This study investigated the specific patient factors that predict responsiveness to a cognitive rehabilitation program. The program has previously been demonstrated to be successful at the group level in patients with gliomas, but it is unclear which patient characteristics optimized the effect of the intervention at the individual level. Four categories of possible predictors of improvement were selected for evaluation: sociodemographic and clinical variables, self-reported cognitive symptoms, and objective neuropsychological test performance. Hierarchical logistic regression analyses were conducted, beginning with the most accessible (sociodemographic) variables and ending with the most difficult (baseline neuropsychological) to identify in clinical practice. Nearly 60% of the participants of the intervention were classified as reliably improved. Reliable improvement was predicted by age (p = .003) and education (p = .011). Additional results suggested that younger patients were more likely to benefit specifically from the cognitive rehabilitation program (p = .001), and that higher education was also associated with improvement in the control group (p = .024). The findings are discussed in light of brain reserve theory. A practical implication is that cognitive rehabilitation programs should take the patients’ age into account and, if possible, adapt programs to increase the likelihood of improvement among older participants. (JINS, 2011, 17, 256–266)

Elucidating the relationship between fatigue and depression in multiple sclerosis (MS) patients is complicated by ambiguity regarding how these two constructs should be delineated. Neurovegetative symptoms of depression may reflect depression in MS patients, as they do in non-neurological populations; instead these items may measure disease-related fatigue; or disease-related fatigue and depression may reflect the same syndrome in MS patients. The present study sought to evaluate these possibilities by characterizing the underlying factor structure of self-report items designed to measure fatigue and depression symptoms. Questionnaires designed to measure fatigue and depression were administered to 174 MS patients and 84 healthy controls, and these items were subject to factor analysis. Results suggest that neurovegetative symptoms are poor indicators of depression in MS patients. Neurovegetative depression items were removed from the final model due to poor psychometric properties, or they loaded on Fatigue or Sleep Disturbance factors. The correlation between latent factors Depression and Fatigue was large (.47), but does not indicate that these phenomena are manifestations of the same construct. Hence, the results of this study support the notion that vegetative symptoms of depression do not reflect depression in MS patients, but instead measure symptoms of fatigue and sleep disturbance. (JINS, 2010, 17, 000–000)

We examined the association of social activity with cognitive decline in 1138 persons without dementia at baseline with a mean age of 79.6 (SD = 7.5) who were followed for up to 12 years (mean = 5.2; SD = 2.8). Using mixed models adjusted for age, sex, education, race, social network size, depression, chronic conditions, disability, neuroticism, extraversion, cognitive activity, and physical activity, more social activity was associated with less cognitive decline during average follow-up of 5.2 years (SD = 2.7). A one point increase in social activity score (range = 1–4.2; mean = 2.6; SD = 0.6) was associated with a 47% decrease in the rate of decline in global cognitive function (p < .001). The rate of global cognitive decline was reduced by an average of 70% in persons who were frequently socially active (score = 3.33, 90th percentile) compared to persons who were infrequently socially active (score = 1.83, 10th percentile). This association was similar across five domains of cognitive function. Sensitivity analyses revealed that individuals with the lowest levels of cognition or with mild cognitive impairment at baseline did not drive this relationship. These results confirm that more socially active older adults experience less cognitive decline in old age. (JINS, 2011, 17, 998–1005)

Healthy elderly adults are slower to initiate and produce speech. However, the sources of the slowing remain poorly understood. The present study evaluates to which extent psychomotor and cognitive changes influence age-related slowing in speech generation. Four verbal tasks varying in degree of difficulty and cognitive demands were used to evaluate 30 young and 30 healthy elderly. Speed of word production was measured by reaction times and pronunciation durations. Stroop test and Digits backwards were used as cognitive predictors while the Purdue Pegboard and Finger Tapping were used as psychomotor predictors. The relative contribution of cognitive and psychomotor functioning was evaluated by hierarchical regression analyses and based on the processing speed hypothesis. Results showed that Vocabulary and psychomotor execution significantly explained a portion of the variance in RTs depending on type of verbal task. These variables explained 36% of the total variance in reading, 26% in naming, 31% in phonemic fluency and 47% in semantic fluency. Also, Vocabulary and psychomotor functions strongly predicted pronunciation speed. Conversely, tests related to executive functions and working memory were not significant predictors. These data demonstrate the importance of the interplay between Vocabulary and psychomotor decline on speed of language production among healthy elderly adults. (JINS, 2011, 17, 807–821)

