Measures Of Neuropsychological Functioning Research Articles

Cancer-related cognitive impairment and wellbeing in patients with newly diagnosed aggressive lymphoma compared to population norms and healthy controls: an exploratory study

PurposeThere has been little dedicated research on cancer-related cognitive impairment in patients with aggressive lymphoma. We describe and compare patients’ cognitive function with that of healthy controls and patients’ wellbeing and distress with general population values. We also explore associations between patients’ neuropsychological test performance and self-reported cognitive function and distress.MethodsSecondary analysis of data from a feasibility study of 30 patients with newly diagnosed aggressive lymphoma and 72 healthy controls. Patients completed neuropsychological tests and self-report measures before and 6–8 weeks after chemotherapy. Healthy controls completed neuropsychological tests and the FACT-Cog at enrolment and 6 months later. Mixed models were used to analyze neuropsychological test and FACT-Cog scores. One-sample t-tests were used to compare patients’ self-reported wellbeing and distress with population norms. Associations were explored with Kendall’s Tau b.ResultsPatients and healthy controls were well matched on socio-demographics. Differences between neuropsychological test scores were mostly large-sized; on average, patients’ scores on measures of information processing speed, executive function, and learning and memory were worse both before and after chemotherapy (all p ≤ 0.003). The same pattern was observed for impact of perceived cognitive impairment on quality-of-life (both p < 0.001). Patients’ physical and emotional wellbeing scores were lower than population norms both before and after chemotherapy (all p ≤ 0.018). Associations between neuropsychological performance and other measures were mostly trivial (all p > 0.10).ConclusionFor many patients with aggressive lymphoma, impaired neuropsychological test performance and impact of perceived impairments on quality-of-life precede chemotherapy and are sustained after chemotherapy. Findings support the need for large-scale longitudinal studies with this population to better understand targets for interventions to address cognitive impairments.

The impact of suppressing puberty on neuropsychological function: A review.

Concerns have been raised regarding the impact of medications that interrupt puberty, given the magnitude and complexity of changes that occur in brain function and structure during this sensitive window of neurodevelopment. This review examines the literature on the impact of pubertal suppression on cognitive and behavioural function in animals and humans. All studies reporting cognitive impacts of treatment with GnRH agonists/antagonists for pubertal suppression in animals or humans were sought via a systematic search strategy across the PubMed, Embase, Web of Science and PsycINFO databases. Sixteen studies were identified. In mammals, the neuropsychological impacts of puberty blockers are complex and often sex specific (n = 11 studies). There is no evidence that cognitive effects are fully reversible following discontinuation of treatment. No human studies have systematically explored the impact of these treatments on neuropsychological function with an adequate baseline and follow-up. There is some evidence of a detrimental impact of pubertal suppression on IQ in children. Critical questions remain unanswered regarding the nature, extent and permanence of any arrested development of cognitive function associated with puberty blockers. The impact of puberal suppression on measures of neuropsychological function is an urgent research priority.

59 Investigating the Relationship Between Neuropsychological Test Performance and Electrophysiological Measures of Semantic Functioning in Alzheimer's Disease.

