Mild Stage Of Disease Research Articles

Natural History and Longitudinal Outcomes of Patients with Mild-to-Moderate Ulcerative Proctitis or Ulcerative Proctosigmoiditis: A Single-Center, Retrospective Study.

Ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS) are special forms of ulcerative colitis. The disease burdens of UP and UPS are increasing. However, the natural history and prognosis of patients with mild-to-moderate UP or UPS have been poorly studied. The aim of this study is to evaluate the characteristics, short-term and long-term outcomes of patients with mild-to-moderate UP or UPS followed at a single center over a period of 3years. A retrospective study of patients with UP and UPS followed at a single center from 2021 to 2023 was performed. After scanning for inclusion and exclusion criteria, patient demographics and clinical data were collected. Disease severity was accessed by Myao endoscopy scores and ulcerative colitis endoscopic index of severity. Endoscopic improvement was defined as decreased scores at the last follow-up. Disease extension was defined as endoscopic evidence of a greater extent of disease at the last follow-up. A total of 414 patients were included for evaluation, of which 292 patients (70.53%) were at mild disease stage, and 122 patients (29.47%) had moderate diseases. At the last follow-up, 315 patients (76.09%) showed endoscopic improvement, and 247 patients (59.66%) showed endoscopic remission. An overall extension rate of 11.11% was observed at the last follow-up. Subgroup analysis revealed a better prognosis in younger patients. The disease extension rate was higher in moderate group and symptomatic patients. Promising outcomes were observed in patients with mild-to-moderate ulcerative proctitis or ulcerative proctosigmoiditis. Disease severity and symptoms are correlated with the risk of extension.

Comprehensive analysis of hyperspectral features for monitoring canopy maize leaf spot disease

Accurate quantification of hyperspectral features altered by plant disease infection is pivotal for effective disease management. However, the sensitivity of hyperspectral features to plant disease progression remains elusive, primarily because these features are often influenced by plant growth and environmental factors in addition to the specific disease. This study explores the sensitivity of biophysical and spectral features as indicators for maize adaptation to leaf spot disease. Using high-resolution UAV hyperspectral imaging, we captured maize adaptation dynamics over 30 days post-infection. We evaluated the sensitivity and importance of hyperspectral features for disease monitoring, including biophysical parameters retrieved by the PROSAIL model, and spectral features, including spectral reflectance, vegetation indices (VIs), and wavelet features (WFs). Our findings reveal that WFs first indicate disease response as early as 6 days after infection (DAI), followed by VIs at DAI 8, and variations in chlorophyll content (Cab) become apparent by DAI 10. The Cab, plant senescence reflectance index (PSRI), and normalized photosynthetic reflectance index (NPRI) are determined to be important features at the early stage of the disease. Our experimental results show that the different feature sets are complementary at the early and severe stages of the disease. Our classification models integrating Cab, VIs, and WFs showed higher overall accuracy than models using only spectral features or VIs, with a maximum improvement of 9.36 %. However, these feature sets are redundant in the mild and initial severe disease stages, where models using only spectral features achieve the highest overall accuracy of 86.21 %. This study underscores the novel insights by offering an understanding of plant responses to disease infection and enhancing early detection strategies.

Prevalence Estimation of Dementia/Alzheimer’s Disease Using Health and Retirement Study Database in the United States

