Cognitive Health Services Research

Project Description

We have collaborated with PI Hyunmi Choi, MD, at Columbia University in New York, for the study entitled “Effects of Vascular Risk Factors on Risk for Dementia and Stroke After Late-Onset Epilepsy (EPILEPSY COG).” U-M is a subcontract and Deb Levine is the U-M site PI. At U-M, Emily Briceño is a co-I on the study alongside her Consultant Christopher Gonzalez and U-M Site Project Manager Adam Kollipara, MPH.

Immediate objectives are to rigorously investigate relationships of late-onset epilepsy (LOE) and pre-epilepsy vascular risk factors (VRFs) with cognitive decline and characterize potential biological mechanisms, develop risk prediction algorithms for ADRD and stroke/cardiovascular disease (CVD) that accurately estimate risk in the setting of LOE, and integrate LOE into a microsimulation modeling paradigm for testing the effects of VRF interventions in clinical trials. To accomplish these objectives, six existing NIH-funded US-based cardiovascular cohort studies will be pooled and epilepsy ascertainment will be added to these cohorts.

Harmonized measures of VRFs and longitudinal trajectories of global cognitive ability, executive function, and memory in five of these cohorts (ARIC, CHS, MESA, NOMAS, REGARDS) have been created. An additional cohort (WHICAP) will be integrated to increase racial/ethnic diversity and improve generalizability. Comprising over 69,000 older adults with cognitive data harmonization and 1,600 LOE cases, this innovative resource will be unprecedented in epilepsy research, directly addressing the absence of a large-scale study of consequences of LOE, an unfulfilled priority of the 2012 Institute of Medicine report on epilepsy.

It is expected that this study will propel clinical care models for LOE to include accurate vascular risk assessment and treatment. Long-term objectives are to increase awareness of LOE as a vascular risk marker, incorporate LOE into prevention guidelines, and disseminate prevention strategies to slow ADRD and reduce stroke and CVD risk in individuals with LOE.

This work is supported by National Institutes of Health - National Institute on Aging (R01AG074355)

Project Manager

Contact Lia Marshall at [email protected] for more information about this project.

Project Description

Stroke survivors are much more likely than stroke-free adults to develop Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD). The STROKE COG study is an National Institutes of Health (NIH)-funded R01 study that aims to advance the understanding of post-stroke AD/ADRD and how post-stroke blood pressure, glucose, and lipid levels independently contribute to post-stroke AD/ADRD risk.

This is a multi-center study in collaboration with researchers from Columbia University, Johns Hopkins University, and the University of Alabama at Birmingham. The study involves pooling and harmonizing data from 4 existing longitudinal cohorts, secondary data analysis, and simulation modeling.

This work is supported by the National Institutes of Health - National Institute on Aging (R01AG068410).

Publications

Trajectory of cognitive decline after incident stroke
Levine DA, et al. JAMA. 2015; 314(1):41-51. PMID: 26151265.

Risk factors for post-stroke cognitive Decline: the REGARDS study
Levine DA, et al. Stroke. 2018;49(4):987-994. PMID: 29581343.

Association of blood pressure and cognition after stroke
Levine DA, et al. J Stroke Cerebrovasc Dis. 2020;29(7):104754. PMID: 32370925

Media

Trajectory of Cognitive Decline After Incident Stroke
Jama Network Original Investigation, July 7, 2015
(includes video and audio interviews)

Project Manager

Contact Rebecca Ferber at [email protected] for more information about this project.

Project Description 

The Type 2 Diabetes Mellitus and Vascular Contributions to Cognitive Impairment and Dementia (T2DM-VCID) project, called DIABETES COG by the team, aims to address a critical knowledge gap regarding the impact of cumulative hyperglycemia beginning in young adulthood (ages 18–45) on cognitive decline and the risk of Alzheimer’s disease and related dementias (ADRD). With the increasing prevalence of type 2 diabetes (T2DM) and prediabetes in younger populations, there is a pressing need to understand how suboptimal glycemic control contributes to vascular contributions to cognitive impairment and dementia (VCID). The central hypothesis is that higher cumulative hyperglycemia and poor T2DM management accelerate cognitive decline and increase ADRD risk. Leveraging robust preliminary data, the multidisciplinary research team will pursue three aims: (1) quantify the influence of cumulative hyperglycemia from young adulthood through late life on cognitive trajectories and ADRD risk, including effect modification by sex, race, and hyperglycemia duration; (2) evaluate the impact of T2DM management, using cumulative HbA1c, on cognitive decline through individual participant data meta-analyses of three clinical trials; and (3) identify potential mechanisms by examining cerebral small vessel disease and stroke as mediators in the relationship between hyperglycemia and cognitive decline. The study will integrate data from large, racially and geographically diverse pooled cohort studies and clinical trials, offering unprecedented power to assess life course glycemic exposure and VCID outcomes. This work will generate critical empirical evidence to inform clinical guidelines, shared decision-making, and future intervention trials aimed at preserving cognitive function and reducing ADRD risk in individuals with hyperglycemia.

