Brain Α-Tocopherol Concentration is Inversely Associated with Neurofibrillary Tangle Counts in Brain Regions Affected in Earlier Braak Stages: A Cross-Sectional Finding in the Oldest Old.

Objectives: Higher vitamin E status has been associated with lower risk of Alzheimer's disease (AD). However, evidence of the association of vitamin E concentration in neural tissue with AD pathologies is limited. Design: The cross-sectional relationship between the human brain concentrations of α- and γ-tocopherol and the severity of AD pathologies - neurofibrillary tangle (NFT) and neuritic plaque (NP) - was investigated. Setting & Participants: Brains from 43 centenarians (≥ 98 years at death) enrolled in the Phase III of the Georgia Centenarian Study were collected at autopsy. Measurements: Brain α- and γ-tocopherol concentrations (previously reported) were averaged from frontal, temporal, and occipital cortices. NP and NFT counts (previously reported) were assessed in frontal, temporal, parietal, entorhinal cortices, amygdala, hippocampus, and subiculum. NFT topological progression was assessed using Braak staging. Multiple linear regression was performed to assess the relationship between tocopherol concentrations and NP or NFT counts, with and without adjustment for covariates. Results: Brain α-tocopherol concentrations were inversely associated with NFT but not NP counts in amygdala (ß = -2.67, 95% CI [-4.57, -0.79]), entorhinal cortex (ß = -2.01, 95% CI [-3.72, -0.30]), hippocampus (ß = -2.23, 95% CI [-3.82, -0.64]), and subiculum (ß = -2.52, 95% CI [-4.42, -0.62]) where NFT present earlier in its topological progression, but not in neocortices. Subjects with Braak III-IV had lower α-tocopherol (median = 69,622 pmol/g, IQR = 54,389-72,155 pmol/g) than those with Braak I-II (median = 72,108 pmol/g, IQR = 64,056-82,430 pmol/g), but the difference was of borderline significance (p = 0.063). γ-Tocopherol concentrations were not associated with either NFT or NP counts in any brain regions assessed. Conclusions: Higher brain α-tocopherol level is specifically associated with lower NFT counts in brain structures affected in earlier Braak stages. Our findings emphasize the possible importance of α-tocopherol intervention timing in tauopathy progression and warrant future clinical trials.

Correlates of functional capacity among centenarians.

This study investigated correlates of functional capacity among participants of the Georgia Centenarian Study. Six domains (demographics and health, positive and negative affect, personality, social and economic support, life events and coping, distal influences) were related to functional capacity for 234 centenarians and near centenarians (i.e., 98 years and older). Data were provided by proxy informants. Domain-specific multiple regression analyses suggested that younger centenarians, those living in the community and rated to be in better health were more likely to have higher functional capacity scores. Higher scores in positive affect, conscientiousness, social provisions, religious coping, and engaged lifestyle were also associated with higher levels of functional capacity. The results suggest that functional capacity levels continue to be associated with age after 100 years of life and that positive affect levels and past lifestyle activities as reported by proxies are salient factors of adaptation in very late life.

Age group differences in positive and negative affect among oldest-old adults: findings from the Georgia Centenarian Study.

OBJECTIVES: The developmental adaptation model (Martin & Martin, 2002) provides insights into how current experiences and resources (proximal variables) and past experiences (distal variables) are correlated with outcomes (e.g., well-being) in later life. Applying this model, the current study examined proximal and distal variables associated with positive and negative affect in oldest-old adults, investigating age differences. METHODS: Data from 306 octogenarians and centenarians who participated in Phase III of the Georgia Centenarian Study were used. Proximal variables included physical functioning, cognitive functioning, self-rated health, number of chronic conditions, social resources, and perceived economic status; distal variables included education, social productive activities, management of personal assets, and other learning experiences. Analysis of variance and block-wise regression analyses were conducted. RESULTS: Octogenarians showed significantly higher levels of positive emotion than centenarians. Cognitive functioning was significantly associated with positive affect, and number of health problems was significantly associated with negative affect after controlling for gender, ethnicity, residence, and marital status. Furthermore, four significant interaction effects suggested that positive affect significantly depended on the levels of cognitive and physical functioning among centenarians, whereas positive affect was dependent on the levels of physical health problems and learning experiences among octogenarians. CONCLUSION: Findings of this study addressed the importance of current and past experiences and resources in subjective well-being among oldest-old adults as a life-long process. Mechanisms connecting aging processes at the end of a long life to subjective well-being should be explored in future studies.

