Browsing by Subject "Cognition Disorders"
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Item Analysis of Neurocognitive Elements of Attention Following Chemotherapy Treatment(2013-01-16) Grosch, Maria Catherine; Cullum, Colin Munro, Ph.D., ABPP-CNBreast cancer affects approximately 123 out of 100,000 women per year in the United States, with 207,090 new cases estimated each year (Altekruse et al., 2010). Adjuvant chemotherapy has become a staple of care to improve long-term outcomes for several types of breast cancers (de Boer, Taskila, Ojajärvi, van Dijk, & Verbeek, 2009). Because of advances in treatment, the overall 5-year survival rate for breast cancer patients is now estimated at 89% (Altekruse et al., 2010). With increased survival comes a greater concern for issues related to quality of life, including cognitive function. Unfortunately, cancer treatments may result in cognitive changes or impairment, with deficits ranging from minor to debilitating (Argyriou, Assimakopoulos, Iconomou, Giannakopoulou, & Kalofonos, 2011). The phenomenon of cognitive dysfunction following cancer treatment is often called “chemo-brain” by patients and in the media. Despite an increase in the number of published studies in recent years, many aspects of chemotherapy-related cognitive dysfunction remain poorly understood. The pattern of cognitive impairment and neurological damage (as seen on neuroimaging) is reflective of disruption of frontal subcortical networks (Meyers, 2008). Because attention and related constructs are of central importance in this so-called “subcortical profile,” it is important to have a thorough understanding of how these domains are impacted by chemotherapy. However, available literature is difficult to interpret, in part because of various methodological factors, including the use of singular or otherwise limited neuropsychological tests, inconsistent use of tests across studies, and variability in the conceptualization of domains believed to be affected by chemotherapy (such as attention and related constructs). Thus, conclusions regarding attentional impairment in women treated for breast cancer are limited, and its role in the clinical syndrome known as chemo-brain remains poorly understood.Item Characterization and Differences Between Possible and Probable Mild Cognitive Impairment(2009-06-15) Denney, David Austin; Lacritz, LauraMild Cognitive Impairment (MCI) is the period of subtle cognitive decline that occurs between normal aging and clinical Alzheimer's Disease (AD). Patients' subjective memory complaints (SMCs) are essential to the diagnosis of MCI. In cases where memory complaints are not verifiable by objective measures, patients are left without a formal diagnosis of cognitive impairment. The current proposal describes a study designed to compare the cognitive features and risk factors of AD in subgroups of patients with SMCs with (Probable MCI) and without (Possible MCI) objective memory deficits in relation to controls. It is predicted that the Probable MCI group will demonstrate lower performance and have a greater decline on neuropsychological measures than patients diagnosed with Possible MCI, who will demonstrate lower performance and have a greater decline on those measures than controls. Also, it is predicted that Probable MCI patients will have greater incidence of vascular risk factors and presence of the apolipoprotein element 4 (APOE-4) allele than the Possible MCI patients, who will have higher incidence of these variables than controls. There is also a demographic analysis designed to identify any differences in age, education, and gender between the groups. Implications of possible outcomes of the study are then discussed.Item The Effect of Rapamycin Paired with Traumatic Memory Activation on Cognitive Performance in Veterans Diagnosed with PTSD(2012-05-18) Anderson, Elizabeth Hallen; Sur's, AlinaMany individuals with posttraumatic stress disorder (PTSD) experience cognitive impairment in addition to the characteristic psychological symptoms. Animal studies have shown that rapamycin, a protein synthesis inhibitor that targets the protein kinase mTOR, can prevent the reconsolidation of a reactivated fear memory, thereby reducing its emotional strength at a neurochemical level. The aim of the current study was to determine if pairing rapamycin with traumatic memory reactivation in male veterans with combat-related PTSD would lead to an improvement in cognitive performance, based on scores from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline and 1-month follow-up. In a double-blind, placebo-controlled study, male veterans with combat-related PTSD were administered either a single dose of rapamycin or placebo, followed by a script-driven memory reactivation task. Measures included the RBANS, Clinician Administered PTSD Scale (CAPS), and the Quick Inventory of Depressive Symptomatology (QIDS). A repeated measures ANOVA was conducted to assess the impact of two different interventions (rapamycin, placebo) on participantsÕ scores on the RBANS, across two time periods (baseline, one-month follow-up). The main effect comparing the two type of interventions revealed no significant differences in the effectiveness of the two interventions in the entire sample; F (1,48) = .01, p = .921, partial eta squared < .001. When the sample was limited to participants who demonstrated a clinically significant reduction (³ 20 points) in their CAPS score, a repeated measures ANOVA revealed a significant interaction between time and treatment intervention; Wilks Lambda = .44, F (1, 13) = 16.74, p = .001, partial eta squared = .563. Pairwise comparisons showed a significant improvement between baseline and one-month follow-up on the RBANS for participants in the placebo group, mean difference = 10.00, p = .002. Based on these results, a single rapamycin