BackgroundUpdated prevalence estimates along the continuum of Alzheimer’s disease (AD) can foster a more nuanced and effective approach to managing AD within the current healthcare landscape.ObjectivesThis study aims to estimate the prevalence and severity distribution of dementia/AD (including mild, moderate, and severe stages) and all-cause mild cognitive impairment (MCI) in the United States using data from the Health and Retirement Study (HRS).DesignRetrospective study.SettingData from the bi-annual HRS surveys involving in-depth interviews of a representative sample of Americans aged >50 years.ParticipantsDementia/AD and all-cause MCI patients from the 4 most recent HRS surveys (2014, 2016, 2018 and 2020).MeasurementsAD was identified based on diagnosis (self-report). Cognitive performance (modified Telephone Interview of Cognitive Status [TICS-m]) scores in the dementia/AD range were also captured; all-cause MCI was similarly identified using the TICS-m. Dementia/AD and MCI prevalence, as well as the distribution by dementia/AD stage (mild, moderate, or severe), were estimated. Sampling weights developed by HRS were applied to ensure the sample’s representativeness of the target population and unbiased estimates for population parameters.ResultsAcross the four HRS surveys, the total number of HRS respondents ranged from 15,000 to 21,000 (unweighted); 7,000 to 14,000 had TICS-m scores. The estimated prevalence of AD (all severity categories combined) in the 2014, 2016, 2018, and 2020 HRS surveys was 1.2%, 1.2%, 1.3% and 1.0%, respectively using the diagnosis-based approach; using the cognitive performance-based approach, 23–27% patients had scores in the dementia/AD ranges across the 4 surveys. The estimated prevalence of all-cause MCI was consistently 23% in each survey. In the 2020 survey, the distribution of mild, moderate, and severe disease stages was 34%, 45%, and 21%, respectively, in patients self-reporting an AD diagnosis, and 55%, 40%, and 5%, respectively in all patients meeting TICS-m threshold for dementia/AD.ConclusionThe prevalence of AD diagnosis based on self-report was approximately 1% across the 4 most recent HRS surveys and may reflect the proportion of patients who have actively sought healthcare for AD. Among HRS survey respondents with cognitive scores available, over 20% were in the dementia/AD range. The distribution of disease by stage differed for self-reported AD diagnosis vs dementia/AD based on cognitive scores. Discordance in estimates of dementia/AD and stage distributions underscores a need for better understanding of clinical practice patterns in AD diagnosis, use of clinical assessment tools, and severity classification in the United States. Accurate patient identification is needed, especially early in the AD disease continuum, to allow for timely and appropriate initiation of new anti-amyloid treatments.

Generating real-world evidence in Alzheimer's disease: Considerations for establishing a core dataset.

Ongoing assessment of patients with Alzheimer's disease (AD) in postapproval studies is important for mapping disease progression and evaluating real-world treatment effectiveness and safety. However, interpreting outcomes in the real world is challenging owing to variation in data collected across centers and specialties and greater heterogeneity of patients compared with trial participants. Here, we share considerations for observational postapproval studies designed to collect harmonized longitudinal data from individuals with mild cognitive impairment or mild dementia stage of disease who receive therapies targeting the underlying pathological processes of AD in routine practice. This paper considers key study design parameters, including proposed aims and objectives, study populations, approaches to data collection, and measures of cognition, functional abilities, neuropsychiatric status, quality of life, health economics, safety, and drug utilization. Postapproval studies that capture these considerations will be important to provide standardized data on AD treatment effectiveness and safety in real-world settings.

Mechanism of action and clinical trial results of Lecanemab (Leqembi® 200 ‍mg, 500 ‍mg for Intravenous Infusion), a novel treatment for Alzheimer's disease

Lecanemab is a humanized monoclonal antibody directed against human soluble amyloid-β aggregates. It was developed for the treatment of early Alzheimer's disease (mild cognitive impairment or mild dementia stage of Alzheimer's disease). Among the amyloid-β (Aβ) involved in Alzheimer's disease, Lecanemab selectively binds to the highly neurotoxic Aβ protofibrils, and is thought to reduce Aβ protofibrils and amyloid plaques (Aβ plaques) in the brain. The efficacy and safety of Lecanemab in early Alzheimer's disease were investigated in an international Phase II placebo-controlled study (Study 201) and an international Phase III placebo-controlled study (Study 301). Both studies included Japanese subjects. Lecanemab was given accelerated approval in the United States in January 2023, followed by traditional approval in July 2023. In Japan, it was approved for "control of the progression of mild cognitive impairment or mild dementia stage of Alzheimer's disease" in September 2023, and was added to the NHI drug price list in December 2023.

