Browsing by Subject "Cognition disorders"

Now showing 1 - 6 of 6
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    Cognitive dysfunction in cancer: Neuroimaging and genetic approaches to identify biological mechanisms
    (2015-04-22) Nudelman, Kelly N. H.; Saykin, Andrew J.; Foroud, Tatiana M.; McDonald, Brenna Cathleen; Schneider, Bryan Paul; Shen, Li
    Although cancer and treatment-associated cognitive dysfunction has been well-documented in the literature, much work remains to elucidate the biological mechanisms driving this effect, hampering current therapeutic efforts. To address this gap, we first reviewed studies utilizing neuroimaging to characterize cognitive dysfunction in cancer, as studies of neurodegenerative diseases point to neuroimaging as a sensitive measure of cognitive dysfunction. This review highlighted the need for longitudinal imaging studies of cancer and treatment-related changes in cerebral structure and function. Subsequently, we utilized multimodal neuroimaging techniques in a female breast cancer cohort to investigate the longitudinal impact of cancer and chemotherapy treatment on cerebral perfusion and gray matter. Our findings indicate that chemotherapy is associated with elevated perfusion, primarily in posterior brain regions, as well as depressed frontal perfusion associated with decreased frontal gray matter density. This pattern of results suggests the involvement of multiple mechanisms of chemotherapy-induced cognitive dysfunction. We also investigated the relationship of cognitive dysfunction and chemotherapy-induced peripheral neuropathy (CIPN), another type of chemotherapy-related nervous system sequelae, again utilizing multimodal, longitudinal neuroimaging, and found that peripheral neuropathy symptoms following chemotherapy were associated with changes in cerebral perfusion and gray matter density. Together, these findings support the hypothesis that multiple biological mechanisms drive cancer and treatment-related cognitive dysfunction. Interestingly, although cancer is associated with cognitive dysfunction, epidemiological studies have shown that cancer and Alzheimer's disease (AD) are inversely correlated. To extend our imaging analysis beyond breast cancer, we leveraged the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to investigate the inverse relationship of cancer and AD and investigate the impact of both of these diseases on gray matter density. We found that though the inverse relationship of these diseases was replicated in the ADNI cohort, cancer history was associated with lower gray matter density, similar to findings from breast cancer studies, independent of AD diagnostic group. Finally, we reviewed microRNA studies, as microRNAs are important regulators of many cell signaling pathways and have been actively investigated in relation to both diseases. This review suggests several pathways that may be driving the inverse association and may contribute to cognitive dysfunction.
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    Depressed mood in informal caregivers of individuals with mild cognitive impairment
    (Sage, 2007) Lu, Yueh-Feng Yvonne; Austrom, Mary Guerriero; Perkins, Susan M.; Bakas, Tamilyn; Farlow, Martin R.; He, Feng; Jin, Shelia; Gamst, Anthony; School of Nursing
    This study estimates the prevalence of depressed mood in caregivers of individuals with mild cognitive impairment (MCI) and assesses whether demographics, stressors, intrapsychic strain, and gain are associated with depressed mood. A secondary analysis of baseline data from the Alzheimer's Disease Cooperative Study MCI trial was conducted using a cross-sectional, correlational design. Descriptive statistics to estimate the prevalence of caregiver depressed mood and univariate and block-wise logistic regression analyses were used. The prevalence of depressed mood in 769 caregivers was 24.6% (95% confidence interval, 21.5-27.7). The odds of being depressed were significantly higher in younger, nonspousal caregivers with less education, who cared for MCI patients with lower activities of daily living functioning, and who perceived greater relational deprivation, higher levels of self-loss, and personal gain. Controlling for relevant variables, relational deprivation and caregiver education continued to be significantly associated with depressed mood. Relational deprivation may be important for future interventions.
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    Experience and participation implications of daily enhancement meaningful activity in persons with mild cognitive impairment
    (2016-04-01) Ellis, Jennifer L.; Arnold, Brent Lee; Lu, Yvonne Yueh-Feng; Altenburger, Peter Andrew; Munk, Niki
    Background: Persons with Mild Cognitive Impairment (PwMCI) battle progressive disengagement from personally meaningful activities that results in functional decline. Little is known about PwMCI experience of engaging in meaningful activities and relationships among MCI stage, confidence, depressive symptoms, and function. Daily Engagement of Meaningful Activity (DEMA) is a multicomponent, family-focused, tailored intervention designed to benefit PwMCI and their caregivers by facilitating goal identification, preserve engagement, and support adjustments to cognitive and functional changes. Objectives: The aims of this secondary analysis were to: (i) describe PwMCI experience of engagement in DEMA, (ii) evaluate for potential relationship among MCI stage, confidence, depressive symptoms, activity type, activity performance, physical function and (iii) evaluate ability of select outcomes to predict change in depressive symptoms and physical function, (iv) determine difference between participants when sub-grouped by ICF level. Methods: Mixed methodology was used to conduct a secondary analysis from the parent study. The parent study used a two-group randomized trial involving PwMCI and informal caregivers participating in the Indiana Alzheimer Disease Center DEMA program. Quantitative analysis (dyads: DEMA N=20, Information Support N = 20) examined outcomes at baseline, posttest and follow-up. Analysis employed: (i) Colaizzi's Method of empirical phenomenology to describe PwMCI experience of engagement in activity intervention related to perceptions of changes in confidence, activity performance, and physical function; (ii) Pearson's and Spearman's correlation to ascertain relationship; (iii) Linear regression to model the relationship between explanatory and dependent variables; (iv) Independent t-test to determine significant difference in activities and physical function. Results: Qualitative themes confirm improved awareness, adjustment, problem-solving, confidence and optimized function. Significant correlations were found at baseline and posttest for MCI stage, depressive symptoms, activity type and physical function. At posttest, change in self-rated performance predicted change in depressive symptoms. Additionally, those who engaged in activity at the ICF level of participation demonstrated a significant increase in confidence and physical function. Conclusion: Qualitative themes and quantitative results clearly indicate the positive impact of DEMA. Future research should employ a larger, randomized controlled longitudinal trial to ascertain DEMA impact on physical function, reduction of participation restriction and improved QOL.
