Wechsler Adult Intelligence Scale-Revised Digit Research Articles

Age Association Analysis between Tricarboxylic Acid Metabolites and Neurocognitive Impairment in Persons Living with HIV

ObjectiveInflammation may contribute to neurocognitive impairment (NCI) in people with HIV (PWH). Lipopolysaccharide‐mediated macrophage activation induces a shift from oxidative phosphorylation to glycolysis in‐vitro with accumulation of the tricarboxylic acid (TCA) metabolites succinate (SA) and citrate (CA). These metabolites engage diverse cellular inflammatory pathways and may indicate mitochondrial dysfunction. In this study, we developed and optimized an LC‐MS metabolomic method to allow the simultaneous detection and analysis of plasma SA and CA metabolites in in people with HIV.MethodsGeneralized estimating equations were used in a random sample of older PWH from the prospective, multicenter HAILO cohort. Plasma sample was mixed with methanol‐acetonitrile‐water (5:3:1) and 0.1mg/mL internal standard (ISTD, D4‐citric acid). The mixture was vortexed for 30 minutes and centrifuged at 10,000g for 10 minutes. The supernatants were dried, reconstituted in 0.2% formic acid/0.1mg/ml ISTD. Samples were analyzed using Kinetex ‐ C18 column coupled to an Agilent 6540 Q‐TOF LC‐MS. Metabolites identification was achieved based on retention time and product ions. Calibration curves were obtained by using SA and CA authentic standards spiked into 0.2% formic acid/0.1mg/mL ISTD. Using Agilent MassHunter Qualitative B.07 Software, the ratio of analyte and ISTD peak area was plotted against the corresponding concentration to obtain calibration curves. The peak area and the concentration of each analyte were determined using the peak area ratio. Neurocognition was assessed every 48 wks, where NCI was defined as ≥1 z‐scores ≥2 SD below 0 or ≥2 z‐scores ≥1 SD below 0 on Trailmaking A and B and the Wechsler Adult Intelligence Scale‐Revised Digit Symbol tests.Results200 participants were followed a mean ±SD of 160 ±51 wks with a mean of 4 ±1.1 assessments. The mean age was 51 ±7 yrs, 84% were men, 49% were white non‐Hispanic and 59% were current or past smokers. HIV‐1 RNA levels were <400 copies/ml in 97% and the mean nadir and baseline CD4 counts were 234 and 664 cells/mm3, respectively. The mean education was 14 ±4 yrs and NCI was detected at entry in 53 participants (27%). Age modified associations between each metabolite and NCI (P=0.01 for interactions by age with each metabolite). A 1 SD increase of SA or CA levels associated with a 2.2 [95%CI 1.1, 4.3] or a 1.9 [1.3, 2.8] greater odds of NCI, respectively, in the oldest age‐tertile but not in younger age‐groups (Table).ConclusionAssociations between plasma TCA metabolite levels and NCI were evident among older PWH, possibly implicating inflammatory effects on neurocognition that associate with these metabolites or mitochondrial dysfunction and warrant further study.Support or Funding InformationNHLBI (K23HL116209) and NIAD (P30 AI036219)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of aging on neurocognitive performance in previously antiretroviral-naive HIV-infected individuals on their first suppressive regimen.

Despite treatment with virologically suppressive antiretroviral therapy (ART), neurocognitive impairment may persist or develop de novo in aging HIV-infected individuals. We evaluated advancing age as a predictor of neurocognitive impairment in a large cohort of previously ART-naive individuals on long-term ART. The AIDS Clinical Trials Group Longitudinal Linked Randomized Trials was a prospective cohort study of HIV-infected individuals originally enrolled in randomized ART trials. This analysis examined neurocognitive outcomes at least 2 years after ART initiation. All participants underwent annual neurocognitive testing consisting of Trail making A and B, the wechsler adult intelligence scale-revised Digit Symbol and Hopkins Verbal Learning Tests. Uni and multivariable repeated measures regression models evaluated factors associated with neurocognitive performance. Predictors at parent study entry (ART naive) included entry demographics, smoking, injection drug use, hepatitis B surface antigen, hepatitis C virus serostatus, history of stroke, ART regimen type, pre-ART nadir CD4 cell count, and plasma viral load and as well as time-updated plasma viral load and CD4 cell count. The cohort comprised 3313 individuals with median pre-ART age of 38 years, 20% women; 36% Black, non-Hispanic; 22% Hispanic. Virologic suppression was maintained at 91% of follow-up visits. Neurocognitive performance improved with years of ART. After adjusting for the expected effects of age using norms from HIV-negative individuals, the odds of neurocognitive impairment at follow-up visits among the HIV infected increased by nearly 20% for each decade of advancing age. Despite continued virologic suppression and neurocognitive improvement in the cohort as a whole, older individuals were more likely to have neurocognitive impairment than younger individuals.

