Chitinase-3-like protein 1 (CHI3L1/YKL-40) is a well-known biomarker for the early detection of neuroinflammation and Alzheimer’s disease. This study aims to define the signaling mechanism whereby CHI3L1 governs neurodegeneration caused by glial activation, and to develop the translational potential of these signaling mechanisms to prevent neuronal damage in Alzheimer’s disease.

Principal investigator: Alvin Huang

Evidence suggests that microbial exposure and the ensuing immune response has a large role in the incidence and progression of age-associated neurodegenerative diseases, including in Alzheimer’s disease. This study aims to define the contribution of a pathogen-rich environment and matured plus heightened immune system on Alzheimer’s mouse models of amyloid pathology.

Principal investigator: Greg Valdez

Locus coeruleus (LC) dysfunction and degeneration occur early in Alzheimer’s disease. This study aims to define early metabolic mechanisms of LC vulnerability in Gpt2-null mice, and also in AD and DS mouse models, across the lifespan, including in gene-by-environment experiments using an extended wakefulness paradigm. This research may lead to important new strategies for preventive treatments for LC degeneration in AD/ADRD.

Principal investigator: Eric Morrow

A multidisciplinary team of investigators at Brown University and Rhode Island Hospital  is studying whether the mRNA, miRNA, and protein composition of salivary extracellular vessicles will provide valid biomarkers for early diagnosis and following disease progression in patients with Alzheimer’s disease and related neurodegenerative disorders.

Principal investigator: Jill Kreiling 

This study aims to determine the atomistic details of the assembly of a helical sub-region of the TAR DNA binding protein of 43 kDa (TDP-43), its contribution to splicing function, and its structural conversion in disease aggregates, and to identify promising therapeutic targets. The results of these studies on TDP-43 complexes, phase-separation, function, and aggregation will provide direct structural and mechanistic input to the design of strategies to prevent toxic disruption of TDP-43 in Alzheimer’s disease related dementias and motor neuron disease.

Principal investigator: Nick Fawzi

Deficits in cerebral microvascular structures and functions may play a key role in the onset and development of Alzheimer’s disease. This study will develop, optimize, and integrate experimental and computational technologies for the lifespan tracking and analysis of progressive microvascular alterations in Alzheimer’s versus normal aging in model mice.

Principal investigator: Jonghwan Lee  

The Frost laboratory employs a multi-system approach to rapidly identify, test, and validate hypotheses that are relevant to human aging and disease. Early discovery takes place in Drosophila, a model organism that is well-suited for investigating issues of causality in disease processes.

Principal investigator: Bess Frost 

Improve our understanding of the age-specific pathophysiology of Alzheimer’s disease, determining the precise relationship between tau and cognition, with the ultimate goal of guiding therapeutic development and trials for Alzheimer’s treatment.

Principal Investigator: Sarah Ackley

The overall objective of this project is to identify the determinants of better end-of-life care experiences in assisted living.

Principal Investigator: Emmanuelle Belanger

This project identifies a novel vulnerable population using a mixed-methods approach to understand and address variability in use of palliative care. The results of this study will be used to identify modifiable care processes as targets for clinical and policy interventions to improve care. Subaward to Brown University from Oregon Health & Science University.

Brown Site Principal Investigator: Pedro Gozalo

This project calculates the prevalence and incidence of herpes zoster (HZ) following nursing home admission and validates a case definition of HZ severity using free-text clinical notes.

Principal Investigator: Kaleen Hayes

This project evaluates the longitudinal risk and long-term health consequences of a crash among older drivers with MCI or varying severities of dementia.

Principal Investigator: Nina Joyce

This project will be the first to compare the effectiveness,  cost-effectiveness, and affordability of nondrug ADRD interventions, by race and ethnicity, on outcomes of family time caregiving, days in a nursing home, costs to families/Medicaid/Medicare, and the person with ADRDs and their caregiver’s quality-adjusted life-years.

Principal Investigator: Eric Jutkowitz

This project examines drivers of migration and migration rates and the mediating effects on migration health outcomes among Medicare older adults with and without preexisting ADRD in Puerto Rico.

Principal Investigator: Maricruz Rivera-Hernandez

This project seeks to understand how the high-need ADRD patients at various stages of disease progression fare under alternative payment and regulatory structures.

