# Contribution of child development, biological aging, and beta-amyloid to cognitive function of the Louisville twins at midlife

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $996,398

## Abstract

Project Summary/Abstract
The proposed study will test whether accelerated biological aging at midlife predicts higher levels of preclinical
AD biomarkers, as measured with a highly reliable plasma beta-amyloid (Aβ) marker, and whether the Aβ
accumulation contributes to cognitive decline in midlife. The causal basis of the associations will be established
by studying 750 individual twins age 40-64 from the Louisville Twin Study (LTS), who were studied extensively
in childhood. We will relocate and recruit the twins, conduct in person cognitive functioning and physical
assessments, collect 50cc of blood to quantify biological age, plasma-Aβ, and genotype. Our ability to recruit
twins to the new phase of study is demonstrated by our 2018 Midlife Pilot Study, in which we collected cognitive
ability, physical measurements, and blood to construct a biological aging measure for 40 participants, with a
consent rate of 100%. Preliminary results suggest that accelerated biological age is a better predictor of episodic
memory than global functioning, consistent with prior research. The LTS is the only twin study capable of linking
biological aging, Aβ accumulation, and cognitive functioning at midlife to cognitive functioning in childhood, as
other comparable longitudinal twin study samples are currently too young. Our study will address two research
questions that can only be answered by longitudinal twin studies with intensive childhood measurements: 1) Do
people with genetic and environmental predispositions for accelerated biological aging have greater Aβ
accumulation and perform worse cognitively in midlife?; and 2) Do early life developmental characteristics cause
accelerated biological aging, Aβ, and midlife cognitive functioning? We will complete the following specific aims:
Quantify several markers of biological aging to test whether accelerated biological aging predicts Aβ
accumulation and lower cognitive functioning at midlife by collecting biological, cognitive, memory, and functional
ability data from LTS twins age 40-64 (Aim 1); Determine whether Aβ accumulation mediates effects of
accelerated biological aging on declining cognitive functioning, adjusting for confounding genetic and
environmental factors (Aim 2); Evaluate effects of early life characteristics on accelerated biological aging, Aβ
accumulation, and cognitive functioning in midlife, adjusting for confounding genetic and environmental factors
(Aim 3). The significance of the proposed research is specifying causal effects of biological aging in midlife on
Aβ accumulation and cognitive functioning, using blood-based aging measures to predict Aβ accumulation, and
specifying causal effects of early life developmental mechanisms on accelerated biological aging, Aβ
accumulation, and cognitive functioning at midlife. The innovation of the proposed work is the application of a
longitudinal twin design, affording us the capability to establish causal effects of biological aging on preclinic...

## Key facts

- **NIH application ID:** 10409686
- **Project number:** 5R01AG063949-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Christopher Ryan Beam
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $996,398
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409686

## Citation

> US National Institutes of Health, RePORTER application 10409686, Contribution of child development, biological aging, and beta-amyloid to cognitive function of the Louisville twins at midlife (5R01AG063949-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10409686. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*