Impairment of executive functions and memory in unaffected siblings of patients with bipolar disorder

Objective: Neurocognitive impairments in bipolar patients as a possible endophenotype is a growing field of research. Impairments in executive functions and memory have been reported in relatives of patients with bipolar disorder, suggesting that they could be potential endophenotypes for genetic studies. In this study, neuropsychological performance in unaffected siblings of patients diagnosed as bipolar I disorder is compared to that of matched healthy controls. Method: We evaluated 35 unaffected siblings of probands with bipolar I disorder and 35 healthy controls using tests of verbal fluency, attention, executive functions and memory. Rey Auditory Verbal Learning Test (RAVLT), Wechsler Memory Scale-Revised (WMS-R) visual memory test, Stroop Colour-Word Interference test (SCWIT), Trail Making Test-A and B, Wechsler Adult Intelligence Scale-Revised Digit Span test, categoric verbal fluency test (Isaac SET Test) , and clock drawing tests were performed. Results: Unaffected siblings of patients with bipolar disorder performed poorly on the RAVLT, SCWIT, forward Digit Span Test, TMT-A and B, visual recall test. Using stepwise logictic regression TMT-B alone could highly differentiate siblings from controls. Conclusion: We found significant impairment of set shifting task measured with TMT-B in siblings of patients with BD. Our study suggests that set shifting/cognitive flexibility could be a potential cognitive endophenotype for bipolar disorder.

Proteinuria is associated with neurocognitive impairment in antiretroviral therapy treated HIV-infected individuals.

Proteinuria is a marker of vascular dysfunction that predicted increased cardiovascular mortality and is associated with neurocognitive impairment (NCI) in population-based studies. We examined associations between proteinuria and HIV-associated NCI. Multivariable logistic regression was used to examine associations between NCI at the first neurocognitive assessment (baseline) and simultaneous, clinically significant proteinuria [as random spot urine protein-to-creatinine ratios (UP/Cr) ≥200 mg/g] in a prospective multicenter observational cohort study. Generalized estimating equations were used to examine associations between baseline proteinuria and subsequent NCI among subjects without NCI at baseline. NCI was defined as a Z-score, derived from the combination of normalized scores from the Trailmaking A and B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol tests. A total of 1972 subjects were included in this analysis. Baseline proteinuria was associated with increased odds of NCI [odds ratio (OR): 1.41, 95% confidence interval (CI): 1.08 to 1.85; P = 0.01] and with subsequent NCI among subjects without NCI at baseline (OR: 1.39, 95% CI: 1.01 to 1.93; P = 0.046) in multivariable models adjusted for risk factors and potential confounders. Similar associations were evident when these analyses were limited to visits at which time study subjects maintained plasma HIV RNA levels <200 copies per milliliter. The association between proteinuria and NCI observed in this study adds to a growing body of evidence implicating contributions by vascular disease to NCI in antiretroviral treated individuals. Studies examining interventions that improve vascular function are warranted.

The relationship between obesity and neurocognitive function in Chinese patients with schizophrenia

BackgroundStudies have reported that up to 60% of individuals with schizophrenia are overweight or obese. This study explored the relationship between obesity and cognitive performance in Chinese patients with schizophrenia.MethodsOutpatients with schizophrenia aged 18–50 years were recruited from 10 study sites across China. Demographic and clinical information was collected. A neuropsychological battery including tests of attention, processing speed, learning/memory, and executive functioning was used to assess cognitive function, and these 4 individual domains were transformed into a neurocognitive composite z score. In addition, height and weight were measured to calculate body mass index (BMI). Patients were categorized into 4 groups (underweight, normal weight, overweight and obese) based on BMI cutoff values for Asian populations recommended by the World Health Organization.ResultsA total number of 896 patients were enrolled into the study. Fifty-four percent of participants were overweight or obese. A higher BMI was significantly associated with lower scores on the Wechsler Memory Scale-Revised (WMS-R) Visual Reproduction subscale, the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol subscale, and the composite z score (p’s ≤ 0.024). Obese patients with schizophrenia had significantly lower scores than normal weight patients on the Trail Making Test B, the WMS-R Visual Reproduction subscale, the WAIS Digit Symbol subscale, and the composite z score (p’s ≤ 0.004).ConclusionsOur study suggests that, in addition to its well established risk for various cardiometabolic conditions, obesity is also associated with decreased cognitive function in Chinese patients with schizophrenia. Future studies should explore if weight loss and management can improve cognitive function in obese patients who suffer from schizophrenia.

