Premorbid Ability Research Articles

Genetic Risk, Vascular Function, and Subjective Cognitive Complaints Predict Objective Cognitive Function in Healthy Older Adults: Results From the Brain in Motion Study.

Aging is associated with subjective memory complaints. Approximately half of those with subjective memory complaints have objective cognitive impairment. Previous studies have provided evidence of an association between genetic risk for Alzheimer’s disease (AD) and dementia progression. Also, aging is a significant risk factor for vascular pathology that may underlie at least some of the cognitive changes. This study investigates the relative contribution of subjective cognitive complaints (SCC), vascular function, and genetic risk for dementia in predicting objective cognitive performance. Multiple regression and relative importance analysis were used to investigate the relative contribution of vascular function, self-reported SCC, and dementia genetic risk, in predicting objective cognition in a sample of 238 healthy community-dwelling older adults. Age, sex, premorbid cognitive abilities, subjective verbal memory complaints, higher cerebrovascular blood flow during submaximal exercise, and certain dementia risk alleles were significant predictors of worse objective verbal memory performance (p < 0.001, R2 = 35.2–36.4%). Using relative importance analysis, subjective verbal memory complaints, and certain dementia risk alleles contributed more variance than cerebrovascular measures. These results suggest that age-related changes in memory in healthy older adults can be predicted by subjective memory complaints, genetic risk, and to a lesser extent, cerebrovascular function.

Neurocognitive outcomes in adults following cerebral hypoxia: A systematic literature review.

Hypoxic ischemic brain injury (HIBI) occurs as a result of complete or partial disruption of cerebral oxygen supply. The physical and cognitive sequelae of adults following hypoxia varies widely. To systematically review studies exploring the neuropsychological outcomes following hypoxic brain insult in adults. Data was sourced using six databases (CINAHL, Cochrane, Embase, Medline, PsycInfo and Web of Science). Initial MESH terms identified 2,962 articles. After a three-stage independent review process, 18 articles, 9 case studies and 9 group studies were available for data synthesis from 1990-2012. Case study data was converted to standardised scores and compared to available test norms. Cohen's d was calculated to permit group data interpretation. Intellectual decrement was observed in some studies although difficult to delineate given the lack of use of measures of premorbid ability. Cognitive sequelae varied albeit with predominant disturbance in verbal memory, learning ability and executive function observed across studies. Wechsler Memory Scale Revised (WMS-R) visual memory was comparable to normative data. Impaired Rey Osterrieth Complex Figure (ROCFT) performance was found among group studies. Across visuo-constructional and attention domains, performance varied, although no significant difference relative to reported means was observed. Future studies should consider the use of standardised assessment protocols, which include measures of premorbid functioning and performance validity.

Predicting resistance to amyloid-beta deposition and cognitive resilience in the oldest-old.

To explore long-term predictors of avoiding β-amyloid (Aβ) deposition and maintaining unimpaired cognition as outcomes in the oldest old. In a longitudinal observational cohort study, 100 former participants of the Ginkgo Evaluation of Memory Study (GEMS; 2000-2008) completed biannual Pittsburgh compound B-PET imaging and annual clinical-cognitive evaluations beginning in 2010. Most recent Aβ status and cognitive status were selected for each participant. Longitudinal outcomes included change in serial Aβ and cognitive tests. Baseline predictors from GEMS included neuropsychological tests, daily functioning, APOE genotype, lifestyle variables, occupational measures, health history, sleep, subjective memory, physical and cognitive activities, depressive symptoms, and physical performance and health indices, among others. Mean age at the last cognitive evaluation was 92.0 (range 86-100) years. Mean follow-up time from baseline to last measured Aβ status was 12.3 (SD 1.9) years and to last cognitive evaluation was 14.1 (SD 1.9) years. The APOE*2 allele predicted last Aβ status (n = 34 Aβ negative vs n = 66 Aβ positive). Baseline cognition predicted cognitive status (n = 30 unimpaired vs n = 70 impaired). Predictors of cognitive status among Aβ-positive participants only (n = 14 normal cognition vs n = 52 impaired) were baseline cognitive test scores and smoking history. Baseline pulse pressure predicted longitudinal Aβ increase; paid work engagement and life satisfaction predicted less cognitive decline. The APOE*2 allele and lower pulse pressure predict resistance to Aβ deposition in advanced aging. Cognitive test scores 14 years prior, likely reflecting premorbid abilities, predict cognitive status and maintenance of unimpaired cognition in the presence of Aβ. Several lifestyle factors appear protective.