Principal Investigator: Amal Trivedi

The Screening and Survey Instrument Development The National Dementia Workforce Study (NDWS) will be launched by a national team of experts in clinical care of persons living with dementia, survey research, and health workforce research. The goal of the NDWS data infrastructure is to allow researchers and policymakers to ask and answer scientific questions to help build the workforce of clinicians and other professional care providers required by the growing population of persons living with dementia in the U.S. The Screening and Survey Instrument Development Core will develop the survey content and procedures to launch four nationally representative surveys of Community Clinicians, Nursing Home Staff, Assisted Living Staff, and Home Care Staff. This team will: 1) Develop sampling frames for the four NDWS surveys from data sources including national Medicare and Medicaid claims and assessment data to create efficient sample designs; 2) Develop questionnaires targeting specific professional workforce providers relevant to the particular survey setting (e.g., physicians, nurses, direct care workers) with a focus on training, compensation, payment models, and care practices; 3) Test questionnaires using focus groups, cognitive interviews, expert review, and several innovative online methods in order to ensure reliable and valid measurement; and 4) Develop a process to solicit proposals for new items to be added to ongoing surveys. Subaward to Brown University from University of Michigan.

Brown Site Principal Investigator: Elizabeth

This project will generate new empirical evidence on prescribing cascades to guide medication optimization efforts to reduce adverse drug events in New Hampshire residents with ADRD.

Principal Investigator: Andrew Zullo

This study aims to identify, test, and validate clinically significant drug interactions in nursing home residents with Alzheimer’s disease and related dementias through a series of rigorous epidemiological studies that employ novel drug interaction screening and causal inference methods. The central hypothesis is that multiple clinically significant drug interactions will increase the risk of fall-related injuries, and that this risk will be greatest among individuals with the most severe cognitive impairment and on higher medication doses.

Principal investigator: Andrew Zullo

The overall objectives of this study are to assess the impact of I-SNP enrollment on long-term care quality for nursing home residents with Alzheimer’s disease and related dementias both during the pre- and post-pandemic periods, understand factors contributing to I-SNP enrollment and growth, and characterize how I-SNP care practices influence resident outcomes. The central hypothesis is that I-SNP enrollees with ADRD experience fewer hospitalizations and better care quality than enrollees in traditional fee-for-service Medicare or other Medicare Advantage plans due to comprehensive care management.

Principal investigator: Momotazor Rahman  

Investigators at Brown are following 720 infants — now in their 60s — in a novel ground-breaking longitudinal study of risks for Alzheimer’s disease and cognitive decline. Selected from a larger group of 17,000 births in Providence and Boston, the study includes neuropsychological testing, blood biomarkers, structural and functional magnetic resonance imaging (fMRI), and survey questionnaires to understand neurocognitive mechanisms underlying the risk for and resilience to Alzheimer's disease pathology among older adults.

Principal investigators: Stephen Buka and William Heindel

Study of amyloid in the retina recruiting people 55-80 years old who are cognitively normal or who have mild Alzheimer’s disease symptoms.

Principal investigators: Jessica Alber (URI), Louisa Thompson (Brown) and Athene Lee (Butler)

An initiative to create a well-characterized, biomarker-confirmed, trial-ready cohort to facilitate rapid enrollment recruiting people 50-85 years old who are preclinical or have early signs or symptoms of Alzheimer’s disease.

Principal investigator: Athene Lee (Butler)

A study investigating the safety and tolerability of the treatment emtricitabine in a six-month blinded placebo-controlled trial is recruiting people 50-85 years old with mild cognitive impairment or moderate symptoms of Alzheimer’s disease.

Principal investigators: John Sedivy (Brown) and Meghan Riddle (Butler)

A study testing the safety and efficacy of CT1812 in an 18-month, double-blind, placebo-controlled trial recruiting people 50-85 with mild cognitive impairment or moderate symptoms of Alzheimer’s disease.

Principal investigators: Meghan Riddle and Chris Van Dyke (Yale)

Contracted by National Institutes on Aging to harmonize and analyze genetic data from the Alzheimer’s Disease Sequencing Project and the Alzheimer’s Disease Sequencing Project Follow-up Study related to neuropsychiatric and other non-cognitive symptoms of Alzheimer’s disease.

Principal investigators: Ted Huey, Christiane Reitz (Columbia), Gary Beecham (Wake Forest)

A study creating a cohort of cognitively normal and amyloid negative screen failures from AHEAD.

Principal investigator: Meghan Riddle 

An observational study of people who are cognitively normal to moderate symptoms of Alzheimer’s disease that will create a database accessible to researchers worldwide

Principal investigator: Meghan Riddle 

An observational study to harmonize registry data and use large cohorts to generate machine learning algorithms to predict amyloid PET positivity.

Principal investigators: Jessica Alber (URI), Louisa Thompson and Athene Lee  

A study of digital tools in the primary care environment enrolling patients 55-85 years old with no impairment or mild cognitive impairment.