Relationships Between Behavioral Syndromes and Cognitive Domains in Alzheimer Disease: The Impact of Mood and Psychosis

Behavioral disturbances occur in nearly all Alzheimer disease (AD) patients together with an array of cognitive impairments. Prior investigations have failed to demonstrate specific associations between them, suggesting an independent, rather than shared, pathophysiology. The objective of this study was to reexamine this issue using an extensive cognitive battery together with a sensitive neurobehavioral and functional rating scale to correlate behavioral syndromes and cognitive domains across the spectrum of impairment in dementia. Cross-sectional study of comprehensive cognitive and behavioral ratings in subjects with AD and mild cognitive impairment. Memory disorders research center. Fifty subjects with AD and 26 subjects with mild cognitive impairment; and their caregivers. Cognitive rating scales administered included the Mini-Mental State Examination; the Modified Mini-Mental State Examination; the Boston Naming Test; the Benton Visual Retention Test; the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychology Assessment; the Controlled Oral Word Test; the Wechsler Memory Scale logical memory I and logical memory II task; the Wechsler Memory Scale-Revised digit span; the Wechsler Adult Intelligence Scale-Revised digit symbol task; and the Clock Drawing Task together with the Clinical Dementia Rating Scale and the Neuropsychiatric Inventory. Stepwise regression of cognitive domains with symptom domains revealed significant associations of mood with impaired executive function/speed of processing (Δr = 0.22); impaired working memory (Δr = 0.05); impaired visual memory (Δr = 0.07); and worsened Clinical Dementia Rating Scale (Δr = 0.08). Psychosis was significantly associated with impaired working memory (Δr = 0.13). Mood symptoms appear to impact diverse cognitive realms and to compromise functional performance. Among neuropsychological indices, the unique relationship between working memory and psychosis suggests a possible common underlying neurobiology.

Magnetic resonance spectroscopy, β-amyloid load, and cognition in a population-based sample of cognitively normal older adults

To determine the relationship between proton magnetic resonance spectroscopy ((1)H MRS) metabolites and β-amyloid (Aβ) load and the effects of Aβ load on the association between (1)H MRS metabolites and cognitive function in cognitively normal older adults. We studied 311 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging from January 2009 through September 2010. Participants underwent (11)C-Pittsburgh compound B (PiB) PET, (1)H MRS from the posterior cingulate gyri, and neuropsychometric testing to assess memory, attention/executive, language, and visual-spatial domain functions within 6 months. Partial Spearman rank order correlations were adjusted for age, sex, and education. Higher PiB retention was associated with abnormal elevations in myoinositol (mI)/creatine (Cr) (partial r(s) = 0.17; p = 0.003) and choline (Cho)/Cr (partial r(s) = 0.13; p = 0.022) ratios. Higher Cho/Cr was associated with worse performance on Auditory Verbal Learning Test Delayed Recall (partial r(s) = -0.12; p = 0.04), Trail Making Test Part B (partial r(s) = 0.12; p = 0.04), Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol (partial r(s) = -0.18; p < 0.01), and WAIS-R Block Design (partial r(s) = -0.12; p = 0.03). Associations between (1)H MRS metabolites and cognitive function were not different among participants with high vs low PiB retention. In cognitively normal older adults, the (1)H MRS metabolite ratios mI/Cr and Cho/Cr are associated with the preclinical pathologic processes in the Alzheimer disease cascade. Higher Cho/Cr is associated with worse performance on domain-specific cognitive tests independent of Aβ load, suggesting that Cho/Cr elevation may also be dependent on other preclinical dementia pathologies characterized by Cho/Cr elevation such as Lewy body or ischemic vascular disease in addition to Aβ load.

Cognitive functioning in schizophrenia with or without diabetes.

