Browsing by Subject "Cognitive dysfunction"
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Item Association between Cardiovascular Disease and Cognitive Dysfunction in Breast Cancer Survivors(Wolters Kluwer, 2023) Von Ah, Diane; Crouch, Adele; Arthur, Elizabeth; Yang, Yesol; Nolan, Timiya; School of NursingBackground: Breast cancer survivors (BCS) may have a greater risk for cardiovascular disease [congestive heart failure (CHF) and hypertension (HTN)], which in turn, can affect cognitive dysfunction, a frequent, bothersome, and potentially debilitating symptom. Objective: The purpose of this study was to examine the relationship of cardiovascular disease on cognitive function in BCS. Methods: Baseline data from a double-blind RCT for cognitive training of BCS were examined. Early stage BCS (Stage I-IIIA) who were ≥21 years of age, completed adjuvant therapy (≥ 6 months), and reported cognitive concerns completed questionnaires and a brief neuropsychological assessment, including tests of memory, attention and working memory, speed of processing, and verbal fluency. Descriptive statistics, Pearson’s correlation coefficient and separate linear regression models for each cognitive domain were conducted. Results: 47 BCS, who were on average 57.3 (SD=8.1) years old, 58% White and had some college education (75%), completed the study. 44.7% of the BCS had cardiovascular disease (CHF or HTN). In linear regression models, cardiovascular disease was significantly related to immediate and delayed memory and attention and working memory (p<0.01–0.05). Conclusions: BCS who have cardiovascular disease may also be at a greater risk for cognitive dysfunction post-treatment. Results from this study inform both clinical practice and future research, specifically by examining the intersect between cancer, cardiovascular disease (cardiotoxicity), and cognition. Implications for Practice: Nurses should be aware that BCS with co-occurring cardiovascular disease are at higher risk for cognitive dysfunction, and work within the multidisciplinary team to optimize BCS health and function.Item Association of peripheral blood DNA methylation level with Alzheimer’s disease progression(BMC, 2021-10-15) Li, Qingqin S.; Vasanthakumar, Aparna; Davis, Justin W.; Idler, Kenneth B.; Nho, Kwangsik; Waring, Jeffrey F.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of MedicineBackground: Identifying biomarkers associated with Alzheimer's disease (AD) progression may enable patient enrichment and improve clinical trial designs. Epigenome-wide association studies have revealed correlations between DNA methylation at cytosine-phosphate-guanine (CpG) sites and AD pathology and diagnosis. Here, we report relationships between peripheral blood DNA methylation profiles measured using Infinium® MethylationEPIC BeadChip and AD progression in participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Results: The rate of cognitive decline from initial DNA sampling visit to subsequent visits was estimated by the slopes of the modified Preclinical Alzheimer Cognitive Composite (mPACC; mPACCdigit and mPACCtrailsB) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) plots using robust linear regression in cognitively normal (CN) participants and patients with mild cognitive impairment (MCI), respectively. In addition, diagnosis conversion status was assessed using a dichotomized endpoint. Two CpG sites were significantly associated with the slope of mPACC in CN participants (P < 5.79 × 10-8 [Bonferroni correction threshold]); cg00386386 was associated with the slope of mPACCdigit, and cg09422696 annotated to RP11-661A12.5 was associated with the slope of CDR-SB. No significant CpG sites associated with diagnosis conversion status were identified. Genes involved in cognition and learning were enriched. A total of 19, 13, and 5 differentially methylated regions (DMRs) associated with the slopes of mPACCtrailsB, mPACCdigit, and CDR-SB, respectively, were identified by both comb-p and DMRcate algorithms; these included DMRs annotated to HOXA4. Furthermore, 5 and 19 DMRs were associated with conversion status in CN and MCI participants, respectively. The most significant DMR was annotated to the AD-associated gene PM20D1 (chr1: 205,818,956 to 205,820,014 [13 probes], Sidak-corrected