Life events and personality predicting loneliness among centenarians: findings from the Georgia Centenarian Study.

Regarding the purpose of this study, the researchers analyzed the roles that both life events (life-time positive events and life-time negative events) and personality (Neuroticism, Extraversion, Trust, Competence, and Ideas) played in participants of the Georgia Centenarian Study. The researchers analyzed these variables to determine whether they predicted loneliness. Analyses indicated that life-time negative events significantly predicted loneliness. In essence, the higher was the number of life-time negative life events, the higher was the loneliness score. Moreover, Neuroticism, Competence, and Ideas were all significant predictors of loneliness. The higher was the level of Neuroticism and intellectual curiosity, the higher was the level of loneliness, whereas the lower was the level of Competence, the higher was the level of loneliness. In addition, both life-time positive and life-time negative life events were significant predictors of Neuroticism. The higher was the number of life-time positive events, the lower was the level of Neuroticism, and the higher was the number of life-time negative events, the greater was the level of Neuroticism. These results indicated that life-time negative events indirectly affect loneliness via Neuroticism. Last, our results indicated that the Competence facet mediated the relationship between lifetime negative life events and loneliness. Life-time negative life events significantly affected centenarians' perceived competence, and Competence in turn significantly affected the centenarians' loneliness. These results as a whole not only add to our understanding of the link between personality and loneliness, but also provide new insight into how life events predict loneliness.

Multidimensional predictors of fatigue among octogenarians and centenarians.

BACKGROUND: Fatigue is a common and frequently observed complaint among older adults. However, knowledge about the nature and correlates of fatigue in old age is very limited. OBJECTIVE: This study examined the relationship of functional indicators, psychological and situational factors and fatigue for 210 octogenarians and centenarians from the Georgia Centenarian Study. METHODS: Three indicators of functional capacity (self-rated health, instrumental activities of daily living, physical activities of daily living), two indicators of psychological well-being (positive and negative affect), two indicators of situational factors (social network and social support), and a multidimensional fatigue scale were used. Blocked multiple regression analyses were computed to examine significant factors related to fatigue. In addition, multi-group analysis in structural equation modeling was used to investigate residential differences (i.e., long-term care facilities vs. private homes) in the relationship between significant factors and fatigue. RESULTS: Blocked multiple regression analyses indicated that two indicators of functional capacity, self-rated health and instrumental activities of daily living, both positive and negative affect, and social support were significant predictors of fatigue among oldest-old adults. The multiple group analysis in structural equation modeling revealed a significant difference among oldest-old adults based on residential status. CONCLUSION: The results suggest that we should not consider fatigue as merely an unpleasant physical symptom, but rather adopt a perspective that different factors such as psychosocial aspects can influence fatigue in advanced later life.

The oldest old: red blood cell and plasma folate in African American and white octogenarians and centenarians in Georgia.

OBJECTIVE: To determine the overall folate status of a population-based multi-ethnic sample of octogenarians and centenarians and the specific dietary, demographic and physiological factors associated with observed abnormalities. DESIGN: Population-based multiethnic sample of adults aged 80 to 89 and 98 and above. SETTING: Northern Georgia, USA. PARTICIPANTS: Men and women aged 80 to 89 (octogenarians, n = 77) and 98 and older (centenarians, n = 199). ANALYSES: Wilcoxon rank sum tests, and Chi square and logistic regression analyses were used to examine associations of low and high folate status with hematological indicators and other variables of interest. RESULTS: The prevalence of low red blood cell (RBC) folate was low overall, but tended to be higher in centenarians than in octogenarians (6.5% vs. 1.3%, p = 0.058; defined as RBC folate < 317 nmol/L). The risk of having lower RBC folate (< 25th vs. > 25th percentile for RBC folate for 60yr+ in NHANES 1999-2000) was greater in association with vitamin B12 deficiency (OR = 5.36; 95%CI: 2.87-10.01), African American race (OR = 4.29; 95%CI: 2.08-8.83), and residence in a skilled nursing facility (OR = 3.25; 95%CI: 1.56-6.78) but was not influenced by age, gender, B-vitamin supplement use, high/low food score or presence of atrophic gastritis. Combined high plasma folate and low vitamin B12 status was present in some individuals (n=11), but was not associated with increased prevalence of anemia or cognitive impairment in this study. CONCLUSIONS: Low RBC folate status (< 317 nmol/L) was rare in this post folic acid fortification sample of octogenarians and centenarians. RBC folate status (< 25th percentile) was strongly associated with 1) vitamin B12 deficiency, which has strong implications for vitamin treatment, and 2) with being African American, suggesting racial disparities exist even in the oldest old.

