intraindividual standard deviation (ISD) score and maximum discrepancy score (MDS), were created from 11 indices. The relationship between the IIV and PDQ were assessed with individual linear regressions, controlling for demographics and disease-related characteristics, while Spearman correlations examined the associations with the number of reported functional memory problems. Results The PDQ was not significantly associated with either the ISD (b = −0.03, 95% CI: −0.15, 0.10, p = 0.672) or MDS (b = −0.01, 95% CI: −0.51, 0.32, p = 0.645). The overall number of functional memory problems was correlated with both the PDQ (ρ = 0.40, p = 0.018) and ISD (ρ = −0.35, p = 0.039), but not MSD (ρ = −0.22, p = 0.201). Conclusion(s) Perceived cognitive dysfunction was not associated with IIV. However, self-reported functional problems with memory were associated with perceived cognition, as well as one metric of IIV. ISD may better reflect moment to moment fluctuations that lead to difficulties with daily functioning, as opposed to MDS which may reflect underlying variation (e.g., base rates of impairment) in cognitive performance.

B - 111 Community Resource Access and Neuropsychological Outcomes in a Post-SARS-CoV-2 Clinical Sample

Abstract Objective Lower access to resources, income, education, and housing quality has been linked with poorer neuropsychological outcomes. This study evaluated the relationship between community resource access and several cognitive and psychological outcomes among clinical patients with persisting cognitive concerns following SARS-CoV-2 infection. Method The sample consisted of 49 patients (30.6% male; 35.3% White; Mage = 45.3, SD = 12.1; Meducation = 15.5, SD = 3.0) referred for neuropsychological evaluation to assess for long-term cognitive changes following SARS-CoV-2 infection. All patients were administered a uniform neuropsychological test battery that included measures of working memory, processing speed, and verbal learning/memory, as well as measures of depression, anxiety, and perceived stress. Area deprivation index (ADI) was determined using the national decile of the 2021 Neighborhood Atlas. Linear regression models were conducted between ADI and each cognitive and psychological outcome. Results No significant associations were identified between ADI and cognitive (working memory [F = 3.16, p = 0.08]; processing speed [F = 0.89, p = 0.32]; total learning [F = 0.41, p = 0.52]; delayed recall [F = 0.08, p = 0.78]) nor psychological (depressive symptoms [F = 0.09, p = 0.77]; anxiety symptoms [F = 0.05, p = 0.82]; perceived stress [F = 0.49, p = 0.49]) variables. Conclusions In this preliminary study, community access to resources did not significantly predict long-term cognitive or psychological symptoms following SARS-CoV-2 infection. This unexpected result suggests that neighborhood deprivation may be one particular social determinant of health that is less impactful for post-SARS-CoV-2 neuropsychological outcomes in similar populations. Generalizability is limited by sample characteristics (highly educated; uncomplicated disease course) and small sample size. Thus, replication in a larger database and further research involving other social determinants is indicated.

The association between physical activity and delayed neurocognitive recovery in elderly patients: a mediation analysis of pro-inflammatory cytokines

BackgroundDelayed neurocognitive recovery (dNCR) can result in unfavorable outcomes in elderly surgical patients. Physical activity (PA) has been shown to improve cognitive function, potentially by reducing systemic inflammatory responses. However, there is a lack of supportive data indicating whether PA has a protective effect against dNCR.AimsTo examine the correlation between dNCR and PA, and to further analyze if pro-inflammatory cytokines mediate this relationship.MethodsThis study is a prospective nested case-control investigation of elderly patients who had knee replacement surgery. dNCR was defined as a decline in cognitive function compared with baseline by using a battery of neuropsychological tests. PA was assessed with the Physical Activity Scale for the Elderly (PASE). Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentrations of IL-6, IL-1β, and TNF-α. Multivariable logistic regression analysis was conducted to assess the association between PA and dNCR. Mediation analysis was employed to evaluate whether pro-inflammatory cytokines mediate the relationship between them.ResultsA cohort of 152 patients was included, resulting in an incidence rate of dNCR of 23.68%. PA was associated with dNCR after full adjustment [OR = 0.199, (95% CI, 0.061; 0.649), P = 0.007]. Mediation analysis showed that the IL-6 mediated the statistical association between PA and dNCR, with mediation proportions (%) of 77.68 (postoperative concentration of IL-6) or 27.58 (the absolute change in IL-6 before and after surgery).ConclusionsPA serves as a protective factor against dNCR, possibly through the reduction of pro-inflammatory cytokine concentrations.The Chinese Clinical Trail Registry: www.http://chictr.org.cn, Registration No. ChiCTR2300070834, Registration date: April 24, 2023.

