IU Indianapolis ScholarWorks :: Browsing by Subject "Mild cognitive impairment (MCI)"

Browsing by Subject "Mild cognitive impairment (MCI)"

Now showing 1 - 10 of 12

A DAT1 gene and APOE ε4 interaction is associated with apathy and structural brain changes in Alzheimer’s Disease
(Wiley, 2025-01-09) Malik, Rubina; Beaton, Derek; Saykin, Andrew J.; Nho, Kwangsik; Finger, Elizabeth; Radiology and Imaging Sciences, School of Medicine
Background: Apathy in patients with Alzheimer’s disease (AD) is associated with significant morbidity. We examined whether interactions between genetic variants related to neurotransmitter systems and regional brain atrophy are associated with apathy in patients with mild cognitive impairment (MCI) and AD. Method: For 1162 participants in the Alzheimer’s Disease Neuroimaging Initiative, including those with AD, MCI and cognitively normal individuals, a partial least squares correspondence analysis (PLS‐CA) modeled interactions between single nucleotide polymorphisms (SNPs), structural whole‐brain imaging variables, and apathy. Result: An interaction between apathy, the possession of an APOE (apolipoprotein E) ε4 allele combined with minor homozygosity for the DAT1 (dopamine transporter 1) gene, and brain atrophy. Conclusion: The results point to an association of a dopaminergic genetic marker and apathy in AD and may inform future design of clinical trials of apathy, as well as new treatment targets.
Antiphospholipid autoantibodies as blood biomarkers for detection of early stage Alzheimer's disease
(Taylor & Francis, 2015-08) McIntyre, John A.; Ramsey, Curtis J.; Gitter, Bruce D.; Saykin, Andrew J.; Wagenknecht, Dawn R.; Hyslop, Paul A.; Department of Radiology and Imaging Sciences, IU School of Medicine
A robust blood biomarker is urgently needed to facilitate early prognosis for those at risk for Alzheimer's disease (AD). Redox reactive autoantibodies (R-RAAs) represent a novel family of antibodies detectable only after exposure of cerebrospinal fluid (CSF), serum, plasma or immunoglobulin fractions to oxidizing agents. We have previously reported that R-RAA antiphospholipid antibodies (aPLs) are significantly decreased in the CSF and serum of AD patients compared to healthy controls (HCs). These studies were extended to measure R-RAA aPL in serum samples obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI). Serum samples from the ADNI-1 diagnostic groups from participants with mild cognitive impairment (MCI), AD and HCs were blinded for diagnosis and analyzed for R-RAA aPL by ELISA. Demographics, cognitive data at baseline and yearly follow-up were subsequently provided by ADNI after posting assay data. As observed in CSF, R-RAA aPL in sera from the AD diagnostic group were significantly reduced compared to HC. However, the sera from the MCI population contained significantly elevated R-RAA aPL activity relative to AD patient and/or HC sera. The data presented in this study indicate that R-RAA aPL show promise as a blood biomarker for detection of early AD, and warrant replication in a larger sample. Longitudinal testing of an individual for increases in R-RAA aPL over a previously established baseline may serve as a useful early sero-epidemiologic blood biomarker for individuals at risk for developing dementia of the Alzheimer's type.
Author Correction: Predicting Alzheimer’s disease progression using multi-modal deep learning approach
(Springer Nature, 2023-08-01) Lee, Garam; Nho, Kwangsik; Kang, Byungkon; Sohn, Kyung‑Ah; Kim, Dokyoon; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
Correction to: Scientific Reports 10.1038/s41598-018-37769-z, published online 13 February 2019 This Article contains errors. A Supplementary Information file was omitted from the original version of this Article. The Supplementary Information file is now linked to this correction notice.