Older African Americans tend to perform poorly in comparison with older Whites on episodic memory tests. Observed group differences may reflect some combination of biological differences, measurement bias, and other confounding factors that differ across groups. Cognitive reserve refers to the hypothesis that factors, such as years of education, cognitive activity, and socioeconomic status, promote brain resilience in the face of pathological threats to brain integrity in late life. Educational quality, measured by reading test performance, has been postulated as an important aspect of cognitive reserve. Previous studies have not concurrently evaluated test bias and other explanations for observed differences between older African Americans and Whites. We combined data from two studies to address this question. We analyzed data from 273 African American and 720 White older adults. We assessed DIF using an item response theory/ordinal logistic regression approach. DIF and factors associated with cognitive reserve did not explain the relationship between race, and age- and sex-adjusted episodic memory test performance. However, reading level did explain this relationship. The results reinforce the importance of considering education quality, as measured by reading level, when assessing cognition among diverse older adults. (JINS, 2011, 17, 625–638)

Participation in cognitively stimulating leisure activities such as crossword puzzles may delay onset of the memory decline in the preclinical stages of dementia, possibly via its effect on improving cognitive reserve. We followed 488 initially cognitively intact community residing individuals with clinical and cognitive assessments every 12–18 months in the Bronx Aging Study. We assessed the influence of crossword puzzle participation on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. Crossword puzzle participation at baseline delayed onset of accelerated memory decline by 2.54 years. Inclusion of education or participation in other cognitively stimulating activities did not significantly add to the fit of the model beyond the effect of puzzles. Our findings show that late life crossword puzzle participation, independent of education, was associated with delayed onset of memory decline in persons who developed dementia. Given the wide availability and accessibility of crossword puzzles, their role in preventing cognitive decline should be validated in future clinical trials. (JINS, 2011, 17, 1006–1013)

Early stages of affective or psychotic disorders may be accompanied by neuropsychological changes that help to predict risk of developing more severe disorders. A comprehensive set of neuropsychological measures was collected in 109 help-seeking young people (16 to 30 years; 54 females), recently diagnosed with an affective or psychotic disorder and presenting with current depression. Hierarchical cluster analysis determined three clusters: one deemed to have a “poor memory” profile (n = 40); another with a “poor mental flexibility” profile (n = 38) and a third with widespread difficulties plus “impaired attention and memory” (n = 31). In general, the three clusters were comparable in demographic, functional and clinical factors suggesting some unique role for neurocognitive impairments. A discriminant function analysis confirmed that the clusters were best characterized by performance in “attentional” versus “learning/memory” measures. Furthermore, profiles of independent neuropsychological variables validated the original solution for two of the clusters, distinguishing all cluster-groups on an attentional measure. The findings of this study suggest that despite presenting with very similar levels of current depressive symptomatology, young help-seeking individuals in the early stages of illness have underlying neuropsychological heterogeneity. Distinct neuropsychological profiling may help to predict later psychiatric outcomes and enhance individually-tailored early intervention strategies. (JINS, 2011, 17, 267–276)

Patterns of cerebral asymmetry related to visuospatial functions may change with age. The typical leftward bias on a line bisection task may reflect cerebral asymmetry. With age, such leftward bias decreases. This study demonstrated that the age-related decrease of leftward bias may actually be sex-specific. In addition, previous research suggests that young adults’ deviation in line bisection may reflect asymmetric hemispheric activation of perceptual–attentional “where” spatial systems, rather than motor-intentional “aiming” spatial systems; thus, we specifically fractionated “where” and “aiming” bias of men and women ranging in age from 22 to 93 years old. We observed that older men produced greater rightward line bisection errors, of primarily “where” spatial character. However, women's errors remained leftward biased, and did not significantly change with age. “Where” spatial systems may be linked to cortico-cortical processing networks involving the posterior part of the dorsal visuospatial processing stream. Thus, the current results are consistent with the conclusion that reduced right dorsal spatial activity in aging may occur in the male, but not female, adult spatial system development. (JINS, 2011, 17, 455–462)

