Measures Of Global Impairment Research Articles

Self-Endorsed Cognitive Problems Vs. Objectively-Assessed Cognitive Impairment in Blood or Marrow Transplantation (BMT) Recipients — a Longitudinal Study

Background: Cognitive impairment in BMT survivors is well-documented, and may include deficits in memory, attention, executive functioning and processing speed. However, the clinical relevance of self-endorsed cognitive problems and their relation to objectively-assessed cognitive impairment is not established.Methods: We assessed cognitive impairment in 379 BMT recipients (median age = 52.2y; 40% females; 68% non-Hispanic whites) at 5 pre-determined timepoints: baseline (pre-BMT), 6mo, 1y, 2y and 3y after BMT. Self-endorsed cognitive problems (0: not at all to 4: extremely) were evaluated using the Neuropsychological Impairment Scale (NIS) - a 95-item survey. Responses were used to derive a Global Measure of Impairment (GMI) T-score; higher scores indicated greater cognitive problems. A standardized 2h battery of objective cognitive testing was also administered at each timepoint to derive a Global Deficit Score (GDS); individuals with GDS >0.5 were considered impaired. Healthy controls (HC: n = 98; median age = 55.1y; 46% females; 62% non-Hispanic whites) also completed the NIS and underwent cognitive testing at the 5 corresponding timepoints. At each timepoint, a multivariable analysis of covariance was performed to examine the magnitude of difference in GMI between BMT recipients and HC. Multilevel modeling was employed to examine participants' rates of change in GMI across time. Among BMT recipients, we used multivariable analyses to identify clinical/demographic variables associated with greater self-endorsed cognitive problems; variables examined included age at BMT, sex, race/ethnicity, education, pre-BMT IQ, fatigue, type of BMT (autologous, allogeneic [myeloablative, reduced-intensity]) and use of total body irradiation. To evaluate the relation between NIS subscales and corresponding objective cognitive domains, within-group first-order partial correlation analyses were conducted at each timepoint. We also examined the association between cognitive impairment and return to work at 3y.Results: Significant differences (p<.001) were observed in mean GMI scores with BMT recipients having consistently higher scores than HC at all timepoints. Multilevel modeling revealed that the rate of change in NIS scores was significantly greater in BMT recipients when compared with HC, after adjusting for age, sex, education level, fatigue and baseline IQ (Fig 1). Among BMT recipients, predictors of endorsement of cognitive problems across all timepoints (p ≤.003) included younger age at study (Wilks' λ = .797), higher pre-BMT IQ (Wilks' λ = .858) and greater fatigue (Wilks' λ = .811). Overall, there was a statistically-significant, modest correlation between GMI and GDS scores (range: .401 to .445, p ≤ .01), with mean GMI scores being generally higher (indicating greater endorsement of cognitive impairment) among those who were found to be cognitively impaired (GDS) via objective testing (Fig 2); these relationships were statistically significant at 6mo, 1y and 2y. Multivariable analysis adjusting for age, sex, education level, fatigue and IQ revealed that higher self-reported cognitive impairment (GMI) and higher objectively assessed cognitive impairment (GDS) were associated with a 3.7-fold (p = .02) and 4.3-fold (p = .02) higher odds of not returning to work at 3y, respectively.Conclusions: BMT recipients are more likely to report cognitive problems as compared with HC. Further, these problems increase with time from BMT. Younger age at BMT, higher pre-BMT IQ and greater fatigue are associated with greater self-endorsed cognitive problems. Further, there is a modest-to-high correlation between self-endorsed cognitive problems and objectively determined cognitive impairment. Finally, both self-endorsed cognitive problems and objectively assessed cognitive impairment are associated with a higher likelihood of not returning to work. Overall, this study demonstrates that self-endorsed cognitive problems can serve as a good screen for identifying those with cognitive impairment. DisclosuresForman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

A comparison of clinician-rated neuropsychological and self-rated cognitive assessments in patients with asthma and rheumatologic disorders

