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Previous research indicates that individuals with Anorexia Nervosa (AN) often experience some degree of neuropsychological dysfunction. Although most aspects of cognition improve with treatment, factors that predict neuropsychological improvement remain elusive. The present study investigated whether cognitive reserve, the estimated level of premorbid cognitive functioning, and AN subtype predicted neuropsychological improvement during inpatient treatment for AN. Neuropsychological functioning was assessed pre- and post-hospitalization in 28 women with AN (18 with restricting type and 10 with binge-eating/purging type), and cognitive reserve was estimated at admission using a word reading test. Level of cognitive reserve and AN subtype were both significant predictors of neuropsychological improvement in this sample. Cognitive reserve was significantly associated with improvements in verbal memory, semantic fluency, basic auditory attention and visuospatial construction. Participants with AN binge-eating/purging type demonstrated significantly greater neuropsychological improvement during treatment than did participants with AN restricting type. Information about cognitive reserve and AN subtype may provide clinicians with valuable prognostic information and help guide treatment.

Objective: This study compares self-paced timing performance (cross-sectionally and longitudinally) between participants with prodromal Huntington's disease (pr-HD) and a comparison group of gene non-expanded participants from affected families (NC)., Method: Participants (747 pr-HD: 188 NC) listened to tones presented at 550-ms intervals, matched that pace by tapping response keys and continued the rhythm (self-paced) after the tone had stopped. Standardized cross-sectional and longitudinal linear models examined the relationships between self-paced timing precision and estimated proximity to diagnosis, and other demographic factors., Results: Pr-HD participants showed significantly less timing precision than NC. Comparison of pr-HD and NC participants showed a significant performance difference on two task administration conditions (dominant hand: p < .0001; alternating thumbs: p < .0001). Additionally, estimated proximity to diagnosis was related to timing precision in both conditions, (dominant hand: t = -11.14, df = 920, p < .0001; alternating thumbs: t = -11.32, df = 918, p < .0001). Longitudinal modeling showed that pr-HD participants worsen more quickly at the task than the NC group, and rate of decline increases with estimated proximity to diagnosis in both conditions (dominant hand: t = -2.85, df = 417, p = .0045; alternating thumbs: t = -3.56, df = 445, p = .0004). Effect sizes based on adjusted mean annual change ranged from -0.34 to 0.25 in the longitudinal model., Conclusions: The self-paced timing paradigm has potential for use as a screening tool and outcome measure in pr-HD clinical trials to gauge therapeutically mediated improvement or maintenance of function.

Assessing cognitive change in older adults is a common use of neuropsychological services, and neuropsychologists have utilized several strategies to determine if a change is "real," "reliable," and "meaningful." Although standardized regression-based (SRB) prediction formulas may be useful in determining change, SRBs have not been widely applied to older adults. The current study sought to develop SRB formulas on a group of 127 community-dwelling older adults for several widely used neuropsychological measures. In addition to baseline test scores and demographic information, the current study also examined the role of short-term practice effects in predicting test scores after 1 year. Consistent with prior research on younger adults, baseline test performances were the strongest predictors of future test performances, accounting for 25%-58% of the variance. Short-term practice effects significantly added to the predictability of all nine of the cognitive tests examined (3%-22%). Future studies should continue extending SRB methodology for older adults, and the inclusion of practice effects appears to add to the prediction of future cognition.

Standardized regression based (SRB) formulas, a method for predicting cognitive change across time, traditionally use baseline performance on a neuropsychological measure to predict future performance on that same measure. However, there are instances in which the same tests may not be given at follow-up assessments (e.g., lack of continuity of provider, avoiding practice effects). The current study sought to expand this methodology by developing SRBs to predict performance on different tests within the same cognitive domain. Using a sample of 127 non-demented community-dwelling older adults assessed at baseline and after 1 year, two sets of SRBs were developed: (1) those predicting performance on the same test, and (2) those predicting performance on a different test within the same cognitive domain. The domains examined were learning and memory, processing speed, and language. Across both sets of SRBs, 1-year scores were significantly predicted by baseline scores, especially for the learning and memory and processing speed measures. Although SRBs developed for the same test were comparable to those developed for different tests within the same domain, less variance was accounted for as tests became less similar. The current results lend preliminary support for additional development of SRBs, both for same and different tests, as well as beginning to examine domain-based SRBs.

Memory assessment is an important component of a neuropsychological evaluation, but far fewer visual than verbal memory instruments are available. We examined the preliminary psychometric properties and clinical utility of a novel, motor-free paper and pencil visuospatial memory test, the Indiana faces in places test (IFIPT). The IFIPT and general neuropsychological performance were assessed in 36 adults with amnestic mild cognitive impairment (aMCI) and 113 older adults with no cognitive impairment at baseline, 1 week, and 1 year. The IFIPT is a visual memory test with 10 faces paired with spatial locations (three learning trials and non-cued delayed recall). Results showed that MCI participants scored lower than controls on several variables, most notably total learning (p < .001 at all three time points), delayed recall (baseline p = .03, 1 week p < .001, 1 year p < .001), and false-positive errors (range p = .03 to <0.001). The IFIPT showed similar test-retest reliability at 1-week and 1-year follow-up to other neuropsychological tests (r = 0.71-0.84 for MCI and 0.53-0.72 for controls). Diagnostic accuracy was modest for this sample (areas under the receiver operating characteristic curve between 0.64 and 0.66). Preliminary psychometric analyses support further study of the IFIPT. The measure showed evidence of clinical utility by demonstrating group differences between this sample of healthy adults and those with MCI.

Structural magnetic resonance imaging (MRI) studies of the human brain have reported evidence for sexual dimorphism. In addition to sex differences in overall cerebral volume, differences in the proportion of gray matter (GM) to white matter (WM) volume have been observed, particularly in the parietal lobe. To our knowledge there have been no studies examining the relationship between the sex differences in parietal lobe structure and function. The parietal lobe is thought to be involved in spatial ability, and particularly involved in mental rotation. The purpose of this study is to examine whether sex differences in parietal lobe structure are present, and if present to relate these differences to performance on the mental rotations test (MRT). We found that women had proportionately greater gray matter volume in the parietal lobe compared to men, and this morphologic difference was disadvantageous for women in terms of performance on the MRT. In contrast, we found that men compared to women had proportionately greater parietal lobe surface area, and this morphologic difference was associated with a performance advantage for men on mental rotation. These findings support the possibility that the sexual dimorphism in the structure of the parietal lobe is a neurobiological substrate for the sex difference in performance on the mental rotations test.