Objective:Improving the timeline for intervention in Alzheimer's disease (AD) has considerable potential to delay and mitigate disability and suffering. Neuropsychological assessment is useful for distinguishing AD from normal aging and other dementias but is less useful in preclinical detection due to its limited sensitivity. The N400 (N4), a language-based EEG event-related potential (ERP) related to semantic functioning, is a promising candidate marker of AD with potential to improve early detection and monitoring of AD. For example, studies have shown that individuals with AD show a reduced N4 "effect"—a smaller difference in the size of the N4 to semantically congruent vs. incongruent word-pairs. The goal of this study is to assess the presence of the N4 effect in healthy seniors, and those with amnestic mild cognitive impairment (MCI) or mild AD, and to evaluate associations between performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the N4 across these samples.Participants and Methods:Fifty older adults (intact=27, combined MCI/mild AD group=23; "impaired") completed neuropsychological testing, including the RBANS, as part of a larger study. Participants were re-contacted and returned for EEG assessment between several weeks to one year later. During EEG recording, participants completed a word-pair judgement paradigm, which involved distinguishing between semantically congruent and incongruent word-pairs. Data was collected and analyzed according to customized N4 analysis scripts provided as part of ERPCORE, an online resource for acquiring and analyzing common ERP components (Kappenman et al., 2021; https://osf.io/thsqg/). The change in N4 amplitude between congruent and incongruent trials (the N4 effect) was used as an index of participants' semantic functioning. Participants' N4 effect was quantified using the mean amplitude from 300-550 milliseconds poststimulus at electrode Cz.Results:Repeated measures ANOVAs indicated a significant effect of trial type on the N400 amplitude in the intact individuals (F(1, 26)=77.66, p&lt;.001), which remained significant in the sample as a whole (F(1, 48)=65.18, p&lt;.001). Although intact participants numerically showed a larger N4 effect (intact: M=-4.02, SD=2.37; impaired: M=-2.60, SD=3.40), the expected group-by-trial interaction was not significant (F(1, 48)=3.01, p=.089). Correlational analyses revealed no significant associations between the N4 effect and the RBANS Total Scale scores (r=-.14, p=.32), nor for the Immediate Memory (r=-.002, p=.99), Visuospatial/Constructional (r=-.069, p=.63), Language (r=-.15, p=.30) Attention (r=-.21, p=.14), or Delayed Memory (r=-.18 p=.58) indexes.Conclusions:Results confirmed the presence of the N4 effect in intact participants and in the sample as a whole. Although the N4 effect was numerically smaller in the impaired group as expected, this difference was not significant in the present sample. Likewise, we observed no evidence for associations between the size of N4 effect and performance on RBANS indexes. Overall, the present study provides mixed evidence for the utility of the N4 as a biomarker in mild AD. Factors that may have contributed to the lack of associations between the N4 effect and the RBANS include the limited sample size and variable lengths of time between participants' initial cognitive assessments and EEG testing.

Cognitive correlates of reduced driving performance in healthy older adults: A meta-analytic review

Aims / ObjectivesThis meta-analytic review examines the evidence for the relationship between cognitive function and driving performance in older adults. The primary aims of this review were: (a) to identify cognitive correlates of reduced driving performance in older adults and (b) to determine whether such measures reliably predict reductions in driving performance over time. MethodsThis review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Peer reviewed studies that examined the (cross-sectional or longitudinal) relationship between standardised neuropsychological test performance measures and driving performance (e.g., via an on-road test, in-vehicle monitoring system, hazard perception test or driving simulator) in healthy adults aged 60 years and older, were included. Results/DiscussionEighteen studies were eligible for inclusion, of which 12 met requirements for meta-analysis. The results indicated that reaction time and Trail Making Test (TMT) A scores exhibited small-to-moderate correlations with driving performance, with moderate effects identified for block design, TMT B, Useful Field of View (UFOV) 2 and 3 tests. Further, no significant relationships were observed between the Mini-Mental State Examination and UFOV 1 with driving performance. Due to a paucity of data, the longitudinal relationship between such measures and driving could not be identified. The findings highlight (a) the potential of cognitive assessments to identify older adults at risk of driving impairment (as part of a larger diagnostic assessment), and (b) the urgent need for prospective longitudinal studies in investigating the impact of age-related changes in cognition on driving performance over time.

Subjective cognitive complaints are important in PD-MCI criteria: Associations with CSF markers and cognitive decline

IntroductionAccording to the Movement Disorder Society (MDS), subjective cognitive complaints (SCC) are a diagnostic criterion for PD-mild cognitive impairment (PD-MCI); however, studies often do not incorporate SCC when classifying PD-MCI. This inconsistent use may reflect mixed findings regarding the association between SCC and objective measures of cognitive impairment. Our study aimed to describe the extent that inclusion/exclusion of SCC affects the occurrence of PD-MCI, and if the inclusion of SCC is associated with faster cognitive decline and cerebrospinal fluid markers (CSF) of alpha-synuclein, amyloid beta, total tau, and phophorylated-tau. MethodsIndividuals with PD (N = 358) from the PPMI cohort whom completed measures of neuropsychological performance, subjective cognitive complaints, motor severity, and CSF markers were included. Participants were classified as cognitively normal (CN), PD-MCI with subjective cognitive complaints (PD-MCI + SCC) and PD-MCI without subjective cognitive complaints (PD-MCI –SCC). ResultsPD-MCI rates were consistently higher (16.5–19.1%) across the 5 years when SCC was not included in the diagnostic criteria as opposed to when SCC was included (4.4–11.0%). PD-MCI + SCC experienced greater cognitive decline and had significantly higher levels of tau/ab and p-tau/ab relative to both the CN and PD-MCI - SCC groups. ConclusionsInconsistent implementation of an SCC requirement in PD-MCI classifications may have important implications in terms of the occurrence of PD-MCI and its prognostic value. Classifying PD-MCI only using neuropsychological cut-off criterion, without regard to SCC, may lead to higher rates of PD-MCI. Inclusions of SCC in PD-MCI criteria in newly diagnosed PD participants may strengthen the ability to detect individuals at risk for future cognitive decline, though it is possible that this decline is related to Alzheimer's disease changes rather than worse PD pathology.

