Drug Development.

Background: The ability to monitor cognitive trajectories over the course of trials can provide valuable insights into treatment efficacy. However, existing trial methods are limited in monitoring cognition in real-time and at high frequencies. Gameplay-based assessments hold promise as complementary cognitive tools.

Drug Development.

Background: Clinical trials should strive to yield results that are clinically meaningful rather than solely relying on statistical significance. However, the determination of clinical meaningfulness of dementia clinical trials lacks standardization and varies based on the trial's nature. To tackle this issue, a proposed approach involves assessing the time saved before reaching a specific threshold in cognitive status.

Drug Development.

Preclinical Alzheimer's disease (AD) trials can involve multiple years of follow-up and burdensome procedures for older individuals. Optimizing the design and conduct of these trials requires input from participants and their families. Since 2020, the Alzheimer's Clinical Trials Consortium (ACTC) Research Participant Advisory Board has provided input on study attributes including: participant and study partner compensation, consent language, and result communication tools.

Drug Development.

Background: Human pluripotent stem cell (hPSC)-derived brain organoids patterned towards the cerebral cortex are valuable models of interactions occurring in vivo in cortical tissue. We and others have used these cortical organoids to model dominantly inherited FTD-tau. While these studies have provided essential insights, cortical organoid models have yet to reach their full potential.

Drug Development.

Background: Anti-amyloid immunotherapies modestly slow disease progression in early symptomatic AD; addition of other therapeutic modalities may be necessary to achieve larger treatment effects. Therapies that directly target tau can potentially produce substantial clinical benefit because the accumulation of insoluble tau protein is strongly correlated with the progression of AD. Which tau therapies are likely to be efficacious, whether or not to combine them with anti-amyloid therapies, and which individuals are most likely to benefit are important unresolved questions that would require multiple parallel design trials to answer.

Drug Development.

Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to amyloid-beta (Aβ) protofibrils, was formally evaluated as a treatment for early Alzheimer's disease in a phase 2 study (Study 201) and the phase 3 Clarity AD study. These trials both included an 18-month, randomized study (core) and an open-label extension (OLE) phase where eligible participants received open-label lecanemab for up to 30 months to date. Clinical (CDR-SB, ADAS-Cog14, and ADCS-MCI-ADL), biomarker (PET, Aβ42/40 ratio, and ptau181) and safety outcomes were evaluated.

Drug Development.

Background: Protein misfolding is a key pathological phenomenon driving neurodegenerative diseases that affect millions of people. Visualizing this misfolding process with smart imaging probes would greatly facilitate early diagnosis, etiology elucidation, disease progression monitoring, and drug discovery of neurodegeneration. Although numerous probes have been reported, several unmet needs still exist.

Drug Development.

The most recent Alzheimer's clinical trials, including those which reported successful outcomes, use neuroimaging biomarkers of both amyloid and tau for screening participants and demonstrating a treatment effect on pathology. Some of these trials, notably Lecanemab, hint at a potential sex bias in treatment outcome, alluding to major implications for clinical practice when recommending treatment options. Sex differences in treatment response are not surprising given that women are at greater risk of progression to AD dementia, particularly if they carry APOEe4.

Dementia Care Research and Psychosocial Factors.

Background: The National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's Disease and Alzheimer's Related Dementia (AD/ADRD) Clinical Trials (IMPACT) Collaboratory, in partnership with the Alzheimer's Association, convened a Lived Experience Panel (LEP), a group of 9-12 individuals, including people living with cognitive symptoms, proxies representing people with an advanced cognitive disorder or who are deceased, and care partners of a person living with dementia. The aim was for the LEP members to share their experiences with research, inform the development of research priorities, and provide input on conducting embedded pragmatic clinical trials (ePCTs) of dementia care interventions. Given the importance of providing a space for people with lived experiences to share their thoughts and recommendations, we continue to report on the final stage of LEP in its original design.

Dementia Care Research and Psychosocial Factors.

Background: Caregivers of individuals living with dementia frequently make medical decisions for care recipients, often without a clear understanding of those needs. Educational tools are needed to guide caregivers about when and how to raise the topic of advance care planning (ACP).

Method: Caregivers of individuals living with dementia (N = 130) were randomized into control (N = 64) (ACP verbal educational script) or intervention (N = 66) (ACP verbal educational script and video) groups.

Dementia Care Research and Psychosocial Factors.

Background: Dementia is a life-changing condition for patients and caregivers. Response to a diagnosis often includes grief, shock, and despair. Unfortunately, evidence demonstrates inadequate use of person-centered communication practices during diagnostic disclosure, which adds to psychological distress.

Dementia Care Research and Psychosocial Factors.

Background: Many treatments targeting frontotemporal lobar degeneration (FTLD) are in the developmental pipeline, but the rarity of the disease, coupled with the behavioral and motor features of FTLD, make it challenging to identify sufficient trial participants who can attend frequent in-person visits. Decentralized clinical trial designs with remote evaluations are attractive alternatives but require validated tools for symptom tracking. Our previous cross-sectional analyses showed that cognitive tasks deployed via the ALLFTD Mobile App are reliable and sensitive to early stages of disease.

Dementia Care Research and Psychosocial Factors.

The Congressionally Directed Medical Research Programs (CDMRP) originated in 1992 via a Congressional appropriation to foster novel approaches to biomedical research in response to the expressed needs of its stakeholders-the American public, the military, and Congress. Currently there are 35 CDMRP programs each addressing a specific disease or condition. The Peer Reviewed Alzheimer's Research Program (PRARP) began in 2011 and has a vision to mitigate the impact of Alzheimer's and related dementias associated with military and diverse risks.

Dementia Care Research and Psychosocial Factors.