The original structure of the RBANS includes five Indexes; however, recent factor analyses support a two-factor solution (Duff et al., 2006; Wilde, 2006). Unfortunately, normative and psychometric data do not currently exist on these two new Indexes. Building on prior work, the current study provides age- and education-corrected normative data to calculate the factor-derived Verbal and Visual RBANS Indexes (Duff et al., 2006) in a large cohort (n = 718) of older adult primary care patients. Psychometric data (e.g., discrepancy scores, internal consistency, retest reliability) on these new Indexes are also presented. These data might allow clinicians and researchers to better assess laterality effects of brain dysfunction when using the RBANS, although clinical validation is needed.

Executive function and denial of illness were examined among 24 patients who received double-blind antidepressant treatment following stroke. Between end-of-treatment at 3 months and follow-up at 2 years, significant correlation was found between improvement in executive function and decrease in denial of illness.

Objective: Obsessive and compulsive symptoms (OCS) are more prevalent in patients with diagnosed Huntington's disease (HD) than in the general population. Although psychiatric symptoms have been reported in individuals with the HD gene expansion prior to clinical diagnosis (pre-HD), little is known about OCS in this phase of disease., Method: The goal of this study was to assess OCS in 300 pre-HD individuals and 108 non-gene-expanded controls from the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) study (enrolled between November 2002 and April 2007) using a multidimensional, self-report measure of OCS, the Schedule of Compulsions, Obsessions, and Pathologic Impulses (SCOPI). Additionally, pre-HD individuals were classified into 3 prognostic groups on the basis of age and CAG repeat length as "near-to-onset" (< 9 estimated years to onset), "mid-to-onset" (9-15 years to onset), and "far-to-onset" (> 15 years to onset). We compared the 3 pre-HD groups to the controls on SCOPI total score and 5 subscales (checking, cleanliness, compulsive rituals, hoarding, and pathologic impulses), controlling for age and gender., Results: All models showed a significant (p < .05) group effect except for hoarding, with an inverted-U pattern of increasing symptoms: controls < far-to-onset < mid-to-onset, with the near-to-onset group being similar to controls. Although the mid-to-onset group showed the most pathology, mean scores were below those of patients with diagnosed obsessive-compulsive disorder. SCOPI items that separated pre-HD individuals from controls were focused on perceived cognitive errors and obsessive worrying., Conclusion: Subclinical OCS were present in pre-HD participants compared to controls. The OCS phenotype in pre-HD may present with obsessive worrying and checking related to cognitive errors and may be a useful target for clinical screening as it could contribute to functional status., (Copyright 2008 Physicians Postgraduate Press, Inc.)

Background: Practice effects have been widely reported in healthy older adults, but these improvements due to repeat exposure to test materials have been more equivocal in individuals with mild cognitive impairment (MCI)., Methods: The current study examined short-term practice effects in MCI by repeating a brief battery of cognitive tests across one week in 59 older adults with amnestic MCI and 62 intact older adults., Results: Participants with amnestic MCI showed significantly greater improvements on two delayed recall measures (p < 0.01) compared to intact peers. All other practice effects were comparable between these two groups. Practice effects significantly improved scores in the MCI group so that 49% of them were reclassified as "intact" after one week, whereas the other 51% remained "stable" as MCI. Secondary analyses indicated the MCI-Intact group demonstrated larger practice effects on two memory measures than their peers (p < 0.01)., Conclusions: These results continue to inform us about the nature of memory deficits in MCI, and could have implications for the diagnosis and possible treatment of this amnestic condition.

Background: This study evaluated brain volumes in healthy older subjects without dementia who presented with memory complaints. The objective was to examine cortical volumes in relation to cognitive performance among patients who do not have dementia, but who do have mild cognitive deficits., Methods: Fifteen participants were evaluated (mean age = 71.8 +/- 6.2). Brain structure was measured via high-resolution magnetic resonance imaging to quantify gray and white matter volumes. Volumetric measures were assessed relative to cognitive function in separate regression models controlling for total cerebral volume. Reported here are measures of global cognitive performance using the Mattis Dementia Rating Scale (DRS) in relation to volumetric measures., Results: Baseline MMSE scores ranged from 27 to 30 (mean = 29.3; SD = 0.9). After controlling for total cerebral volume, we observed that lower white matter volume in the temporal lobe [F(1,14) = 5.72, p = 0.03] was associated with lower performance on the Mattis Dementia Rating Scale (DRS)., Conclusions: Structural imaging may help provide useful clinical information in the context of mild cognitive decline. Currently, the diagnosis of dementia relies on longitudinal measures of cognition. Future studies will help determine whether the addition of brain imaging may enhance diagnostic certainty as well as predict long-term outcome.

Objectives: To assess decisional capacity performance and the neuropsychological correlates of such performance to better understand higher-level instrumental activities of daily living in individuals with mild cognitive impairment (MCI)., Design: Cross-sectional., Setting: Research center, medical center, or patient's home., Participants: Forty participants with MCI and 40 cognitively normal older controls (NCs) aged 60 to 90 (mean age+/-standard deviation 73.3+/-6.6; 54% female)., Measurements: Capacity to provide informed consent for a hypothetical, but ecologically valid, clinical trial was assessed using the MacArthur Competence Assessment Tool for Clinical Research. Neuropsychological functioning was assessed using a comprehensive protocol., Results: Adjusted between-group comparisons yielded significant differences for most decisional capacity indices examined, including Understanding (P=.001; NC>MCI) and Reasoning (P=.002; NC>MCI). Post hoc analyses revealed that participants with MCI who were categorized as capable of providing informed consent according to expert raters had higher levels of education than those who were categorized as incapable., Conclusion: The findings suggest that many individuals with MCI perform differently on a measure of decisional capacity than their NC peers and that participants with MCI who are incapable of providing informed consent on a hypothetical and complex clinical trial are less educated. These findings are consistent with prior studies documenting functional and financial skill difficulties in individuals with MCI.