Principal investigator: Louisa Thompson 

A five-year observational study to assess changes in fluid biomarkers, assess the predictive ability of a variety of biomarkers on amyloid PET positivity, and assess the psychological and behavioral impact of biomarker data disclosure.

Principal investigator: Ted Huey 

Using multimodal neuroimaging approaches that include the-state-of-the-field PET scans that image brain amyloid and tau pathologies and structural and functional MRI, this study aims to identify more sophisticated behavioral phenotypes and neural markers at the early stage of Alzheimer’s disease pathologies. These findings will enable a non-invasive and more affordable and accessible screening test of the disease with clinical utility in aiding early diagnosis and treatment monitoring.

Principal investigator: Hwamee Oh

This study aims to examine different characteristics associated with tau PET tracers and to improve generalization of findings obtained in studies and clinical practice using distinct tau tracers. The study will recruit 620 healthy young, cognitively normal older adults and patients with Alzheimer’s disease who will undergo amyloid and tau PET scans, along with MRI scans, at two time points.

Principal investigator: Hwamee Oh

A landmark NIH-funded study, “Blood-brain Barrier Disruption as a Biomarker for Perioperative Neurocognitive Disorders: Cognitive Recovery After Elective Surgery (CREATES)” aims to build upon previous research by using an innovative brain imaging technique to investigate whether perioperative health of the blood-brain barrier is associated with delirium and cognitive decline. This five-year study will recruit 200 older adults undergoing major elective surgery at Rhode Island Hospital or The Miriam Hospital.

Principal investigator: Lori Daiello

The goal of this project is to identify molecular biomarkers for normal pressure hydrocephalus (NPH) diagnosis and the prediction of shunt surgery benefits. NPH causes prominent cognitive and motor symptoms and eventually leads to dementia. The project's multidisciplinary team has undertaken a holistic approach that leverages state-of-the-art molecular biology tools and data science approaches to determine the molecular mechanisms underlying NPH symptoms and disease progression. By integrating data from multi-omics platforms, the researchers aim to develop a rapid, accurate and cost-effective diagnostic test.

Principal investigators: Alexander Fleischmann, Petra Klinge, Thomas Serre, Maria Grazia Ruocco, and Danny Warshay

A longitudinal, multi-site natural history study on the early stages of CADASIL, and is actively recruiting negative and positive gene carrier family members.

Principal investigator: Ted Huey 

The purpose of the LEADS study is to explore the development of early-onset Alzheimer’s disease and how it compares to the more common late-onset Alzheimer’s disease. Better understanding of this form of the disease may ultimately lead to more effective treatments.

Principal investigator: Stephen Salloway

A longitudinal observational study of cognitively normal people with a family history of dominantly inherited Alzheimer’s disease ages 18 and over.

Principal investigator: Ted Huey  

A consortium-led observational study including those with a diagnosis of a Frontotemporal Lobar Degeneration (FTLD) disorder and their family members.

Principal investigator: Ted Huey

A single, four- to five-hour observational study research visit aimed at developing a gold standard neuropsychiatric symptom measure in neurodegenerative disease based on underlying neuroanatomical changes.

Principal investigator: Ted Huey

A single four to five hour observational study research visit for people who are cognitively normal, those with mild cognitive impairment, and mild dementia (Alzheimer’s disease, behavioral variant Frontotemporal Dementia, Primary Progressive Aphasia, Huntington’s disease) to investigate systems of arousal and reward in neurodegenerative disease neuroanatomical changes.

Principal investigator: Ted Huey

Survey of cognitively normal older adults and those with mild cognitive impairment asking about their experiences with technology, opinions of passive remote monitoring techniques for detecting cognitive change as well as questions about mood and cognitive status. Actively recruiting people 50 to 80 years old.

Principal investigator: Alyssa De Vito 

Alzheimer’s Association/CMS collaborative to collect real-world outcomes and treatment data for people receiving a clinically prescribed disease modifying treatment.

Principal investigator: Steve Salloway  

The U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a Phase 3, two-year clinical trial to evaluate whether lifestyle interventions that simultaneously target multiple risk factors protect cognitive function in older adults at increased risk for cognitive decline. 

This training grant supports predoctoral trainees in the Brown University School of Public Health with a focus on aging health and health services for dementia care. The objective is to meet the growing demand for investigators conducting research on the biological, psychological, and social forces that shape the manner in which older Americans, particularly older adults living with dementia, utilize health services and how those services affect their health and well-being.

Principal investigator: Vince Mor