Family history and adaptation among centenarians and octogenarians.

BACKGROUND: The purpose of this study was to analyze various 'family history' variables (i.e. childhood health, financial situation while growing up, living with grandparents before age 17, and number of children) among participants of the Georgia Centenarian Study. OBJECTIVE: To determine whether family history variables predict critical outcome areas such as cognitive functioning, activities of daily living, mental health, and economic dependence. METHODS: A total of 318 older adults (236 centenarians and 82 octogenarians) were assessed with regard to their mental status, ADL (activities of daily living) functioning, depression, family history, loneliness, and perceived economic status. RESULTS: Analyses indicated that the number of children significantly predicted the ability to engage in activities of daily living and loneliness. In essence, the more children, the higher the activities of the daily living score and the lower the loneliness scores. In addition, childhood health significantly predicted loneliness. The poorer one's health in childhood, the higher the loneliness scores. CONCLUSION: The results of this study confirm the importance of distal family history variables on present-day functioning.

Predicting happiness among centenarians.

BACKGROUND: Happiness is believed to evolve from the comparison of current circumstances relative to past achievement. However, gerontological literature on happiness in extreme old age has been limited. OBJECTIVE: The purpose of this study was to determine how perceptions of health, social provisions, and economics link past satisfaction with life to current feelings of happiness among persons living to 100 years of age and beyond. METHODS: A total of 158 centenarians from the Georgia Centenarian Study were included to conduct the investigation. Items reflecting congruence and happiness from the Life Satisfaction Index were used to evaluate a model of happiness. Pathways between congruence, perceived economic security, subjective health, perceived social provisions, and happiness were analyzed using structural equation modeling. RESULTS: Congruence emerged as a key predictor of happiness. Furthermore, congruence predicted perceived economic security and subjective health, whereas perceived economic security had a strong influence on subjective health status. CONCLUSION: It appears that past satisfaction with life influences how centenarians frame subjective evaluations of health status and economic security. Furthermore, past satisfaction with life is directly associated with present happiness. This presents implications relative to understanding how perception of resources may enhance quality of life among persons who live exceptionally long lives.

Distal and proximal resource influences on economic dependency among the oldest old.

BACKGROUND: As exceptional survivors, centenarians may have characteristics that reduce their dependency on family and community support systems despite the expectation that their extreme age creates a burden on those systems. The Georgia Centenarian Study obtained information about assistance for income, medical care, and caregiving of all types for a sample of centenarians and octogenarians. Previous studies have not established which characteristics may contribute to economic dependency among the oldest old. OBJECTIVE: To identify distal and proximal resource influences on economic dependency, considering past lifestyle, proximal health, economic resources, personality, and coping behavior. METHODS: Analysis sample sizes ranged from 109 to 138 octogenarians and centenarians. Blockwise multiple regressions predicted whether they received income assistance, number of medical care events, number of caregiving types, and total caregiving hours. RESULTS: Past life style, gender, ethnicity, socioeconomic status, functional health, and coping were not related to economic dependency. With the exception of the number of types of care, centenarians were not more dependent than octogenarians. Cognitive ability had the strongest effects for medical care and caregiving services. 'Extraversion', 'ideas', 'neuroticism', and 'competence' personality factors had significant effects for caregiving types and total hours of care received. CONCLUSION: Monitoring and intervention to maintain cognitive ability are critical practices for autonomy and reduced economic dependency among the oldest old. Psychological resources are more important influences on social support than functional health and other proximal economic resources.

Social resources and longevity: findings from the Georgia centenarian study.