To determine the influence of schizophrenia patients with diabetes on cognitive function. Altogether 78 schizophrenia patients with diabetes and 118 patients with schizophrenia were enrolled and Negative and Positive Syndrome Scale, Wechsler Memory Scale-Revised Visual Reproduction Test, Wechsler Adult Intelligence Scale-Revised Digit Symbol Test, Computerized Wisconsin Card Sorting Test,Trail Making Tests, Part A and B, and Wechsler Adult Intelligence Scale-Revised Digit Span Test were used to assess the clinical syndrome and to test the cognitive function. Impairment of Processing Speed, Attention/Working Memory, Executive Functioning and Visual Memory in schizophrenia patients with diabetes was significantly poorer than that of the schizophrenia patients (all P<0.05). WAIS-R Digit Symbol Test score and Trail Making Test A and B scores were associated with diabetes duration and age at diabetes onset (P<0.01). The impairment of cognitive function in schizophrenia patients with diabetes is severer than schizophrenia patients, suggesting that the prevention and management of diabetes may improve cognitive outcome in schizophrenia patients.

Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort.

Differences in antiretroviral distribution into the central nervous system (CNS) may impact neurocognitive status. We assessed the relationship between estimates of antiretroviral therapy penetration into the CNS, using a published ranking system, and neurocognitive status in HIV-positive participants with plasma HIV-1 RNA (vRNA) suppression. Participants with at least 6 weeks ongoing antiretroviral drug use and vRNA less than 50 copies/ml (N = 2636; 83% male, median baseline CD4 T cells: 244 cells/μl) had at least one neuroscreen assessment [Trail Making Test, Part A and B; Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol] at 10 413 neurovisits. Neuroscreen test scores were demographically adjusted and converted to Z-scores (NPZ3: lower scores imply more impairment). Central nervous system penetration effectiveness (CPE) ranks of 0.0 (low), 0.5 (medium), or 1.0 (high) were assigned to antiretrovirals and summed per regimen, per neurovisit. Multivariate linear regression models using generalized estimating equations assessed NPZ3 scores with respect to antiretroviral regimen. Covariates were retained if P ≤ 0.1. A final model demonstrated that better NPZ3 scores were associated with higher CPE among participants taking more than three antiretroviral drugs (+0.07 per one unit increase in CPE score; P = 0.004) but not among participants with three or less antiretroviral drugs in the regimen (+0.01; P = 0.5). Results were adjusted for demographics, injection drug use, hepatitis C virus serostatus, CD4 cell count (current and nadir), baseline vRNA, antiretroviral experience, and years since first antiretroviral drug use. Use of antiretroviral drugs with better estimated CNS penetration may be associated with better neurocognitive functioning; some people may require more than three antiretroviral drugs to treat HIV in the CNS. Clinically this means antiretroviral regimens could be designed to optimize estimated CNS penetration without sacrificing virologic and immunologic benefits.

Cognitive performance in patients with burnout, in relation to diurnal salivary cortisol

This study investigated cognitive performance in patients with burnout, in relation to the flexibility of the hypothalamic–pituitary–adrenal (HPA) axis. Clinical cases with work stress-induced burnout (n = 65), and demographically matched, healthy reference subjects (n = 65), were given six neuropsychological tests and a self-rating scale for cognitive problems. Diurnal salivary cortisol was measured among burnout cases and an external reference group (n = 174), including a dexamethasone suppression test (DST) among burnout cases. Compared with referents, the burnout group under-performed in a cognitive speed test (Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol), but not in any other test of sustained attention, episodic memory, or vocabulary. Burnout cases had considerably more subjective cognitive problems, but ratings were unrelated to test performance. Compared with referents, burnout cases had similar morning salivary cortisol levels and similar awakening response, but lower evening cortisol. Among burnout cases, lower diurnal cortisol variability was related to slower performance in several tests. The DST response showed no consistent relationship with any cognitive parameter. Hence, despite considerable subjective cognitive problems, the burnout group showed only a partial, mild deviation in cognitive performance. A flatter diurnal cortisol profile was related to lower cognitive processing speed, but diurnal cortisol pattern and DST response were normal, suggesting a maintained HPA axis flexibility.

