Studies

ADNI4 Engagement Core


NIH U19AG024904
Subcontract to UW-Madison (Okonkwo, MPI of the Engagement Core)
9/15/2022 – 7/31/2027
PI: Michael Weiner

ADNI is the NIH’s landmark study of the biomarkers of Alzheimer’s disease and their validation for clinical trials. The objective of the Engagement Core is to increase the engagement of underrepresented populations (URPs; e.g., Black, Latinx, low SES) in ADNI4; cultivate a diverse, culturally competent workforce to work with URPs; and investigate ethnocultural disparities in dementia.

HABS-HD Development Core


NIH U19AG078109
Subcontract to UW-Madison (Okonkwo, PI of the Development Core)
9/30/2022 – 8/31/2027
PI: Sid O’ Bryant

HABS-HD is the first large-scale, community-based project to study ATN biomarkers across the three largest racial/ethnic groups in the US: African Americans, Mexican Americans, and non-Hispanic whites. The Development Core will recruit, support, and provide targeted mentored training to an annual cohort of URG trainees (HABS-HD Fellows) to ensure their research proficiency and cultural competency.

Study to Uncover Pathways to Exceptional Cognitive Resilience in Aging (SUPERAging)


NIH U19AG073153
Subcontract to UW-Madison (Okonkwo, Site PI)
9/30/2021 – 5/31/2026
PI: Emily Rogalski

The primary goal of this study is to establish a multicenter SuperAging Consortium to identify behavioral, health, biologic, genetic, environmental, socioeconomic, psychosocial, anatomic and neuropathologic factors associated with SuperAging. These goals will be achieved through an organizational structure with 3 Cores (Administrative/Biostatistics, Clinical/Imaging, and Biospecimen/Neuropathology) and 2 Research Projects. The Consortium will enroll 500 participants, with particular focus on Black SuperAgers, across 4 US Sites located in Illinois, Wisconsin, Michigan and Georgia, and a Canadian Site in Southwest Ontario. In addition to SuperAgers, the study will also enroll cognitively-average older adults (Controls) with similar demographics as the SuperAgers.

ADNI3 Diversity Taskforce


NIH U19AG024904
Subcontract to UW-Madison (Okonkwo, Leader of the Diversity Taskforce)
8/1/2020 – 7/31/2022
PI: Michael Weiner

The ADNI Diversity Taskforce is an initiative to accelerate enrollment of under-represented minorities (URMs) during the final two years of ADNI3, in preparation for ADNI4. The charge of the Taskforce is to (1) develop strategies for significantly increasing the rate of recruitment of URMs into ADNI3, (2) analyze and publish existing ADNI data related to diversity and health disparities, and (3) generate scientific aims relevant to health disparities for ADNI4.

E2: Sex Hormones & Alzheimer’s Disease Prevention Study


NIH R01AG066203
Subcontract to UW-Madison (Okonkwo, Site PI)
9/15/2019 – 5/31/2024
PI: Whitney Wharton/ William Hu

The main objectives of the study are to test whether cerebrospinal fluid (CSF) and serum sex hormone levels (estradiol, estrone, progesterone, testosterone) differentially influence Alzheimer’s disease (AD) risk factors (inflammation, cerebral blood flow and sleep), and if sex hormone levels moderate the relationship between these risk factors and AD biomarkers (CSF Aβ and p- and t-tau, neuroimaging and cognition).

Longitudinal Investigation of Cardiorespiratory Fitness and AD Biomarkers in an At-Risk Cohort


NIH R01AG062167
1/15/2019 – 11/30/2023
PI: Ozioma Okonkwo

The overarching goal of this proposal is to rigorously characterize the longitudinal relationship between cardiorespiratory fitness (CRF) and the biomarker and cognitive features of Alzheimer’s disease (AD) in a well-characterized cohort of cognitively healthy adults at increased risk for AD. We further purpose to interrogate candidate mechanisms underlying the beneficial effects of CRF and determine the extent to which observed effects are sex-dependent.

Longitudinal Assessment of Physical Activity, Cerebral Glucose Metabolism, and Cognitive Function in an At-Risk Cohort


NIH F31AG062009
9/1/2018 – 8/31/2020
Awardee: Ryan Dougherty
PI: Ozioma Okonkwo

The overarching goal of this study is to rigorously characterize the longitudinal relationship between cardiorespiratory fitness—a physiological indicator for habitual physical activity—and the biomarker and cognitive features of Alzheimer’s disease (AD) in a well-characterized cohort of cognitively healthy adults at increased risk for AD.

Longitudinal Assessment of Physical Activity and AD Biomarkers in an At-Risk Cohort


UW-Madison OVCRGE
7/1/2018 – 9/30/2022
PI: Ozioma Okonkwo

In this prospective study, we investigate the linkage between changes in aerobic capacity and concomitant changes in hippocampal volume, cerebral perfusion, and Alzheimer’s disease biomarkers; and also interrogate whether these associations are independent of the influence of physical activity.