Background: Personality traits are long-standing characteristics of behavior and emotion. Personality might influence cognitive health in later life by affecting responses to stressful events and engagement in cognitively stimulating activities, such as interpersonal interaction. The current study examined associations between personality traits and cognition in late life, and potential mediation by positive and negative emotion, depression, and social connectedness.

Dementia Care Research and Psychosocial Factors.

Background: Underdiagnosis of Alzheimer's disease and related dementias (ADRD) leads to lost opportunities for timely intervention, increased healthcare costs, and underestimation of the true burden of disease. To address this problem, we developed an AI algorithm, Decipher-AI (DEtection of Cognitive Impairment PHenotypes in EHR), to screen primary care patients for undiagnosed cognitive impairment (CI). We evaluated performance across sociodemographic groups using 3 years of EHR data before the first diagnosis or most recent visit.

Dementia Care Research and Psychosocial Factors.

Background: Video interfacing is increasingly being used in research and health care. The 'VCog' Study seeks to determine whether remote research cognitive assessments are reliable and valid by directly comparing results from in-person administration of a standardized cognitive battery to the same battery administered remotely by video. The study also assesses technology use and comfort amongst participants of varying levels of cognitive impairment.

Dementia Care Practice.

Aims: The Alzheimer Association (AA) has proposed new diagnostic criteria for Alzheimer's disease (AD) based on biomarkers coinciding with β-amyloidosis onset. However, there are concerns regarding the implications of these criteria.

Methods: We reviewed several perspectives, including disease definition, public health, philosophy, therapeutic, and diagnostic.

Technology and Dementia Preconference.

Background: Mild Cognitive Impairment (MCI) is the prodromal stage of dementia, including Alzheimer's Disease (AD). Early identification and accurate assessment of MCI are critical for clinical trial enrichment as well as the early intervention of AD. Digital makers offered a unique opportunity for ecologically valid and affordable early detection approaches.

Clinicopathological Characteristics and Long-Term Outcomes of Cystic vs. Solid Pancreatic Neuroendocrine Tumors: A Multi-Institutional Experience with 1727 Patients.

Objective: To investigate the clinicopathological features and long-term outcomes of cystic and solid pancreatic neuroendocrine tumors (PanNETs).

Summary Background Data: PanNETs uncommonly present as cystic lesions. Whether cystic PanNETs represent a distinct clinical entity compared to solid PanNETs is controversial.

Technology and Dementia Preconference.

Background: Underdiagnosis of Alzheimer's disease and related dementias (ADRD) leads to lost opportunities for timely intervention, increased healthcare costs, and underestimation of the true burden of disease. To address this problem, we developed an AI algorithm, Decipher-AI (DEtection of Cognitive Impairment PHenotypes in EHR), to screen primary care patients for undiagnosed cognitive impairment (CI). We evaluated performance across sociodemographic groups using 3 years of EHR data before the first diagnosis or most recent visit.

Technology and Dementia Preconference.

Background: The National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) was developed to address the need for a brief yet comprehensive instrument to facilitate more uniform assessment in large-scale research studies. Here, we investigated whether the cognitive measures of the NIHTB detect cognitive decline in biomarker-confirmed Alzheimer's disease (AD).

Method: We used data from N = 178 participants (age 76.

Advancing Monogenic Diabetes Research and Clinical Care by Creating a Data Commons: The Precision Diabetes Consortium (PREDICT).

Monogenic diabetes mellitus (MDM) is a group of relatively rare disorders caused by pathogenic variants in key genes that result in hyperglycemia. Lack of identified cases, along with absent data standards, and limited collaboration across institutions have hindered research progress. To address this, the UChicago Monogenic Diabetes Registry (UCMDMR) and UChicago Data for the Common Good (D4CG) created a national consortium of MDM research institutions called the PREcision DIabetes ConsorTium (PREDICT).

What should constitute a control condition in psychedelic drug trials?

Over the past decade there has been a surge in interest in placebo-controlled trials using non-classical 3,4-methylenedioxymethamphetamine (MDMA) and classical psychedelics such as psilocybin, lysergic acid diethylamide (LSD) and ,-dimethyltryptamine (DMT) to treat neuropsychiatric disorders. However, the success and reliability of these trials depend on the design of the trials, the choice of control conditions, and the ability to blind both participants and researchers. When appropriate control conditions are lacking, it becomes difficult to disentangle placebo and expectation effects from medication effects.

Clinical implications of mineralocorticoid receptor overactivation.

The mineralocorticoid receptor (MR) is a nuclear transcription factor that plays a critical role in regulating fluid, electrolytes, blood pressure, and hemodynamic stability. In conditions such as chronic kidney disease (CKD) and heart failure (HF), MR overactivation leads to increased salt and water retention, inflammatory and fibrotic gene expression, and organ injury. The MR is essential for transcriptional regulation and is implicated in metabolic, proinflammatory, and pro-fibrotic pathways.

All-Soft-Tissue Medial Patellofemoral Complex Reconstruction for Revisions and Skeletally Immature Knees.

The medial patellofemoral complex provides the primary static restraint to lateral patellar translation and is composed of the medial patellofemoral ligament and medial quadriceps tendon femoral ligament. Multiple techniques including medial patellofemoral ligament and/or medial quadriceps tendon femoral ligament reconstruction have demonstrated good results; however, modification of the femoral fixation technique is required for skeletally immature patients or revision cases in which anatomic bony fixation on the femur is not possible. This technique describes an all-soft-tissue procedure for single-bundle medial patellofemoral complex reconstruction in which the graft is fixed on the adductor tendon while using the medial collateral ligament as a distalizing pulley, for anatomic and isometric recreation of the native ligament.