Hippocampal and entorhinal atrophy in mild cognitive impairment

To evaluate the utility of MRI hippocampal and entorhinal cortex atrophy in predicting conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). Baseline brain MRI was performed in 139 patients with MCI, broadly defined, and 63 healthy controls followed for an average of 5 years (range 1 to 9 years). Hippocampal and entorhinal cortex volumes were each largest in controls, intermediate in MCI nonconverters, and smallest in MCI converters to AD (37 of 139 patients converted to AD). In separate Cox proportional hazards models, covarying for intracranial volume, smaller hippocampal volume (risk ratio [RR] 3.62, 95% CI 1.93 to 6.80, p < 0.0001), and entorhinal cortex volume (RR 2.43, 95% CI 1.56 to 3.79, p < 0.0001) each predicted time to conversion to AD. Similar results were obtained for hippocampal and entorhinal cortex volume in patients with MCI with Mini-Mental State Examination (MMSE) scores > or = 27 out of 30 (21% converted to AD) and in the subset of patients with amnestic MCI (35% converted to AD). In the total patient sample, when both hippocampal and entorhinal volume were entered into an age-stratified Cox model with sex, MMSE, education, and intracranial volume, smaller hippocampal volume (RR 2.21, 95% CI 1.14 to 4.29, p < 0.02) and entorhinal cortex volume (RR 2.48, 95% CI 1.54 to 3.97, p < 0.0002) predicted time to conversion to AD. Similar results were obtained in a Cox model that also included Selective Reminding Test (SRT) delayed recall and Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol as predictors. Based on logistic regression models in the 3-year follow-up sample, for a fixed specificity of 80%, the sensitivities for MCI conversion to AD were as follows: age 43.3%, MMSE 43.3%, age + MMSE 63.7%, age + MMSE + SRT delayed recall + WAIS-R Digit Symbol 80.6% (79.6% correctly classified), hippocampus + entorhinal cortex 66.7%, age + MMSE + hippocampus + entorhinal cortex 76.7% (85% correctly classified), age + MMSE + SRT delayed recall + WAIS-R Digit Symbol + hippocampus + entorhinal cortex 83.3% (86.8% correctly classified). Smaller hippocampal and entorhinal cortex volumes each contribute to the prediction of conversion to Alzheimer disease. Age and cognitive variables also contribute to prediction, and the added value of hippocampal and entorhinal cortex volumes is small. Nonetheless, combining these MRI volumes with age and cognitive measures leads to high levels of predictive accuracy that may have potential clinical application.

Neuropsychological Prediction of Conversion to Alzheimer Disease in Patients With Mild Cognitive Impairment

The likelihood of conversion to Alzheimer disease (AD) in mild cognitive impairment (MCI) and the "optimal" early markers of conversion need to be established. To evaluate conversion rates to AD in subtypes of MCI and to identify neuropsychological measures most predictive of the time to conversion. Patients were followed up semiannually and controls annually. Subtypes of MCI were determined by using demographically adjusted regression norms on neuropsychological tests. Survival analysis was used to identify the most predictive neuropsychological measures. Memory disorders clinic. One hundred forty-eight patients reporting memory problems and 63 group-matched controls. A consensus diagnosis of probable AD. At baseline, 108 patients met criteria for amnestic MCI: 87 had memory plus other cognitive domain deficits and 21 had pure memory deficits. The mean duration of follow-up for the 148 patients was 46.6 +/- 24.6 months. In 3 years, 32 (50.0%) of 64 amnestic-"plus" and 2 (10.0%) of 20 "pure" amnestic patients converted to AD (P = .001). In 148 patients, of 5 a priori predictors, the percent savings from immediate to delayed recall on the Selective Reminding Test and the Wechsler Adult Intelligence Scale-Revised Digit Symbol Test were the strongest predictors of time to conversion. From the entire neuropsychological test battery, a stepwise selection procedure retained 2 measures in the final model: total immediate recall on the Selective Reminding Test (odds ratio per 1-point decrease, 1.10; 95% confidence interval, 1.05-1.14; P < .0001) and Digit Symbol Test coding (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .01). The combined predictive accuracy of these 2 measures for conversion by 3 years was 86%. Mild cognitively impaired patients with memory plus other cognitive domain deficits, rather than those with pure amnestic MCI, constituted the high-risk group. Deficits in verbal memory and psychomotor speed/executive function abilities strongly predicted conversion to AD.

Are There Sex Differences in Neuropsychological Functions Among Patients With Obsessive-Compulsive Disorder?