Critical review of the Appropriate Use Criteria for amyloid imaging: Effect on diagnosis and patient care
(Elsevier, 2016-12-18) Apostolova, Liana G.; Haider, Janelle M.; Goukasian, Naira; Rabinovici, Gil D.; Chetelat, Gael; Ringman, John M.; Kremen, Sarah; Grill, Joshua; Restrepo, Lucas; Mendez, Mario F.; Silverman, Daniel H.; Department of Neurology, IU School of Medicine
INTRODUCTION: The utility of the Appropriate Use Criteria (AUC) for amyloid imaging is not established. METHODS: Fifty-three cognitively impaired patients with clinical F18-florbetapir imaging were classified as early and late onset, as well as AUC-consistent or AUC-inconsistent. Chi-square statistics and t test were used to compare demographic characteristics and clinical outcomes as appropriate. RESULTS: Early-onset patients were more likely to be amyloid positive. Change in diagnosis was more frequent in late-onset cases. Change in therapy was more common in early-onset cases. AUC-consistent and AUC-inconsistent cases had comparable rates of amyloid positivity. We saw no difference in the rate of treatment changes in the AUC-consistent group as opposed to the AUC-inconsistent group. DISCUSSION: The primary role of amyloid imaging in the early-onset group was to confirm the clinically suspected etiology, and in the late-onset group in detecting amyloid-negative cases. The rate of therapeutic changes was significantly greater in the early-onset cases.
Feasibility of Recruiting People With Mild Cognitive Impairment in the Context of Heart Failure
(Oxford University Press, 2024-12-31) Jung, Miyeon; Pressler, Susan; Hammers, Dustin; Apostolova, Liana; School of Nursing
Recruiting people with mild cognitive impairment (MCI) with another chronic condition such as heart failure (HF) can be arduous. Our investigative group will discuss the challenges encountered while recruiting older adults with both MCI and HF using data from a pilot study testing the efficacy of cognitive interventions to improve cognitive function and the strategies to overcome them. Initially, eligibility criteria included age ≥65 years, HF confirmed by echocardiography, and MCI defined using a 2-step process: (1) Montreal Cognitive Assessment (MoCA) ≤23; and (2) diagnostic consensus of MCI based on the presence of cognitive impairment in the absence of functional decline. Enrollment began on 4/3/2023 by screening Cardiology and Neurology clinics patients. Only 12 participants were enrolled over the next 7 months (rate=1.5 participants/month) due to high screen failure rates (59%) owing to MoCA performances above the eligibility threshold and low recruitment rate (5%). To meet recruitment goals (8 participants/month), eligibility criteria were modified by lowering the age cutoff from 65 to 55 years and removing the MoCA screen and the MCI requirements, while adding the requirement of subjective cognitive concern allowing both those with normal cognition and MCI but not dementia. Phone recruitment was added by screening electronic health records of people who diagnosed with HF. 7 months after implementing the modifications, additional 58 participants were consented exceeding our recruitment goals (69% of those consented=MCI, 26%=normal cognition, 5%=dementia/excluded from the study). In conclusion, feasibility of our original strategies recruiting older adults with both MCI and HF was not supported.
Florbetapir positron emission tomography and cerebrospinal fluid biomarkers
(Elsevier, 2015-08) Hake, Ann Marie; Trzepacz, Paula T.; Wang, Shufang; Yu, Peng; Case, Michael; Hochstetler, Helen; Witte, Michael M.; Degenhardt, Elisabeth K.; Dean, Robert A.; Department of Neurology, IU School of Medicine
BACKGROUND: We evaluated the relationship between florbetapir-F18 positron emission tomography (FBP PET) and cerebrospinal fluid (CSF) biomarkers. METHODS: Alzheimer's Disease Neuroimaging Initiative-Grand Opportunity and Alzheimer's Disease Neuroimaging Initiative 2 (GO/2) healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia subjects with clinical measures and CSF collected ±90 days of FBP PET data were analyzed using correlation and logistic regression. RESULTS: In HC and MCI subjects, FBP PET anterior and posterior cingulate and composite standard uptake value ratios correlated with CSF amyloid beta (Aβ1-42) and tau/Aβ1-42 ratios. Using logistic regression, Aβ1-42, total tau (t-tau), phosphorylated tau181P (p-tau), and FBP PET composite each differentiated HC versus AD. Aβ1-42 and t-tau distinguished MCI versus AD, without additional contribution by FBP PET. Total tau and p-tau added discriminative power to FBP PET when classifying HC versus AD. CONCLUSION: Based on cross-sectional diagnostic groups, both amyloid and tau measures distinguish healthy from demented subjects. Longitudinal analyses are needed.