treatment does not appear to be detrimental or beneficial to cognitive performance. Furthermore, a clinically significant reduction in PTSD symptoms due to rapamycin is not associated with an improvement in cognitive performance.Item Functional Connectivity of the Posterior Cingulate in Mild Cognitive Impairment and Alzheimer's Disease(2008-09-12) Fields, Julie A.; Allen, GregMild cognitive impairment (MCI) has been implicated as an early stage of Alzheimer's disease (AD) by some, while others argue this is not necessarily the case. While controversy around this issue continues, it is undisputed that MCI is a risk factor for AD. Finding a biomarker of AD would lead to early intervention that could potentially slow the progression of the disease and guide further research towards targets for a cure. Recent findings suggest that reduced connectivity between the posterior cingulate cortex (PCC) and associated brain regions may make an important contribution in this regard, as changes in the PCC/precuneus and entorhinal cortex are implicated as early biomarkers for AD. The current study used functional connectivity magnetic resonance imaging (fcMRI) to examine the posterior cingulate's connectivity with other brain regions in subjects with AD (n=10), MCI (n=9), and age-matched elderly normal controls (NC; n=10). As hypothesized, results revealed that subjects with AD showed decreased connectivity in regions of the frontal lobe, temporal lobe, and cingulate gyrus when compared to NC, and in the frontal and temporal gyri when compared to MCI. When MCI was compared to NC, decreased connectivity was observed in the cingulate gyrus and parahippocampal gyrus while increased connectivity was found in prefrontal cortex and cerebellar regions. The latter finding of increased connectivity in the MCI group in the prefrontal cortex and cerebellum was interpreted as evidence of compensatory recruitment of alternate brain regions in the face of deficient processing in parahippocampal regions in the early stage of disease. It is possible that the connectivity between the PCC and cerebello-frontal structures in MCI may be helping to sustain episodic memory and executive functions that deteriorate in AD. This study showed that fcMRI may be sensitive enough to detect subtle changes in brain structure, and while it is premature to say that fcMRI might prove to be a biomarker of AD, these preliminary findings are encouraging and may serve as an impetus for further research.Item Intelligence and Academic Achievement in Ten-Year Survivors of Childhood Medulloblastoma(2005-05-11) McDonald, Noelle Kristen; Silver, Cheryl H.Advances in the treatment of childhood medulloblastoma have markedly increased survival rates in recent decades. Although survival rates have improved, research has demonstrated that significant cognitive consequences are common in patients who have survived medulloblastoma. Few studies exist that examine the extent of long-term cognitive impairment as far as 10 years after treatment. The present pilot study examined the intellectual and academic achievement in a sample of 16 ten-year survivors of childhood medulloblastoma treated with surgery and craniospinal radiation. In addition, the relationships between the medical variables of age at treatment and dose of craniospinal radiation and cognitive and academic functioning were explored. The sample demonstrated significant cognitive impairment on measures of intellectual functioning and three measures of academic achievement. The academic domains that were most severely impaired were writing skills and practical math problem solving. The majority of participants demonstrated impairment in at least one domain of academic achievement, but the extent of achievement problems was underestimated when applying the traditional discrepancy model, in which an achievement score must be at least 15 points below the intelligence score to represent a learning disability. Age at treatment and dose of craniospinal radiation were not associated with performance on measures of intelligence and academic achievement in the present study; however, the small sample size may have limited the ability to detect significant results among these variables. The results of the present study demonstrate significant impairment in intellectual functioning and academic achievement in ten-year survivors of childhood medulloblastoma.Item Neurologin function in excitatory and inhibitory synapses(2008-09-19) Zang, Tong; Sudhof, Thomas C.Neuroligins (NLs) are postsynaptic cell adhesion molecules which by binding to presynaptic neurexins (NRXs) are thought to mediate synapse formation and function. Both NLs and NRXs are discussed in the genetic correlation to Autism. Over-expression of NLs could induce the formation of synaptic contacts with axons in non-neuronal cells and increase the synaptic density and response in cultured neurons, through binding and recruiting NRXs; however, little is known about NL signaling though NRXs or inside the cell. First, we hypothesized that NLs signal through their cytoplasmic region. Over-expression of NL1 with cytoplasmic tail truncation abolished the increase of synaptic density by NL1 full length. By yeast two hybrid screening using NL2 cytoplasmic region, we identified potential interaction partners, of which Necab2 and NRP/B (also named as ectodermal cortex 1, EC1) are two promising candidates and the interactions were confirmed. NL1 or NL2 c-tail truncations partially abolished the change in miniature IPSC, but not the evoked responses. NL c-tail binding partners?ver-expression does not show any change in evoked responses. It suggested that NL cytoplasmic region is important for some neuronal changes but does not contribute to the major phenotype of NLs. And we investigated the contribution of NL-NRX binding by using NL extracellular NRX binding