We previously reported a relationship between forearm resistance vessel function and global neuropsychological performance in patients with atherosclerotic vascular disease (AVD). This study was conducted to determine the relationships among vascular smooth muscle function, endothelial function, and initiation and processing speed in this sample. Participants were 80 individuals with AVD. Resistance vessel function was measured before and after infusion of vasoactive agents. Neuropsychological assessment included measures of estimated premorbid cognitive function, current global cognitive function, initiation, and processing speed. Vascular smooth muscle function was significantly associated with the initiation/processing speed composite score [R-Square Change = .152; F Change (1,71) = 16.61; p < .001], above and beyond the variance accounted for by age, education, premorbid cognitive function, and endothelium-dependent vascular function. This relationship remained significant when controlling for current level of global cognitive functioning and 10 vascular risk factors. Endothelium-dependent vascular function was not significantly associated with test performance. Decreased vascular smooth muscle function in forearm resistance vessels was significantly associated with relatively poor initiation and processing speed in individuals with AVD. With additional research, measures of vascular function might become useful in the early identification of those individuals at greatest risk for vascular-related cognitive dysfunction.

Objectives: To characterize cognition in patients with moderate to severe heart failure and examine the association between 2 measures of systemic perfusion (ie, ejection fraction and cardiac index) and cognition., Background: Decreased systemic perfusion has been implicated as an etiologic factor in the development of cognitive deficits in cardiovascular disease., Method: Thirty-one patients with moderate to severe heart failure and 31 patients with cardiovascular disease and no heart failure completed a medical history interview and neuropsychologic assessment. Participants with heart failure additionally underwent an echocardiogram to assess cardiac function., Results: Patients with heart failure performed significantly worse than the cardiovascular disease-no heart failure group on several measures of executive functioning and psychomotor speed. Among the heart failure group, lower ejection fraction was associated with weaker global cognition, performance on several, but not all, measures of executive functioning, and was marginally associated with delayed memory. Decreased cardiac index was associated with poorer immediate memory and weakly associated with global cognition., Conclusions: Findings suggest that depressed systemic perfusion is associated with cognitive deficits among patients with heart failure. Research including measures of cardiac function, cerebral perfusion, and cognition will be necessary to clarify the causal nature of the suggested mechanism.

Introduction: Pathological gambling disorder (PG) has been associated with fronto-temporal dysfunction and maladaptive personality traits, such as impulsivity and novelty seeking. The purpose of this study was to examine the predictive variance of neuropsychological and personality characteristics in PG., Methods: Persons with PG (n=25) and a comparison group (n=34) were administered a battery of neuropsychological tests, the Temperament and Character Inventory, and the Barratt Impulsiveness Scale. Subjects with PG had evidence of fronto-temporal dysfunction as assessed by the Stroop, Wisconsin Card Sorting Test-64, Wechsler Adult Intelligence Scale Letter-Number Sequencing, Controlled Oral Word Association Test, and Boston Diagnostic Aphasia Examination Animal Naming Test., Results: Subjects with PG also had impaired decision making on the Iowa Gambling Task. PG subjects had elevated levels of impulsivity, novelty seeking, and harm avoidance, and lower levels of self-directedness and cooperativeness. Logistic regression analyses indicated that neuropsychological variables did not add significant incremental variance over personality traits in predicting PG (Block chi-square=5.19, P=.074), while personality variables added significant incremental variance over neuropsychological traits in predicting PG (Block chi-square=25.13, P<.001)., Conclusion: These results suggest that personality traits are better predictors than neuropsychological characteristics of whether someone has PG.

Identification of memory impairment is important for neuropsychological diagnostic and research applications, and retention rates on verbal and visual memory tests can provide useful information when characterizing a variety of neurological and psychiatric disorders. Although the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is becoming a popular screening battery for cognitive functions, normative data on retention rates are not available. The retention rates of verbal and visual material were evaluated in a sample of clinical patients (n = 109) compared to a healthy control group (n = 718). Individual subtest retention rates were converted to age-corrected scaled scores based on the cumulative distribution of raw scores obtained by an elderly community-dwelling sample. Compared with the healthy normative sample, the percent retention found for the clinical group was significantly lower on all 3 RBANS memory subtests. These preliminary data suggest that retention rates of the RBANS memory subtests may add to the clinical utility of this test as a neuropsychological diagnostic and research tool.

Context: The term vascular depression (VD) has been used to describe late-life depressive disorders in patients with clinical evidence of cerebrovascular disease. Preliminary data on poststroke depression suggest that repetitive transcranial magnetic stimulation (rTMS) might also be effective among patients with VD., Objective: To examine the efficacy and safety of rTMS to treat VD., Design: Prospective, randomized, sham-controlled study., Setting: University hospital., Methods: After discontinuation of antidepressant therapy, 92 patients with clinically defined VD were randomly assigned to receive active or sham rTMS of the left dorsolateral prefrontal cortex. Approximately half of the patients met criteria for magnetic resonance imaging-defined VD. In experiment 1, we administered a total cumulative dose (TCD) of 12 000 pulses (TCD-12K); in experiment 2, 18,000 pulses (TCD-18K). Sham stimulation was performed using a sham coil., Results: In experiment 1, the sham group showed a 13.6% decrease in the 17-item Hamilton Depression Rating Scale (HAMD-17) scores compared with a 33.1% decrease in the TCD-12K group (P = .04). Response rates were 6.7% in the sham group and 33.3% in the active-stimulation group (P = .08); remission rates were 6.7% and 13.3%, respectively (P = .50). In experiment 2, the sham group showed a 17.5% decrease in the 17-item Hamilton Depression Rating Scale scores compared with a 42.4% decrease observed in the TCD-18K group (P < .001). Response rates were 6.9% in the sham group and 39.4% in the active-stimulation group (P = .003); remission rates were 3.5% and 27.3%, respectively (P = .01). Response rates to rTMS were negatively correlated with age and positively correlated with higher frontal gray matter volumes., Conclusions: To our knowledge, this is the first controlled trial that demonstrates the efficacy of rTMS among geriatric patients with VD. Older age and smaller frontal gray matter volumes were associated with a poorer response to rTMS.