M62. PERIPHERAL INFLAMMATION MARKERS IDENTIFY SUBSET OF PATIENTS WITH SCHIZOPHRENIA AND RELATED PSYCHOSES WHO HAVE INTELLECTUAL DECLINE FROM PREMORBID LEVELS

BackgroundHigher inflammation has been identified in a substantial subset of both high-risk and chronically ill patients with schizophrenia and related psychoses and this may account for some of the heterogeneity of the schizophrenia. There is also much heterogeneity in cognitive deficits related to schizophrenia with some patients showing a marked decline from premorbid intellectual levels while others show little change from either normal or low intellect. However, the relationship between intellectual change with the illness onset and inflammation in schizophrenia has not been established.MethodsHere, we report the assessment of two common markers of inflammation from two independent samples of generally chronically ill patients with schizophrenia and related psychoses (one sample of 73 patients versus 70 healthy controls from Sydney, NSW, Australia and one sample of 297 patients from Syracuse, NY, USA). Peripheral venous blood samples were collected from all patients and blood markers of inflammation (C-Reactive Protein, CRP, and Neutrophil to Lymphocyte Ratio, NLR) were assayed using standard procedures. Assessment of premorbid and current intellectual abilities were obtained from the Sydney cohort of patients.ResultsGrouping the patients and controls from the Sydney sample into those with elevated (> 3 mg/L) versus normal (< 3 mg/L) CRP levels revealed 42% of the patients versus 20% of the healthy controls had elevated CRP (Chi Square = 9.16, p = .002) and further evidence of inflammation with an elevated mean NLR of 2.5. The frequency of peripheral inflammation was confirmed by the independent sample from Syracuse in which 39% of the patients (n= 115) had an elevated NLR above a cutoff score for normal of 2.2 which was consistent with the Sydney sample. Patients from the Sydney sample who had an elevated CRP also had a significant mean 15-point IQ decline from premorbid IQ levels, whereas the patients with CRP levels within normal limits did not show a statistically significant drop in IQ from premorbid levels (mean IQ decline 7.6 points). Healthy controls with normal CRP had no IQ change (0.0 points) and healthy controls with elevated CRP has a slight, non-significant IQ decline (mean 2.3 points).DiscussionThus, our study showed supportive evidence of elevated peripheral inflammation markers in subgroups of chronically ill patients with schizophrenia from two independent samples and a link between marked intellectual decline from premorbid levels and current peripheral inflammation in one chronically ill subgroup of patients with schizophrenia suggesting a role for inflammation in the cognitive impairment of a substantial proportion (40%) of patients with schizophrenia.

DIAGNOSING COGNITIVE DECLINE: COMPARING NIA-AA TO DSM-5 APPROACHES

Introduction Both the DSM-5 and NIA-AA (Albert et al., 2011) stipulate methods for assessing and diagnosing cognitive decline but differ in their approach for estimating cognitive ability. The DSM suggests that evidence of cognitive decline is demonstrated either through culturally normed neuropsychological evaluation or through the use of “bedside” assessments such as the Mini Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA). By contrast, the 2011 recommendations from the National Institute of Aging – Alzheimer Association (NIA–AA) emphasize the use of objective testing ideally via a neuropsychological evaluation of cognitive impairment in one or more cognitive domains. The current study compared differences in diagnostic rates between these two standards. Since the NIA-AA standards emphasize a more detailed cognitive assessment, we hypothesized that these criteria would identify a larger proportion of individuals with cognitive impairment than the DSM-5 criteria. We then examined possible clinical predictors of this discrepancy, including demographic, psychosocial, health-related, and genetic factors. Methods Data was drawn from 604 participants who were recruited into the Prevention of Alzheimer's Disease With Cognitive Remediation Plus tDCS in Mild Cognitive Impairment and Depression (PACt-MD; ClinicalTrials.gov Identifier: NCT02386670) trial. This is a randomized, controlled trial to evaluate brain stimulation and computerized brain training interventions for the prevention of cognitive decline in older adults. Participants either had a clinical history of mild cognitive impairment (MCI), major depressive disorder in remission, both, or were recruited as healthy controls without history of cognitive difficulty or mental disorder. All participants underwent a clinical and neuropsychological evaluation. Cognitive diagnoses were determined during biweekly consensus conferences. Both the DSM-5 and NIA-AA criteria were used during each consensus conference. The current analysis is based on the baseline data (i.e., prior to the intervention) of the 455 participants for whom a consensus conference was completed. We first compared diagnostic rates of MCI (NIA-AA) vs. mild neurocognitive disorder (DSM-5), as well as dementia (NIA-AA) vs. major neurocognitive disorder (DSM-5). We then used binary logistic regression models to examine demographic (age, education, race, sex, premorbid intellectual ability), psychosocial (English as a primary language, history of depression), health-related (severity of medical illness burden), and genetic (APOE e4 carrier status) predictors of diagnostic discrepancy between DSM-5 and NIA-AA criteria. Analyses were conducted separately for two groups of participants: (i) the group for which NIA-AA diagnoses reflected greater cognitive impairment than did the DSM-5 diagnoses (e.g., NIA-AA diagnosis of dementia but DSM-5 diagnosis of mild neurocognitive disorder); and (ii) the group for which DSM-5 diagnoses reflected greater cognitive impairment (e.g., DSM-5 diagnosis of major neurocognitive disorder but NIA-AA diagnosis of MCI. Results At baseline, there were 103 (22.6%) cases of discrepant diagnoses between the two classification systems: 50 cases had a NIA-AA diagnosis of MCI and no DSM-5 cognitive diagnosis (i.e., normal cognitive status); 41 cases had a NIA-AA diagnosis of dementia and a DSM-5 diagnosis of mild neurocognitive disorder; 12 cases had a DSM-5 diagnosis of mild neurocognitive disorder and no NIA-AA diagnosis. Compared to the 352 cases in agreement, the 91 cases with NIAA diagnoses reflecting greater cognitive impairment were more likely to have a history of major depressive disorder in remission (46% vs. 39%; B=-1.058, p=.003), be an APOE4 carrier (50% vs. 27%; B=-1.120, p=.001), and be older (72?vs. 71 years; B=.063, p=.02). APOE4 status, history of depression, and age were independent predictors. Compared to the 352 cases in agreement, the 12 cases with DSM-5 diagnosis reflecting greater cognitive impairment were less likely to have a history of depression (17% vs. 41%; B=2.414, p=.025). Conclusions While there was overall agreement with cognitive diagnoses when using NIA-AA or DSM-5 criteria, the two systems were discrepant in 22.6% of cases. Discrepancies were more likely to occur in participants with a history of depression, who were APOE4 carriers, or who were older. Overall, NIA-AA criteria yielded diagnoses reflecting greater cognitive impairment, especially in participants with a history of prior depression or those who were APOE4 carriers. These results suggest that more detailed neuropsychological evaluations may be indicated in older adults with a history of depression or who have a genetic vulnerability to dementia. This research was funded by: This project has been made possible by Brain Canada through the Canada Brain Research Fund, with the financial support of Health Canada and the Chagnon Family.