Stimulation of PSTPIP1 to trigger proinflammatory responses in asymptomatic SARS-CoV-2 infections

BackgroundA hyperinflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection gravely worsens the clinical progression of coronavirus disease 2019 (COVID-19). Although the undesirable effects of inflammasome activation have been correlated to the severity of COVID-19, the mechanisms of this process in the asymptomatic infection and disease progression have not yet been clearly elucidated. MethodsWe performed strand-specific RNA sequencing in 39 peripheral blood mononuclear cell (PBMC) samples from asymptomatic individuals（n = 10）, symptomatic patients（n = 16） and healthy donors（n = 13）. ResultsDysregulation of pyrin inflammasomes along with the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene was identified in SARS-COV-2 infection. Notably, the PSTPIP1 expression level showed a significant negative correlation with an adjacent long-noncoding RNA (lncRNA) RP11-797A18.6 in the asymptomatic individuals compared with the healthy controls. In addition, a decline in the nuclear factor kappa B subunit 1 (NFKB1) gene expression was observed in asymptomatic infection, followed by a rise in the mild and moderate disease stages, suggesting that altered NFKB1 expression and associated proinflammatory signals may trigger a disease progression. ConclusionsOverall, our results indicate that PSTPIP1-dependent pyrin inflammasomes-mediated pyroptosis and NF-κB activation might be potential preventive targets for COVID-19 disease development and progression.

PRESENCE OF DYSPHAGIA IN A COHORT OF PERSONS LIVING WITH DEMENTIA: OUTCOMES FROM A MULTIDISCIPLINARY CLINIC

Abstract The Cognitive Care Clinic (CCC) provides evaluation for Veterans living with dementia. Speech-language pathology (SLP) is incorporated to facilitate early identification and proactive management of dysphagia. This project sought to describe dysphagia frequency in persons living with dementia (PWD) in CCC. Multidisciplinary assessments led to consensus diagnosis of dementia subtype. Stage was determined using the Functional Assessment Staging Tool (FAST). Validated dysphagia screening tools included Eating Assessment Tool (EAT-10), water swallow test (WST), and Test of Mastication and Swallowing Solids (TOMASS). Penetration-Aspiration Scale (PAS) scores were determined following videofluoroscopic swallow studies (VFSS); scores were classified as “safe” (PAS< 3) or “unsafe” (PAS>=3). Descriptive statistics were calculated for dementia subtype, stage, and dysphagia measures. 78 Veterans were diagnosed with dementia between 2017 and 2023 (mean age=77 years; 5% female) and completed dysphagia screening. The majority had Alzheimer’s disease (43%) and were in the mild disease stage (61%). 37% failed the WST, suggesting impaired safety. 49% failed the TOMASS, indicating masticatory inefficiency. 26% scored 3 or higher on EAT-10, indicating increased dysphagia risk. 22 patients completed VFSS; 55% exhibited unsafe swallows. No significant differences in EAT-10 total scores were observed between those with safe and unsafe PAS scores. Nearly half of this cohort demonstrated signs of swallowing impairment based on clinical testing and/or VFSS. Additionally, EAT-10 scores were low overall with no differences based on dysphagia status on VFSS, which suggests underreporting of dysphagia. These findings highlight the necessity of SLPs in dementia care teams to support early identification and management of dysphagia.

1528. Retrospective cohort study of factors associated with non-initiation of antiretroviral therapy among adults newly diagnosed with HIV in Andijan, Uzbekistan, 2018-2021

Abstract Background Immediate uptake of antiretroviral therapy (ART) by people newly diagnosed with HIV reduces morbidity and viral transmission. Since 2018, in Uzbekistan people newly diagnosed with HIV are immediately offered ARVs, but just over half of people living with HIV are estimated to be on ART. To reach global targets, we assessed factors associated with ART non-initiation. Methods We conducted a retrospective cohort study using secondary data from Andijan Region Republican AIDS Center. Our study included all people 18 years of age and older newly diagnosed with HIV between January 1, 2018, and June 31, 2021. We analyzed sociodemographic and behavioral factors associated with non-initiation of ART, defined as not having initiated ART by December 31, 2021. Using multivariable analysis, we calculated risk ratios (RR) and 95% confidence intervals (CI). Results From 2018 to 2021 in Andijan Province, 1,098 people were newly diagnosed with HIV, of which 113 (10.3%) did not initiate ART. Participants were mostly 30-49 years old (49%), male (56%), married (46%), and with secondary education (74%). Also, 39% and 31% had HIV clinical stage I and II, respectively. Risk for non-initiation was higher among people with secondary education (RR=8.6 [CI: 1.2–60.9]) compared to higher education, with multiple partners (RR=2.7 [1.5-5.0]), with disease stage I (RR=3.3 [2.0–5.2]) and stage II (RR=4.4 [2.8–7.0]). People with sexual partners living with HIV had higher risk of non-initiation (RR=1.8 [1.2–2.9]) than people with partners that did not have HIV. Being single was associated with reduced risk of non-initiation (RR=0.1 [0.03–0.3]). Factors associated wtih initiation of ARV treatment among people newly diagnosed with HIV, Uzbekistan Conclusion People with multiple partners and with partners living with HIV should be prioritized for ART initiation support. Increased risk of non-initiation among people in non-symptomatic or mild disease stages earlier disease stages points to the need for interventions to increase awareness of test-and-start among providers. Disclosures All Authors: No reported disclosures