BACKGROUND: As the proportion of adults aged 85 and older increases, investigations of resources essential for adapting to the challenges of aging are required. OBJECTIVE: To comprehensively investigate the social resources of cognitively intact centenarians participating in the Georgia Centenarian Study and the association between these resources and residence status. METHODS: Two widely used measures of social resources were investigated among participants living in private homes, personal care facilities, and nursing homes. Logistic regression was used to determine significant predictors of nursing home residence. RESULTS: Differences in levels of social resources were found between centenarians and octogenarians, and among centenarians in different living situations. Analyses revealed differential findings between self- and proxy reports. Controlling for education, activities of daily living, and financial ability to meet needs, only one of the two social resources measures significantly reduced the odds of nursing home residence. CONCLUSION: The findings of this study add to the existing literature on one of the basic adaptive resources (social resources) for centenarians. Whether a more specific assessment of network contact is employed, or a more global assessment is used, differences in these constructs exist between centenarians and octogenarians, among centenarians in differing living conditions, and across types of informants. Researchers examining the different resources that may contribute to extraordinary longevity and positive adaptation may find it essential to differentiate between the oldest old and centenarians, and to account for differences based upon measure, reporter type, and centenarian residence status.

Semantic memory activation in individuals at risk for developing Alzheimer disease.

OBJECTIVE: To determine whether whole-brain, event-related fMRI can distinguish healthy older adults with known Alzheimer disease (AD) risk factors (family history, APOE epsilon4) from controls using a semantic memory task involving discrimination of famous from unfamiliar names. METHODS: Sixty-nine cognitively asymptomatic adults were divided into 3 groups (n = 23 each) based on AD risk: 1) no family history, no epsilon4 allele (control [CON]); 2) family history, no epsilon4 allele (FH); and 3) family history and epsilon4 allele (FH+epsilon4). Separate hemodynamic response functions were extracted for famous and unfamiliar names using deconvolution analysis (correct trials only). RESULTS: Cognitively intact older adults with AD risk factors (FH and FH+epsilon4) exhibited greater activation in recognizing famous relative to unfamiliar names than a group without risk factors (CON), especially in the bilateral posterior cingulate/precuneus, bilateral temporoparietal junction, and bilateral prefrontal cortex. The increased activation was more apparent in the FH+epsilon4 than in the FH group. Unlike the 2 at-risk groups, the control group demonstrated greater activation for unfamiliar than familiar names, predominately in the supplementary motor area, bilateral precentral, left inferior frontal, right insula, precuneus, and angular gyrus. These results could not be attributed to differences in demographic variables, cerebral atrophy, episodic memory performance, global cognitive functioning, activities of daily living, or depression. CONCLUSIONS: Results demonstrate that a low-effort, high-accuracy semantic memory activation task is sensitive to Alzheimer disease risk factors in a dose-related manner. This increased activation in at-risk individuals may reflect a compensatory brain response to support task performance in otherwise asymptomatic older adults.

Semantic memory activation in amnestic mild cognitive impairment.

Cognitively intact older individuals at risk for developing Alzheimer's disease frequently show increased functional magnetic resonance imaging (fMRI) brain activation presumably associated with compensatory recruitment, whereas mild cognitive impairment (MCI) patients tend not to show increased activation presumably due to reduced neural reserve. Previous studies, however, have typically used episodic memory activation tasks, placing MCI participants at a performance disadvantage relative to healthy elders. In this event-related fMRI study, we employed a low effort, high accuracy semantic memory task to determine if increased activation of memory circuits is preserved in amnestic MCI when task performance is controlled. Fifty-seven participants, aged 65-85 years, comprised three groups (n = 19 each): amnestic MCI patients; cognitively intact older participants at risk for developing Alzheimer's disease based on having at least one ApoE epsilon4 allele and a positive family history of Alzheimer's disease (At Risk); and cognitively intact participants without Alzheimer's disease risk factors (Control). fMRI was conducted on a 3T MR scanner while participants performed a famous name discrimination task. Participants also underwent neuropsychological testing outside the scanner; whole brain and hippocampal atrophy were assessed from anatomical MRI scans. The three groups did not differ on demographic variables or on fame discrimination performance (>87% correct for all groups). As expected, the amnestic MCI participants demonstrated reduced episodic memory performance. Spatial extent of activation (Fame--Unfamiliar subtraction) differentiated the three groups (Control = 0 ml, At Risk = 9.7 ml, MCI = 34.7 ml). The MCI and At Risk groups showed significantly greater per cent signal change than Control participants in 8 of 14 functionally defined regions, including the medial temporal lobe, temporoparietal junction, and posterior cingulate/precuneus. MCI participants also showed greater activation than Controls in two frontal regions. At Risk, but not MCI, participants showed increased activity in the left hippocampal complex; MCI participants, however, evidenced increased activity in this region when hippocampal atrophy was controlled. When performance is equated, MCI patients demonstrate functional compensation in brain regions subserving semantic memory systems that generally equals or exceeds that observed in cognitively intact individuals at risk for Alzheimer's disease. This hyperactivation profile in MCI is even observed in the left hippocampal complex, but only when the extent of hippocampal atrophy is taken into consideration.