Although data are mixed, asthma and rheumatologic conditions may be associated with cognitive impairment. Medications may play a role because corticosteroids are associated with memory impairment. Therefore, an easily administered assessment of cognition would be useful in these patients. We assessed relationships between self-rated and clinician-rated cognitive performance and mood in patients with asthma and rheumatologic diseases. Participants included 31adults treated for asthma or rheumatologic disorders (17 receiving chronic prednisone therapy, and 14 not receiving prednisone). An objective assessment of a variety of cognitive domains was administered through clinician and patient-rated assessments of cognition. Composite scores for the objective (Global Clinical Rating [GCR]) and subjective (Neuropsychological Impairment Scale: Global Measure of Impairment [GMI]) measures of cognition were derived. Depression was assessed with the 17-item Hamilton Rating Scale for Depression (HRSD-17). A linear regression was conducted with GMI scores as dependent variable and GCR, HRSD-17 scores, and prednisone-use status, as independent variables. Significant differences between prednisone-treated patients and other patients were observed on the GCR, GMI, and HRSD-17. In the regression analysis, HRSD-17 scores, but not GCR scores, significantly predicted GMI scores. Prednisone-treated patients had higher levels of depressive symptoms and subjective and objective cognitive deficits than those not taking prednisone. In the combined patient groups, subjective cognitive assessment was more strongly related to depressive symptoms than objective cognition. Findings suggest physicians should be aware of the potential for cognitive deficits in patients taking corticosteroids and, when appropriate, should consider the use of objective neurocognitive tests or neuropsychology consultation to better characterize its presence and severity.

Prevalence and Predictors of Self-Reported Neuropsychological Impairment in Patients Undergoing Hematopoietic Cell Transplantation (HCT) - Impact On Return to Work After HCT.

Abstract 808The growing population of HCT survivors may be at risk for neuropsychological impairment due to exposure to neurotoxic agents. HCT survivors frequently report problems with memory and attention (Cancer 2002;95:183-192), and even though the patients are acutely aware of neuropsychological declines, these changes do not correlate well with impairment on standardized neuropsychological assessments (Bone Marrow Transplant 2005;36:695-702). This discrepancy suggests that the tests may not be sensitive enough to detect subtle changes that could nonetheless impact patients' societal reintegration, highlighting the importance of self-report instruments. The present study aims to assess the longitudinal trajectory of self-reported neuropsychological impairment in patients from pre-HCT to 1 year post-HCT; to evaluate the impact of demographic and clinical factors on self-reported neuropsychological impairment; to examine the relationship between self-reported neuropsychological impairment data and objective data collected using standardized assessments; and to understand the relationship between self-reported impairment and return to work. Participants were 182 adult patients undergoing HCT for hematological malignancies. Mean age at HCT was 50 years (range, 18-73); 60% were males; 68% were non-Hispanic whites; 62% received autologous HCT. Patients completed a 2-hour battery of standardized neuropsychological tests (domains: processing speed; immediate, general, and working memory; cognitive reserve; executive function) and a self-reported Neuropsychological Impairment Scale (NIS – scales: Global Measure of Impairment [GMI, an overall summary score], Cognitive Efficiency [COG], Attention [ATT], Memory [MEM], Learning-Verbal [L-V], Academic Skills [ACD]). Self-reported information on return to work was obtained at 6 months and 1 year after HCT. Demographic (sex, age, race/ethnicity, education, income, marital status) and clinical data (diagnosis, donor source, risk of relapse, conditioning exposures) were collected. Raw scores were converted to t-scores using normative data; individuals with t-scores above 1 SD of the normative distribution were classified as impaired. Generalized estimating equations were used to examine longitudinal trends. The prevalence of domain-specific impairment at specified time points is shown in the Table. After adjusting for significant covariates, GMI worsened at 6 months and plateaued thereafter (p=0.04) and ATT worsened at 6 months but returned to baseline at 1 year (p=0.006) (Figure). Multivariate analyses revealed the following risk factors: at pre-HCT: female gender and less than high school education (higher MEM impairment, p=0.03, p=0.05, respectively); at both 6 months and 1 year post-HCT: annual household income less than $20,000 (higher GMI impairment, p=0.02); exposure to total body irradiation (TBI: higher COG impairment, p=0.006, and higher ATT impairment, p=0.05); female gender (p=0.05) and 4-year college education (p=0.058) (higher MEM impairment). Correlations between NIS scores and standardized assessments were weak (range, r= -0.3 to 0.09). At 6 months, 57% of the patients had not returned to work. Patients with COG impairment were less likely to return to work (p=0.05), while patients with higher cognitive reserve were more likely to return to work (p=0.03). These results suggest that a significant proportion of patients undergoing HCT report neuropsychological impairment that may not be readily captured by standardized assessments. The present study identifies low household income, TBI, female gender, and college education as risk factors and describes the impact of self-reported neuropsychological impairment on the ability to return to work. This study therefore helps characterize a vulnerable population that needs to be followed closely for appropriate intervention to ensure appropriate societal reintegration after HCT.TablePrevalence of neuropsychological impairment (t>60) by time pointGMICOGATTMEML-VACDPre-HCT29%33%25%25%24%22%6 months (n=94)32%40%32%27%33%22%1 year (n=69)32%29%23%29%25%23% [Display omitted] Disclosures:Forman:City of Hope: Employment.

