[R01] Past, Present, and Future Risk of Cognitive Decline and Cognitive Impairment in the Louisville Twin Study
Ente: National Institute on Aging
Scadenza: 2031-05-31
Importo max: 2.057.196 EUR
Paese: US
Descrizione
Project Summary/Abstract
The proposed study will use twins from the Louisville Twin Study (LTS), their siblings, and their still-living
parents to clarify early-life, mid-life, and late-life risk factors of cognitive decline and cognitive impairment.
Cohort studies of Alzheimer’s disease and related dementias (ADRD) increasingly have focused on risk and
protective factors at the earliest stages of the lifespan. Few lifespan studies of cognitive decline and
impairment – and certainly none using twins – exist, as many premier studies of cognitive aging (e.g., Health &
Retirement Study, the Dunedin Cohort Study) began data collection no earlier than adolescence. The LTS is
uniquely positioned to fill this research gap because LTS families were followed from the twins’ births through
15 years of age and again in midlife (R01AG063949). Moreover, the twins’ parents were administered cognitive
assessments when the twins were children, and all siblings were assessed according to the same study visit
schedule during childhood and adolescence as the twins. In this competitive renewal, we will expand on our
current study of midlife cognitive and biological functioning in the Louisville twins to include all twins, their
siblings, and their parents (N = 1,750) to better understand lifespan cognitive health risk factors associated
with ADRD. We will study all twins who were eligible to participate in the current project (2019-2026), one
sibling from each family, and the twins’ still-living parents. We also will conduct an MRI substudy to investigate
within-family differences in brain health using a subset of 120 LTS families (600 total individuals), 60 identified
as having elevated risk of ADRD using an a priori set of risk criteria and 60 identified as being at low risk for
ADRD. This sub-study will be a first-of-its-kind family-based MRI study to test whether parents’ cognitive ability,
functional and structural brain activity, blood-based AD biomarkers, and epigenetic age acceleration measures
in midlife correlate with middle-aged twins’ and siblings’ risk of cognitive decline and AD biomarkers. We
propose to address the following aims: Define early-life risk factors of cognitive decline and preclinical
symptoms of ADRD at the individual and family level using twins', siblings, and parents' cognitive, physical, and
psychosocial data collected from birth through age 15 years (Aim 1); Define concurrent midlife risk factors of
cognitive decline and preclinical symptoms of ADRD in middle adulthood using epigenetic, genetic, physical,
and psychological data (Aim 2); Define how parents' cognitive ability, functional and structural brain activity,
epigenetic aging, and AD biomarkers predict their middle-aged children’s cognitive ability, functional and
structural brain activity, epigenetic aging, and AD biomarkers (Aim 3); and Define childhood, concurrent and
prospective risk factors that contribute to brain health in middle adulthood (Aim 4). Study findings will
Istituzione: UNIVERSITY OF SOUTHERN CALIFORNIA
PI: Christopher Ryan Beam, DEBORAH WINDERS DAVIS, ERIC Nathan TURKHEIMER
Progetto: 2R01AG063949-06A1
Settori: National Institute on Aging
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