Genetic and Lifestyle Determinants of Cognitive Resilience in Midlife


NIH R21AG051858
5/15/2016 – 2/29/2020
PI: Ozioma Okonkwo

In this integrative and translational study, we leverage the wealth of pre-existing multi-modal data from ~2000 longitudinally followed, at-risk, middle-aged adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center to determine whether genetic and lifestyle factors—individually or jointly—confer resilience against age- and APOE4-mediated changes in (1) cognitive course and (2) brain/cerebrospinal fluid biomarkers of Alzheimer’s disease.

Therapeutic Effects of Exercise in Adults with Amnestic Mild Cognitive Impairment


NIH U19AG010483
Subcontract to UW-Madison (Okonkwo, Site PI)
3/1/2016 – 2/28/2021
PI: Laura Baker

A phase 3, multicenter, randomized single-blind study to examine the effects of aerobic exercise on cognition, functional status, whole and regional brain atrophy, whole and regional cerebral blood flow, and cerebrospinal fluid biomarkers of Alzheimer’s disease in 300 adults with amnestic mild cognitive impairment.

Cardiorespiratory Fitness and AD Biomarkers in an At-Risk Cohort


Extendicare Foundation
12/2/2014 – 12/31/2019
PI: Ozioma Okonkwo

The overall aim of this project is to rigorously characterize the relationship between cardiorespiratory fitness (CRF)—an indicator for habitual physical activity—and Alzheimer’s disease (AD) biomarkers and cognition in 250 at-risk, middle-aged adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center; and preliminarily assess the biological mechanisms by which CRF affects AD biomarkers and cognition.

Allostatic Load Alters Brain and Cognitive Markers of Alzheimer’s Disease


NIH K23AG045957-S1
Beeson Supplement
9/1/2016- 8/31/2018
Awardee: Megan Zuelsdorff
PI: Ozioma Okonkwo

The purpose of this research is to explore differences in allostatic load (AL) burden across demographic strata and determine the impact of primary and secondary subindices of AL on Alzheimer’s disease-related brain changes and cognitive decline in midlife.

Aerobic Exercise for AD Prevention in At-Risk Middle-Aged Adults


2014-NIRGD-305257
Alzheimer’s Association
6/1/2014 -11/30/2017
PI: Ozioma Okonkwo

The main objective of this proposal is to pilot a 26-week trial of aerobic exercise among asymptomatic, middle-aged adults with and without family history of Alzheimer’s disease (AD) enrolled in the Wisconsin Registry for Alzheimer’s Prevention and/or the Wisconsin Alzheimer’s Disease Research Center. Our near-term goal is to assess the feasibility and acceptability of this structured intervention and preliminarily evaluate (i) its effect on AD-relevant outcomes such as glucose metabolism and (ii) the mechanism for such effects. Our longer-term goal is to use the data gathered via this pilot to further refine the intervention, estimate effect sizes for key outcomes, and seek NIH funding for a longer and more definitive assessment of whether aerobic exercise can effectively curtail AD progression in midlife.

Early Detection of Asymptomatic Middle-Age Adults at Risk for AD


NIH K23AG045957
Beeson Award
9/1/2013 – 8/31/2018
PI: Ozioma Okonkwo

The aims of this project are: (1) specify the pattern of brain changes on MRI that is characteristic of Stage 3 preclinical Alzheimer’s disease, (2) prospectively assess the prognostic utility of an aggregate measure of midlife structural-functional MRI brain changes, and (3) preliminarily evaluate how individual differences related to cognitive reserve and genetic risk modify the association between early brain changes and future decline.

Neuromorphometric Alterations in Middle-Aged Adults with Family History of Alzeimer’s Disease: Relationship to Genetic Variants


NIH P50AG033514-S1
(ADRC Diversity Supplement)
4/1/2012 – 9/1/2013
PI: Ozioma Okonkwo

The main purpose of this project is to determine whether neuromorphometric changes are present in the preclinical stages of Alzheimer’s disease (AD) and whether they are influenced by genetic variations (either established or novel) that are associated with AD.

Identification of Antecedent Biomarkers of Alzheimer’s Disease in Cerebrospinal Fluid Using a Clinically-Available Endophenotype


UW-Madison Institute for Clinical and Translational Research
4/1/2012- 3/31/2013
PI: Ozioma Okonkwo

The objective of this research is to use intelligent machine learning algorithms to derive a multi-modal marker of preclinical Alzheimer’s disease (AD) and deploy this marker as an endophenotype in the identification of novel cerebrospinal fluid biomarkers of AD.