Early High-Dose Erythropoietin and Cognitive Functions of School-Aged Children Born Very Preterm

Children born very preterm are at risk for long-term neurodevelopmental sequelae. Prophylactic high-dose recombinant human erythropoietin (rhEpo) shortly after birth has not been shown to improve cognitive, motor, and behavioral development at 2 and 5 years. To investigate whether early high-dose rhEpo is associated with better executive functions and processing speed-late-maturing cognitive functions-in school-aged children born very preterm. This single-center cohort study was a prospective, observational follow-up study of a multicenter neonatal clinical trial; 365 children born very preterm (mean gestational age, 29.3 weeks [range, 26.0-31.9 weeks]) who had been enrolled in the Swiss EPO Neuroprotection Trial at birth between 2005 and 2012, and who were included in the primary outcome analyses at 2 years, were eligible to be recruited for the EpoKids study between 2017 and 2021 when they were at school age. Term-born children were additionally recruited and included in a control group. Data were analyzed between May and September 2022. Administration of rhEpo (3000 IU/kg) or placebo (saline, 0.9%) intravenously 3 times within the first 2 days of life as part of the Swiss EPO Neuroprotection Trial. A comprehensive neuropsychological test battery assessed executive functions and processing speed, and parents reported on their child's executive functions in everyday life to test the hypothesis that early high-dose rhEpo administration is associated with better cognitive outcomes at school age. In the EpoKids study, 214 children born very preterm (58.6% of 365 children in eligible cohort) were assessed at a mean age of 10.4 years (range, 6.9-13.4 years); 117 (54.7%) were boys. There was no evidence that the 117 children who had received rhEpo differed from the 97 children who had received placebo in any of the 15 executive function and processing speed tests, nor in parent-rated executive functions (estimates ranged from -0.138 to 0.084, all 95% CIs included 0). Irrespective of rhEpo or placebo allocation, children born very preterm scored lower on 11 of 15 executive function and processing speed tests than term-born peers (estimates ranged from 0.112 to 0.255, 95% CIs did not include 0). This study found no evidence for a positive association between prophylactic early high-dose rhEpo administration and long-term neurodevelopmental outcomes after very preterm birth. These results suggest that a comprehensive approach, including pharmacological and nonpharmacological prevention and intervention strategies, is needed to support these children's neurodevelopmental outcome.

Low Intake of Total Antioxidant Nutrients as a Risk Factor for Incident Dementia in Older Adults: The Shanghai Aging Study

Introduction: Previous longitudinal studies reported the impact of antioxidant nutrients (ANs) on cognitive impairment in the older population, but the conclusions were inconsistent. This study aimed to verify the hypothesis that dietary intake of total AN was associated with incident dementia among older individuals. Methods: Community residents without dementia aged ≥60 years were prospectively followed up for an average of 5.2 years in the Shanghai Aging Study. At baseline, daily intakes of total dietary AN (the sum of carotene, vitamin C, vitamin E, lutein, and flavonoids) and energy were calculated based on an interviewer-administered food frequency questionnaire measuring the dietary intake over the past 1 year for each participant. A battery of neuropsychological tests was used to evaluate cognitive function, and a consensus diagnosis of dementia was made according to the DSM-IV criteria at baseline and follow-up. Results: Among 1,550 dementia-free participants, 135 (8.7%) incident dementia cases were identified during the average of 5.2 years of follow-up. Participants with low AN intake (<112 mg/day) had a significantly higher risk of incident dementia than those with high AN intake (≥112 mg/day) (hazard ratio 1.87, 95% confidence interval 1.26–2.77) after adjusting for age, gender, education, obesity, APOE-ε4, hypertension, diabetes, depression, baseline Mini-Mental State Examination score, and total energy intake. The significant association of total AN intake with incident dementia was only found in individuals ≥70 years. Conclusion: Low total AN intake may be a risk factor for incident dementia among older adults. Maintaining sufficient AN intake may be beneficial against age-related cognitive decline.