Resting State Glucose Utilization and Adult Reading Test Performance.

Adult reading tests (ART) have been widely used in both research and clinical settings as a measure of premorbid cognitive abilities or cognitive reserve. However, the neural substrates underlying ART performance are largely unknown. Furthermore, it has not yet been examined whether the neural substrates of ART performance reflect the cortical regions associated with premorbid intelligence or cognitive reserve. The aim of the study is to identify the functional neural correlates of ART performance using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in the cognitively normal (CN) middle- and old-aged adults. Voxel-wise analyses revealed positive correlations between glucose metabolism and ART performance in the frontal and primary somatosensory regions, more specifically the lateral frontal cortex, anterior cingulate cortex and postcentral gyrus (PCG). When conducted again only for amyloid-β (Aβ)-negative individuals, the voxel-wise analysis showed significant correlations in broader areas of the frontal and primary somatosensory regions. This is the first neuroimaging study to directly demonstrate the cerebral resting-state glucose utilization associated with ART performance. Our findings provide important evidence at the neural level that ART predicts premorbid general intelligence and cognitive reserve, as brain areas that showed significant correlations with ART performance correspond to regions that have been associated with general intelligence and cognitive reserve.

Assessing Cognitive Functioning in People Living With HIV (PLWH): Factor Analytic Results From CHARTER and NNTC Cohorts.

Single summary scores, such as the Global Deficit Score, are often used to classify overall performance on neuropsychological batteries. The factor structure of test scores that underlie Global Deficit Score in studies of people living with HIV (PLWH) was assessed to determine whether individual test scores loaded onto a unitary factor to summarize performance. Secondary data analysis on baseline data of PLWH from National NeuroAIDS Tissue Consortium and CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Study. Primary analyses included testing model structure and fit of neuropsychological test scores with confirmatory and exploratory factor analyses. Secondary analyses involved receiver operating characteristic curves, and associations with psychosocial and medical variables. Participants with confounds were excluded, leading to 798 (National NeuroAIDS Tissue Consortium) and 1222 (CHARTER) cases. When confirmatory factor analysis models were structured to be consistent with theoretically-based cognitive domains, models did not fit adequately. Per exploratory factor analyses, tests assessing speeded information processing, working memory, and executive functions loaded onto a single factor and explained the most variance in both cohorts. This factor tended to be associated with age, estimated premorbid ability, and aspects of substance use history. Its relation to age, in context of demographically corrected neuropsychological scores, suggested accelerated aging. Results indicate that individual neuropsychological tests did not load exactly onto expected domains, suggesting another framework for future analyses of cognitive domains. The possibility of a new index, and its use to assess cognitive impairment in PLWH, is suggested for further diagnostic and prognostic purposes.

