# Effect of baseline and intercurrent medical factors on 6-year cognitive trajectory: Secondary analysis of the SAGES Study

> **NIH NIH R03** · HEBREW REHABILITATION CENTER FOR AGED · 2022 · $159,757

## Abstract

Responding to PAS-19-391, this proposal will leverage existing data to advance our understanding of
Alzheimer’s disease and related dementias (AD/ADRD) and to nurture the career of a promising early stage
investigator, Dr. Tammy Hshieh. This proposal will use data drawn from a clinically rich cohort, the Successful
Aging after Elective Surgery (SAGES), involving 560 older adults (age 70+) without clinical dementia evaluated
prior to major elective surgery and followed for 6 years with repeated neuropsychological testing. We plan to
explore a priority area in the PA: ‘to advance our understanding of how cognitive function may change from
normal to pathological cognitive aging’, which we here define broadly as including both AD- and ADRD-related
processes. SAGES has collected data on intercurrent illnesses, hospitalizations, surgeries, and major
treatments (e.g., chemotherapy, hemodialysis) for up to 6 years. We propose to evaluate the effects of these
intercurrent factors on cognitive trajectory, along with the moderating effects of delirium and/or ApoE-E4 status,
which may serve as markers of brain vulnerability.
 Our specific aims are: (1) To evaluate the effect of intercurrent medical factors on cognitive trajectory for up
to 6 years: We will examine factors first singly then cumulatively with the hypothesis that certain factors will
have greater decrements considered singly and that a higher number of factors will result in a steeper slope of
decline over time, achieving rates of decline comparable to MCI or early AD/ADRD. (2) To examine the effect
of abnormal baseline laboratory results and inflammatory biomarkers (e.g., C-reactive protein, interleukin-6) on
cognitive trajectory: We hypothesize that a higher number of abnormal laboratory values and/or biomarkers will
have a highest rate of cognitive decline, achieving rates of decline comparable to MCI or early AD/ADRD. (3)
To elucidate whether development of delirium and/or genetic risk (ApoE-E4 status) moderates the association
of major intercurrent factors or abnormal laboratory- or bio- markers, either singly or cumulatively, on cognitive
trajectory. Our analyses will utilize an innovative longitudinal data analysis approach with time-varying
predictors to generate a weighting algorithm for a dynamic index (an index that can change within a person
over time), representing the cumulative effect of potential cognitive insults. We have demonstrated adequate
statistical power to achieve our aims. Success of the proposed work is further assured by a highly skilled
interdisciplinary team who have been close collaborators for over 10 years, and who will mentor Dr. Hshieh.
 This project will help to identify intercurrent factors or abnormal laboratory- or bio- markers that may lead to
cognitive decline, particularly in those individuals with more vulnerable brains, as signaled by ApoE-E4 or by
development of delirium. Understanding these factors will help us to identify potential pathways which m...

## Key facts

- **NIH application ID:** 10350415
- **Project number:** 1R03AG075434-01
- **Recipient organization:** HEBREW REHABILITATION CENTER FOR AGED
- **Principal Investigator:** Tammy T Hshieh
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $159,757
- **Award type:** 1
- **Project period:** 2022-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350415

## Citation

> US National Institutes of Health, RePORTER application 10350415, Effect of baseline and intercurrent medical factors on 6-year cognitive trajectory: Secondary analysis of the SAGES Study (1R03AG075434-01). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/10350415. Licensed CC0.

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