Risk Factors for Postoperative Delirium Severity After Deep Brain Stimulation Surgery in Parkinson's Disease.

Postoperative delirium (POD) is a serious complication following deep brain stimulation (DBS) but only received little attention. Its main risk factors are higher age and preoperative cognitive deficits. These are also main risk factors for long-term cognitive decline after DBS in Parkinson's disease (PD). To identify risk factors for POD severity after DBS surgery in PD. 57 patients underwent DBS (21 female; age 60.2±8.2; disease duration 10.5±5.9 years). Preoperatively, general, PD- and surgery-specific predictors were recorded. Montreal Cognitive Assessment and the neuropsychological test battery CANTAB ConnectTM were used to test domain-specific cognition. Volumes of the cholinergic basal forebrain were calculated with voxel-based morphometry. POD severity was recorded with the delirium scales Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and Nursing Delirium Scale (NU-DESC). Spearman correlations were calculated for univariate analysis of predictors and POD severity and linear regression with elastic net regularization and leave-one-out cross-validation was performed to fit a multivariable model. 21 patients (36.8%) showed mainly mild courses of POD following DBS. Correlation between predicted and true POD severity was significant (spearman rho = 0.365, p = 0.001). Influential predictors were age (p < 0.001), deficits in attention and motor speed (p = 0.002), visual learning (p = 0.036) as well as working memory (p < 0.001), Nucleus basalis of Meynert volumes (p = 0.003) and burst suppression (p = 0.005). General but also PD- and surgery-specific factors were predictive of POD severity. These findings underline the multifaceted etiology of POD after DBS in PD. Valid predictive models must therefore consider general, PD- and surgery-specific factors.

Depressive symptoms-Not apredictor for five-year mortality in patients with subjective cognitive decline, non-amnestic and amnestic mild cognitive impairment.

The main aim of the present study is to evaluate the influence of depressive symptoms on mortality in patients with SCD (subjective cognitive decline), naMCI (non-amnestic mild cognitive impairment), and aMCI (amnestic mild cognitive impairment). Additional factors (age, sex, years of school attendance, and neuropsychological performance) were considered to determine the impact on survival probability. Amonocentric retrospective data analysis based on adjusted patient protocols (n = 1221) from the observation period 1998-2021, using the Cox Proportional Hazards model, assessed whether depressivity had an explanatory value for survival, considering SCD as the reference level in relation to naMCI and aMCI. Covariates were included blockwise. Cox regression revealed that depressiveness (Beck Depression Inventory, Geriatric Depression Scale) did not make asignificant contribution as arisk factor for mortality in all five model blocks, BDI-II with HR 0.997 [0.978; 1.02] and GDS-15 with HR 1.03 [0.98; 1.08]. Increasing age with HR 1.09 [1.07; 1.11] and male sex with HR (inverted) 1.53 [1.17; 2.00] appeared as risk factors for increased mortality across all five model blocks. aMCI (vs. SCD) with HR 1.91 [1.33; 2.76] showed asignificant explanatory value only up to the fourth model block. By adding the six dimensions of the Neuropsychological Test Battery Vienna in the fifth model block, the domains attention and perceptual speed with HR 1.34 [1.18; 1.53], and executive functions with HR 1.24 [1.11; 1.39], showed substantial explanatory values for survival. Accordingly, no tendency can be attributed to depressiveness as arisk factor on the probability of survival, whereas the influence of certain cognitive dimensions, especially attention and perceptual speed, and executive functions, can be seen as protective for survival.

Neuropsychological performance in women at risk of postpartum depression and postpartum psychosis.