Neuropsychological Profile of Traumatic Brain Injury Patients with Medicolegal Cases: A Pilot Study

Abstract Introduction Traumatic brain injury (TBI) is a global health problem and is a silent epidemic of the modern times. Studies indicate litigation is a prominent factor that accounts for poor outcome and prolonged recovery from mild TBI. Depression is the most frequently diagnosed psychiatric disorder after TBI. Postconcussion symptoms, litigation, and suboptimal effort could contribute to the neuropsychological functioning of TBI patients medicolegal cases (MLCs). With increase in TBI and medicolegal cases, there is a requirement for comprehensive neuropsychological assessment. Method The aim of the study was to evaluate the cognitive functions, postconcussion, and depressive symptoms in TBI patients with MLC and without MLCs (non-MLC). Patients were also assessed on electrophysiological parameters. An observational cross-sectional design was adopted, the sample size was 30 TBI patients in total, 15 (MLC) and 15 (non-MLC), and 11 patients from each group for electrophysiological assessment. The patients were in the age range of 18 to 50 years. Results The MLC group had poor performance compared with the non-MLC group on both neuropsychological and electrophysiological measures. There was evidence of significant difference in verbal working memory, verbal learning, and memory and visuoconstructive ability. In the MLC group, postconcussion and depressive scores were negatively correlated with visuospatial span. Conclusion Findings from this study indicate differences in the neuropsychological performance and electroencephalographic measures in between MLC and non-MLC groups. The results could be indicative of persistent cognitive problems associated with TBI for patients pursuing litigation. Poor performance could also be attributed to suboptimal level of effort. However, being a preliminary study with a small sample size, the findings need to be treated with caution.

P300 Modulation via Transcranial Alternating Current Stimulation in Adult Attention-Deficit/Hyperactivity Disorder: A Crossover Study.

ObjectiveA repeated finding regarding event-related potentials (ERPs) is that patients with ADHD show a reduced P300 amplitude. This raises the question of whether the attention of ADHD patients can be increased by stabilizing the P300. Assuming that the P300 is generated by event-related oscillations (EROs) in the low frequency range (0–8 Hz), one approach to increase the P300 could be to stimulate the patient’s P300 underlying ERO by means of transcranial alternating current stimulation (tACS). The aim of this follow-up study was to investigate this hypothesized mechanism of action in adult ADHD patients.Materials and MethodsUndergoing a crossover design, 20 adult ADHD patients (10 female) received an actual stimulation via tACS on one day and a sham stimulation on another day. Before and after each intervention, EEG characteristics (P300 amplitudes, low frequency power) and attention performances (d2 attention test, visual oddball task (VOT)) were recorded.ResultsElectrophysiological analyses revealed no evidence for an enhanced P300 amplitude or low frequency power increase after actual stimulation compared to sham stimulation. Instead, a significant effect was found for a stronger N700 amplitude increase after actual stimulation compared to sham stimulation. Consistent with the P300 null results, none of the examined neuropsychological performance measures indicated a tACS-induced improvement in attentional ability.ConclusionContrary to a previous study using tACS to modulate the P300 in adult ADHD patients, the current study yields no evidence that tACS can increase the P300 amplitude in adult ADHD patients and that such P300 enhancement can directly improve neuropsychological parameters of attention.