Measures of brain and hippocampal volume in 40 healthy young (aged 18–30 years) and 36 healthy elderly (aged 60–83 years) subjects were compared with composite cognitive function scores in three conceptual domains: memory ability, processing speed, and general fluid intelligence. Through a series of general linear models testing the relationship between these brain measures and cognitive performance scores, a significant positive relationship between hippocampal volume and fluid intelligence ability was found in elderly subjects but not in young. No relationship between the other cognitive domains and brain or hippocampal volume was found. The findings suggest a role of hippocampal atrophy in the decline in fluid intelligence in the elderly. (JINS, 2011, 17, 000–000)

Neuropsychological deficits are commonly found to be part of depression in old age and might simultaneously represent early symptoms of dementia. We investigated the influence of depression on processing speed and executive function in subjects who did not develop dementia during the following 5 years to examine whether these neuropsychological dysfunctions are due to depression or are influenced by other causes (e.g., education, cerebral comorbidity). A total of 287 subjects aged 75 (mean: 75.76) were available for analyses. Processing speed was measured by the Trail Making Test-A, Executive Function by the Trail Making Test-B and Verbal Fluency. DSM-IV-criteria were used for diagnosing depression. Cerebral comorbidity (e.g., stroke, Parkinson's disease), sex, education, antidepressant, and/or benzodiazepine medication, and a history of depression were taken into account as covariates. Univariate analyses and multiple regression analyses were calculated. Higher education was strongly related to better performance in all three psychometric tests. Cerebral comorbidity significantly slowed TMT-A performance and reduced Verbal Fluency scores. In multiple regression analysis depression showed only a minor, slowing influence on TMT-A and TMT-B performance. Depression only had a minor influence on processing speed and executive function in this sample of nondemented subjects. By comparison, the influence of education and cerebral comorbidity was seen to be stronger. (JINS, 2011, 17, 822–831)

A strong tendency toward left hemisphere (LH) language dominance has been well established, as evidenced by the high prevalence of language impairment following sudden onset lesions in the LH. In the presence of progressive LH pathology, such as epilepsy, substantial deviations in language organization can occur. However, the question regarding whether reorganization involves both expressive and receptive language functions or only the one directly affected by the primary location of pathology has not been settled. Using Wada testing scores from 296 epilepsy patients and estimated rates of typical dominance in the normal population, we assessed the frequency with which left frontal and temporal pathology resulted in reorganization of only the expressive or receptive language function or both. The comparisons revealed: (1) a significantly higher prevalence of atypical organization (i.e., deviations from LH dominance) among the LH patients compared to normal population estimates and right hemisphere patients, and (2) that regardless of pathology location within the LH, the rates of atypical reorganization for both expressive and receptive language were essentially equal. These results constitute evidence that the two language functions are intimately yoked and that when disruption to the system results in reorganization, it usually yields functional changes throughout the system. (JINS, 2010, 17, 000–000)

An objective in current research on children with fetal alcohol spectrum disorders (FASD) is to determine neurobehavioral profiles to identify affected individuals. Deficits observed when children with FASD are compared to typically developing controls may be confounded by lower IQ scores in the subjects with FASD. To determine if prenatal alcohol exposure is associated with neurobehavioral deficits after controlling for IQ differences, multivariate analyses were conducted to compare alcohol-exposed (ALC) subjects to a comparison group closely matched on IQ (IQC). The initial analysis included a broad neuropsychological battery with measures of language, executive function, visual–motor integration, motor ability, and academic achievement. Additional, in depth comparisons focused on visual sustained attention, verbal learning and memory and parent/guardian-reported behavior problems. Group differences (ALC < IQC) were found on verbal learning and parent-rated behavior problems. Group differences were marginally significant (measures within the broad neuropsychological comparison) or not significant (visual attention, retention of verbal material) on the remaining comparisons. Therefore, some deficits (e.g., verbal learning and behavior problems) in children with heavy prenatal alcohol exposure cannot be explained by the lower FSIQ observed in the population. These areas of relative weakness could be useful in distinguishing children with FASD from other children with lowered IQ. (JINS, 2011, 17, 463–473)