History of Sport-Related Concussion and Long-Term Clinical Cognitive Health Outcomes in Retired Athletes: A Systematic Review.

Sport-related concussions (SRCs) are known to have short-term effects on cognitive processes, which can result in diverse clinical presentations. The long-term effects of SRC and repeated exposure to head impacts that do not result in SRC on specific cognitive health outcomes remain unclear. To synthesize and appraise the evidence base regarding cognitive health in living retired athletes with a history of head-impact exposure or SRC. A systematic search of the EMBASE, PsycINFO, MEDLINE/PubMed, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science databases was conducted from inception to April 2018 using common key words and medical subject headings related to 3 components: (1) the participant (eg, retired athlete), (2) the primary outcome measure (eg, cognitive test used), and (3) the secondary outcome measure (eg, history of sport concussion). Cross-sectional studies of living retired male or female athletes in which at least 1 cognitive test was used as an outcome measure were included. Two reviewers independently screened studies. Data extraction was performed using Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Methodologic quality was assessed independently by 2 reviewers using the Downs and Black tool. The search yielded 46 cross-sectional observational studies that were included in a qualitative synthesis. Most included studies (80%, n = 37) were published in the 5 years before our review. A large proportion of these studies (n = 20) included retired American National Football League players. The other research investigated professional, university, high school, and amateur retired athletes participating in sports such as American and Australian football, boxing, field and ice hockey, rugby, and soccer. The total sample consisted of 13 975 participants: 7387 collision-sport athletes, 662 contact-sport athletes, 3346 noncontact-sport athletes, and 2580 participants classified as controls. Compared with control participants or normative data, retired athletes displayed worse performance in 17 of 31 studies (55%) of memory, 6 of 11 studies (55%) of executive function, and 4 of 6 studies (67%) of psychomotor function and increased subjective concerns about cognitive function in 11 of 14 studies (79%). The authors of 13 of 46 investigations (28%) reported a frequency-response relationship, with poorer cognitive outcomes in athletes who had greater levels of exposure to head impacts or concussions. However, these results must be interpreted in light of the lack of methodologic rigor and moderate quality assessment of the included studies. Evidence of poorer cognitive health among retired athletes with a history of concussion and head-impact exposure is evolving. Our results suggest that a history of SRC may more greatly affect the cognitive domains of memory, executive function, and psychomotor function. Retired athletes appeared to have increased self-reported cognitive difficulties, but the paucity of high-quality, prospective studies limited the conclusions that could be drawn regarding a cause-and-effect relationship between concussion and long-term health outcomes. Future researchers should consider a range of cognitive health outcomes, as well as premorbid ability, in diverse samples of athletes with or without a history of concussion or head-impact exposure to delineate the long-term effects of sport participation on cognitive functioning.

Adding Suicide Prevention to the Triple Advantages of Injectable Long-Acting Second-Generation Antipsychotics

