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Biomedical subjects

David J Moser

Publications and source records attributed to David J Moser.

At least 19 recordsLinked to original sources

Endothelial function and white matter hyperintensities in older adults with cardiovascular disease.

BACKGROUND AND PURPOSE: The presence of white matter hyperintensities on brain MRI is common among elderly individuals. Previous research suggests that cardiovascular risk factors are associated with increased white matter hyperintensities. Examining the role of direct physiological measures of vascular function will help to clarify the vascular mechanisms related to white matter hyperintensities. The aim of the present study was to examine the association between endothelial-dependent and endothelial-independent vasodilatation and white matter hyperintensity volume. METHODS: Twenty-five older adults with a range of cardiovascular diseases underwent brain MRI and completed assessments of blood vessel integrity using endothelial-dependent and independent flow-mediated dilation of the brachial artery. A semi-automated pixel-based method was used to quantify total brain volume and white matter hyperintensity volume, with white matter hyperintensity volume corrected for total brain volume. The association between measures of flow-mediated dilation and log-transformed white matter hyperintensities was examined. RESULTS: Correlation analysis revealed that endothelial-dependent vasodilatation was significantly and inversely associated with white matter hyperintensity volume. In contrast, endothelial-independent vasodilatation was not associated with white matter hyperintensities. Neither endothelial-dependent nor endothelial-independent vasodilatation was associated with total brain volume. CONCLUSIONS: These data provide preliminary evidence that the integrity of the vascular endothelium is associated with white matter hyperintensities in older adults with cardiovascular disease. Impaired vascular function may be one mechanism that contributes to the development of white matter hyperintensities in the brain. Additional longitudinal research combining measures of vessel function, neuroimaging and cognition will be helpful in clarifying this potential mechanism.

Aged↗

Neuropsychological and psychiatric functioning pre- and posthematopoietic stem cell transplantation in adult cancer patients: a preliminary study.

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.

Adult↗

Practice effects in the prediction of long-term cognitive outcome in three patient samples: a novel prognostic index.

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.

Adult↗

Neuropsychological performance is associated with vascular function in patients with atherosclerotic vascular disease.

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.

Aged↗

Evaluation of the GTRACT diffusion tensor tractography algorithm: a validation and reliability study.

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.

Algorithms↗

Perception of socially relevant stimuli in schizophrenia.

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.

Adult↗

Cognitive predictors of functional decline in vascular dementia.

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.

Activities of Daily Living↗

Aggressive behavior in patients with stroke: association with psychopathology and results of antidepressant treatment on aggression.

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.

Aged↗

Examining the repeatable battery for the assessment of neuropsychological status: factor analytic studies in an elderly sample.

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.

Aged↗

Using a brief intervention to improve decisional capacity in schizophrenia research.

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.

Adult↗

Progressive morphometric and cognitive changes in vascular dementia.

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.

Aged↗

Phobic anxiety in late-life in relationship to cognition and 5HTTLPR polymorphism.

Anxiety in late-life may functionally impair the older adult. In this study the polymorphic region 5HTTLPR of the SLC6A4 gene was examined in relation to phobic anxiety and cognitive function. Sixty-four community-dwelling older adults were genotyped for the 5HTTLPR polymorphism to examine whether late-life phobias are associated with the short (s) allele and whether cognitive impairment may precipitate phobic behaviors in association with the s allele. Our findings suggested that phobic anxiety symptoms are significantly related to lower cognitive function. However, in this sample we did not detect a significant association between phobic anxiety and the 5HTTLPR genotype. The interaction between age-related changes in cognition and anxiety remain an important area for future studies.

Aged↗

White matter volume and cognitive dysfunction in early Huntington's disease.

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.

Adult↗

Informed consent in medication-free schizophrenia research.

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.

Adult↗

Blood vessel function and cognition in elderly patients with atherosclerosis.

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.

Aged↗

The neuropsychological profile of vascular cognitive impairment--no dementia: comparisons to patients at risk for cerebrovascular disease 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.

Aged↗

Concordance between the CVLT and the WMS-III word lists test.

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.

Adult↗