# Integrative Pathways to Cognitive, Affective, and Brain Health

> **NIH NIH U01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $3,708,132

## Abstract

ABSTRACT
MIDUS has unprecedented opportunities to advance knowledge of risk and protective factors for cognitive
decline as well as for Alzheimer’s Disease (AD) and Related Dementias (ADRD). Such potential stems from its
comprehensive assessments from two national samples (Core, Refresher) of behavioral, social, psychological,
and biological assessments from prior decades in the participants’ lives. Identifying markers of risk before
disease symptomatology is foremost to AD/ADRD prevention science. Key aims are to: (1) Conduct additional
waves of cognitive assessments on both national samples and obtain new measures focused on cognitive
impairment. The Brief Test of Adult Cognition will be re-administered to ~ 4,000 adults (Core n = 2,062; Refresher
n = 1,935), ages 25 to 95 at the last wave with key neuropsychological assessments of memory, speed, fluency,
reasoning, and executive functioning. Global cognitive status will be assessed with the Telephone Interview for
Cognitive Status and self-reported symptoms. (2) Conduct additional waves of emotion-related functional
neuroimaging and psychophysiological assessments on Core and Refresher Neuroscience subsamples and
obtain comprehensive measures of brain aging. Multimodal neuroimaging and psychophysiological data will be
collected on ~ 450 adults (Core n = 215 longitudinal + 60 new; Refresher n = 115 longitudinal + 60 new).
Longitudinal analyses will examine changes in affective chronometry of emotional processes, computed brain
age, atrophy, white matter structural integrity and hyperintensities, microstructural complexity of dendrites and
axons, and network connectivity and modularity. (3) Quantify AD and neurovascular disease burden and collect
new ADRD-related plasma and neuropsychological measures and clinical assessments in the Biomarker
subsamples. Conduct advanced molecular amyloid PET to identify individuals exhibiting amyloid accumulation
indicative of AD neuropathic change, and neurovascular MRI to identify vascular diseases including vessel
stiffness and oligemic tissue perfusion. Cross-validate plasma markers of amyloid beta (42/40) against amyloid
imaging in participants who have both, and in conjunction with the MIDUS U19 collect aβ42/aβ40, p-tau181,
ptau217, total tau, and neurofilament light (NFL) on the full biomarker samples (~ 1280 participants; Core n = 630;
Refresher n = 647), thereby extending the reach of MIDUS to include ADRD biomarkers. In conjunction with the
U19 application, these new measures will be used to test hypotheses regarding cognitive decline and the
precursors of AD/ADRD and neurovascular disease via cumulative stress over 30 years and consider
socioeconomic and race disparities and resilience. The protective influence of biopsychosocial
resources, affective style, and lifestyle factors assessed over multiple prior waves of MIDUS will be examined
in relation to early indicators to gain a better understanding of the relations of these factors to cognitive
imp...

## Key facts

- **NIH application ID:** 10558956
- **Project number:** 1U01AG077928-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Sterling C Johnson
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $3,708,132
- **Award type:** 1
- **Project period:** 2022-09-30 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10558956

## Citation

> US National Institutes of Health, RePORTER application 10558956, Integrative Pathways to Cognitive, Affective, and Brain Health (1U01AG077928-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10558956. Licensed CC0.

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