BACKGROUND: We hypothesized that changes in vascular flow dynamics resulting from age and cardiovascular disease (CVD) would correlate to neurocognitive capacities, even in adults screened to exclude dementia and neurological disease. We studied endothelial-dependent as well as endothelial-independent brachial responses in older adults with CVD to study the associations of vascular responses with cognition. Comprehensive neurocognitive testing was used to discern which specific cognitive domain(s) correlated to the vascular responses. METHODS: Eighty-eight independent, community-dwelling older adults (70.02+7.67 years) with mild to severe CVD were recruited. Enrollees were thoroughly screened to exclude neurological disease and dementia. Flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) brachial artery responses were assessed using 2-d ultrasound. Cognitive functioning was assessed using comprehensive neuropsychological testing. Linear regression analyses were used to evaluate the relationships between the endothelial-dependent and endothelial-independent vascular flow dynamics and specific domains of neurocognitive function. RESULTS: Endothelial-dependent and endothelial-independent brachial artery responses both correlated with neurocognitive testing indices. The strongest independent relationship was between endothelial function and measures of attention-executive functioning. CONCLUSIONS: Endothelial-dependent and endothelial-independent vascular responsiveness correlate with neurocognitive performance among older CVD patients, particularly in the attention-executive domain. While further study is needed to substantiate causal relationships, our data demonstrate that brachial responses serve as important markers of risk for common neurocognitive changes. Learning and behavior-modifying therapeutic strategies that compensate for such common, insidious neurocognitive limitations will likely improve caregiving efficacy.

Assessing cognitive change during a single visit requires the comparison of estimated premorbid abilities and current neuropsychological functioning. As newer instruments are developed to measure current cognitive functioning, their relationships with premorbid estimates need to be evaluated. The current study examined the clinical utility of discrepancy scores between an estimate of premorbid intellect derived from demographic variables (i.e., Barona) and the Total score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in three geriatric samples. A large community-dwelling "control" sample and two clinical samples were examined. As expected, there was little difference between estimated premorbid intellect and current RBANS Total Scale scores in the community-dwelling sample, while estimated premorbid intellect obtained from the two clinical samples significantly differed from obtained RBANS Total scores. Similar findings were observed on Discrepancy scores for the five Indexes of RBANS. The current findings, along with normative data on these discrepancy scores, can provide additional confidence for clinicians and researchers who need to determine cognitive decline when using these screening measures of neuropsychological status.

Introduction: We investigated the stability of neuropsychological performance and eating disorder (EDO) symptoms before, immediately after, and 2 years after inpatient treatment. We also examined relationships between neuropsychological and EDO measures., Methods: Sixteen women who were admitted for inpatient treatment of anorexia nervosa participated in three evaluations: (1) at admission to the hospital, (2) at discharge, and (3) at a follow-up exam approximately two years after discharge., Results: Body mass index increased significantly from each testing session to the next. Endorsement of eating disorder symptoms was significantly decreased at discharge and at follow-up compared to admission. In terms of cognitive performance, total scores on a brief neuropsychological battery (RBANS) were significantly greater at follow-up than at admission. We found no relationships between EDO symptoms and cognitive function at any of the three sessions., Conclusions: The current findings suggest that EDO symptoms and cognitive performance in anorexia nervosa patients can show improvement as long as two years after hospitalization, but there is no evidence that EDO symptoms are related to neuropsychological performance.

We investigated whether Persian Gulf War veterans (GWVs) were more likely than Persian Gulf War-era veterans deployed elsewhere (GEVs) to have noncredible neuropsychological examinations. A total of 301 GWVs and 99 GEVs underwent neuropsychological testing. The credibility of 173 examinations showing impairment was evaluated based on test performances, clinical background, psychometric measures, and other self-report data. All 11 examinations judged less than fully credible by one neuropsychologist, plus 19 examinations judged impaired but credible, were then evaluated independently by two more neuropsychologists. Noncredibility was judged with excellent reliability (93% agreement). Seven examinations were judged noncredible. Rates of noncredibility did not differ between GWVs (1%) and GEVs (4%). The pattern of associations of noncredible examinations with cognitive, psychological, and clinical variables generally indicated defective neuropsychological scores, with no coherent pattern, and personality disorder. Findings supported the validity of noncredibility judgments and suggested that noncredible examinations are not a significant problem in neuropsychological investigations of GWVs.

The clinical literature in Huntington's disease (HD) suggests that unawareness of deficits is prevalent among HD patients. However, few studies have characterized unawareness of different types of impairment within this neuropsychiatric disorder. The purpose of the current study was to examine self-awareness of functioning across symptom domains in HD patients and to explore the association between impaired awareness and cognitive dysfunction. A total of 66 pairs of HD patients and collaterals of the patients completed symptom-rating measures regarding both the patients' and the collaterals' behavior. A subset of 19 patients also underwent neurological and neuropsychological assessments. The results indicated that patients lacked awareness across symptom domains (i.e., behavioral control, emotional control, activities of daily living), which was significantly greater for their perception of their own behavior than for their perception of their collateral's behavior. Exploratory analyses revealed associations between impaired self-awareness, global cognition, and deficits in executive functioning and memory. The current findings underscore the importance of examining different types of impaired awareness including both over- and underreporting of abilities. Future studies will benefit also from examining the association between awareness and cognition in larger samples.

Objective: The objective of this study was to describe the relationship among cognitive test performance, psychological symptoms, and subjective cognitive difficulties in older adults with atherosclerotic vascular disease., Method: Participants were 80 adults over the age of 55 with an unequivocal diagnosis of atherosclerotic vascular disease. Participants completed measures of neuropsychological functioning, psychological symptoms, and two measures of subjective cognitive difficulties., Results: Psychological symptoms were most strongly associated with higher levels of reported cognitive difficulties. Overall neuropsychological functioning was modestly related to subjective cognitive difficulties but did not remain significant after controlling for psychological symptoms., Conclusions: In this sample of older adults with atherosclerotic vascular disease, self-reported cognitive difficulties were most strongly related to overall level of psychological distress and not to actual cognitive test scores. Therefore, psychological factors may play an important role in the phenomenon of self-perceived cognitive decline in geriatric populations.