Monoamines, such as serotonin, dopamine, and norepinephrine, play a crucial role in the regulation of emotion processing and mood. In this study, we investigated how polymorphisms of the serotonin transporter (5-HTT) and catechol-O-methyltransferase (COMT) influence emotion recognition abilities. We recruited 88 female undergraduate students and assessed 5-HTT genotype and the COMT Val158Met polymorphism. The subjects completed two computerized tasks: The Penn Emotion Recognition Test (ER40) and the Penn Emotion Acuity Test (PEAT). For the ER40, we found that s-allele carriers performed significantly worse in the recognition of happy faces, but did better in the recognition of fearful faces, compared with homozygous l-carriers of the 5-HTT gene. Neither 5-HTT nor COMT genotypes influenced the ability to discriminate between different intensities of sadness or happiness on the PEAT. Moreover, there was no significant interaction between the two polymorphisms in their effect on performance on the ER40 or the PEAT. (JINS, 2011, 17, 1014–1020)

Impairments in executive cognition (EC) may be predictive of incident dementia in patients with mild cognitive impairment (MCI). The present study examined whether specific EC tests could predict which MCI individuals progress from a Clinical Dementia Rating (CDR) score of 0.5 to a score ≥1 over a 2-year period. Eighteen clinical and experimental EC measures were administered at baseline to 104 MCI patients (amnestic and non-amnestic, single- and multiple-domain) recruited from clinical and research settings. Demographic characteristics, screening cognitive measures and measures of everyday functioning at baseline were also considered as potential predictors. Over the 2-year period, 18% of the MCI individuals progressed to CDR ≥ 1, 73.1% remained stable (CDR = 0.5), and 4.5% reverted to normal (CDR = 0). Multiple-domain MCI participants had higher rates of progression to dementia than single-domain, but amnestic and non-amnestic MCIs had similar rates of conversion. Only three EC measures were predictive of subsequent cognitive and functional decline at the univariate level, but they failed to independently predict progression to dementia after adjusting for demographic, other cognitive characteristics, and measures of everyday functioning. Decline over 2 years was best predicted by informant ratings of subtle functional impairments and lower baseline scores on memory, category fluency, and constructional praxis. (JINS, 2011, 17, 277–288)

Neuropsychologists frequently are asked to comment on everyday functioning, but the research relies mostly on questionnaire-based assessment of daily functioning. While performance-based assessment of everyday functioning has many advantages over commonly used questionnaires, there are few empirically validated comprehensive performance-based measures. We present data here on a performance-based battery of daily living skills, the Functional Impact Assessment (FIA) in 47 unilateral stroke patients and 37 matched healthy controls. The FIA was validated by comparing it to performance on the self- and informant-report version of the Functional Activities Questionnaire (FAQ). We also examined the relationship between the FIA and cognitive functioning using the Neuropsychological Assessment Battery (NAB). The stroke group's performance on the FIA, FAQ (self and informant), and NAB (total and domain scores) was significantly (d′s ≥ .80) lower than the control group. The NAB total score and all domain scores were highly correlated with the FIA in the stroke group (r's > .7), and only one NAB domain score (visuospatial) was a unique predictor. This may be due to the fact that most of the NAB domains have a statistical problem of multicollinearity, which may explain why only the spatial domain was a unique predictor. While the informant FAQ was significantly correlated with FIA total score (r = .48, p < .01), the NAB total score was a significantly better predictor (r = .83, p < .001) than the informant FAQ. NAB total scaled score of less than 86 predicted impairment on the FIA with 92% sensitivity and 84% specificity. Our findings argue that the FIA is sensitive to deficits associated with stroke and is highly associated with all neuropsychological domains (attention, executive functions, language and spatial skills, and memory). (JINS, 2011, 17, 832–840)