Poor Response Inhibition and Symptoms of Inattentiveness Are Core Characteristics of Lifetime Illicit Substance Use among Young Adults in the General Norwegian Population: The HUNT Study

Background Impairments in neurocognitive functioning are associated with substance use behavior. Previous studies in neurocognitive predictors of substance use typically use self-report measures rather than neuropsychological performance measures and suffer from low sample sizes and use of clinical diagnostic cut offs. Methods Crossectional data from the HUNT4 Study (Helseundersøkelsen i Trøndelag) was used to study executive neuropsychological performance and self-reported measures of neurocognitive function associated with a history of illicit substance use in a general population sample of young adults in Norway. We performed both between group comparisons and logistic regression modeling and controlled for mental health symptomatology. Results Subjects in our cohort with a self-reported use of illicit substances had significantly higher self-reported mental health and neurocognitive symptom load. A logistic regression model with substance use as response included sex, commission errors and self-reported inattentiveness and anxiety as significant predictors. After 10-fold cross-validation this model achieved a moderate area under the receiver-operator curve of 0.64. To handle the class imbalance typically found in such population data, we also calculated balanced accuracy with a optimal model cut off of 0.234 with a sensitivity of 0.50 and specificity of 0.76 as well as precision recall—area under the curve of 0.28. Conclusions Subtle cognitive dysfunction differentiates subjects with and without a history of illicit substance use. Neurocognitive factors outperformed the effects of depressive symptoms on substance use behavior in this cohort. We highlight the need for using adequate statistical tools for evaluating the performance of models in unbalanced datasets.

Age-based stereotype threat and neuropsychological performance in older adults

ABSTRACT The current study investigated the effects of age-based stereotype threat on neuropsychological assessment outcomes in an older adult population. Community volunteers (n = 49) age 65 and older were screened for cognitive impairment, depression, and anticholinergic medication use. Screened individuals were randomly stratified into either an ABST or a Control group. All participants were administered a broad range of neuropsychological measures of cognition as well as a self-rating measure assessing subjective concern about cognitive ability. A main effect of ABST on subjective concern about cognitive ability was supported. Specifically, individuals in the ABST group were significantly more likely to attribute their memory errors to the onset of dementia (F(1,41) = 5.334, p = .026). However, results showed no significant difference between groups on objective neuropsychological performance measures. The current study discusses the importance of considering ABST effects in the context of neuropsychological assessment in older adult populations.

Modifiable predictors of self-reported and performance-based functioning in individuals with schizophrenia-spectrum disorders and high levels of negative symptoms

Individuals with schizophrenia who have high negative symptoms are at high risk for poor functional outcomes. However, the determinants of psychosocial functioning in this group are not well understood. We aimed to examine modifiable predictors of both objective, performance-based functional capacity and social skills, and self-reported functioning in individuals with schizophrenia and schizoaffective disorder and high negative symptoms. Fifty-five adults with moderate-to-severe negative symptoms were administered measures of neuropsychological performance, performance-based functional capacity and social competence, self-reported functioning, psychiatric symptom severity, defeatist/asocial beliefs, and intrinsic motivation. In the context of multiple significant predictor variables identified through bivariate correlations, multiple regression models showed that neuropsychological performance was the only significant predictor of performance-based functional capacity; neuropsychological performance and motivation/pleasure negative symptoms were significant predictors of performance-based social competence. For two different measures of self-reported functioning, intrinsic motivation, asocial beliefs, and diminished expression emerged as significant predictors. Neurocognitive ability was a better predictor of performance-based functional skills whereas motivation and beliefs more strongly predicted self-reported real-world functioning. The findings of this study suggest a complex picture of predictors of performance-based functional capacity (objective neuropsychological functioning) and self-reported functioning (motivation and beliefs), underscoring the clinical and scientific utility of including both self-reported and objective measures of functioning to identify treatment approach. Individuals with high negative symptoms and a cognitive/functional skills deficit may benefit from interventions such as cognitive remediation or skills training, whereas individuals with motivational difficulties may benefit from treatments such as cognitive behavioral therapy.

Differentiating Individuals with and without Alcohol Use Disorder Using Resting-State fMRI Functional Connectivity of Reward Network, Neuropsychological Performance, and Impulsivity Measures.