Cross-validation of prediction equations for Wechsler Memory Scale-III Indexes.

Six prediction equations were previously found to predict to Wechsler Memory Scale-III (WMS-3) Immediate Memory Index (IM) and General Memory Index (GM) using two- or three-subtest combinations. The equations were cross-validated on a sample of 214 mixed clinical patients from an entirely different location in the Midwest. The two three-subtest prediction equations (including Logical Memory, Verbal Paired Associates, and either Faces or Family Pictures) better estimated IM and GM than did the two-subtest equations (Logical Memory and Verbal Paired Associates). Correlations for the former equations correlated .97 and .96 with full WMS-3 IM and GM, respectively. In addition, at least 95% of the predicted scores were within two SEMs of obtained IM and GM scores. The two-subtest equations correlated only .89 for IM and .92 for GM. The predicted scores that fell within two SEMs captured 78% and 88% of the cases for IM and GM, respectively. The results provide support for the use of the three-subtest prorated forms of the WMS-3 to estimate IM and GM.

Repetitive transcranial magnetic stimulation does not replicate the Wada test.

The authors compared inferior frontal speech arrest from repetitive transcranial magnetic stimulation (rTMS) with bilateral Wada tests in 17 epilepsy surgery candidates. Although rTMS lateralization correlated with the Wada test in most subjects, rTMS also favored the right hemisphere at a rate significantly greater than the Wada test. Postoperative language deficits were more consistent with Wada results. Available methods for inducing speech arrest with rTMS do not replicate the results of Wada tests.

Parsimonious prediction of Wechsler Memory Scale--III memory indices.

Equations for prorating the Wechsler Memory Scale--III (WMS-III) Index scores were derived and validated on a sample of 252 mixed clinical cases. Regression equations were performed using age-scaled scores as predictors and the sum of age-scaled scores for Immediate Memory (IM) and General Memory (GM) as the criteria. Including Logical Memory and Verbal Paired Associates with either Faces or Family Pictures resulted in estimated scores that accounted for 95% to 97% of the variance for IM and GM. Over 80% of these cases had estimated sum of scaled scores that fell within 3 points of actual sum of scaled scores, within 1 standard error of measurement. When only Logical Memory and Verbal Paired Associates were included, estimations accounted for only 87% of the variance, and only 60% of the estimated scores fell within 3 points of actual sum of scaled scores. The regression equations are presented, as are the confidence intervals derived from a bootstrapping procedure that created 15,000 different samples.

Convergent and discriminant validity of the CVLT (dementia version). California Verbal Learning Test.

This study investigated the convergent and discriminant validity of the 9-item "dementia version'' of the California Verbal Learning Test (CVLT-9) in a sample of 130 geriatric patients evaluated for memory complaints. Moderate correlations were observed between the CVLT-9 sum of words recalled for trials 1-5 (Trial 1-5 Recall) and Long-Delay Free Recall (LDFR) measures and the immediate and delayed Logical Memory (LM I and LM II) and Visual Reproduction (VR I and VR II) subtests from the Wechsler Memory Scale-Revised (WMS-R). However, the CVLT-9 Trial 1-5 Recall and VR I measures demonstrated significant correlations with a number of additional measures of language and visuospatial ability. The CVLT-9 LDFR, and the WMS-R LM I, LM II, and VR II showed less overlap with non-episodic memory functioning. A principal components analysis yielded a three-component solution consisting of a general or "g'' component, a specific memory component, and a mood component. The CVLT-9 Trial 1-5 Recall and VR I loaded on both the "g'' and the memory components, whereas LM I, LM II, and VR II loaded on only the memory component. We conclude that the CVLT-9 Trial 1-5 Recall and VR I demonstrate low discriminant validity, suggesting diminished specificity as memory measures.