Frontal Memory‐related Brainwaves Differentially Correlate with AD and Astrocyte Plasma Biomarkers
(Wiley, 2025-01-09) Jiang, Yang; Wu, Xian; Katsumata, Yuriko; Clark, Maria F.; Foley, Kate E.; Wang, Baoxi; Sudduth, Tiffany L.; Wilcock, Donna M.; Jicha, Gregory A.; Norris, Christopher M.; Neurology, School of Medicine
Background: We currently lack in the dementia field accurate, noninvasive, quick, and affordable screening tools for brain dysfunctions associated with early subtle risk of mild cognitive impairment (MCI). Our Kentucky aging cohort demonstrates that asymptomatic older individuals with MCI‐like frontal memory‐related brainwave patterns convert to MCI within a short 5‐year period, as opposed to individuals with NC‐like patterns (1) that remain normal 10 years later (2). Astrocyte reactivity influences amyloid‐β effects on tau pathology in preclinical Alzheimer’s disease (3). Leveraging blood‐based AD and astrocyte biomarkers and the cognitive electroencephalogram (EEG) signatures (4), we test the hypothesis that predictive frontal memory‐related EEG changes correlate with preclinical and early AD plasma biomarkers. Method: 34 (19 women) older volunteers with or without MCI, average age 79 (SD 8.53) years old, from a longitudinal cohort followed by University of Kentucky ADRC participated. Each participant’s EEG was recorded (64‐ or 14‐channels) during a working memory (modified delayed match‐to‐sample) task. Principal component analysis (PCA) was performed on 64‐channel EEG data to create PC scores (PC1 & PC2). For multiple linear regression of EEG PC scores on multiple neurodegenerative plasma biomarkers including Aβ42/40, pTau181, total Tau, and GFAP (Astrocyte reactivity), we adjusted age, sex, education, and gap years between collection dates. Result: The 61% of variance in frontal signals can be explained by PC1 in normal cognition (NC) and MCI individuals, and PC2 counts for 35% of variance (Figure 1). The decreased brainwaves (MCI‐like) seen in left frontal sites significantly correlate with increased pTau181, GFAP, and PC2 (Figure 2). Curiously, right frontal EEG relations with pTau181, GFAP showed the opposite trend. Bilateral frontal signals showed negative correlations with Aβ42/40 and positive correlations with total Tau. Conclusion: Our results indicate that GFAP & pTau181 trend in similar asymmetry ways with frontal cognitive brainwaves, but Aβ42/40 & total Tau correlate to a different component of frontal EEG. That is, distinct cognitive brainwaves correlate with astrocyte reactivity differentially that influence pathologies of beta‐amyloid accumulations and Tau development. Cognitive pathophysiological signatures and AD–Astrocyte plasma biomarkers have great potential for predicting subtle cognitive decline and specific dementia risk in healthy normal individuals.
How do short‐term practice effects compare to biomarkers of Alzheimer’s disease?
(Wiley, 2025-01-03) Duff, Kevin; Hammers, Dustin B.; Koppelmans, Vincent; King, Jace B.; Hoffman, John M.; Neurology, School of Medicine
Background: Practice effects on cognitive testing in Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) remain understudied, especially with how they compare to biomarkers of AD. The current study sought to add to this growing literature. Method: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) repeated a brief battery of cognitive tests twice across one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE e4 status. Result: The intact participants showed significantly larger practice effects than the other two groups on an overall composite measure, and those with MCI showed significantly larger practice effects than those with AD. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact>MCI>AD). For APOE e4, the intact had significantly fewer copies of e4 than MCI and AD. Overall, the effect sizes of practice effects were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons (see Table). Conclusion: Short‐term practice effects on cognitive tests appear to be a sensitive marker in late life cognitive disorders, as they separated groups better than commonly‐used biomarkers in AD. Further refinement of short‐term practice effects as a tool for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.