Individuals with alcohol use disorder (AUD) may manifest an array of neural and behavioral abnormalities, including altered brain networks, impaired neurocognitive functioning, and heightened impulsivity. Using multidomain measures, the current study aimed to identify specific features that can differentiate individuals with AUD from healthy controls (CTL), utilizing a random forests (RF) classification model. Features included fMRI-based resting-state functional connectivity (rsFC) across the reward network, neuropsychological task performance, and behavioral impulsivity scores, collected from thirty abstinent adult males with prior history of AUD and thirty CTL individuals without a history of AUD. It was found that the RF model achieved a classification accuracy of 86.67% (AUC = 93%) and identified key features of FC and impulsivity that significantly contributed to classifying AUD from CTL individuals. Impulsivity scores were the topmost predictors, followed by twelve rsFC features involving seventeen key reward regions in the brain, such as the ventral tegmental area, nucleus accumbens, anterior insula, anterior cingulate cortex, and other cortical and subcortical structures. Individuals with AUD manifested significant differences in impulsivity and alterations in functional connectivity relative to controls. Specifically, AUD showed heightened impulsivity and hypoconnectivity in nine connections across 13 regions and hyperconnectivity in three connections involving six regions. Relative to controls, visuo-spatial short-term working memory was also found to be impaired in AUD. In conclusion, specific multidomain features of brain connectivity, impulsivity, and neuropsychological performance can be used in a machine learning framework to effectively classify AUD individuals from healthy controls.

Genome-Wide Association Study of Alzheimer's Disease Brain Imaging Biomarkers and Neuropsychological Phenotypes in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Dataset.

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, aging populations. AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. Most of these GWAS used dichotomized clinical diagnostic status, i.e., case vs. control classification, as outcome phenotypes, without the use of biomarkers. An alternative and potentially more powerful study design is afforded by using quantitative AD-related phenotypes as GWAS outcome traits, an analysis paradigm that we followed in this work. Specifically, we utilized genotype and phenotype data from n = 931 individuals collected under the auspices of the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study to perform a total of 19 separate GWAS analyses. As outcomes we used five magnetic resonance imaging (MRI) traits and seven cognitive performance traits. For the latter, longitudinal data from at least two timepoints were available in addition to cross-sectional assessments at baseline. Our GWAS analyses revealed several genome-wide significant associations for the neuropsychological performance measures, in particular those assayed longitudinally. Among the most noteworthy signals were associations in or near EHBP1 (EH domain binding protein 1; on chromosome 2p15) and CEP112 (centrosomal protein 112; 17q24.1) with delayed recall as well as SMOC2 (SPARC related modular calcium binding 2; 6p27) with immediate recall in a memory performance test. On the X chromosome, which is often excluded in other GWAS, we identified a genome-wide significant signal near IL1RAPL1 (interleukin 1 receptor accessory protein like 1; Xp21.3). While polygenic score (PGS) analyses showed the expected strong associations with SNPs highlighted in relevant previous GWAS on hippocampal volume and cognitive function, they did not show noteworthy associations with recent AD risk GWAS findings. In summary, our study highlights the power of using quantitative endophenotypes as outcome traits in AD-related GWAS analyses and nominates several new loci not previously implicated in cognitive decline.

Rationale for an anti‐inflammatory insulin sensitizer in a phase 3 Alzheimer's disease trial

AbstractBackgroundNE3107 (3α‐ethynyl‐androst‐5‐ene‐3β,7β,17β‐triol), shows safety, antiinflammatory and insulin‐sensitizing activities in vitro, in animals, and humans. NE3107 binds ERK1/2 and inhibits inflammatory, but not homeostatic NFkB/ERK signaling in vitro, in animals and in humans. NE3107 is blood‐brain permeable, and does not affect neurotransmitter receptors. NE3107 inhibits TNFα‐stimulated NFκB transcription in human macrophages. It also inhibits NFκB nuclear translocation and LPS‐stimulated inflammatory signal transduction. NE3107 prevented IκBα proteolysis in murine macrophages. NE3107 decreased EAE optic nerve microglia, and increased nuclear NFκB in collicular and retinal neurons (homeostatic), but decreased optic nerve head glial nuclear NFκB (inflammatory) in a glaucoma model. NE3107 preserved dopaminergic neurons in MPTP‐treated mice and marmosets. In obese impaired glucose tolerance (IGT) humans, NE3107 decreased CRP, which is involved in AD inflammation and tissue damage, and increased antiinflammatory HDL, which decreases risk of AD pathogenesis. NE3107 increased adiponectin, which suppresses insulin resistance, inflammation, and AD pathology. In obese, inflamed IGT and type 2 diabetes (T2D) subjects, NE3107 decreased insulin resistance, which drives neurodegeneration and AD. Importantly, in obese inflamed T2D subjects, NE3107 decreased inflammation‐driven systems deregulation, known to contribute to AD progression.MethodSafety and activity data from preclinical, toxicology, human clinical trials, and a protocol synopsis for a pivotal trial in AD were submitted, and the FDA allowed NeurMedix to proceed with the NM101 trial.ResultA Phase 3, Double Blind, Randomized, Placebo Controlled, Parallel Group, Multicenter Study of NE3107 in Subjects Who Have Mild to Moderate Alzheimer's Disease (NCT04669028) will evaluate safety and efficacy of oral 20 mg BID NE3107 vs. placebo in 316 subjects with mild to moderate AD. Two coprimary outcome measures ADAS Cog12 and ADCS CGIC will be evaluated as the change from Baseline to Week 30. Secondary endpoints include measures of neuropsychological deficits, functional performance, glycemic control and resource utilization. A subset of patients may volunteer for exploratory vMRI and FDG‐PET scans at baseline and week 30.ConclusionInflammation and insulin resistance drive AD. NE3107 decreases these insults that drive systems dysregulation in AD. This trial is well‐positioned to examine the effects of NE3107 on progression of AD dementia, affecting more than 40 million people globally.