With the advent of new treatment perspectives for schizophrenic patients, long-acting injectable antipsychotics promise to provide relapse prevention, neuroprotection, and lower mortality rates (1). In preliminary studies, scholars have also indicated that such treatments could play a central role in suicide prevention in patients (2, 3) for whom suicide is the most likely cause of premature death, in addition to repercussions for caregivers and clinicians. Both Kraepelin (4) and Bleuler (5) highlighted the issue of suicide risk among patients suffering from schizophrenia. Modern studies provided an intricate list of risk factors for suicide, pointing to numerous issues in the management and treatment of schizophrenic patients. Individuals at higher risk are generally unmarried young white males who achieved proper functioning before the onset of the disorder (6). Such patients may easily be overwhelmed by hopelessness and depression, as well as becoming demoralized and being aware that their previous lifestyle cannot be maintained. Such patients feel socially isolated, fear further mental deterioration, have higher rates of substance abuse, and may lose faith in the treatments. Suicide attempts and hospitalizations are frequent, and each time they may realize that both medical and family support is limited; moreover, ad hoc interventions are not available or are difficult to implement. There are also further risk factors for suicide in schizophrenia, such as post-psychotic depression, agitation or motor restlessness, poor adherence to treatment, and command hallucinations (although not well ascertained in terms of statistical significance). However, risk factors often yield too many false positives, pointing to the need for suicide assessments based on factors such as an understanding of mental pain and demoralization, as well as therapeutic relationships, foreseeable life events that may impact the patient, social support, and the available resources. Furthermore, suicide risk is indirectly related to relapse, illness progression, the number of hospitalizations, and plans for rehabilitation after discharge (7). Each admission to a psychiatric ward may represent a further loss of hope and faith in the treatments. The risk of suicide seems to peak not only shortly after discharge, as reported routinely in the literature, but also shortly after admission (7). This fact points to the implementation of human–environmental factors for providing ward safety and close supervision in both inpatient and community settings, especially in the cases of reduced adherence to treatment. Among the various risk factors, preventative actions should be directed over those factors that are modifiable and can be targeted by proper treatment actions (8). Furthermore, suicide risk seems to be higher when patients develop demoralization syndrome, in which repeated exacerbations of psychotic symptoms, functional deterioration compared with premorbid abilities, and a non-delusional awareness of the effects of an illness can lead to feelings of hopelessness, depression, and, ultimately, suicide. Suicidal behavior is also a major issue among patients with first-episode psychosis (9, 10). It is noteworthy that integrated compared with typical treatment proved to be effective in reducing both suicide and other causes of death; the Opus Study (9) demonstrated the effectiveness of this strategy. Such an intervention involved a) assertive community treatment (ACT); b) antipsychotic medication; c) psychoeducational family treatment; and d) social skills training. It resulted in lower mortality for any cause and lower suicide rates. Mortality in Schizophrenia and Pharmacological Treatment A recent study by Bitter et al. (11) highlighted the reduction in life expectancy among patients with schizophrenia. Of note is the fact that, compared with the controls, 20-year-old males with schizophrenia had their life expectancy reduced by 11.5 years and females by 13.7 years; the analogous numbers for 45-year-old schizophrenics were 8.1 and 9.6 years, respectively. Taipale et al. (12) explored mortality in a large sample of approximately 30,000 patients and found that second-generation long-acting antipsychotic therapies [SG LATs; ranking: paliperidone palmitate > oral aripiprazole > long-acting injection (LAI) risperidone > LAI haloperidol > LAI perphenazine > oral perphenazine > LAI olanzapine > LAI zuclopenthixol] were associated with the lowest cumulative mortality rate. In 7.5 years, a follow-up SG LAT observation revealed the lowest cumulative mortality rate as compared with first-generation (FG) and SG oral and with no antipsychotic use. The use of LATs reduces the risk of death by 33% when compared to the corresponding oral equivalent. Such results are in line with further investigations by the same group of researchers (13), who reported their observations over 8 years. They observed that the risk of treatment failure or relapse after discontinuing antipsychotics does not decrease over time and that patients maintaining long-term antipsychotic treatment had increased survival rates.

The cognitive training version of the MUSIC® model of motivation inventory: A follow-up validity study

Further validation of the MUSIC® Model of Motivation Inventory (MMI) for use in Cognitive Remediation (CR) for schizophrenia is needed. The MMI was compared to the Intrinsic Motivation Inventory - Schizophrenia Research and Perceived Competency Scale following early treatment exposure in a CR clinical trial. MMI Usefulness, Success, and Interest scales were significantly correlated with corresponding comparison scales. The MMI was not correlated with pre-morbid cognitive ability. Higher expectancy for success and perceived usefulness were significantly associated with greater intensity of session attendance. Results support the convergent, divergent, and predictive validity of the MMI for CR research and clinical use.

Benzodiazepine Use Is Associated With an Increased Risk of Neurocognitive Impairment in People Living With HIV.

Despite potential for dependence and adverse neurological effects, long-term benzodiazepine (BZD) use is common among people living with HIV (PLWH). As PLWH are at risk for central nervous system dysfunction, we retrospectively examined the association between BZD use and HIV-associated neurocognitive impairment (NCI). Three hundred six PLWH underwent comprehensive neurobehavioral evaluations. Current BZD use (BZD+) was determined through self-report. Using propensity scores, 153 BZD- individuals were matched to 153 BZD+ participants on demographics and medical comorbidities. Multiple regression models examined NCI and demographically adjusted neurocognitive T-scores as a function of BZD status, adjusting for estimated premorbid ability, current affective symptoms, and nadir CD4 count. Secondary analyses explored neurocognitive correlates of positive BZD urine toxicology screens (TOX+) and specific BZD agents. Median duration of BZD use was 24 months. Current BZD use related to higher likelihood of NCI (odds ratio = 2.13, P = 0.003) and poorer global (d = -0.28, P = 0.020), processing speed (d = -0.23, P = 0.047), and motor T-scores (d = -0.32, P = 0.008). Compared with BZD-/TOX-, BZD+/TOX+ exhibited additional decrements in executive function (d = -0.48, P = 0.013), working memory (d = -0.49, P = 0.011), and delayed recall (d = -0.41, P = 0.032). For individual agents, diazepam, lorazepam, and alprazolam were most strongly associated with NCI (odds ratios >2.31). BZD use may elevate risk for NCI in PLWH, potentially through diffuse neurocognitive slowing and acute compromise of recall and higher-order capacities. These effects are robust to psychosocial and HIV-specific factors and occur in comparison with a tightly matched BZD- group. Prospective and interventional studies should evaluate causal associations between NCI and BZD use and explore treatment alternatives to BZDs in PLWH.