This research is funded by the National Institutes of Health - National Institute on Aging (RF1NS136499).  

Project Manager

Contact Rebecca Ferber at [email protected] for more information about this project.

One of the most frequent challenges clinicians face is managing serious illness in older patients with mild cognitive impairment (MCI), a condition that affects up to 1 in 5 older Americans. The MCI DeM study is an National Institutes of Health (NIH) / National Institute on Aging (NIA)-funded R01 study that aims to compare the quality of cardiovascular disease care in adults with and without mild cognitive impairment and to determine the influence of mild cognitive impairment on patient preferences and physician recommendations for heart attack and stroke treatment.

This is a multi-center, mixed methods study in collaboration with researchers from Duke University. The study involves secondary data analysis of two existing longitudinal cohorts as well as primary data collection using semi-structured interviews and surveys of patients, care partners, and physicians.

Publications

Mild cognitive impairment and receipt of treatments for acute myocardial infarction in older adults
Levine DA et al. J Gen Intern Med. 2020. 35(1):28-35. PMID: 31410812

Physician decision-making and recommendations for stroke and myocardial infarction treatments in older adults with mild cognitive impairment
Levine DA, Langa KM, Fagerlin A, et al. PLoS One. 2020 17;15(3):e0230446. PMID: 32182264/PMCID: PMC7077853

Mild cognitive impairment and receipt of procedures for acute ischemic stroke in older adults
Levine DA, et al. J Stroke Cerebrovasc Dis. 2020. In press.

The association of cognitive impairment and dementia with receipt of cataract surgery among community-dwelling US Medicare Beneficiaries
Stagg BC, Ehrlich JR, Choi H, Levine DA. JAMA Ophthalmol. 2019;137(1):114-117. PMID: 30422225

The Predictors and Long-Term Trajectory of Poststroke Cognitive Decline study is a completed National Institutes of Health (NIH) / National Institute on Aging (NIA)-funded study (K23AG040278; principal investigator, Deborah Levine) that aimed to determine the predictors and long-term trajectory of cognitive decline after stroke.

This study has advanced the science of vascular cognitive impairment by improving our understanding of post-stroke cognitive impairment trajectory and predictors. For the first time, this study showed that stroke is associated with an acute decline in cognition and also accelerated and persistent cognitive decline over several years, published in JAMA. The study used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and linear mixed-effect models to measure changes in cognitive function over time. The editorial praised the “novel” methods, the “clinically meaningful” results, and the research for serving as “a catalyst for future targeted investigations.”

The study identified risk factors for post-stroke cognitive decline using data from the REGARDS cohort, published in Stroke. The results suggested that race, sex, geography, and hypertension status might modify the risk of poststroke cognitive decline. Faster declines in cognition over years after stroke were greater in survivors who were older or had a particular type of ischemic stroke, cardioembolic stroke.

The study examined the association between blood pressure and cognition after stroke, published in the Journal of Stroke and Cerebrovascular Disease. In a cross-sectional analysis of data from the Brain Attack Surveillance in Corpus Christi (BASIC) project, stroke survivors’ blood pressure levels were not associated with cognitive performance at 90 days independent of sociodemographic and clinical factors.

Based on this work, the study team received funding for the NIH/NIA-funded STROKE COG study to understand how post-stroke blood pressure, glucose, and lipid levels independently contribute to post-stroke dementia risk.

With the expertise of Darin Zahuranec, MD, MSc, and Adam Stein, MD, the Levine Team has conducted two pilot studies from April to September 2023 in preparation for a November 2023 grant submission.

Pilot 1 involves testing the feasibility of recruitment and data collection procedures planned for a multi-center trial of decision aids in older patients with MCI and normal cognition hospitalized with a Type 1 non-ST-elevated myocardial infarction (NSTEMI), care partners, and clinicians.

Pilot 2 involves conducting interviews of individuals with normal cognition and MCI, identified by the Michigan Alzheimer’s Disease Center (MADC). These interviews tested the effectiveness of a heart attack treatment decision aid  and validation of a brief survey consisting of two sections asking questions about knowledge and values. A mailing of surveys to an additional 258 MADC-identified individuals was done in July 2023 with a goal of receiving 100 completed surveys to provide preliminary data for the grant submission.

Cognitive impairment and dementia as well as high blood pressure disproportionately affect Blacks and Hispanics in the US. The BP COG study is an National Institutes of Health (NIH) / National Institute of Neurological Disorders and Stroke (NINDS)-funded R01 study (R01NS102715) that aims to determine the effect of high blood pressure over the life course on the risk of cognitive impairment and dementia in Blacks, Hispanics, and Whites, and to estimate the potential impact of optimal high blood pressure treatment intensity to reduce racial/ethnic disparities in cognitive impairment and dementia.

This is a multi-center study in collaboration with researchers from Columbia University and Johns Hopkins University. The study involves pooling and harmonizing data from six existing longitudinal cohorts, secondary data analysis, and simulation modeling.