Voxel Extraction and Multiclass Classification of Identified Brain Regions across Various Stages of Alzheimer's Disease Using Machine Learning Approaches.

This study sought to investigate how different brain regions are affected by Alzheimer's disease (AD) at various phases of the disease, using independent component analysis (ICA). The study examines six regions in the mild cognitive impairment (MCI) stage, four in the early stage of Alzheimer's disease (AD), six in the moderate stage, and six in the severe stage. The precuneus, cuneus, middle frontal gyri, calcarine cortex, superior medial frontal gyri, and superior frontal gyri were the areas impacted at all phases. A general linear model (GLM) is used to extract the voxels of the previously mentioned regions. The resting fMRI data for 18 AD patients who had advanced from MCI to stage 3 of the disease were obtained from the ADNI public source database. The subjects include eight women and ten men. The voxel dataset is used to train and test ten machine learning algorithms to categorize the MCI, mild, moderate, and severe stages of Alzheimer's disease. The accuracy, recall, precision, and F1 score were used as conventional scoring measures to evaluate the classification outcomes. AdaBoost fared better than the other algorithms and obtained a phenomenal accuracy of 98.61%, precision of 99.00%, and recall and F1 scores of 98.00% each.

Neuropharmacology of Lecanemab-irmb: A new drug granted in the treatment of Alzheimer's disease

United state food and drug administration approved on 6 January 2023, Lecanemab-irmb via the accelerated approval pathway for the treatment of Alzheimer’s disease. Researchers evaluated Lecanemab-irmb’s efficacy in a double-blind, placebo-controlled, parallel-group, dose-finding study of 856 patients with Alzheimer’s disease. Treatment was initiated in patients with mild cognitive impairment or mild dementia stage of disease and confirmed the presence of amyloid beta pathology. Patients receiving the treatment had significant dose and time-dependent reduction of amyloid beta plaque, with patients receiving the approved dose of lecanemab, 10 milligram/kilogram every two weeks, having a statistically significant reduction in brain amyloid plaque from baseline to Week 79 compared to the placebo arm, which had no reduction of amyloid beta plaque. These results support the accelerated approval of Lecanemab-irmb, which is based on the observed reduction of amyloid beta plaque, a marker of Alzheimer’s disease. The amyloid beta plaque was quantified using positron emission tomography (PET) imaging to estimate the brain levels of amyloid beta plaque in a composite of brain regions expected to be widely affected by Alzheimer’s disease pathology compared to a brain region expected to be spared of such pathology.

ELBOW OSTEOARTHRITIS: PATHOGENESIS, CLINICAL PRESENTATION, WORK-UP

ABSTRACT Degenerative joint disease of the elbow, although much rarer than in lower limbs, affecting about 2% of population, may be the result of primary and secondary etiologies and may significantly affect the quality of life, leading to pain, loss of motion and functional disability. A detailed medical history combined with physical examination and imaging modalities can help to locate the source of symptoms and choose the appropriate treatment. Nonoperative management is the initial therapy for elbow arthritis and is limited to relief of pain by rest, activity modification, analgesics and nonsteroid anti-inflammatory medications. When conservative management fails, surgical treatment should be used according to the patient’s expectations, age, severity and etiology of elbow arthritis. Patients with posttraumatic and primary elbow osteoarthritis in mild and moderate stage of disease may be treated by arthroscopic osteocapsular arthroplasty which consist of soft tissue and bony debridement, osteophytes and loose bodies removal, synovectomy, capsular release and bony contouring of humerus and ulnae. Total elbow arthroplasty is dedicated to low-demand, elderly patients with rheumatoid, inflammatory, posttraumatic or primary elbow osteoarthritis in severe stage. For younger, high-demand patients with severe osteoarthritis of the elbow which affects the majority of the ulnohumeral articular surface a good option for surgical treatment is interposition arthroplasty with/using auto or allografts.