Diagnostic value of plasma P‐tau217 in frontotemporal dementia spectrum disorders

AbstractBackgroundFrontotemporal dementia spectrum disorders (FTD) display complex neuropathological substrates and poor clinicopathological correlations, which hinders therapy development. Plasma P‐tau217 is an emerging tool to screen for Alzheimer’s disease (AD) pathology and may have diagnostic value in FTD.MethodPlasma P‐tau217 was measured cross‐sectionally by electrochemiluminescence in FTD patients referred to ALLFTD from ARTFL (n = 628, 45.7% female, median age 66 ± 12 years). P‐tau217 differences by baseline phenotype, disease severity and genotype were determined with non‐parametric tests and general linear models. Associations between P‐tau217 and measures of disease severity and neuropsychological performance were determined with linear regressions corrected for age, sex, phenotype and APOE.ResultThe sample included 33% behavioral variant FTD, 23.6% primary progressive aphasia (PPA), 28.5% atypical parkinsonism, 1.6% amnestic dementia (AmDem), 2.8% FTD/motoneuron disease, 3% mild cognitive/behavioral impairment and 7.5% healthy controls. Only 1.6% carried FTD‐causing mutations. P‐tau217 was not related to age (r = 0.034, 95%CI ‐0.03 – 0.12, p = 0.4). Compared to controls (0.18 ± 0.07 pg/mL), P‐tau217 was elevated only in AmDem (0.58 ± 0.9 pg/mL, p = 0.001) and logopenic PPA (lvPPA, 0.71 ± 0.62 pg/mL p &lt; 0.001). P‐tau217 ≥ 0.42 pg/mL effectively discriminated AmDem and lvPPA from all other phenotypes (AUC 0.87, 95%CI 0.77 – 0.96, p = 0.001, 77% sensitivity, 92% specificity). AmDem (60%) and lvPPA (91.7%) had the highest prevalence of high (≥ 0.42 pg/mL) P‐tau217, and the highest prevalence of APOE4 (AmDem 40%, lvPPA 63.6%). APOE4 carriers (0.23 ± 0.22 pg/mL) had higher P‐tau217, than non‐carriers (0.19 ± 0.09 pg/mL), regardless of phenotype (APOE effect p = .002, APOE x phenotype, p = 0.44). P‐tau217 was associated with worse clinical severity, mood, memory and executive function, but not with worse motor symptoms or social cognition.ConclusionWhen FTD is suspected, high plasma P‐tau217 is strongly associated with amnestic dementia and logopenic PPA phenotypes. Pending completion of ongoing neuropathological, CSF and molecular neuroimaging analyses, the data support the use of plasma P‐tau217 to identify atypical AD as a cause or AD as a co‐pathology contributing to FTD clinical presentation.