Estimating Premorbid Ability in Rehabilitation Patients Using the Test of Premorbid Functioning and Wide Range Achievement Test-Fourth Edition.

Objective: This study examined premorbid ability estimate concordance using Test of Premorbid Functioning predicted Full Scale Intelligent Quotient (TOPF-IQ) and Wide Range Achievement Test-Fourth Edition Word Reading (WRAT4-WR). Method: The sample (N = 145) was 28% female with average age and education of 40.6 and 13.2 years, respectively. Outpatient neuropsychological evaluations were conducted in a rehabilitation setting. Measures included the TOPF, WRAT4-WR, Wechsler Adult Intelligence Scale-Fourth Edition, and other neuropsychological tests. Non-WAIS measures defined impairment groups. Analyses included t tests, pairwise correlations, concordance correlation coefficients, and root mean square differences. Results: TOPF-IQ, WRAT4-WR, and Full Scale Intelligent Quotient scores were not significantly different but were lower than normative mean. TOPF-IQ and WRAT4-WR showed acceptable agreement (concordance correlation coefficient = .92; root mean square difference = 5.9). Greater premorbid-current ability differences were observed in the impaired group. TOPF-IQ and WRAT4-WR showed lower but similar agreement with Full Scale Intelligence Quotient in the unimpaired group. Conclusions: Findings support the WRAT4-WR in predicting premorbid ability in rehabilitation settings.

Comparing the North American Adult Reading Test (NAART) and the Test of Premorbid Functioning (TOPF) to estimate premorbid Wechsler Adult Intelligence Scale - 4th edition FSIQ in a clinical sample with epilepsy

Estimating premorbid general cognitive functioning is an essential component to the neuropsychological evaluation process. The North American Adult Reading Test (NAART) is a method to predict premorbid general cognitive functioning based on word reading skills developed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R), which is currently in its fourth edition (WAIS-IV). The Test of Premorbid Function (TOPF) was developed using the WAIS-IV, based on the same method as the NAART, to estimate premorbid intellectual ability. There is a paucity of research comparing estimates of premorbid general intellectual ability between the NAART and TOPF. This study evaluated the clinical utility of premorbid estimates of FSIQ derived from the NAART and TOPF in a sample of 101 patients with temporal lobe epilepsy (TLE). Differences between NAART-derived premorbid FSIQs and TOPF simple demographic predicted FSIQs were significant (p < .001) with large effect sizes. NAART estimated premorbid FSIQ (M = 104.04, SD = 8.42) was significantly greater than TOPF premorbid estimates (M = 99.83, SD = 9.26). Results suggested NAART-derived estimates of premorbid FSIQ may be more accurate than TOPF-based estimates, which likely underestimated premorbid FSIQ in this sample of patients with epilepsy. Limitations and future directions are discussed.

A Systematic Review of Neurocognitive Functioning in Behçet's Disease.

Behçet's disease (BD) is a vascular, inflammatory multisystem disorder with neuro-Behçet's (NBD) diagnosed in a subset of patients with neurological manifestations. The objective of this review was to determine whether neurocognitive dysfunction is observed in BD, in which neurocognitive domains, and whether there are differences in rates of dysfunction observed between BD and NBD groups. Studies of any methodology were included that reported results from standardized neurocognitive assessment measures in participants with BD or NBD. Twelve group comparison studies met the criteria for inclusion in the review (totalling 284 BD and 157 NBD participants), as well as 17 case study/series papers (11 BD, 35 NBD). Issues with blinding, incomplete data reporting and selective reporting bias were found across the group and case study/series papers, as well as inadequate statistical adjustment for multiple comparisons in the group studies, and the lack of the use of appropriate norms or adjustment for premorbid ability in the case series/studies papers. These quality issues impacted on the conclusions that could be drawn from the current literature. Neurocognitive dysfunction was found in NBD compared to health controls (HC) in a higher proportion of results across studies, than in comparisons between BD and HC groups. The domains in which neurocognitive attenuation was most often reported were visual spatial ability, working memory and acquired knowledge, with more than 25% of these results showing significantly lower functioning in both the BD and NBD groups compared to HC. More than 25% of the processing speed and long-term memory encoding and retrieval results were also lower for the NBD group, compared to HC. Group comparisons between NBD and multiple sclerosis participants indicated few significant differences in neurocognitive test results. The majority of case study/series participants were found to have some degree of attenuated neurocognitive functioning, as defined by case study/series authors.

Dementia Risk Elevates Brain Activity During Memory Retrieval: A Functional MRI Analysis of Middle Aged and Older Adults.