Lecanemab: First Approval.

Lecanemab (lecanemab-irmb; LEQEMBI™) is a humanized immunoglobulin gamma 1 (IgG1) against aggregated soluble and insoluble forms of amyloid-β peptide. It is being developed by Eisai, under a global licence from BioArctic (formerly BioArctic Neuroscience), and in collaboration with Biogen, for the treatment of Alzheimer's disease, and received its first approval for this indication on 6January 2023 in the USA under the Accelerated Approval Pathway. According to the US prescribing information, treatment should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, and a confirmed presence of amyloid beta pathology (i.e. the population in which treatment was initiated in clinical trials). There are no effectiveness or safety data on initiating treatment at earlier or later stages of the disease than were studied. Lecanemab is undergoing regulatory review in the EU, Japan and China, with clinical development underway in several other countries worldwide. This article summarizes the milestones in the development of lecanemab leading to this first approval for the treatment of Alzheimer's disease.

Experience of the United Arab Emirates in the use of monoclonal antibody drug sotrovimab in high-risk vaccinated and unvaccinated patients with COVID-19: an observational cohort study

ObjectivesMonoclonal antibodies can slow COVID-19 progression. This study describes the experience of using sotrovimab in patients with COVID-19 at high risk for disease progression and hospitalisation within the United Arab...

Association Between Body Mass Index Variation and Early Mortality Among 834 Ethiopian Adults Living with HIV on ART: A Joint Modelling Approach.

Body mass index (BMI) is a simple and cost-effective tool for monitoring the clinical responses of patients living with human immunodeficiency virus (HIV) after antiretroviral therapy (ART) initiation, especially in resource-limited settings where access to laboratory tests are limited. Current evidence on the association between longitudinal BMI variation and clinical outcomes among adults living with HIV receiving ART is essential to inform clinical guidelines. Therefore, this study examines the association between BMI variation and premature mortality in adults living with HIV on ART. An institution-based retrospective cohort study was conducted among 834 adults living with HIV receiving ART from June 2014 to June 2020 at Debre Markos Comprehensive Specialized Hospital in Northwest Ethiopia. We first identified predictors of mortality and BMI variation using proportional hazards regression and linear mixed models, respectively. Then, the two models were combined to form an advanced joint model to examine the effect of longitudinal BMI variation on mortality. Of the 834 participants, 49 (5.9%) died, with a mortality rate of 4.1 (95% CI 3.1, 5.4) per 100 person-years. A unit increase in BMI after ART initiation corresponded to an 18% reduction in mortality risk. Patients taking tuberculosis preventive therapy (TPT), mild clinical disease stage, and changing ART regimens were at lower risk of death. However, patients with ambulatory/bedridden functional status were at higher risk of death. Regarding BMI variation over time, patients presenting with opportunistic infections (OIs), underweight patients, patients who started a Dolutegravir (DGT)-based ART regimen, and those with severe immunodeficiency had a higher BMI increase over time. However, patients from rural areas and overweight/obese patients experienced a lower BMI increase over time. BMI improvement after ART initiation was strongly associated with a lower mortality risk, regardless of BMI category. This finding implies that BMI may be used as a better predictor tool for death risk in adults living with HIV in Ethiopia. Additionally, patients who took a DGT-based ART regimen had a higher BMI increase rate over time, which aligns with possible positive effects, such as weight gain, of the DGT-based ART regimen in developing countries.

76-Year-Old Woman With Hemoptysis

A 76-year-old woman presented with 2 years of hemoptysis that had been increasing in frequency until it was happening on a daily basis. She had also experienced new hypoxia, exertional dyspnea, fatigue, and weight loss. Her past medical history was pertinent for severe scoliosis, remote myocardial infarction, heart failure with preserved ejection fraction (HFpEF), mild aortic stenosis, hypertension, and chronic kidney disease stage IV. She had no history of atrial fibrillation. Her medications included aspirin, high-intensity atorvastatin, furosemide, metoprolol tartrate, and lisinopril.

Living With Frontotemporal Degeneration: Diagnostic Journey, Symptom Experiences, and Disease Impact.