Background: Executive dysfunction is common after stroke and may impair long-term outcome. Remedies for this condition are limited., Aims: To examine the effect of antidepressants on executive function after stroke., Method: Forty-seven patients who had had a stroke during the prior 6 months received 12 weeks of antidepressant treatment in double-blind placebo-controlled fashion, followed by assessment of executive function at the end of treatment and after 2 years., Results: No significant group effect was found at the end of treatment. However, 21 months after the end of treatment the placebo group showed deterioration of executive function, whereas the active treatment group showed clear and significant improvement independent of depressive symptoms (F=12.1, d.f.=1,45, P= 0.001)., Conclusions: Antidepressant treatment fosters long-term improvement of executive function following stroke. This phenomenon is consistent with a reorganisation of neuronal networks associated with prefrontal functions based on modulation of monoaminergic neurotransmission and the activity of neurotrophins.

Practice effects, defined as improvements in cognitive test performance due to repeated exposure to the test materials, have traditionally been viewed as sources of error. However, they might provide useful information for predicting cognitive outcome. The current study used three separate patient samples (older adults with mild cognitive impairments, individuals who were HIV+, individuals with Huntington's disease) to examine the relationship between practice effects and cognitive functioning at a later point. Across all three samples, practice effects accounted for as much as 31-83% of the variance in the follow-up cognitive scores, after controlling for baseline cognitive functioning. If these findings can be replicated in other patients with neurodegenerative disorders, clinicians and researchers may be able to develop predictive models to identify the individuals who are most likely to demonstrate continued cognitive decline across time. The ability to utilize practice effects data would add a simple, convenient, and non-invasive marker for monitoring an individual patient's cognitive status. Additionally, this prognostic index could be used to offer interventions to patients who are in the earliest stages of progressive neurodegenerative disorders.

Objective: We previously reported preliminary data (N=14) demonstrating a significant and positive relationship between forearm vascular function and neuropsychological performance in individuals with atherosclerotic vascular disease (AVD). The current study was conducted to confirm and extend those findings in a much larger, nonoverlapping sample., Methods and Results: Participants were 82 individuals with AVD, with no history of stroke, cardiac surgery, or dementia. Forearm vascular function was measured before and after brachial artery infusion of vasoactive agents (acetylcholine, nitroprusside, verapamil). Neuropsychological functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status. Statistical analysis included multiple regression and partial correlations, controlling for education. Vascular function was significantly and positively associated with neuropsychological performance [R2 change = 0.116, F change (3,74) = 3.72, P = 0.015]. Follow-up analyses indicated that smooth muscle function was the aspect of vascular function most strongly associated with neuropsychological performance. Individual vascular risk factors were not significantly associated with neuropsychological performance when controlling for vascular function., Conclusions: Better vascular function is significantly associated with better neuropsychological performance in individuals with AVD. It is possible that this relationship exists in healthy elderly individuals as well, although this cannot be determined based on the existing data, because a healthy comparison group was not studied. With additional research, measures of vascular function might be useful in the early identification of individuals who are at greatest risk for developing vascular cognitive impairment.

The current study characterizes cognitive and psychiatric status in hematopoietic stem cell transplantation (HSCT) patients shortly before and after transplant. Thirty adult patients were assessed prospectively 1-2 weeks before transplantation and 100 days posttransplantation on neuropsychological and psychiatric measures. Before transplant, participants showed mild impairments on several neuropsychological measures, with the poorest performances occurring on learning and attention. Psychiatric functioning was significantly elevated compared with normative data. Significant improvements, however, were observed on neuropsychological measures by 100 days after transplant. Depression and anxiety scores also improved. Candidates for HSCT experienced mild diffuse cognitive dysfunction and psychiatric morbidity before the procedure, but these symptoms significantly improved by 3 months following their transplant in this small sample. Education about these possible pretransplant sequelae and the potential for rebound may be helpful to patients and families as they prepare for this treatment and the recovery period.

Objective: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a recently developed cognitive assessment instrument, has been shown to be useful with a variety of neuropsychiatric conditions, but its factor structure has not been examined., Method: Using 824 community-dwelling elders, the RBANS was examined with confirmatory and exploratory factor analyses., Results: The existing structure of the RBANS was not supported; however, a two-factor solution was., Conclusions: Clinicians and researchers using the RBANS should be cautious when interpreting this measure with its existing structure.

Purpose: This study was undertaken to explore the mechanisms underlying cognitive reserve in subjects with mild memory deficits by using positron emission tomography (PET)., Methods: Global cerebral blood flow (gCBF) and cerebrovascular reserve (CVR) measurements were performed in 15 elders (5 men, 10 women, 62-84, 71.8 +/- 6.2 years) meeting criteria for mild cognitive impairment (MCI). PET consisted of quantitative [(15)O]water determinations of CBF, two at baseline and one postadministration of acetazolamide (ACZ)., Results: Mean gCBF were 44.9 +/- 5.5 during counting, 44.5 +/- 6.7 for the memory task, and 60.2 +/- 4.8 ml/min/100 g for post-ACZ (CVR of 33.9 +/- 13.2%). Task-related gCBF change was significantly related to memory score, performance on the Trail Making Test B (Trails-B), premorbid IQ, and education, and differed significantly between the learning-based groups., Conclusions: Cognitive reserve appears analogous to cardiac reserve. The ability to alter gCBF paralleled performance on general cognitive measures, was enhanced in higher levels of cognitive reserve, and was impaired in individuals who no longer appear to benefit from repeated exposure to testing.