Longitudinal research suggests that genetic, lifestyle, and environmental factors enhance one's risk for developing Alzheimer's disease and related dementias (ADRD). However, it is not known how an accumulation of such factors impact brain functioning. One barrier to this research is that increased risk for ADRD affects the cerebrovascular system and, therefore, alters the link between neural activity and the fMRI BOLD signal. To better interpret fMRI findings, several steps were taken to adjust fMRI activity thereby reducing such cerebrovascular effects. We hypothesized that as the number of ADRD risk factors increase, brain regions within the medial temporal lobes and the default mode network would exhibit altered brain activity during an episodic memory retrieval task. Middle-aged and older adults (aged 50-74) free of dementia were recruited with varying levels of risk and underwent a neuropsychological battery and fMRI. In the memory task, participants viewed a pair of pictures. In an alternative-forced-choice test, participants viewed a picture cue and had to determine which of four pictures was paired with the cue. Increased dementia risk was positively associated with brain activity in regions of interest within the default mode network, the hippocampus, and the entorhinal cortex during memory retrieval. Whole-brain analyses revealed additional positive associations in prefrontal and occipito-temporal cortices. Risk factors most contributing to these elevated levels of brain activity included hypertension, diabetes, obesity, and cholesterol. We also ruled out confounds due to in-scanner performance and premorbid ability. Cumulative risk might represent early signs of burnout in brain regions underlying episodic memory.

Biased Recognition of Surprised Facial Expressions Following Awake Craniotomy of a Right Temporal Lobe Tumor.

Lesion studies have shown that the right temporal lobe is crucial for recognition of facial expressions, particularly fear expressions. However, in previous studies, premorbid abilities of the patients were unknown and the effects of epileptic discharge could not be excluded. Herein, we report a case of a patient who underwent assessments of facial recognition before and after brain surgery and exhibited biased recognition of facial expressions. The patient was a 29-year-old right-handed male who underwent an awake craniotomy. Compared with the preoperative assessment, after the surgery, he showed biased recognition of surprised facial expressions, and his ability to recognize other facial expressions either improved or remained unchanged. These findings support the idea that the right temporal lobe is crucial for the recognition of facial expressions of surprise and that functional connectivity between various brain regions plays an important role in the ability to recognize facial expressions.

A-83 The Applicability of the Word Accentuation Test (WAT) in a Diverse Spanish Speaking Population: A Pilot Study

Abstract Objective A valid estimate of premorbid ability (PA) is important when attempting to identify cognitive decline. Measures of PA in English have been widely validated, but there is a lack of PA instruments for Spanish speakers. The findings of a pilot study assessing the feasibility of using the Word Accentuation Test (WAT) as a PA measure in a diverse, traditionally underserved, Spanish speaking population are described. Method The WAT was administered as part of comprehensive neuropsychological evaluations and neurobehavioral status exams (NBSE) completed with Spanish speaking patients at Montefiore Medical Center (MMC) in a 6-month period. Sixty-one patients completed the WAT- 12 as part of comprehensive testing (mean age 60 (SD 11.05) range 43-80, 67% female) and 49 during NBSEs within the context of multidisciplinary memory disorders clinics (mean age 74.35 (SD 8.60) range 51-93, 80% female). T-tests and correlations with WAT performances were completed. Results Overall, our population correctly read an average of 19.67 (SD 7.61) words. There was no statistical difference by gender or age, but years of education predicted WAT performance (p = .004). For those individuals who had comprehensive cognitive evaluations, WAT scores were correlated with performance on the vocabulary subtest of the EIWA-III (p = .003). All patients without severe dementia were able to complete the task. Conclusions Analysis of pilot data from our diverse Spanish population demonstrated that the WAT is an PA appropriate task that appears to have good correlation with years of education and vocabulary performance. Additional research is necessary to validate the measure in this cohort and other cohorts.

B-07 Benzodiazepine Use Is Associated with an Increased Risk for HIV-Associated Neurocognitive Disorders

Abstract Objective Despite potential for dependence and adverse neurological effects, long-term benzodiazepine (BDZ) use is common among persons living with HIV (PLWH). As PLWH are at risk for CNS dysfunction, we retrospectively examined the association between BDZ use and HIV-associated neurocognitive disorders (HAND). Methods 306 PLWH (mean age = 45.1 years) underwent comprehensive neurobehavioral evaluations. Current BDZ use (BDZ+) was determined via self-report. Using propensity scores, 153 BDZ- individuals were matched to 153 BDZ+ participants on demographics, HIV disease characteristics, and comorbidities. Multiple regression models examined HAND and demographically-adjusted neurocognitive T-scores as a function of BDZ group, adjusting for estimated premorbid ability, current affective symptoms, and nadir CD4 count. Secondary analyses explored neurocognitive correlates of positive BDZ urine toxicology screens (TOX+). Results Median BDZ use was 24 months. Compared to BDZ-, BDZ+ had higher likelihood of HAND (OR = 2.14; p = .003) and poorer global (d = -0.33, p = .005), processing speed (d = -0.29, p = .013), and motor T-scores (d = -0.35, p = 0.003). Compared to BDZ+/TOX-, BDZ+/TOX+ users exhibited additional decrements in global (p = .033), executive function (p = .019), and delayed recall T-scores (p = .006). Conclusions BDZ use may elevate risk for HAND, potentially through diffuse neurocognitive slowing and acute compromise of recall and higher-order capacities. These effects are robust to psychosocial and HIV-specific factors and occur in comparison to a tightly-matched BDZ- group. Indications for BDZs (e.g., insomnia) may also impact neurocognition and/or manifest from latent neuropathology. Longitudinal studies should evaluate potential causal associations between HAND and BDZs. Given the extent of BDZ use and possibility of neurocognitive recovery post-abstinence, interventional studies should explore treatment alternatives to BDZs in PLWH.