DONEPEZIL TREATMENT OF PATIENTS WITH MCI: A 48-WEEK RANDOMIZED, PLACEBO- CONTROLLED TRIAL

Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms.In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function.The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%).Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.

Donepezil treatment of patients with MCI

Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms. In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function. The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%). Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.

ADHD Correlates, Comorbidity, and Impairment in Community and Treated Samples of Children and Adolescents

Patterns of correlates, comorbidity and impairment associated with attention-deficit hyperactivity disorder (ADHD) in children and youth were examined in representative samples from the community and from treatment facilities serving medically indigent youth in Puerto Rico. Information from caretakers and youths was obtained using the Diagnostic Interview Schedule for Children, (version IV), measures of global impairment, and a battery of potential correlates. In the community (N = 1,896) and the treated samples (N = 763), 7.5 and 26.2% of the children, respectively, met criteria for DSM-IV ADHD in the previous year. Although the prevalence rates and degree of impairment differed, the general patterns of correlates, comorbidity and impairment were similar in both populations. The exceptions were associated with conduct disorder, anxiety, impairment in the ADHD comorbid group, and age factors that appeared to be related to selection into treatment.

Assessing Functional Impairment and Social Adaptation for Child Mental Health Services Research: A Review of Measures

The need for assessing impairment in functioning as an integral part of child mental health services research is discussed. Methodologic difficulties related to problems in case definition, the conceptual definition of impairment and social adaptation, and the assessment of the construct across cultures are also addressed. In addition, a critical review of existing child impairment measures with published psychometric properties is presented. The measures are divided into three types: measures of global impairment, domain-specific measures, and symptom-specific measures. The paper concludes that the choice of the measure to use in health services research needs to be determined according to the main goals of the study, the population in which the instrument is going to be used, and the interviewer's knowledge of the child. Other characteristics of the measures of impairment that the researcher should consider are also discussed.

Transient fluctuations in cognitive functioning in schizophrenia based on single-case study methods

The stability of cognitive performance in four schizophrenia patients was examined over a short time period. A cognitive battery highly sensitive to organismic state (the Repeatable Cognitive-Perceptual-Motor Battery, RCPM) was utilized. Single-case statistical methods tested for within-individual change across five assessments at two week intervals. All four subjects showed statistically significant post-baseline variation in a global measure of impairment (average impairment rating score) and in at least 50% of the individual tests having adequate test-retest reliability. Data are interpreted as providing suggestive evidence of transient fluctuations in performance within a stable window of impaired cognitive functioning. These fluctuations appear substantial enough to influence both research and clinical outcomes. The benefits of the single-case methodology employed are discussed. The data suggest that significant transient fluctuations in cognitive performance can be observed in schizophrenia in domains purported to represent vulnerability markers of the disorder. The importance of accounting for these transient fluctuations in the attempt to identify enduring, trait-like characteristics of cognitive functioning in schizophrenia is discussed.