P = 7.74 × 10-24), which was associated with both the slope of CDR-SB and the MCI conversion status. Conclusion: Candidate CpG sites and regions in peripheral blood were identified as associated with the rate of cognitive decline in participants in the ADNI cohort. While we did not identify a single CpG site with sufficient clinical utility to be used by itself due to the observed effect size, a biosignature composed of DNA methylation changes may have utility as a prognostic biomarker for AD progression.Item Association of Urinary Cadmium Concentration With Cognitive Impairment in US Adults: A Longitudinal Cohort Study(Wolters Kluwer, 2024) Lu, Liping; Zhang, Yijia; Angley, Meghan; Bejerano, Shai; Brockman, John D.; McClure, Leslie A.; Unverzagt, Frederick W.; Fly, Alyce D.; Kahe, Ka; Psychiatry, School of MedicineBackground and objectives: Studies have indicated that cadmium (Cd) exposure is associated with neurotoxicity. However, data linking Cd exposure to cognitive impairment are sparse. We aimed to investigate the association between urinary Cd concentration and cognitive impairment in US adults. Methods: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study is an ongoing population-based prospective cohort study that enrolled 30,239 Black and White US adults aged 45 years or older at baseline (2003-2007). In a randomly selected subcohort of REGARDS participants who were free of cognitive impairment or stroke at baseline, certain trace element concentrations, including urinary creatinine-corrected Cd, were measured using biospecimens collected and stored at baseline. During an average of 10 years of follow-up, global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment, including verbal learning, memory, and executive function, was evaluated every other year using the Enhanced Cognitive Battery. Multivariable-adjusted logistic regression models were used to examine the association between urinary Cd concentration and the odds of global or domain-based cognitive impairment. Results: A total of 2,172 participants (mean age: 64.1 ± 9.0 years; female: 54.8%; Black participants: 38.7%) with available data on urinary Cd concentration, including 195 cases of global cognitive impairment and 53 cases of domain-based cognitive impairment, were included in the analyses. While there was no association between Cd and cognitive impairment in the full sample, there was a significant positive association of urinary Cd concentration with global cognitive impairment among White but not Black participants. The odds of cognitive impairment for White participants in the high urinary Cd concentration group (≥median) were doubled compared with those in the low urinary Cd group (odds ratio 2.07, 95% CI 1.18-3.64). Sex, age, region, smoking pack-years, alcohol consumption, and other related metals did not materially modify the associations of interest. Discussion: Findings from this prospective cohort study suggest that urinary Cd concentrations are associated with global cognitive impairment among White but not Black individuals. Further studies with repeatedly measured Cd exposure, larger sample sizes, and longer duration are needed to confirm our findings and explore the potential explanations for the observed racial discrepancy, such as the impact of smoking.Item Blood biomarkers for Alzheimer’s disease in clinical practice and trials(Springer Nature, 2023) Hansson, Oskar; Blennow, Kaj; Zetterberg, Henrik; Dage, Jeffrey; Neurology, School of MedicineBlood-based biomarkers hold great promise to revolutionize the diagnostic and prognostic work-up of Alzheimer's disease (AD) in clinical practice. This is very timely, considering the recent development of anti-amyloid-β (Aβ) immunotherapies. Several assays for measuring phosphorylated tau (p-tau) in plasma exhibit high diagnostic accuracy in distinguishing AD from all other neurodegenerative diseases in patients with cognitive impairment. Prognostic models based on plasma p-tau levels can also predict future development of AD dementia in patients with mild cognitive complaints. The use of such high-performing plasma p-tau assays in the clinical practice of specialist memory clinics would reduce the need for more costly investigations involving cerebrospinal fluid samples or positron