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    Imaging Brain Networks After Cancer and Chemotherapy: Advances Toward Etiology and Unanswered Questions
    (The JAMA Network, 2016-02) Nudelman, Kelly N.H.; McDonald, Brenna C.; Saykin, Andrew J.; Department of Radiology and Imaging Sciences, IU School of Medicine
    Comment on Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors. [JAMA Oncol. 2016]
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    Molecular and Cellular Mechanisms Leading to Similar Phenotypes in Down and Fetal Alcohol Syndromes
    (2013-08-22) Solzak, Jeffrey Peter; Roper, Randall J.; Marrs, James; Kusmierczyk, Andrew; Atkinson, Simon
    Down syndrome (DS) and Fetal Alcohol Syndrome (FAS) are two leading causes of birth defects with phenotypes ranging from cognitive impairment to craniofacial abnormalities. While DS originates from the trisomy of human chromosome 21 and FAS from prenatal alcohol consumption, many of the defining characteristics for these two disorders are stunningly similar. A survey of the literature revealed over 20 similar craniofacial and structural deficits in both human and mouse models of DS and FAS. We hypothesized that the similar phenotypes observed are caused by disruptions in common molecular or cellular pathways during development. To test our hypothesis, we examined morphometric, genetic, and cellular phenotypes during development of our DS and FAS mouse models at embryonic days 9.5-10.5. Our preliminary evidence indicates that during early development, dysregulation of Dyrk1a and Rcan1, cardinal genes affecting craniofacial and neurological precursors of DS, are also dysregulated in embryonic FAS models. Furthermore, Caspase 3 was also found to have similar expression in DS and FAS craniofacial neural crest derived tissues such as the first branchial arch (BA1) and regions of the brain. This may explain a developmental deficit by means of apoptosis. We have also investigated the expression of pAkt, a protein shown to be affected in FAS models, in cells located within the craniofacial precursor of Ts65Dn. Recent research shows that Ttc3, a gene that is triplicated and shown to be overexpressed in the BA1 and neural tube of Ts65Dn, targets pAkt in the nucleus affecting important transcription factors regulating cell cycle and cell survival. While Akt has been shown to play a role in neuronal development, we hypothesize that it also affects similar cellular properties in craniofacial precursors during development. By comparing common genotypes and phenotypes of DS and FAS we may provide common mechanisms to target for potential treatments of both disorders. One of the least understood phenotypes of DS is their deficient immune system. Many individuals with DS have varying serious illnesses ranging from coeliac disease to respiratory infections that are a direct result of this immunodeficiency. Proteasomes are an integral part of a competent and efficient immune system. It has been observed that mice lacking immunoproteasomes present deficiencies in providing MHC class I peptides, proteins essential in identifying infections. A gene, Psmg1 (Dscr2), triplicated in both humans and in Ts65Dn mice, is known to act as a proteasome assembly chaperone for the 20S proteasome. We hypothesized that a dysregulation in this gene promotes a proteasome assembly aberration, impacting the efficiency of the DS immune system. To test this hypothesis we performed western blot analysis on specific precursor and processed β-subunits of the 20S proteasome in thymic tissue of adult Ts65Dn. While the β-subunits tested displayed no significant differences between trisomic and euploid mice we have provided further insight to the origins of immunodeficiency in DS.
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    Serum magnesium concentration and incident cognitive impairment: the reasons for geographic and racial differences in stroke study
    (Springer, 2021) Chen, Cheng; Xun, Pengcheng; Unverzagt, Frederick; McClure, Leslie A.; Ryan Irvin, Marguerite; Judd, Suzanne; Cushman, Mary; He, Ka; Psychiatry, School of Medicine
    Purpose: To examine the prospective association between serum Mg level and the incidence of cognitive impairment. Methods: A random sub-cohort (n = 2063) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was included in this study. Baseline serum Mg concentration was measured using inductively coupled plasma mass spectrometry. According to the current reference interval of serum magnesium (0.75-0.95 mmol/L), we classified participants below the interval as Level 1 and used it as the referent. The rest of the study population were equally divided into three groups, named Level 2 to 4. Incident cognitive impairment was identified using the Six-Item Screener. Multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression models. Results: After adjustment for potential confounders, an inverse threshold association between serum Mg level and incident cognitive impairment was observed. Compared to those with hypomagnesemia (Level 1: < 0.75 mmol/L), the relative odds of incident cognitive impairment was reduced by 41% in the second level [OR (95% CI) = 0.59 (0.37, 0.94)]; higher serum Mg level did not provide further benefits [Level 3 and 4 versus Level 1: OR (95% CI) = 0.54 (0.34, 0.88) and 0.59 (0.36, 0.96), P for linear trend = 0.08]. Conclusions: Findings from this prospective study suggest that sufficient Mg status within the normal range may be beneficial to cognitive health in the US general population.