Correlations between neuropsychological performance and functional measures: Preliminary findings from the novel cognitive and functional measure for Alzheimer’s Disease prevention trials (NoMAD)

AbstractBackgroundTwo novel measures of cognition and function, the No Practice Effects (NPE) cognitive battery and the Miami Computerized Functional Assessment Scale (CFAS), were designed to have robust psychometric properties and reduced practice and ceiling effects for use in preclinical and early‐stage Alzheimer’s disease clinical trials. In this preliminary analysis, we sought to identify different cognitive domains in the NPE and evaluate their relationships with the CFAS functional measures.MethodFifty‐one cognitively healthy older adults (mean age 69.44 ± 6.29, 65.30% female) with baseline cognitive and functional assessments were included. We conducted an exploratory factor analysis to identify different cognitive domains within the NPE. We then computed a composite score for each domain and conducted partial Spearman correlations with CFAS functional measures, controlling for age, education and gender, and intracranial volume.ResultThe factor analysis yielded three factors corresponding to 1) episodic memory, 2) non‐verbal executive processes and speed, and 3) verbal working memory (loadings &gt; 0.5). Composite scores from these factors exhibited strong correlations with CFAS functional measures. In particular, a greater executive functioning and speed composite score was significantly associated with a faster completion time (rs’s ≥‐.44) and more efficient performance (rs’s ≥.37) on most CFAS functional measures (p’s&lt;.05).ConclusionMulti‐domain factors were identified in our novel cognitive measures. These cognitive domains strongly correlated with everyday functioning measures. Our results suggest that cognitive measures, particularly processing speed and executive function measures, obtained in clinic may be related to everyday function in older adults.

Mechanisms through which executive dysfunction influences suicidal ideation in combat-exposed Iraq and Afghanistan veterans

Objective: Executive dysfunction has previously been associated with suicidality, but it remains unclear how deficits in executive functioning contribute to increased suicidal thoughts and behaviors. Although it has been proposed that poorer executive functioning leads to difficulty generating and implementing appropriate coping strategies to regulate distress and inhibit suicidal thoughts and behaviors, studies have not systematically examined these relationships. Therefore, the present study examined various hypotheses to elucidate the mechanisms through which executive dysfunction influences suicidal ideation (SI) in combat-exposed Iraq/Afghanistan veterans. Method: Veterans who endorsed SI were compared to those who denied SI on demographic and diagnostic variables and measures of neuropsychological functioning, psychological symptoms, coping styles, and combat experiences. Serial mediation models were tested to examine mechanistic relationships among executive functioning, psychological distress, coping, and SI. Results: Those who endorsed SI had worse executive functioning, greater psychological distress, and greater avoidant coping relative to those who denied SI. Serial mediation model testing indicated a significant indirect path, such that executive dysfunction increased psychological distress, which in turn increased avoidant coping, leading to SI. Conclusions: Findings support and extend previous hypotheses regarding how executive functioning contributes to increased risk of suicidality via increased distress and avoidant coping. Intervention efforts focused on reducing suicidality may benefit from techniques that enhance executive functioning (e.g. computerized training, cognitive rehabilitation) and in turn reduce distress prior to targeting coping strategies.

Effects of anticholinergic medication use on brain integrity in persons living with HIV and persons without HIV.

This study examined relationships between anticholinergic medication burden and brain integrity in people living with HIV (PLWH) and people without HIV (HIV-). Neuropsychological performance z-scores (learning, retention, executive function, motor/psychomotor speed, language domains, and global cognition), and neuroimaging measures (brain volumetrics and white matter fractional anisotropy) were analyzed in PLWH (n = 209) and HIV- (n = 95) grouped according to the Anticholinergic Cognitive Burden (ACB) scale (0 = no burden, 1-3 = low burden, >3 = high burden). Neuropsychological performance and neuroimaging outcomes were compared between HIV- and PLWH with high anticholinergic burden. Within a cohort of PLWH (n = 90), longitudinal change in ACB score over ∼2 years was correlated to the rate of change per month of study interval in neuropsychological performance and neuroimaging measures. A higher number of anticholinergic medications and ACB was observed in PLWH compared with HIV- (P < 0.05). A higher ACB was associated with worse motor/psychomotor performance, smaller occipital lobe, putamen, subcortical gray matter and total gray matter volumes in HIV-; and poorer executive function, retention and global cognition, smaller brain volumes (frontal, parietal and temporal lobes, hippocampus, amygdala, cortex, subcortical gray matter and total gray matter), and reduced fractional anisotropy (posterior corpus callosum, perforant pathway) in PLWH. PLWH with high anticholinergic burden performed worse on tests of learning and executive function compared with HIV- with high anticholinergic burden. Longitudinally, PLWH who reduced their ACB over time had better neuropsychological performance and neuroimaging measures. Anticholinergic medications were associated with worse neuropsychological performance and reduced structural brain integrity, and these effects were more widespread in PLWH. Use of anticholinergic medications should be carefully monitored in older adults with deprescription considered whenever possible.