Clinically significant cognitive dysfunction in OEF/OIF/OND veterans: Prevalence and clinical associations.

Cognitive performance in trauma-exposed populations, such as combat Veterans, has been shown to be worse than in nonexposed peers. However, cognitive performance has typically been within the normal range (within 1 SD of normative mean), and the prevalence of clinically significant cognitive dysfunction (i.e., performance more than 1 SD below the mean on multiple measures in a domain) in younger adults with trauma exposure remains unknown. The objective of our study was to measure this. We applied Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) cutoffs for clinically significant cognitive dysfunction (>1 SD below the mean in multiple measures within a domain) in the domains of memory, executive function, and attention to a sample of combat-exposed Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND; N = 368, mean age = 31.7 years, 90% men) Veterans. We then compared psychiatric, physiological, and neural measures, as well as functional outcomes, between those with and without cognitive dysfunction. Veterans with cognitive dysfunction (n = 129, 35.1%) had lower premorbid reading ability and more severe psychological distress, including increased anxiety, depression, posttraumatic stress disorder (PTSD), sleep difficulties, pain, and alcohol consumption. Those with cognitive dysfunction also had worse functional outcomes, with mild but significant disability. In contrast, we found associations between outcome and age, traumatic brain injury, physiological and neural measures to be weak or not significant. Together, this suggests that premorbid abilities and trauma-related psychological symptoms contribute significantly to cognitive dysfunction in OEF/OIF/OND Veterans, and that neurological insult and aging may play less of a role. Cognitive dysfunction may be at least partially ameliorated by treating trauma-related symptoms. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Instrumental Activities of Daily Living, Neuropsychiatric Symptoms, and Neuropsychological Impairment in Mild Cognitive Impairment.

Neuropsychological deficits, neuropsychiatric symptoms, and problems with instrumental activities of daily living are common in participants with mild cognitive impairment (MCI). To assess how subtle to mildly impaired instrumental activities of daily living (IADLs) might be related to neuropsychological abilities (including executive control and episodic memory) and neuropsychiatric symptoms (including apathy and depression) among participants with a diagnosis of MCI. Participants were evaluated for MCI and possible dementia at an outpatient memory clinic on the basis of a comprehensive neuropsychological evaluation, a geriatric psychiatry evaluation, a magnetic resonance image of the brain, and serum studies to evaluate for a possible reversible cause of cognitive decline. A series of stepwise regression analyses were conducted whereby IADL ability was the dependent variable and neuropsychological abilities, such as executive control and episodic memory, or neuropsychiatric symptoms, including apathy and depression, were the independent or predictor variables. The presence and severity of neuropsychiatric symptoms was assessed using a modified version of the Neuropsychiatric Inventory (mNPI). Participants were grouped by MCI diagnosis status (amnestic MCI, combined dysexecutive/mixed MCI, and no MCI). Twenty-six participants were in the amnestic MCI group, 19 in the combined dysexecutive/mixed MCI group, and 36 participants did not meet criteria for MCI (non-MCI group). Groups did not differ in age, education, Mini-Mental State Examination performance, IADL abilities, estimated premorbid general intellectual abilities, or mNPI ratings for apathy and depression. Stepwise regression analyses found a robust relationship between mild IADL impairment and greater apathy (R=0.497, r21,69=0.247, P<.001; β=-0.497, P<.001). Depression did not enter the final model. A weaker-but statistically significant-relationship was found between mild IADL impairment and worse executive control test performance (R=0.271, r21,68=0.073, P<.023; β=0.271, P<.23). Episodic memory did not enter the final model. When both apathy and executive control were assessed as related to IADL impairment, only apathy entered the final model (R=0.497, R21,69=0.247, P<.001; β=-0.497, P<.001). Mildly impaired IADL functioning can negatively affect quality of life. Moreover, apathy may be amenable to treatment. In a primary geriatric care setting, neuropsychiatric symptoms and neuropsychological abilities should be routinely assessed.