While neuropsychological deficits are commonly observed in affective and psychotic disorders, this remains unexplored in these disorders when they occur during pregnancy and the postpartum period. A neuropsychological test battery was administered to women defined at risk of postpartum depression (PD, N = 53) because having either a current or past diagnosis of major depressive disorder, women at risk of postpartum psychosis (PP, N = 43) because of a diagnosis of bipolar disorder or schizoaffective disorder and/or a previous episode of PP and women not at risk (NR, N = 48) in the third trimester of pregnancy. Generalized and specific cognitive abilities were compared between groups. Women at risk of PP presented worse executive functions and processing speed compared to NR and worse performance compared to women at risk of PD across all cognitive domains. In addition, women at risk of PP who developed a psychiatric relapse in the first four weeks post-partum showed worse verbal learning and memory, visual memory, executive functions and processing speed in pregnancy compared to NR, whereas women at risk of PP who remained well presented neuropsychological performance that was intermediate between that of the women NR and those at risk of PP who developed symptoms. There were no differences in performance between women at risk of PD and the NR women, even if 31 women at risk of PD presented depressive symptoms at the time of cognitive assessment. Our findings in women at risk of PP align with neuropsychological findings in individuals with, or at risk of psychosis unrelated to pregnancy. In addition, initial evidence that women at risk of PP who develop a psychiatric relapse in the postpartum show a particularly poor neuropsychological performance in pregnancy suggests that this could be considered part of a phenotype for the disease and help guiding future preventive strategies in this clinical population. In women at risk of PD, the presence of depressive symptoms did not influence cognitive performance.

Forget me not: The effect of doxycycline on human declarative memory

Investigations into neuroprotective drugs are in high demand for the treatment of neurodegenerative diseases, such as multiple sclerosis or Alzheimer's disease, but also psychiatric disorders, such as depression, trauma, and substance use. One potential drug class being investigated are tetracyclines impacting on a variety of neuroprotective mechanisms. At the same time, tetracyclines like doxycycline have been suggested to affect human fear and spatial memory as well as reducing declarative memory retention. Based on the assumed necessity for synaptic consolidation in hippocampus-dependent learning, we hypothesised declarative memory may be similarly impaired by doxycycline as fear and spatial memory. Therefore, in this study we investigate the potential diminishing effects of doxycycline on consolidation of declarative memory in healthy humans. Additionally, to test for effect specificity we assessed motor memory, sustained attention, and processing speed. We administered a neuropsychological test battery in three independent randomized placebo-controlled double-blind trials (RCTs), in which healthy young volunteers (total N = 252) either received a single oral dose doxycycline (200 mg, n = 126) or placebo (n = 126) in a between-subject design. We found no evidence for a detrimental effect of doxycycline on declarative memory; instead, doxycycline improved declarative learning (p-value=0.022, Cohen's d=0.15) and memory consolidation (p=0.040, d=0.26). Contrarily, doxycycline slightly reduced motor learning (p=0.001, d=0.10) but subtly strengthened long-term motor memory (p=0.001, d=0.10). These results suggest that doxycycline can improve declarative learning and memory without having long term negative effects on other cognitive domains in healthy humans. Our results give hope to further investigate doxycycline in neuroprotective treatment applications.

Toxoplasma gondii IgG serointensity and cognitive function in bipolar disorder

BackgroundAlongside affective episodes, cognitive dysfunction is a core symptom of bipolar disorder. The intracellular parasite T. gondii has been positively associated with both, the diagnosis of bipolar disorder and poorer cognitive performance, across diagnostic boundaries. This study aims to investigate the association between T. gondii seropositivity, serointensity, and cognitive function in an euthymic sample of bipolar disorder.MethodsA total of 76 participants with bipolar disorder in remission were tested for T. gondii-specific IgG and IgM antibodies and for cognitive performance using neuropsychological test battery. Cognitive parameters were categorized into three cognitive domains (attention and processing speed, verbal memory, and executive function). Statistical analysis of associations between continuous indicators of cognitive function as dependent variables in relationship to T. gondii, included multivariate analyses of co-variance for seropositivity, and partial correlations with IgG serointensity in IgG seropositives. All analyses were controlled for age and premorbid IQ.ResultsIn seropositives (n = 27), verbal memory showed significant inverse partial correlations with IgG antibody levels (short delay free recall (r=–0.539, p = 0.005), long delay free recall (r=–0.423, p = 0.035), and immediate recall sum trial 1–5 (r=–0.399, p = 0.048)). Cognitive function did not differ between IgG seropositive and seronegative individuals in any of the cognitive domains (F (3,70) = 0.327, p = 0.806, n = 76). IgM positives (n = 7) were too few to be analyzed.ConclusionsThis investigation is the first to show an association between T. gondii IgG serointensity and memory function in a well-diagnosed bipolar disorder sample. It adds to the existing literature on associations between latent T. gondii infection and cognition in bipolar disorder, while further research is needed to confirm and expand our findings, eliminate potential sources of bias, and establish cause-effect relationships.