Motor impairments and cognitive dysfunction are common in multiple sclerosis (MS). We aimed to delineate the relationship between cognitive capacity and upper and lower motor function in 211 MS patients, and 120 healthy volunteers. Lower and upper motor function were assessed with the Timed 25 Foot Walk (T25FW) and the Nine Hole Peg Test (NHPT) as implemented in the Multiple Sclerosis Functional Composite (MSFC). Subjects also underwent neuropsychological evaluation. Hierarchical linear regression analysis was conducted separately for the MS and healthy groups with the T25FW and NHPT serving as the outcome measures. Cognitive performance indices served as predictors. As expected, healthy subjects performed better than the MS group on all measures. Processing speed and executive function tests were significant predictors of lower and upper motor function in both groups. Correlations were more robust in the MS group, where cognitive tests predicted variability in motor function after controlling for disease duration and physical disability. In conclusion, we find evidence of higher order cognitive control of motor function that appears to be particularly salient in this large and representative MS sample. The findings may have implications for risk assessment and treatment of mobility dysfunction in MS. (JINS, 2011, 17, 643–653)

We analyzed verbal episodic memory learning and recall using the Logical Memory (LM) subtest of the Wechsler Memory Scale-III to determine how gender differences in AD compare to those seen in normal elderly and whether or not these differences impact assessment of AD. We administered the LM to both an AD and a Control group, each comprised of 21 men and 21 women, and found a large drop in performance from normal elders to AD. Of interest was a gender interaction whereby the women's scores dropped 1.6 times more than the men's did. Control women on average outperformed Control men on every aspect of the test, including immediate recall, delayed recall, and learning. Conversely, AD women tended to perform worse than AD men. Additionally, the LM achieved perfect diagnostic accuracy in discriminant analysis of AD versus Control women, a statistically significantly higher result than for men. The results indicate the LM is a more powerful and reliable tool in detecting AD in women than in men. (JINS, 2011, 17, 654–662)

In recent work, we showed that the judgment of affective stimuli is influenced by the degree of congruence between apparently innate hemispheric dispositions (left hemisphere positive and approach, right hemisphere negative and avoidance), and the type of movement produced by the contralateral arm (flexion-approach; extension-avoidance). Incongruent movements (e.g., right arm extension) were associated with attenuation of affective valuations. In the present study, we replicated these results. We also assessed confidence in judgments as a function of stimulus valence and congruence and determined that confidence is maximal with congruent movements and highly positive or negative stimuli, suggesting that congruence effects on affective valuation could be mediated by confidence effects. However, in a second experiment, involving judgments regarding segmented lines, congruence effects were observed only for bisected lines, for which confidence was lowest. Thus, confidence does not provide a unifying explanation for congruence effects in the performance of these two tasks. (JINS, 2011, 17, 289–294)

Neuropsychological models propose qualitatively distinct planning impairments in the psychomotor poverty and disorganization syndromes in schizophrenia. It was proposed that poor plan initiation in psychomotor poverty would lead to longer initial planning times, while poor plan execution in disorganization would lead to greater inefficiency. Participants with psychomotor poverty (n = 30) and disorganization (n = 29) symptoms were contrasted with healthy controls (n = 28) to elucidate distinct planning impairments. Planning was compared in the Tower of London task versus real life analogue performance in the form of a board-game style diary planning task. The specificity of planning impairments was investigated by controlling for current IQ. The disorganization group demonstrated inefficient planning across both tasks, with poor performance on the Tower of London but not on the real life analogue task remaining after intelligence levels were taken into account. Initial planning times did not differ between groups. Previous associations between poor planning and symptoms may have been driven by poor planning with disorganization symptoms and associated lower order impairments in executive function or the semantic system. Targeting these impairments in people with disorganization symptoms may lead to a greater chance of success in promoting generalization to the real world. (JINS, 2011, 17, 474–484)