# RISK OF COGNITIVE IMPAIRMENT AND DEMENTIA IN TOTAL JOINT ARTHROPLASTY

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2021 · $655,238

## Abstract

ABSTRACT
Total joint arthroplasty (TJA) is the fastest growing elective surgery in the nation. Over 7 million
Americans are currently living artificial hip or knee joints and this is expected to reach epidemic
proportions as a result of growing demand for improved mobility and quality of life. Although
TJA is a safe and effective procedure, there is growing concern about the long-term safety of
chronic exposure to TJA implants. Indeed, in a growing number of published case reports, TJA
is associated with neurocognitive deficits several years after surgery. Yet, the long-term effects
of implant debris from TJA implants on brain structure and cognitive function are unknown.
Large scale, population-based studies are needed to assess the potential contribution of chronic
exposure to TJA implant debris and subtypes (cobalt/chromium, polyethylene) to the risk of
cognitive decline and dementia. We propose to leverage the unique data resources of the
Rochester Epidemiology Project (REP, R01-AG034676), the Mayo Clinic Study of Aging
(MCSA, U01-AG006786) and the Mayo Alzheimer's Disease Research Center (ADRC; P50
AG016574) as well as the Mayo Clinic TJA registry to elucidate the long-term risk of dementia
and cognitive impairment in TJA patients.
Using 5-decades of historical data from the REP, we will compare the risk of dementia and
subtypes in population-based cohorts of TJA patients and matched non-TJA subjects adjusting
for well-known confounders (age, sex, obesity). We will further examine the risk according to
implant types. Using cross-sectional and longitudinal cognition and neuroimaging measures
collected as part of the MCSA cohort, we will determine whether cognitive status and
neuroimaging markers of cognitive function are worse in TJA patients compared with non-TJA
subjects. Finally, we will correlate metal ion levels with cognitive function and structural
changes on neuroimaging and postmortem tissues.
Successful completion of the proposed series of studies will be a key step towards
understanding whether chronic exposure to TJA implants is associated with cognitive
impairment. Our unique data resources offer a rare opportunity to efficiently address this
unknown risk. Potential downstream effects are significant including eligibility criteria for TJA,
and monitoring high risk TJA implants and patients who are most likely to suffer from systemic
effects. Even negative findings can exert a significant public health impact by providing
reassurance about the safety of TJA to millions of current and future TJA patients.

## Key facts

- **NIH application ID:** 10064124
- **Project number:** 5R01AG060920-03
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Hilal Maradit Kremers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $655,238
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064124

## Citation

> US National Institutes of Health, RePORTER application 10064124, RISK OF COGNITIVE IMPAIRMENT AND DEMENTIA IN TOTAL JOINT ARTHROPLASTY (5R01AG060920-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10064124. Licensed CC0.

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