“Visuospatial and executive impairments in patients with acute and chronic kidney disease” - Dr. Gord Boyd
James King, MSc Candidate (TMED)
Last week’s Medical Grand Rounds welcomed Dr. Gord Boyd, an associate professor in the Department of Medicine and clinician-scientist practicing neurology and critical care medicine. Dr. Boyd presented on the connection between visuospatial and executive impairments to chronic and acute kidney disease (CKD and AKD, respectively). Afterwards, he sat down with the students of TMED801 to discuss how his research can benefit patients, the press’ representation of similar topics, and his career path.
Rounds initially focused on the high prevalence of cognitive impairments (CIs) in patients with CKD (1). Dr. Boyd explained that most CI tests conducted on CKD patients relied on dementia screening tools, including the Mini-Mental State Examination (MMSE), where pre-dialysis and hemodialysis (HD) patients score significantly worse than non-CKD controls (1). However, Dr. Boyd outlined a need to more accurately quantify rates of CKD-associated CI.
Dr. Boyd’s research group employed the Kinarm robot, a device that objectively and quantitatively assesses cognitive function, with the goal of identifying patients with CIs that may be missed by traditional examinations. The Kinarm characterized more CKD patients as having CIs (especially in areas of perceptual-motor function, executive function, and complex attention) compared to a traditional clinical measure of various aspects of cognition (2). Dr. Boyd also convincingly showed that neurological consequences of AKD exist. In a small cohort study of mostly AKD patients, the Kinarm identified 48%, 50%, and 52% of AKD patients with visuomotor, attention, and executive function deficits, respectively (3).
Dr. Boyd also discussed several examples of translational research that help to elucidate mechanisms underlying CKD-associated CI. Microhemorrhages were 2.0-2.5 times higher in a mouse model of CKD compared to healthy mice, and the CKD mice showed evidence of increased blood-brain barrier permeability (4). There is also evidence that white matter dysfunction and ventricular enlargement may mediate CKD-associated CIs (5). Furthermore, autopsies of CKD patients showed increased ischemic infarcts (blocked arteries that supply blood to the brain), and this was associated with both large artery atherosclerosis and arteriosclerosis, further pointing to CKD-associated CI as a cerebrovascular (blood vessel and blood flow in the brain)-mediated phenomenon (6).
Dr. Boyd also showed several pieces of evidence demonstrating that CKD patients on dialysis experience various worsening CI symptoms. CKD patients that transitioned to HD (from no dialysis) experienced a significant decline in executive function, but no significant change in memory or global cognition (7). HD results in changes to blood flow and function of blood vessels, including intradialytic hypotension (8). Increased HD sessions with intradialytic hypotension were associated with reduced white matter and hippocampal volume, and these patients had lower MMSE scores (8). Patients on HD also performed worse on a test of cerebrovascular function compared to those CKD patients not undergoing HD, which points to a mechanism involving recurrent HD-induced ischemia (decreased blood flow) (9). This work showed that CKD patient’s cerebral blood vessels may have trouble dilating in states of low blood pressure, which can lead to brain damage. One new development that Dr. Boyd believes could lead to improvements in patient care is the use of cooler dialysate during HD which may increase the stability of blood flow and reduce HD-induced ischemia (10). His future research will investigate cerebral oxygenation in patients undergoing HD and attempt to correlate this with long-term cognitive function and brain pathology (11).
In the conversation following Rounds, Dr. Boyd’s long and arduous path to becoming a clinician-scientist stood out. Specifically, Dr. Boyd emphasized his background in neurology and critical care as an asset to his career success and of great benefit to his patients. He also provided excellent insight into daily life as a clinician-scientist.