mutants. The mutants abolished the change of the evoked and miniature inhibitory responses from the NL2 wild type, which suggested the inhibitory responses triggered by NL2 go through NRXs. And the slight change of the paired pulse ratio suggested the change of presynaptic calcium through binding. The study suggested that NL2 facilitate the inhibitory synaptic transmission through extracellular region via neurexin binding, possibly by the increase in presynaptic calcium. We also found Brain-specific Angiogenesis Inhibitors (BAIs), a family of G-protein coupled receptors (GPCRs), will bind to NLs extracellularly and may serve as signaling modules binding to NLs. Over-expression of BAIs do not change evoked IPSCs, but Bai1 decreased evoked EPSCs and increased the burst duration in the spontaneous responses, possibly because of some secondary responses. Therefore, we found NL-NRX though NL extracellular region is important for NL2 function in synaptic transmission, and BAIs may be potential signaling molecules of NLsItem Performance on the Texas Functional Living Scale (TFLS) In Mild Cognitive Impairment(2007-08-08) Binegar, Dani Lyn; Cullum, C. MunroMild cognitive impairment (MCI) describes the transitional state between normal aging and dementia for many individuals, although debate continues over whether MCI represents an initial, separate condition, or if it is, in fact, the earliest presentation of dementia. One criterion for the diagnosis of MCI is an absence of impairment in activities of daily living; however, there is growing evidence that many individuals with MCI have difficulties with some instrumental activities of daily living (IADLs), such as managing finances and medications. The current study examined the performance of individuals diagnosed with MCI and normal control subjects (NC) on a brief, quantifiable measure of IADLs, the Texas Functional Living Scale (TFLS). Additional goals of this study were to examine how the TFLS relates to standard neuropsychological measures of global cognitive function, memory, language, executive functioning, and attention, and to determine whether performance on the TFLS declines over time in MCI. As predicted, the MCI sample (n = 30) scored significantly lower than the NC group (n = 30) on the TFLS total score (t (58) = 2.34, p = .011) and on the TFLS Memory subscale (t (58) = 3.29, p = .002). Performance on the TFLS was significantly correlated with performance on the MMSE (ρ = .26) and The Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD; r = .37). Scores on the TFLS Memory and Communication subscales were also correlated with the CERAD total score (r = .45 and .22, respectively). Across all subjects, the TFLS was associated with standard measures of memory and language (ρ's = .22 to .31). Although the difference did not reach statistical significance, subgroups of MCI and NC were followed over time, and 50% of individuals with MCI declined on the TFLS, compared with 29% of NC sample. These findings suggest that subtle changes in cognitive-related IADLs may be present in individuals with MCI, and that the TFLS is sensitive to such changes.Item Relationhsip between Exercise and Cognitive functioning in Breast Cancer Survivors following Chemotherapy(2013-05-17) Antony, Merlyn; Kendall, JeffreyBACKGROUND: A growing body of research suggests that individuals who undergo chemotherapy for treatment of cancer experience adverse changes in cognitive functioning as a side effect of treatment. While there is not yet a known remedy for such effects, exercise has shown to improve cognitive functioning in individuals within other clinical populations. Therefore, the purpose of this current study is to examine whether any relationships exist between self-reported post-chemotherapy exercise and cognitive functioning. SUBJECTS: The sample consisted of sixty female breast cancer survivors between the ages of 38-71. All participants had been diagnosed with stage I, II, or III breast cancer and had completed chemotherapy between three months to two years prior to their study visit. METHOD: Participants completed a self-report measure of post-chemotherapy exercise behavior and were administered a battery of neurocognitive tests to measure cognitive functioning. Subjects were categorized into one of three exercise groups based on their total exercise score (LSI): sedentary (LSI < 14), moderately active (LSI = 14-23), or active (LSI > 24). Mean scores on cognitive tests between exercise groups were compared to determine whether significant differences existed between groups both before and after controlling for IQ. Additionally, a hierarchical multiple regression was performed to determine how much of the variance in cognitive test scores could be explained by the following predictors: age, education, IQ, anxiety, depression, and exercise. RESULTS: Only three test scores (CVLT, Digit Span Backward, and Digit Symbol Coding) showed significant differences between exercise groups. Before controlling for IQ, CVLT (F=7.40, p=.001) and Digit Span Backward (F=3.01, p=.057) displayed significant differences between groups. After controlling for IQ, CVLT (F=4.19, p=.012), Digit Span Backward (F=5.98, p=.004), and Coding (F=3.05, p=.055) displayed significant differences. Predictors explained a small portion of the variance in cognitive test scores. DISCUSSION: Only three out of seven cognitive test scores demonstrated differences between exercise groups. Even among those tests that showed differences, higher levels of exercise were not consistently associated with better performance. In some cases, a moderate level of exercise seemed to have an optimal effect with regard to cognitive performance, suggesting the possibility of a dosing effect of exercise. Overall these findings suggest that a possible relationship may exist, but additional research is warranted