Background: This study examined changes in cognitive-functional relationships in vascular dementia (VaD) over the course of one year., Methods: Twenty-four patients with probable VaD were administered the Dementia Rating Scale (DRS). Caregivers completed an informant-based measure of instrumental (IADL) and basic activities of daily living (BADL). Follow-up assessment was conducted one-year post-baseline., Results: Logistic regression revealed that changes in the DRS Initiation/Perseveration and DRS Memory subscales were significantly associated with declines in IADLs and BADLs, respectively., Conclusions: Among patients with VaD, longitudinal changes in IADLs and BADLs are most strongly associated with changes in executive functioning and memory abilities, respectively. Findings suggest that different cognitive functions subserve complex instrumental and rote, habituated basic functional activities, and neuropsychological screening measures are useful in the prediction of such functional changes.

Fiber tracking, based on diffusion tensor imaging (DTI), is the only approach available to non-invasively study the three-dimensional structure of white matter tracts. Two major obstacles to this technique are partial volume artifacts and tracking errors caused by image noise. In this paper, a novel fiber tracking algorithm called Guided Tensor Restore Anatomical Connectivity Tractography (GTRACT) is presented. This algorithm utilizes a multi-pass approach to fiber tracking. In the first pass, a 3D graph search algorithm is utilized. The second pass incorporates anatomical connectivity information generated in the first pass to guide the tracking in this stage. This approach improves the ability to reconstruct complex fiber paths as well as the tracking accuracy. Validation and reliability studies using this algorithm were performed on both synthetic phantom data and clinical human brain data. A method is also proposed for the evaluating reliability of fiber tract generation based both on the position of the fiber tracts, as well the anisotropy values along the path. The results demonstrate that the GTRACT algorithm is less sensitive to image noise and more capable of handling areas of complex fiber crossing, compared to conventional streamline methods.

Objective: To examine, in a post hoc analysis of an antidepressant treatment trial, correlates of irritability and aggression after stroke and changes in irritability scores associated with antidepressant treatment., Design: Aggressive patients (n=23) were compared with nonaggressive patients (n=69) on numerous measures of psychopathology, poststroke impairment, and neuroimaging findings., Setting: All patients were hospitalized at the time of the initial evaluation for acute stroke or for rehabilitation therapy., Participants: Ninety-two patients from the Iowa City Stroke Study were classified as aggressive or nonaggressive, based on symptoms elicited by the Present State Examination (PSE) and from family or caretaker reports., Intervention: All patients were randomized to receive nortriptyline, fluoxetine, or placebo using a double-blind methodology., Main Outcome Measure: The change in aggression score as elicited by the PSE at the beginning and the end of a 12-week treatment trial., Results: Twenty-five percent (23/92) of patients reported irritability or aggression. Irritable and aggressive patients had higher total PSE scores, Hamilton Depression Rating Scale scores, Hamilton Anxiety Rating Scale (HAMA) scores, and lower Mini-Mental State Examination scores. They also had lesions that were more proximal to the frontal pole. Stepwise regression analysis showed that HAMA scores and proximity of lesion to the frontal pole were significant independent predictors of irritability. Among irritable and aggressive patients with depression who responded to antidepressants, there was a significantly greater reduction in irritability after treatment, compared with patients whose depression did not lessen with treatment., Conclusions: Several factors, such as severity of impairment, other psychopathology, and neurobiologic factors, appear to contribute to irritable and aggressive behavior in stroke patients. If depression accompanies aggression, the results of this small study suggest that successful treatment of depression may reduce aggressive behavior.

To examine whether patients with schizophrenia have deficits in the appraisal of socially relevant stimuli, we tested 20 patients and 14 healthy volunteers equated for parental socioeconomic status on recognition of gender stimuli, emotional people stimuli, and emotional scenes. Patients with schizophrenia showed deficits in discrimination of subtle gender differences and in the identification of emotion from human shapes and body motion. Patients showed no impairment on measures of hedonic appraisal of emotional scenes and recognition of emotional expression in human face stimuli. Across tasks, subjects with schizophrenia showed poorer identification of happiness, anger, and fear. The findings point towards circumscribed domains of impaired social cognition in schizophrenia and suggest specific further hypotheses about the neural dysfunction that may underlie them.

Studies have shown that individuals with psychiatric or general medical illness can benefit from interventions designed to enhance decisional capacity for research informed consent. In some cases, interventions have been rather lengthy or complex. The current study was designed to determine whether a brief intervention could improve decisional capacity in people with schizophrenia. Thirty individuals with schizophrenia and 30 healthy comparison participants were presented with a hypothetical research scenario. Decisional capacity was assessed with the MacArthur Competence Assessment Tool-Clinical Research version. Those with schizophrenia received a brief intervention aimed at improving understanding of the research protocol, after which decisional capacity was reassessed. A neuropsychological battery and symptom rating scales were also administered. At baseline, the schizophrenia group earned significantly lower scores than the comparison group on 2 aspects of decisional capacity (understanding, appreciation). At follow-up, the schizophrenia group had improved significantly on understanding and was no longer significantly different from the comparison group on any of the 4 dimensions of decisional capacity. Follow-up analyses also showed a significant effect of the intervention on a subset of the schizophrenia group who had performed most poorly at baseline. Participants with schizophrenia earned significantly lower scores than those in the comparison group across multiple neuropsychological domains. These findings add to the existing literature indicating that brief interventions can improve decisional capacity in individuals with schizophrenia, despite the fact that the illness typically causes significant cognitive dysfunction. The use of such interventions will enable a larger number of people with schizophrenia to make informed decisions regarding research participation.

Objective: The authors' goal was to determine whether people with schizophrenia experience changes in decisional capacity when their antipsychotic regimens are discontinued for research purposes., Method: Capacity for informed consent for research, neuropsychological performance, and psychiatric symptoms were assessed before and after discontinuation of antipsychotic medication in 10 individuals with schizophrenia., Results: Overall, participants showed minimal change on most measures during the medication-free interval, although their reasoning ability declined significantly. All participants who demonstrated adequate understanding of study procedures at enrollment retained this capacity throughout the study., Conclusions: Participants in medication-free schizophrenia research do not show a major decline in decisional capacity. However, the apparent decline in reasoning ability found in this study is of concern and underscores the need for both additional research on this topic and the development of remediational interventions aimed at enhancing this aspect of decisional capacity.