emission tomography. Indeed, blood-based biomarkers already facilitate identification of individuals with pre-symptomatic AD in the context of clinical trials. Longitudinal measurements of such biomarkers will also improve the detection of relevant disease-modifying effects of new drugs or lifestyle interventions.Item Blood-based biomarkers for Alzheimer's disease: Current state and future use in a transformed global healthcare landscape(Elsevier, 2023) Hampel, Harald; Hu, Yan; Cummings, Jeffrey; Mattke, Soeren; Iwatsubo, Takeshi; Nakamura, Akinori; Vellas, Bruno; O’Bryant, Sid; Shaw, Leslie M.; Cho, Min; Batrla, Richard; Vergallo, Andrea; Blennow, Kaj; Dage, Jeffrey; Schindler, Suzanne E.; Neurology, School of MedicineTimely detection of the pathophysiological changes and cognitive impairment caused by Alzheimer's disease (AD) is increasingly pressing because of the advent of biomarker-guided targeted therapies that may be most effective when provided early in the disease. Currently, diagnosis and management of early AD are largely guided by clinical symptoms. FDA-approved neuroimaging and cerebrospinal fluid biomarkers can aid detection and diagnosis, but the clinical implementation of these testing modalities is limited because of availability, cost, and perceived invasiveness. Blood-based biomarkers (BBBMs) may enable earlier and faster diagnoses as well as aid in risk assessment, early detection, prognosis, and management. Herein, we review data on BBBMs that are closest to clinical implementation, particularly those based on measures of amyloid-β peptides and phosphorylated tau species. We discuss key parameters and considerations for the development and potential deployment of these BBBMs under different contexts of use and highlight challenges at the methodological, clinical, and regulatory levels.Item Brain Activation Patterns during Visual Scene Encoding and Recognition fMRI Tasks in Early Phase Psychosis(Office of the Vice Chancellor for Research, 2015-04-17) Ayoubi, Nawead Z.; Mehdiyoun, Nicole F.; Yung, Matthew G.; Hummer, Tom; Francis, Michael M.; Breier, AlanSchizophrenia is a chronic and disabling illness that is associated with significant impairments in areas such as independent living, social functioning, and vocational functioning. Cognitive dysfunction is a core facet of schizophrenia with deficits occurring in areas of abstraction, attention, language, and memory. Episodic memory (EM) is a cognitive domain that has been shown to be impaired in schizophrenia. EM combines event-specific autobiographical experiences and information regarding the context in which events took place. Patients with schizophrenia may exhibit broad impairments in EM, with deficits occurring during encoding and retrieval with both visual and verbal tasks. There are a number of inconsistencies in the EM fMRI literature and indicating a need for first episode psychosis (FEP) versus chronic phase schizophrenia research. FEP have fewer and less severe medical comorbidities, shorter durations of antipsychotic treatment exposure, and lower severity of illness, all of which can impact data interpretation. In this study, brain activation patterns were assessed during performance of visual scene encoding and recognition fMRI tasks in FEP patients and healthy control subjects. It is hypothesized that FEP patients would demonstrate decreased activation during encoding and recognition in the main areas that mediate EM function, namely the hippocampus, prefrontal, and parietal cortices. Within the FEP group correlations can be determined by comparing brain activation patterns with cognition (Brief Assessment of Cognition in Schizophrenia [BACS]) and symptom (Positive and Negative Syndrome Scale [PANSS]) outcome measures. Results indicate that during the encoding task FEP exhibited significantly lower activation in the hippocampus and fusiform gyrus when compared to controls. During the recognition task FEP showed a significantly weaker cortical response in the posterior cingulate cortex, the precuneus, and the left middle temporal cortex when compared to controls. These results demonstrate a pattern of alteration in hippocampal, parietal, and temporal activity during EM processes in FEP. Altered hippocampal response in FEP may reflect dysfunctional binding