Can volumetric magnetic resonance imaging evaluations be helpful in the follow-up of cognitive functions in cognitively normal Parkinson's disease patients?

In this study, besides the evaluation of gray and white matter changes in cognitively normal Parkinson's disease (PD-CN) patients with volumetric magnetic resonance imaging (MRI) parameters, it was tried to show that some neuropsychological tests may be impaired in PD-CN patients. Twenty-six PD-CN patients and 26 healthy elderly (HC) participants were included in the current study. Global cognitive status was assessed using the mini-mental state examination (MMSE), and the Montreal cognitive assessment scale (MoCA). Attention and executive functions were evaluated using the Wechsler memory scale-revised (WMS-R) digit span test and trail making test (TMT) part A and part B, the Stroop test, semantic and phonemic fluency tests, and clock drawing test. Magnetic resonance imaging (MRI) was acquired according to the Alzheimer's disease neuroimaging initiative (ADNI) protocol. There were no significant differences among groups regarding age, sex, handedness, and years of education. In the comparison of the PD-CN group and the HC group, there was a statistical decrease in the total animal scores, lexical fluency, TMT part A and TMT part B scores in the PD-CN group. Subcortical gray matter volumes (GMV) were significantly lower in PD-CN patients. The PD-CN group had a significantly reduced total volume of right putamen and left angular gyrus compared to that in the HC group. We observed that putamen and angular gyrus volumes were lower in PD-CN patients. On the other hand, TMT part B may be a useful pretest in detecting the conversion of mild cognitive impairment in PD. Significant MRI volumetric measurements and neuropsychological test batteries can be helpful in the clinical follow-up in PD-CN patients.

The Common Marmoset as a Translational Model for Longitudinal Studies of Cognitive Aging and Individual Vulnerability to Decline.

In humans, cognitive aging is highly variable, with some individuals experiencing decline while others remain stable, and different cognitive domains exhibiting uneven vulnerability to aging. The neural mechanisms driving this intra- and inter-individual variability are not fully understood, making longitudinal studies in translational models essential for elucidating the timelines and processes involved. The common marmoset (Callithrix jacchus), a short-lived nonhuman primate, offers an unprecedented opportunity to conduct longitudinal investigations of aging and age-related disease over a condensed time frame, in a highly translatable animal model. The potential of the marmoset as a model for cognitive aging is indisputable, but a comprehensive cognitive battery tailored for longitudinal aging studies has not yet been developed, applied, or validated. This represents a critical missing piece for evaluating the marmoset as a model and understanding the extent to which marmoset cognitive aging mirrors the patterns found in humans, including whether marmosets have individual variability in their vulnerability to age-related cognitive decline. To address this, we developed a comprehensive touchscreen-based neuropsychological test battery for marmosets (MarmoCog), targeting five cognitive domains: working memory, stimulus-reward association learning, cognitive flexibility, motor speed, and motivation. We tested a large cohort of marmosets, ranging from young adults to geriatrics, over several years. We found significant variability in cognitive aging, with the greatest decline occurring in domains dependent on the prefrontal cortex and hippocampus. Additionally, we observed significant inter-individual variability in vulnerability to age-related cognitive decline: some marmosets declined across multiple domains, others in just one, and some showed no decline at all. This pattern mirrors human cognitive aging, solidifies the marmoset as an advantageous model for age-related cognitive decline, and provides a strong foundation for identifying the neural mechanisms involved.