Background: Structural abnormalities of the striatum and cognitive impairments have consistently been shown in patients with Huntington's disease (HD). Fewer studies have examined other cerebral structures in early HD and potential associations with cognition., Method: Ten patients with early HD and 10 matched control subjects underwent magnetic resonance imaging to provide quantitative measures (volumes) of cortical gray and white matter and the caudate, putamen, and thalamus. Patients completed the Unified Huntington's Disease Rating Scale, including three cognitive tasks., Results: Although striatal volumes were clearly reduced, white matter was also morphologically abnormal. Cortical gray matter volume was not significantly correlated with cognitive performance. However, the cognitive tasks were most highly correlated with cerebral white matter and, to a lesser degree, striatal volume., Conclusions: Cerebral white matter volume may be an important variable to examine in future studies of HD.

Evidence for progressive cognitive decline in vascular dementia (VaD) is mixed, with some studies showing little or no decline over time. One possible explanation for these inconsistent findings is the heterogeneity of pathology encompassed by the VaD diagnosis. It is possible that subtypes of VaD (i.e. those resulting from different lesion distributions) show different patterns of cognitive decline. In the present study, a heterogeneous VaD group demonstrated cognitive decline from baseline to 12-month follow-up. Although this decline was coincident to morphometric changes (i.e. increased subcortical hyperintensities (SH), decreased whole brain volume (WBV)), no relationship emerged between cognitive decline and morphometric changes. Preliminary examination of VaD subtypes revealed patients with subcortical infarct or SH-only exhibited greater decline than VaD patients with cortical lesions. Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact.

Background and Purpose: Although a strong relationship has been established between vascular disease and cognitive decline, the current challenge is to identify vascular risk factors and mechanisms that are associated with cognitive function before the development of severe dysfunction (eg, vascular dementia). This study was conducted to determine the relationship between blood vessel function and cognition in elderly patients with atherosclerosis., Methods: Participants were 14 elderly individuals with atherosclerotic vascular disease, who had no history of stroke, cardiac surgery, or dementia diagnosis. Forearm blood flow was measured before and after brachial artery infusion of 3 vasoactive agents (verapamil, acetylcholine, nitroprusside), and these measures of vessel function were then correlated with neuropsychological performance (total scale score on the Repeatable Battery for the Assessment of Neuropsychological Status)., Results: Positive correlations were found between neuropsychological performance and vasodilation in response to all 3 agents, with 2 reaching statistical significance (verapamil: rho=0.78, P=0.001; nitroprusside: rho=0.56, P=0.038) and the third showing a strong trend toward significance (acetylcholine: rho=0.49, P=0.076). Correlations between neuropsychological performance and more conventional vascular-related variables were much weaker., Conclusions: These data provide preliminary evidence of a relationship between resistance vessel function and neuropsychological performance. With further research, measures of vessel dysfunction may be useful in identifying individuals at risk for cognitive decline and vascular dementia.

Hachinski and co-workers have used the term vascular cognitive impairment-no dementia (VaCIND) to represent the earliest stages of cognitive decline associated with vascular changes [Neurology 57 (4) (2001) 714]. However, the neuropsychological profile of vascular CIND remains unclear. Twenty-five healthy elders, 29 individuals at risk for cerebrovascular disease (R-CVD), 18 individuals with VaCIND, and 26 individuals with vascular dementia (VaD) were examined to determine whether patterns of neuropsychological assessment performance can assist in the differentiation of patients at varying levels of risk and severity for cerebrovascular disease and VaD. The R-CVD group performed within normal expectations on most cognitive measures as compared to the elderly control sample and published clinical norms. Relative to elderly controls, the VaCIND group demonstrated significant difficulties on measures of cognitive flexibility, verbal retrieval, and verbal recognition memory, but not on measures of confrontational naming or verbal fluency. The VaD group was impaired on all cognitive measures assessed. The current findings suggest that poor cognitive flexibility and verbal retrieval in the context of preserved function in other domains may characterize the prodromal stage of VaD.

The California Verbal Learning Test (CVLT) and the Word Lists Test (WLT) from the Wechsler Memory Scale-III are widely used tests of verbal learning and memory. To examine concordance between these popular tests, we administered both to a diagnostically diverse group of 25 patients. As expected, measures from the two tests were highly correlated, although level of concordance was not as high as might be expected. When diagnostic outcomes were discordant for free recall measures, the CVLT indicated impairment more often than did the WLT.

The purpose of this study was to examine the course and predictors of functional decline among patients with vascular dementia (VaD). Twenty-eight VaD patients completed three tests of executive functions and underwent MRI scanning to generate quantitative ratings of subcortical neuropathology at a baseline evaluation. The caregiver-rated Lawton and Brody Activities of Daily Living Questionnaire was used to estimate instrumental activities of daily living (IADLs) at the baseline evaluation and at a 1 year follow-up. We hypothesized that: (a) IADLs would decline significantly over the course of 1 year, and (b) baseline performance on executive tasks and subcortical neuropathology would predict IADL impairment at 1 year follow-up, even after accounting for global cognitive dysfunction. A paired samples t-test demonstrated that IADLs declined significantly over the course of 1 year, and regression analyses revealed that baseline performance on executive tasks was a significant predictor of IADLs at the 1 year follow-up, even after accounting for global cognitive dysfunction. Contrary to our expectation, subcortical neuropathology did not explain unique variance in IADLs after accounting for executive dysfunction. These findings demonstrate that baseline executive dysfunction is a significant and powerful predictor of future functional decline in individuals with VaD.

White matter hyperintensities (WMHs) are frequently found on MRI studies of vascular dementia (VaD) patients. As several studies have demonstrated that WMHs are often associated with severity of illness, cognitive impairment, and functional decline, the accurate and reliable measurement of WMHs on MRI is an important, yet often overlooked, prerequisite for accurate interpretation of neuroimaging studies. Using a sample of 39 VaD patients, we evaluated the reliability and validity of a visual ordinal rating scale and a computer-mediated thresholding technique to evaluate WMHs. Results indicated the computer-mediated technique had slightly stronger inter-rater reliability than the visual ordinal rating scale. Furthermore, the computer-mediated thresholding technique was correlated with measures of neuropsychological functioning believed to be compromised in VaD (i.e., psychomotor speed, executive functioning) while the visual rating scale was not. Results suggest that this computer-mediated thresholding technique is superior to visual ratings of WMHs.