There are several ways that last week’s Rounds apply to the practice of translational medicine and to patient care. Dr. Boyd’s observation of a problem in the clinical setting (underdiagnosing cognitive dysfunction in CKD patients) and subsequent employment of human research to fill this gap, is an excellent example of applying principles of translational medicine that could ultimately lead to improved diagnostics and patient care. Additionally, he emphasized the importance of operationalization and providing objective measurements in the research process. The discussion of mechanisms outlined the importance of biomedical research to the practice of translational medicine, as well. Moreover, the discussion of the perils of HD demonstrated that various translational approaches exist to assessing the same issue, a perspective that can be applied to the study of other diseases.
On behalf of the TMED801 class, I would like to thank Dr. Boyd for his excellent presentation and discussion.
- Vanderlinden, J. A., Ross-White, A., Holden, R., Shamseddin, M. K., Day, A., and Boyd, J. G. (2019). Quantifying cognitive dysfunction across the spectrum of end-stage kidney disease: a systematic review and analysis. Nephrol 24: 5-16.
- Vanderlinden, J. A., Holden, R. M., Scott, S. H., and Boyd, J. G. (2021). Robotic technology quantifies novel perceptual-motor impairments in patients with chronic kidney disease. J Nephrol 34: 1243-1256.
- Vanderlinden, J. A., Semrau, J. S., Silver, S. A., Holden, R. M., Scott, S. H., and Boyd, J. G. (2021). Acute kidney injury is associated with subtle but quantifiable neurocognitive impairments. Nephrol Dial Transplant: 1-13.
- Lau, W. L., Nunes, A. C. F., Vasilevko, V., Floriolli, D., Lertpanit, L., Savoj, J., Bangash, M., Yao, Z., Shah, K., Naqvi, S., Paganini-Hill, A., Vaziri, N. D., Cribbs, D. H., and Fisher, M. (2020). Chronic kidney disease increases cerebral microbleeds in mouse and man. Trans Str Res 11: 122-134.
- Vemuri, P., Davey, C., Johansen, K. L., Zuk, S. M., Reid, R. I., Thostenson, K. B., Reddy, A. L., Jack, C. R., Knopman, D. S., and Murray, A. M. (2021). Chronic kidney disease associated with worsening white matter disease and ventricular enlargement. J Alzheimers Dis: Pre-press.
- Vinters, H. V., Magaki, S. D., Williams, C. K. (2021). Neuropathological findings in chronic kidney disease (CKD). J Str Cerebrovas Dis 30(9): 105657.
- Tamura, M. K., Vittinghoff, E., Hsu, C. Y., Tam, K., Seliger, S. L., Sozio, S., Fischer, M., Chen, J., Lustigova, E., Strauss, L., Deo, R., Go, A. S., and Yaffe, K. (2017). Loss of executive function after dialysis initiation in adults with chronic kidney disease. Kidney Internat 91: 948-953.
- Cedêno, S., Desco, M., Aleman, Y., Macías, N., Fernández-Pena, A., Vega, A., Abad, S., and López-Gómez, J. M. (2021). Intradialytic hypotension and relationship with cognitive function and brain morphometry. Clin Kidn Jour 14: 1156-1164.
- Slessarev, M., Mahmoud, O., Albakr, R., Dorie, J., Tamasi, T., McIntyre, C. W. (2021). Hemodialysis patients have impaired cerebrovascular reactivity to CO2 compared to chronic kidney disease patients and healthy controls: a pilot study. Clin Res 6(7): 1868-1877.
- Eldehni, M. T., Odudu, A., and McIntyre, C. W. (2015). Randomized clinical trial of dialysate cooling and effects on brain white matter. J Am Soc Nephrol 26: 957-965.
- Jawa, N. A., Holden, R. M., Silver, S. A., Scott, S. H., Day, A. G., Norman, P. A., Kwan, B. Y. M., Maslove, D. M., Muscedere, J. Boyd, J. G. (2021). Identifying neurocognitive outcomes and cerebral oxygenation in criticall ill adults on acute kidney replacement therapy in the intensive care unit: the INCOGNITO-AKI study protocol. BMJ Open 11: e049250.