The purpose of this study was to examine whether men and women with obsessive-compulsive disorder (OCD) demonstrate differences in neuropsychological functioning compared to healthy men and women. Participants were 56 consecutive patients (33 male, 23 female) and 40 healthy control participants (20 male, 20 female) of comparable characteristics. Male and female patients had comparable symptom severity, illness duration, comorbidity, in- or out-patient status, and medication usage. An extensive neuropsychological test battery was administered including tests of general nonverbal intelligence, attention, verbal and nonverbal memory, and executive functions. Male and female OCD patients showed comparable neuropsychological performances on most cognitive domains. However, we found some evidence for cross-sex shifts in verbal fluency tasks (FAS and Category Alternation Test [CAT]), the reading component of the Stroop test, and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span-Forward test. Post hoc analyses revealed that female patients showed reduced performance on these tests compared to healthy women, in the male-typical direction. Among OCD women only, there were significant negative correlations between OCD symptom severity and performance on the CAT and the reading Stroop. We conclude that sex does not seem to be a major determinant of neuropsychological function in OCD, but the observed cross-sex shifts on some tasks deserve further examination.

Adult age and digit symbol substitution performance: a meta-analysis.

This article reports the results of a meta-analysis of the effects of age, education, and estimated year of measurement on scores from the Wechsler Adult Intelligence Scale and the Wechsler Adult Intelligence Scale-Revised Digit Symbol Substitution Test. Analysis of effect sizes for age reported in 141 studies published between 1986 and 2002 indicated a mean standardized difference of -2.07. Age accounted for 86% of the variance in a regression model using age, education, and year submitted as predictors of Digit Symbol scores. There was no association between years of education or year submitted and Digit Symbol scores for younger adults or older adults.

A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors.

To investigate longitudinal cognitive functioning in patients with brain tumor treated with modern highly conformal fractionated partial brain radiation therapy (RT). Seventeen (of 22 initial consecutive patients) adults with primarily low-grade brain neoplasms who underwent either biopsy or tumor resection were tested at pre-RT baseline and at 3, 6, 12, and 24 months after baseline. Participants were classified as RT-treated nonprogressors (n = 12) or progressors (n = 3) based on serial follow-up structural imaging. Two patients received surgery only and served as controls to help minimize surgical, practice, test form, or other potential non-RT effects. Serial neuropsychological assessments were conducted using alternate forms of the Selective Reminding Test, 10/36 Spatial Recall Test, and Symbol Digit Modality Test (oral, written) as well as the Shipley Scale (baseline only), Wechsler Adult Intelligence Scale-Revised Digit Span, Trail Making Test, and the Symptom Checklist-90-Revised Global Severity Index scale. There was evidence of subtle attention and memory improvement in RT-treated nonprogressors throughout the 2-year period, with no evidence of cognitive decline. In contrast, patients with disease progression evidenced more substantial decline in memory and attention. Partial brain fractionated RT was not associated with adverse neuropsychological effects through the first 2 years following therapy.

Analysis of Substitution Test Performance Using Eye Movement and Video Data

Substitution tests continue to enjoy widespread popularity in applied neuropsychology. Though highly sensitive, these tests lack specificity, and substitution test decrements are often reported in terms that bear little relation to cognitive or other psychological theory. Objectives were to quantify, using eye movement/video analysis, subitem performance elements for the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol Test (DST); to assess the relative contribution of each of these to standard WAIS-R DST performance in a group; and to assess whether wearing the eye-movement measuring equipment interfered with test performance.

Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study

In a previous cross-sectional study of 100 asymptomatic individuals aged 49–69, we reported age-related decline in immediate and delayed memory that was steeper in apolipoprotein E (apoE)-e4/4 homozygotes than in members of other genetic subgroups. These findings were preliminarily based upon the statistical problem of multiple comparisons. We therefore sought to replicate these findings in a new cohort. From 1998 to 2000, 80 asymptomatic residents of Maricopa County, AZ were recruited through newspaper ads. 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers were matched (1:1:2) by age, gender, and years of education. All had normal neurologic and psychiatric examinations, including Folstein minimental status exam (MMSE) and Hamilton depression scale, and underwent a battery of neuropsychological tests identical to those in our previous study. The groups were well-matched for age (55.9±5.9 years), gender (60% women), and education (15.9±2.2 years), and were demographically similar to our previous cohort. Complex figure test recall was lower in e3/4 heterozygotes than noncarriers, but there was no significant difference between e4/4 homozygotes and noncarriers. There were no other significant differences in mean test scores between groups, but Wechsler adult intelligence scale-revised (WAIS-R) digit span showed a significant negative correlation with age in the e4/4 homozygote group relative to e4 noncarriers ( p=0.008) as we had found in our previous study. In conclusion, we found a significant negative correlation of WAIS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarriers in two separate cohorts, possibly reflecting an age-related effect on frontal lobe function in this genetic subgroup.

