Study To Analyze Memory/Thinking Problems In Older Adults After Surgery

Cognitive impairment after major cardiac or non-cardiac surgery occurs in a high rate for
older adults. The results of previous studies indicate that certain neuro-imaging markers can
determine which individuals pose a greater risk for memory and thinking changes after
surgery. Based on a pilot study, there is evidence that pre-surgical neuroimaging biomarkers
associate with memory and executive decline after a well controlled surgical procedure (total
knee antroplasty). In this study, researchers will use brain imaging studies to determine
which patients are most likely to be affected by cognitive changes after this type of
surgery. The use of Magnetic Resonance Imaging (MRI) will help investigators identify brain
biomarkers that are associated with cognitive problems, such as white matter abnormalities
and changes to small blood vessels. Patients undergoing total knee replacement surgery, as
well as a group of non-surgery participants of similar age, education and health status,will
receive cognitive testing and MRI brain scans before and after surgery/non-surgery.
Researchers will compare and monitor both groups up to one year after surgery/non-surgery.

Prior to enrollment, participants will be asked to review the informed consent and provide
written consent to participate in the study. The enrollment phase will involve in-person
baseline assessment of cognitive functioning within two weeks of the scheduled
surgery/non-surgery in order to rule out exclusion criteria. Testing will be in cooperation
with the University of Florida General Clinical Research Center. Post-baseline MRI will be
conducted on all participants (surgery/control) within 48 hours of the surgery/pseudo-surgery
date to identify acute stroke differences from baseline. Cognitive assessments will be
conducted for each participant at three-weeks, three-months, and one-year after surgery.

The research is highly significant because it will be the first study to use in-vivo
diffusion imaging methods to examine the contribution of specific presurgical neuroanatomical
vulnerabilities on executive and memory cognitive decline after one of the most common
orthopedic surgeries sought by older adults. Additionally, it will be the first study to
examine how specific neuroimaging biomarkers interact negatively with specific peri-operative
variables including emboli number during surgery, embolic changes to the brain, anesthesia
depth, and cerebral oxygenation.

The findings of the study will improve pre-surgery screening procedures for older adults and
assist with the development of peri-operative interventions that will prevent
neurodegenerative disease acceleration.

Inclusion Criteria:

- Planned total unilateral knee antroplasty or non-surgical knee osteoarthritis

- Age 60 years or older at the time of baseline assessment

- Telephone screening and in-person baseline cognitive testing not supportive of
dementia

- Handedness: Right handed; restriction to left-right hemisphere laterality and white
matter pathways

- Participant and family deny presence of difficulties with Instrumental Activities of
Daily Living (IADL)

- All ethnic and racial groups will be recruited

Exclusion Criteria:

- Underlying medical diseases likely to limit lifespan or confound outcome analyses:

1. cancer requiring treatment in past five years

2. serious infectious diseases

3. congestive heart failure

4. chronic hepatitis

5. history of organ transplantation

6. seizure disorders

7. history of head trauma resulting in intensive care

8. current diagnosis of alcoholism, drug dependence, history of major tranquilizer
use

- Neurodegenerative Exclusions:

1. history of major stroke

2. exposure to toxins or neuroleptics

3. history of encephalitis

4. neurological signs of upper motor neuron disease, cerebellar involvement,
supranuclear palsy, or significant orthostatic hypertension

5. signs of dementia.

- Psychiatric Exclusions:

1. major psychiatric disorder

2. major depression

- Conditions or behaviors likely to affect imaging or cognitive testing:

1. claustrophobia

2. non-medical bodily metal, pace-maker device

3. less than five years of formal education

4. inability to read or write

5. self-reported hearing difficulty that interferes with standardized test
administration