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 implant debris 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 adjustingfor 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
The reason for
the admin supplement is the following: We recognized the need to use more sensitive methods for
measuring metal levels on tissues. Therefore, instead of formalin-fixed paraffin-embedded tissues, we
will use frozen brain tissues. In year 4, we incurred substantial additional costs and developed and
validated new laboratory methods to measure metal levels in brain tissue at ‘ultra-trace’ levels.
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. 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 systemiceffects. 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.