Self-perceived cognitive impairments in psychosis ultra-high risk individuals: associations with objective cognitive deficits and functioning

There is a scarcity of evidence on subjectively reported cognitive difficulties in individuals at ultra-high risk (UHR) for psychosis and whether these self-perceived cognitive difficulties may relate to objective cognitive deficits, psychopathology, functioning, and adherence to cognitive remediation (CR). Secondary, exploratory analyses to a randomized, clinical trial were conducted with 52 UHR individuals receiving a CR intervention. Participants completed the Measure of Insight into Cognition—Self Report (MIC-SR), a measure of daily life cognitive difficulties within the domains of attention, memory, and executive functions along with measures of neuropsychological test performance, psychopathology, functioning, and quality of life. Our study found participants with and without objectively defined cognitive deficits reported self-perceived cognitive deficits of the same magnitude. No significant relationship was revealed between self-perceived and objectively measured neurocognitive deficits. Self-perceived cognitive deficits associated with attenuated psychotic symptoms, overall functioning, and quality of life, but not with adherence to, or neurocognitive benefits from, a CR intervention. Our findings indicate that UHR individuals may overestimate their cognitive difficulties, and higher levels of self-perceived cognitive deficits may relate to poor functioning. If replicated, this warrants a need for both subjective and objective cognitive assessment in at-risk populations as this may guide psychoeducational approaches and pro-functional interventions. Self-perceived cognitive impairments do not seem to directly influence CR adherence and outcome in UHR states. Further studies are needed on potential mediator between self-perceived cognitive deficits and functioning and quality of life.

Computer-Assisted Cognitive Remediation in Schizophrenia: Efficacy of an Individualized vs. Generic Exercise Plan.

Computer-assisted cognitive remediation (CACR) is an economical, adjustable, and effective treatment for individuals with schizophrenia. The current randomized controlled study examined whether an individualized or generic exercise plan in CACR is superior in patients with multiple cognitive deficits compared to treatment-as-usual (TAU). Fifty-nine inpatients diagnosed with schizophrenia were randomly assigned to 1) TAU, 2) TAU plus an individualized exercise plan in CACR, or 3) TAU plus a generic exercise plan in CACR. Neuropsychological performance, psychopathology, and functional outcome were assessed at baseline and post-treatment. The results show a medium to large training effect for all neuropsychological performance measures. Contrary to our expectations the neuropsychological improvement over time did not differ between groups. Self-reported depression, global level of functioning, and activity and participation functioning showed a significant improvement from baseline to post-treatment. However no further group, time, or interaction effects for other psychopathology and functional outcome could be demonstrated. Possible implications for clinical use of CACR and future studies are discussed.

Cultural factors related to neuropsychological performance and brain atrophy among Hispanic older adults with amnestic Mild Cognitive Impairment (aMCI): A pilot study

Objectives This study examined the association of cultural factors and literacy to neuropsychological performance and measures of regional brain atrophy among Hispanic elders diagnosed with amnestic Mild Cognitive Impairment (aMCI). Method Acculturation and literacy levels were measured among 45 subjects tested in Spanish; their primary language. Scores for measures of memory, executive functioning, and verbal fluency, as well as volumetric analysis of MRI scans of left hemisphere structures commonly affected by Alzheimer’s disease (AD) were examined. Linear regression models were employed to examine the association of acculturation and literacy to neuropsychological performance and MRI measures. Results After controlling for age, higher literacy levels were associated with better performance on phonemic verbal fluency (r = 0.300, p < .05), while higher levels of acculturation to the U.S. was associated with poorer performance on category verbal fluency (r = 0.300, p < .05). There was a significant inverse relationship after controlling for age between literacy and the left entorhinal cortex (r = –0.455, p < .05), left precuneus (r = –0.457, p < .05), and left posterior cingulate (r = –0.415, p < .05). Conclusions Results of the current pilot study indicate that high acculturation to the U.S. among aMCI immigrants from Latin-American countries may hinder performance on verbal learning measures when they are administered in one’s primary language. Moreover, in this cohort, a higher literacy level, which is indicative of greater cognitive reserve, was associated with better performance in language measures, but with greater atrophy in brain regions susceptible to neurodegenerative disease. These preliminary findings should be further examined among larger cohorts and using more diverse measures, which capture other cultural constructs.