The BP COG study has advanced the science of vascular cognitive impairment by determining the impact of high blood pressure on cognitive decline in Black and White individuals. The study showed that Black individuals’ higher cumulative blood pressure (BP) levels contribute to racial differences in later-life cognitive decline, published in JAMA Neurology. These results suggest that Black individuals’ worse high blood pressure control contributes to their greater dementia risk.

The study used individual participant data from six well-characterized American prospective cohort studies: 

• Atherosclerosis Risk in Communities Study (ARIC)
• Coronary Artery Risk Development in Young Adults Study (CARDIA)
• Cardiovascular Health Study (CHS)
• Framingham Offspring Study (FOS)
• Multi-Ethnic Study of Atherosclerosis (MESA)
• Northern Manhattan Study (NOMAS)

The BP COG study is an innovative national study that created harmonized and pooled, longitudinal cohorts of individuals with calibrated cognition measures from six studies. This innovation provides the sample size and race/ethnic diversity of individuals to answer scientific questions previously impossible.

The BP COG study team also developed and refined a novel simulation model that predicts dementia and cardiovascular disease events. This new simulation model translates the effects of vascular risk factor lowering on dementia into clinical practice and policy and helps plan future vascular risk factor lowering trials to reduce dementia in diverse populations.

Publications

Association between blood pressure and later-life cognition among black and white individuals
Levine DA, Gross AL, Briceño EM, et al. JAMA Neurol. 2020 Apr 13; [Epub ahead of print] PMID: 32282019/PMCID: PMC7154952

Methods and early recruitment of a community-based study of cognitive impairment among Mexican Americans and non-Hispanic whites: the BASIC-Cognitive study
Briceño EM, Mehdipanah R, Gonzales X, Heeringa S, Levine DA, Langa KM, Garcia N, Longoria R, Morgenstern LB. J Alzheimers Dis. 2020;73(1):185-196. PMID: 31771059

Neuropsychological assessment of mild cognitive impairment in Latinx adults: a scoping review.
Briceño EM, Mehdipanah R, Gonzales X, Langa KM, Levine DA, Garcia N, Longoria R, Giordani B, Heeringa S, Morgenstern L. Neuropsychology. 2020. [Epub ahead of print] PMID: 32281811

Our research focuses on cognitive health in culturally and linguistically diverse communities. We aim to identify risk and resilience factors that impact cognitive health, and to optimize precision in assessment of cognition through consideration of factors (e.g., linguistic, cultural, and educational experiences) that may impact the cognitive assessment process.

Publications

Briceño, E.M., Mehdipanah, R., Gonzales, X., Langa, K.M., Levine, D.A., Garcia, N., Longoria, R., Giordani, B., Heeringa, S. & Morgenstern, L.B. (In press). Neuropsychological assessment of Mild Cognitive Impairment in Latinx adults: A scoping review. Neuropsychology

Briceño, E.M., Mehdipanah, R., Gonzales, X., Heeringa, S., Levine, D.A., Langa, K.M., Garcia, N., Longoria, R. & Morgenstern, L.B.: (In press). Methods and early recruitment of a community-based study of cognitive impairment among Mexican Americans and non-Hispanic whites: The BASIC-Cognitive study. Journal of Alzheimer’s Disease

Ortiz, K., Garcia, M.A., Briceño, E.M., Diminich, E.D., Arévalo, S.P., Vega, I.E., Tarraf, W. (In Press). Glycosylated hemoglobin level and racial/ethnic differences in cognition in midlife and early old age. Research in Human Development.

Garcia, MA, Ortiz, K, Arévalo, SP, Diminich, ED, Briceno, E., Vega, IE, Tarraf, W. (In Press).  Age of Migration and Cognitive Function among Older Latinos in the United States Journal of Alzheimer’s Disease.

Dong, L., Briceño, E.M., Morgenstern, L. & Lisabeth, L. (In Press). Post-stroke cognitive outcomes: sex differences and contributing factors. JAHA: Journal of the American Heart Association.

Levine, D.A., Galecki, A., Okullo, D., Briceño, E.M., Kabeto, M.U., Morgenstern, L.B., Langa, K.M., Giordani, B., Brook, R., Sanchez, B.N. & Lisabeth, L.D. (In Press). Association of blood pressure and cognition after stroke. Journal of Stroke and Cerebrovascular Diseases.

One of our areas of research focus is on cognitive instrument harmonization. We aim to improve precision in harmonization of cognitive data across studies through use of detailed documentation and review procedures to ensure comparability of cognitive data.

Presentations

Briceño, E.M. Pre-statistical harmonization of cognitive instruments: The BP-Cog project. Invited oral presentation at the Advanced Psychometrics Methods in Cognitive Aging Research conference, August 2019, Lake Tahoe, CA

Briceño, E.M. & Arce-Renteria, M. (Co-authors with equal contribution). Pre-statistical harmonization of the Harmonized Cognitive Assessment Protocol across the Health and Retirement Study (HRS) and the Mexican Health and Aging Study (MHAS). Invited oral presentation at the 2020 Gateway to Global Aging Data Meeting, August, 2020 (Virtual).