Generalized cognitive deficits in schizophrenia: a study of first-episode patients.

Cognitive impairment is recognized as a core characteristic of schizophrenia. There has always been a debate about the nature, selectivity, and time of onset of these deficits in relationship to the onset of illness and treatment factors. To our knowledge, the present study represents the largest sample of mostly neuroleptic-naive patients with first-episode schizophrenia that has been reported to date. A group of 94 patients experiencing their first episode of schizophrenic illness and 305 normal comparison subjects were administered a comprehensive clinical and neuropsychological evaluation. Seventy-three patients were neuroleptic naive, 14 had received treatment for less than 1 week, and the remaining 7 had been medicated for less than 2 weeks. Patients performed significantly worse than the comparison subjects on every neuropsychological variable except those assessing savings scores (ie, forgetting over time). Twenty-five of 30 tests had an effect size (ES) greater than 0.75 when the 2 groups were compared. An ES analysis within the schizophrenia group revealed that the greatest relative impairments were on the Wechsler Adult Intelligence Scale-Revised digit symbol (ES, -0.52) and comprehension (ES, -0.42) subscales. Our findings are in concert with others demonstrating that significant cognitive impairment across multiple ability domains is a core characteristic of schizophrenia and is not caused by chronic illness, treatment, or institutionalization. The ES analysis emphasizes that patients with schizophrenia have a generalized deficit that is not easily explained by a single anatomical region or ability area.

Comparative study of visual and verbal short-term memory in English and Spanish speakers: testing a linguistic hypothesis.

It has been proposed that differences in digit span performance between English and Spanish speakers are due to the greater number of syllables per digit in the Spanish language. To test this hypothesis, we studied the performance of 30 English- and 30 Spanish-speaking elders on the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span Subtest, a modified digit span test that was linguistically comparable for both languages, and the Corsi Block Test. Consistent with previous reports, we found that English speakers scored significantly higher than Spanish speakers on WAIS-R Digit Span Forward. Group differences were reduced on the modified Digit Span Forward, but remained significant. English and Spanish speakers scored comparably on Digit Span Backward (WAIS-R and modified) and Visual Span. We suggest that although differences in the number of syllables per digit string are in part responsible for the lower performance of Spanish speakers on Digit Span Forward, cultural and educational issues also contribute to the observed differences between English and Spanish speakers.

Neuropsychological function in peripheral vascular disease amputee patients

Approximately 75% of major lower-extremity amputations are the result of peripheral vascular disease (PVD). Factors that predispose a patient to PVD (smoking, hyperlipidemia, diabetes mellitus) are also risk factors for the development of cerebrovascular disease, which could adversely affect rehabilitation. The purpose of this study was to test the hypothesis that cognitive deficits are present in amputee patients with PVD. Fourteen patients with lower-extremity amputations secondary to PVD (4 women, 10 men; mean age = 67.4 years) were recruited from a tertiary-care center for physical rehabilitation. Fourteen community-dwelling healthy volunteers (9 women, 5 men; mean age = 69.9 years) served as age-matched and education-matched controls. To assess a broad range of cognitive function, we administered standard neuropsychological tests of memory and learning, language, praxis, visuospatial skills, and abstract reasoning. PVD patients performed significantly more poorly on certain measures of psychomotor speed (Wechsler Adult Intelligence Scale-Revised Digit Symbol subtest) and problem solving/abstract reasoning (Modified Card Sorting Test) relative to controls (using the Bonferroni correction for multiple comparisons, p < .002). There were trends toward poorer patient performance on certain measures of oral fluency, concentration, reasoning, and visuoperceptual organization and constructional skills (p < .01). We propose that these cognitive deficits may be the result of unrecognized concomitant cerebrovascular disease in PVD patients and are part of a generalized pattern of vascular disease. Future research should control affective factors such as stress or depression surrounding amputation and attempt to identify the etiologic or demographic factors that are associated with neuropsychological deficits in patients with PVD.