Task decomposition analysis of intertrial free recall performance on the Rey Auditory Verbal Learning Test in normal aging and Alzheimer's disease.

Task decomposition provides supplementary data that complement traditionally computed performance indexes of multi-trial list learning. Both traditional and decomposition approaches can be combined to permit a thorough assessment of multiple aspects of learning and memory in patients with memory impairment. We applied task decomposition to investigate the relative roles of acquisition and consolidation in mediating the multi-trial learning deficit in patients with Alzheimer's disease. This goal was accomplished by decomposing recall performance across the five study-and-test trials of the Rey Auditory Verbal Learning Tests into measures that presumably tap intertrial acquisition and intertrial consolidation. As compared to matched controls, patients diagnosed with mild Alzheimer's disease showed lower gained access across trials, indicating that Alzheimer's disease impairs the ability to produce a stable memory representation of new material in long-term memory. Additionally, patients with Alzheimer's disease manifested higher lost access, which suggests that deficient consolidation leading to rapid intertrial forgetting also contributes to their poor learning. We argue that analytically decomposing learning curves will help both in uncovering the cognitive processes that underlie disease-related learning deficits in persons with memory disorders and can help to characterize potential areas for remediation.

A confrontational naming task produces congruent increases and decreases in PET and fMRI.

This work uses the well-established (by PET) confrontation naming task to compare PET and fMRI in a cognitive activation experiment. The signal changes from this task are much less than the changes caused by visual or motor activation tasks used in previous comparisons. ANOVA methods adjusted for multiple comparisons were used to determine significant changes in signal between confrontation naming and figure size discrimination tasks. All 17 significantly increased regions (confrontation naming signal greater) seen on one modality were increased on both modalities. Ten of 13 regions that were significantly decreased on one modality were decreased on the other. Three mismatched regions showed a significant decrease on one modality and a nonsignificant increase on the other. This study could not detect a consistent difference in activation site location between PET and fMRI.

Butanol is superior to water for performing positron emission tomography activation studies.

[15(O)]Butanol has been shown to be superior to [15(O)]water for measuring cerebral blood flow with positron emission tomography. This work demonstrates that it is also superior for performing activation studies. Data were collected under three conditions: a visual confrontation animal-naming task, nonsense figure size discrimination, and a nonvisual darkroom control task. Time-activity curves (TAC) were obtained for regions known to be activated by the confrontation naming task to compare absolute uptake and the different kinetics of the two tracers. Also, t statistic maps were calculated from the data of 10 subjects for both tracers and compared for magnitude of change and size of activated regions. Peak uptake in the whole-brain TAC were similar for the two tracers. For all regions and conditions, the washout rate of [15(O)]butanol was 41% greater than that of [15(O)]water. At a threshold of 0, the [15(O)]water and [15(O)]butanol percent difference (nonnormalized) and t statistic (global normalization) images are nearly identical, indicating that the same property is being measured with both tracers. The [15(O)]butanol parametric images displayed at a threshold of /t/ = 5 look similar to the [15(O)]water parametric maps displayed at a threshold of /t/ = 4, which is consistent with the observation that t statistic values in [15(O)]butanol images are generally greater. The t statistic values were equal when the [15(O)]butanol parametric map was created from any subset of 6 subjects and the [15(O)]water parametric map was created from all 10 subjects. Fewer subjects need to be studied with [15(O)]butanol to reach the same statistical power as an [15(O)]water-based study.

Interpretative guidelines for neuropsychiatric measures with dichotomously scored items.

Neuropsychiatric measures consisting of dichotomously scored items are commonly used in clinical assessment. After summing these items, clinical guidelines frequently recommend cutoff scores to determine the presence or degree of a particular attribute, such as depression. However, blind application of such cutoffs neglects whether the total score is significantly different from chance. This confounding problem is illustrated using the Geriatric Depression Scale (GDS), and recommendations for interpreting the degree to which a GDS score significantly exceeds chance are presented. Specifically, GDS scores between 11 and 20, inclusive, were found not to differ significantly from chance (p > 0.05), assuming a random response pattern. The importance of supportive clinical evidence of depressive symptomatology is increased for scores in this range. These guidelines will be helpful in using such measures with patients who may vary with respect to response accuracy, and in assessing possible incomplete effort or random responding.