Key inflammatory pathway activations in the MCI stage of Alzheimer's disease
(Wiley, 2019-07) Pillai, Jagan A.; Maxwell, Sean; Bena, James; Bekris, Lynn M.; Rao, Stephen M.; Chance, Mark; Lamb, Bruce T.; Leverenz, James B.; Neurology, School of Medicine
OBJECTIVE: To determine the key inflammatory pathways that are activated in the peripheral and CNS compartments at the mild cognitive impairment (MCI) stage of Alzheimer's disease (AD). METHODS: A cross-sectional study of patients with clinical and biomarker characteristics consistent with MCI-AD in a discovery cohort, with replication in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Inflammatory analytes were measured in the CSF and plasma with the same validated multiplex analyte platform in both cohorts and correlated with AD biomarkers (CSF Aβ42, total tau (t-tau), phosphorylated tau (p-tau) to identify key inflammatory pathway activations. The pathways were additionally validated by evaluating genes related to all analytes in coexpression networks of brain tissue transcriptome from an autopsy confirmed AD cohort to interrogate if the same pathway activations were conserved in the brain tissue gene modules. RESULTS: Analytes of the tumor necrosis factor (TNF) signaling pathway (KEGG ID:4668) in the CSF and plasma best correlated with CSF t-tau and p-tau levels, and analytes of the complement and coagulation pathway (KEGG ID:4610) best correlated with CSF Aβ42 levels. The top inflammatory signaling pathways of significance were conserved in the peripheral and the CNS compartments. They were also confirmed to be enriched in AD brain transcriptome gene clusters. INTERPRETATION: A cell-protective rather than a proinflammatory analyte profile predominates in the CSF in relation to neurodegeneration markers among MCI-AD patients. Analytes from the TNF signaling and the complement and coagulation pathways are relevant in evaluating disease severity at the MCI stage of AD.
Optimizing primary care for cognitive impairment screening using agile implementation
(Wiley, 2025-01-09) Summanwar, Diana; Brosch, Jared R.; Hammers, Dustin B.; Fowler, Nicole R.; Willis, Deanna R.; Medicine, School of Medicine
Background: Screening for cognitive impairment in primary care faces challenges, including time constraints, provider apprehension, and limited diagnostic confidence. An effective initiative for improving screening must include strategies to foster behavioral change, and active provider engagement. Agile implementation science integrates findings from behavioral economics, complexity science, and network science, to address these challenges by confirming the demand to solve the problem; local solution adaptation; and the iterative ‘sprints’, or tests of change, that are focused on execution. This study, which is part of the Davos Alzheimer’s Collaborative (DAC) Early Detection Health System Preparedness Flagship program, explored workflows to support Digital Cognitive Assessment (DCA) in primary care, enhancing early detection of mild cognitive impairment (MCI) and dementia. Methods: Between June 1, 2022, and May 31, 2023, seven diverse primary care clinics participated in the DAC program. The initiative’s core was the integration of offering and performing Linus Health Core Cognitive Evaluation Digital Cognitive Assessment (DCA) for patients aged 65 and above. The selection of the digital screening tool, process workflows, and improvement cycles were co‐designed by the primary care providers, clinic staff, the Patient Advisory Council, and the implementation team using Agile Implementation. A Brain Health Navigator (BHN) role was designed to fill workflow gaps in primary care evaluation of abnormal screening and facilitate specialty care transition for patients needing referral. Results: Among the seven sites, five sites engaged in agile implementation and had similar performances, with an increase in DCA completion observed. A total of 1808 DCA screenings were performed on 1722 unique patients. The agile implementation process facilitated clinic‐specific adaptations, which resulted in an increase in the overall number of eligible patients completing the DCA screening. Conclusions: The adoption of an agile implementation process increased DCA screening uptake in primary care settings. The integration of a BHN and streamlined workflows proved crucial in enhancing the screening, diagnosis, and referral journey. This integration aligns with the principles of person‐centered care and facilitates service coordination. It also supports workforce initiatives and advances the field of health services research, ensuring that each step in the patient’s journey is both effective and efficient.

Browsing by Subject "Mild cognitive impairment (MCI)"

Results Per Page

Sort Options