mechanisms and less efficient encoding.Item Brain Imaging in Pediatric Cancer Survivors: Correlates of Cognitive Impairment(American Society of Clinical Oncology, 2021) Kesler, Shelli R.; Sleurs, Charlotte; McDonald, Brenna C.; Deprez, Sabine; van der Plas, Ellen; Nieman, Brian J.; Radiology and Imaging Sciences, School of MedicineItem Change in Cerebrospinal Fluid Tau Microtubule Binding Region Detects Symptom Onset, Cognitive Decline, Tangles, and Atrophy in Dominantly Inherited Alzheimer's Disease(Wiley, 2023) Horie, Kanta; Li, Yan; Barthélemy, Nicolas R.; Gordon, Brian; Hassenstab, Jason; Benzinger, Tammie L. S.; Fagan, Anne M.; Morris, John C.; Karch, Celeste M.; Xiong, Chengjie; Allegri, Ricardo; Mendez, Patricio Chrem; Ikeuchi, Takeshi; Kasuga, Kensaku; Noble, James; Farlow, Martin; Chhatwal, Jasmeer; Day, Gregory; Schofield, Peter R.; Masters, Colin L.; Levin, Johannes; Jucker, Mathias; Lee, Jae-Hong; Roh, Jee Hoon; Sato, Chihiro; Sachdev, Pallavi; Koyama, Akihiko; Reyderman, Larisa; Bateman, Randall J.; McDade, Eric; Dominantly Inherited Alzheimer Network; Neurology, School of MedicineObjective: Identifying cerebrospinal fluid measures of the microtubule binding region of tau (MTBR-tau) species that reflect tau aggregation could provide fluid biomarkers that track Alzheimer's disease related neurofibrillary tau pathological changes. We examined the cerebrospinal fluid (CSF) MTBR-tau species in dominantly inherited Alzheimer's disease (DIAD) mutation carriers to assess the association with Alzheimer's disease (AD) biomarkers and clinical symptoms. Methods: Cross-sectional and longitudinal CSF from 229 DIAD mutation carriers and 130 mutation non-carriers had sequential characterization of N-terminal/mid-domain phosphorylated tau (p-tau) followed by MTBR-tau species and tau positron emission tomography (tau PET), other soluble tau and amyloid biomarkers, comprehensive clinical and cognitive assessments, and brain magnetic resonance imaging of atrophy. Results: CSF MTBR-tau species located within the putative "border" region and one species corresponding to the "core" region of aggregates in neurofibrillary tangles (NFTs) increased during the presymptomatic stage and decreased during the symptomatic stage. The "border" MTBR-tau species were associated with amyloid pathology and CSF p-tau; whereas the "core" MTBR-tau species were associated stronger with tau PET and CSF measures of neurodegeneration. The ratio of the border to the core species provided a continuous measure of increasing amounts that tracked clinical progression and NFTs. Interpretation: Changes in CSF soluble MTBR-tau species preceded the onset of dementia, tau tangle increase, and atrophy in DIAD. The ratio of 4R-specific MTBR-tau (border) to the NFT (core) MTBR-tau species corresponds to the pathology of NFTs in DIAD and change with disease progression. The dynamics between different MTBR-tau species in the CSF may serve as a marker of tau-related disease progression and target engagement of anti-tau therapeutics.Item Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-β 42/40 positivity(Springer Nature, 2024-02-10) Pyun, Jung-Min; Park, Young Ho; Youn, Young Chul; Kang, Min Ju; Shim, Kyu Hwan; Jang, Jae-Won; You, Jihwan; Nho, Kwangsik; Kim, SangYun; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of MedicineVarious plasma biomarkers for amyloid-β (Aβ) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma Aβ42/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as Aβ plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma Aβ42/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET-/plasma-, PET-/plasma+, PET+/plasma-, PET+/plasma+) using Alzheimer's Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET-/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET-/plasma+ showed intermediate changes between PET-/plasma- and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma- represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma Aβ42/40 than IA-Elc. IA-Elc showed more plasma Aβ42/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET-/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.Item Chronic Heart Failure With Memory and Attention Dysfunction: Old Problem, Thinking Anew(Elsevier, 2018) Pressler, Susan J.; Jung, Miyeon; School of Nursing