Cognitive Functioning in Older Adults Nearing End-Stage Renal Disease

In the population of older patients nearing end-stage renal disease (ESRD), the risk for adverse health outcomes and impaired cognitive functioning is higher than among younger patients approaching ESRD. Among older patients receiving maintenance dialysis, the prevalence of impaired cognitive functioning is 30% to 87%. There is a strong association between impaired cognitive function and adverse outcomes in older patients receiving renal replacement therapy (RRT).

There are several possible pathophysiological mechanisms contributing to the high prevalence of impaired cognitive functioning, including vascular, neurodegenerative, and metabolic processes. There are few data available on the systematic assessment of patterns of cognitive functioning and their determinants in older adults approaching ESRD prior to initiation of treatment. Data on the actual brain damage seen on brain magnetic resonance imaging (MRI) are also scarce.

The COPE (Cognitive Decline in Older Patients with ESRD) study was designed to describe patterns of memory, executive function or psychomotor speed and to identify renal, geriatric, and neuroradiologic characteristics associated with cognitive impairment in older patients approaching ESRD who have not yet started RRT. Floor J. van Deudekom, MD, and colleagues in the Netherlands reported results of the COPE study online in BMC Nephrology [doi.org/10.1186/s12882-020-01764-2].

The prospective, multicenter cohort study in five hospitals in the Netherlands included 157 participants ≥65 years of age who were approaching ESRD (estimated glomerular filtration rate ≤20 mL/min/1.73 m2) and were attending the pre-dialysis outpatient clinic between April 2014 and December 2017. As part of a routine pre-dialysis nephron-geriatric work-up the patients underwent a comprehensive geriatric assessment, (CGA) physical examination, laboratory investigation, neuropsychological testing, and a brain MRI scan.

The work-up measured kidney function, metabolic state (urea, phosphate, calcium), and measures of vascular status (blood pressure, ankle/arm index). The Modified Diet in Renal Disease or the Chronic Kidney Disease Epidemiology Collaboration was used to estimate GFR depending on the method used in different hospitals. The CGA included measures of nutrition, frailty, functional independence, and physical capacity (handgrip strength and 6-m gait speed).

Of the 157 study participants, median age was 75 years and 66% (n=103) were men. At enrollment, mean eGFR was 16.2 mL/min/1.73 m2 and the mean decline over the previous 3 years was 9.1 mL/min/1.73 m2. In 66% of the participants (n=99) the cause of primary kidney disease was vascular (hypertension or diabetes mellitus). Nearly half (47%, n=74) had a history of vascular disease. Using the Fried Frailty Index, 25% (n=37) were frail. Measured by the Instrumental Activities of Daily Living scale, eight participants (5%) had functional dependence (score of ≥11).

The cohort had a median Mini-Mental State Examination score of 28 of 30 points. Mean functioning on the memory test was in the 24th percentile; mean functioning on the executive function was in the 18th percentile; and mean functioning on psychomotor speed was in the 20th percentile.

In three cognitive functions of interest (memory, executive function, and psychomotor speed), there were significant associations between older age and lower educational level and cognitive impairment. Patients who performed in the lowest tertile of memory function, compared with those who performed in the highest tertile, were on average 5 years older and more often had a lower level of education.

Following adjustment for age, sex, and educational level, there was a significant association between a higher level of functional dependence and a more impaired memory function. Patients who performed in the lowest tertile of memory function were more functionally dependent compared with those who performed in the highest tertile. There was an association between a history of vascular disease and more impaired memory function; following adjustment for age, sex, and educational level, that association was no longer statistically significant. There were no associations between parameters of metabolic disturbance and impaired memory function.

Following adjustment for age, sex, and educational level, there were significant associations between higher level of functional dependence, presence of frailty, and a lower handgrip strength and a more impaired executive functioning. In the tertile with the worst executive function, the presence of frailty was higher compared with the tertile with the best executive function. There was an association between a history of vascular disease and more impaired executive function; following adjustment for age, sex, and educational level, that association was no longer statistically significant. There were no associations between parameters of metabolic disturbance and impaired executive function.

There were significant associations between a higher presence of frailty, a higher level of functional dependence, and a lower handgrip strength with impaired performance on psychomotor speed. Patients who performed in the lowest tertile of psychomotor speed had a lower handgrip strength compared with those in the highest tertile. There was an association between a history of vascular disease and an impaired performance on psychomotor speed. There were no associations between parameters of metabolic disturbance and impaired performance on psychomotor speed.

Patients who did not have a MRI were older, more frail, more functionally dependent, and had a higher history of vascular disease compared with those who did have a MRI. Among those with MRI results, following adjustment for age, sex, and educational level, there was a significant association between a higher burden of white matter hyperintensities and worse psychomotor speed. Patients who performed in the worst tertile of psychomotor speed had, on average, more white matter hyperintensities than those who performed in the best tertile. There was a trend for the association between a higher burden of white matter hyperintensities and lower executive function scores.

Citing limitations to the study findings, the researchers included the possibility of patient selection bias, the relatively small sample size, and the post hoc design of the study.

In conclusion, the researchers said, “Older patients approaching ESRD have a high prevalence of impaired memory, executive function, and psychomotor speed. The patterns of cognitive impairment and brain changes on MRI are suggestive of vascular cognitive impairment. These findings could be of potential added value in the decision-making process concerning patients with ESRD.”

Takeaway Points

  1. The COPE study examined patterns of memory, executive function, and psychomotor speed to identify characteristics associated with cognitive impairment in older patients approaching end-stage renal disease.
  2. The presence of frailty and a lower handgrip strength were significantly associated with a more impaired executive functioning, and there were significant associations between presence of frailty, high level of functional dependence, and lower handgrip strength and impaired performance on psychomotor speed.
  3. There was a significant association between a higher burden of white matter hyperintensities and worse psychomotor speed.