Prison-based research has been limited due to concern that prisoners may represent a vulnerable population secondary to possible coercion and limited capacity for voluntary informed consent. This study was designed to assess decisional capacity and susceptibility to coercion in prison research subjects. Subjects were 30 mentally ill prisoners and 30 healthy controls. The groups were compared on ability to provide informed consent to a hypothetical drug trial, susceptibility to possible coercion, neuropsychological functioning, and psychiatric symptoms. Results indicated that all controls and all but one of the prisoners demonstrated adequate capacity to consent to the hypothetical drug trial. However, when decisional capacity was measured quantitatively, prisoners performed significantly worse regarding two aspects of this ability. Regarding possible coercion, prisoners' main reasons for participating in research included avoiding boredom, meeting someone new, appearing cooperative in hopes of being treated better, and helping society. Neuropsychological functioning was strongly positively correlated with decisional capacity and negatively correlated with susceptibility to possible coercion, whereas psychiatric symptoms were only weakly correlated with these variables. In conclusion, a very high percentage of particularly vulnerable, mentally ill prisoners demonstrated adequate capacity to consent to research. Lower scores on a quantitative measure of decisional capacity suggest that extra care should be taken during the consent process when working with these subjects. The reasons prisoners gave for participating in our research indicated that the prison setting may have influenced their decision to participate, but that they were not actually coerced into doing so. Despite serious past incidents, ethicists will need to consider the possibility that prisoners have become an overprotected population.

Objective: Previous research has revealed cognitive deficits in patients with anorexia nervosa. It is unclear whether these deficits are linked to co-morbid depression in this population. We examined the relationship between depressive symptoms and cognitive functioning., Method: A large sample of subjects (N = 98) was examined using a common measure of cognitive ability and two measures of depression., Results: We confirmed that there is no relationship between depression and cognitive ability in this group., Discussion: This suggests that alternative explanations be explored for cognitive deficits in patients with anorexia nervosa., (Copyright 2003 by Wiley Periodicals, Inc.)

Objective: To determine whether demographic data, dementia severity, functional status, whole brain volume (WBV), or subcortical hyperintensity volume (SH) predict subsequent cognitive decline in vascular dementia (VaD)., Background: The identification of variables that accurately predict progressive cognitive decline in dementia has important clinical implications., Methods: A cohort of 30 patients with VaD completed neurologic and neuropsychologic examinations and magnetic resonance imaging of the brain at baseline and again after 12 months. All participants met clinical and research criteria for VaD according to standard guidelines. Change scores were computed for measures of verbal fluency, verbal learning, and visual learning. Potential correlates of cognitive change included age, education, score on the Hachinski scale, WBV, SH, and functional ability., Results: As a group, lower WBV and lower Hachinski score correlated with decline in verbal fluency and visual learning, whereas lower Hachinski score correlated with decline in verbal learning. However, when subdivided by disease type, this pattern held only for individuals with evidence of a cortical stroke at baseline. No clinical variables correlated with cognitive decline among individuals without a cortical infarction., Conclusions: Assessment of cognitive decline in VaD should be guided by dementia subtype, with particular attention directed at severity of cerebral atrophy rather than classic symptoms of infarction.

Objective: The influence of psychiatric symptoms and cognitive impairment on daily living skills was explored in a series of nursing home residents. Three categories of symptoms were examined: behavioral disturbances, depression, and delusions., Method: Nursing home residents (N=69) underwent comprehensive psychiatric evaluations. Relationships among psychiatric symptoms, cognitive function, and daily living skills were assessed by using regression and correlation analyses., Results: Cognitive decline had the greatest effect on functional impairment in a standard least squares model, followed by behavioral disturbances. Psychiatric symptoms correlated positively with each other and with functional impairment, and correlated inversely with cognitive functioning., Conclusions: Cognitive decline appears to confer the greatest burden of functional disability in the nursing home setting. After cognitive effects were accounted for, behavioral dysregulation was also associated with functional impairment. In conclusion, interventions to enhance cognition and ameliorate behavioral disturbances are important areas for future studies in long-term care.

Background: The Dementia Rating Scale (DRS) is a common measure of cognitive function, but its sensitivity to identify deficits across cognitive domains in vascular dementia (VaD) remains unclear., Methods: We compared the sensitivity and specificity of two recommended cutoff scores of the DRS. Thirty-eight patients diagnosed with VaD participated in the current study., Results: The original recommendations resulted in poor sensitivity for the DRS total score and attention, construction, and memory subscales. The more recent recommendations greatly improved the sensitivity of the subscales and the total DRS score, but resulted in decreased specificity. Correlations between the specific DRS subscales and criterion measures of cognitive function revealed good convergent and divergent validity for most subscales., Conclusions: The DRS is a valid measure of cognitive dysfunction in VaD, but clinicians should consider using the more recent recommendations developed for AD to determine impaired performances in VaD., (Copyright 2003 S. Karger AG, Basel)

Objective: This study was conducted to determine whether neuropsychological dysfunction associated with anorexia nervosa resolves with inpatient treatment., Method: Subjects were 28 women being treated for anorexia nervosa. Main study variables included body mass index (BMI), Beck Depression Inventory-II, and neuropsychological test scores. Subjects were tested at admission and discharge., Results: Neuropsychological functioning improved across the course of treatment, with significant changes on tests of memory and psychomotor speed. This improvement was not significantly associated with change in BMI or with the other variables that were studied., Discussion: Patients with anorexia nervosa exhibit subtle neuropsychological dysfunction, which resolves at least partially during treatment. This improvement does not appear to be associated with an increase in BMI. However, it is possible that BMI is not a sufficiently sensitive indicator of nutritional status or that longer-term follow-up is necessary to reveal the nutrition-cognition relationship that we were seeking., (Copyright 2002 by Wiley Periodicals, Inc.)