Frontotemporal degeneration (FTD) is an umbrella term encompassing a range of rare neurodegenerative disorders that cause progressive declines in cognition, behavior, and personality. Hearing directly from individuals living with FTD and their care partners is critical in optimizing care, identifying meaningful clinical trial endpoints, and improving research recruitment and retention. The current paper presents a subset of data from the FTD Insights Survey, chronicling the diagnostic journey, symptoms, and the impact of FTD on distress, quality of life, and independence, in the mild to moderate stages of the disease. Survey respondents included 219 individuals diagnosed with FTD and 437 current care partners, representing a range of FTD diagnoses. Around half of survey respondents reported seeing three or more doctors before an FTD diagnosis was given, and a range of prior diagnoses were noted. Most frequently endorsed symptoms tended to be consistent with clinical characteristics of the specific diagnosis, though there was significant variability in symptoms reported within diagnostic categories as well as considerable overlap in symptoms between diagnostic categories. Cognitive and language symptoms of FTD were generally most distressing to the person diagnosed, and a loss of independence was endorsed as affecting quality of life. The distinct perspectives of diagnosed persons and care partners regarding disease impact differed notably for bvFTD/Pick's disease. Participating independently in a range of activities, within the home, outside the home, and with other people, were reported as challenging for people living with FTD, underscoring the degree to which the lives of these individuals are affected even at the mild and moderate stages of disease. Overall, by heeding the perspectives of those living with FTD, we can begin to design more meaningful research studies, provide better care, and develop therapies that improve quality of life.

Outcomes of SARS-CoV-2–Positive Youths Tested in Emergency Departments

The Global Pediatric Emergency Research Network (PERN)–COVID-19 Study sought to understand the risk factors for severe SARS-CoV-2 infections in youth by conducting a cohort study including children, with early or mild stages of disease, seeking emergency department (ED) care. The study identifed that risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.

The role of platelet-rich plasma in the mild and severe stages of atherosclerotic disease in mice.

Background: Platelet-rich plasma (PRP) has a high concentration of growth factors (GFs), which present a therapeutic wound healing effect. Despite having been correlated with an immunomodulatory function, the administration of PRP has not yet been investigated in atherosclerosis models. Aim: Evaluate the effect of lyophilized PRP on atherosclerosis in mice models through serum analysis. Methods: Animals received a high-fat diet for disease induction and a weekly PRP retro-orbital application. Effectiveness was evaluated by measuring inflammatory markers in plasma following the treatment of mice with either PRP or saline solution. Results: PRP was well characterized for platelet and GF concentrations; the atherosclerotic profile was established. Cytokine concentrations were altered after PRP applications. Conclusion: PRP could modulate the inflammatory pattern in the early stages of atherosclerosis.

A Bayesian perspective on Biogen's aducanumab trial.

This perspective is a companion to a recent editorial on the use of Bayesian analysis in clinical research. We aim to introduce and highlight the relevance and advantages that Bayesian inference offers to clinical trials using the data on the amyloid antibody aducanumab presented at a Food and Drug Administration hearing in November 2020 as an applied example. We apply Bayesian analysis of model plausibility and effect sizes based on simulated data of the two phase 3 trials of aducanumab in prodromal and mild dementia stages of Alzheimer's disease (AD). Bayesian analysis can quantify evidence in favor of, or against, the presence of an effect (i.e., provide evidence of absence), as well as assess the strength of the effect. This is in contrast to the binary conclusions provided by frequentist tests.

Dysexecutive Behaviors Mediate the Relationship Between Functional Impairment and Caregiver Burden in Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is often accompanied by executive dysfunction (ED), dysexecutive behaviors (DB), and functional impairment (FI). The respective contributions of ED, DB, and FI to caregiver burden in MCI are not well understood. The present study hypothesized that while all factors would predict caregiver burden in MCI, ED and family-reported DB would account for greater variance in caregiver burden and mediate the relationship between FI and caregiver burden. In our sample (n = 94), linear regression revealed that FI and DB predicted caregiver burden, but that DB predicted caregiver burden above and beyond the contribution of FI. DB mediated the relationship between FI and caregiver burden. These results add to a body of work demonstrating that presence of DB and FI are distressing to family members, even in mild disease stages. Because DB may account for the relationship between FI and caregiver burden, early identification of family members reporting DB in the person with MCI is imperative so that supports can be made available.