LAUSR

Older patients with advanced chronic kidney disease (CKD) often suffer from various comorbidities, including impaired cognitive (executive) functioning, depressive symptoms and apathy. It is thought that these comorbidities in CKD may have a shared underlying vascular pathophysiology, but the exact association with cerebrovascular changes remains unclear. This study therefore investigates whether cerebrovascular changes on MRI are associated with cognitive functioning, depressive symptoms and apathy in older patients with advanced CKD. Patients aged ≥65 years with eGFR <20ml/min/1.73 m2 not on dialysis from the Cognitive Decline in Older Patients with ESRD (COPE) study were included. Cerebrovascular changes were assessed on 3T MRI scans, including markers of cerebral large vessel disease (cortical infarcts) and cerebral small vessel disease (lobar and non-lobar microbleeds, subcortical infarcts, white matter hyperintensity volume and global cerebral blood flow). Global cognitive functioning was assessed with the Mini-Mental State Examination (MMSE), the cognitive domain executive functioning using the Trail Making Test (TMT), part B adjusted for A and Stroop card III, and the domain psychomotor speed using the Letter Digit Substitution Test (LDST, correct answers after 60 seconds), TMT-A and Stroop card II. Z-scores were calculated for each cognitive test, composite mean Z-scores were calculated for executive functioning and psychomotor speed. The number of depressive symptoms and presence of apathy were assessed using the GDS-15 and its GDS-3A subscale (≥2 symptoms being indicative of apathy). Cross-sectional associations between cerebrovascular changes and outcomes were assessed using linear and logistic regression analyses, adjusted for age, sex and educational level. 87 patients with advanced CKD were included (mean age 75.4 ± 6.9 years; mean eGFR 15.9 ± 3.8 mL/min/1.73 m2). The presence of cortical infarcts was significantly associated with lower global cognitive functioning (β -1.00, 95% CI -1.60–0.40, p-value 0.001) and lower psychomotor speed (β -0.67, 95% CI −1.19 –0.14, p-value 0.01). White matter hyperintensity volume was significantly associated with lower executive functioning (β -0.03, 95% CI −0.05 to −0.009, p-value 0.003). No significant associations were found between the remaining cerebral small vessel disease markers (microbleeds, subcortical infarcts, global cerebral blood flow) and cognitive functioning (global and executive), nor between any cerebrovascular changes and depressive symptoms or apathy, including both large and small vessel disease markers. In older patients with advanced CKD, markers of cerebral small vessels disease versus markers of cerebral large vessels disease showed different significant associations with various cognitive functioning domains. These results support an underlying vascular pathophysiology of cognitive impairment in older patients with advanced CKD. In contrast, no were found between cerebrovascular changes (both large and small vessel disease markers) and depressive symptoms and apathy, which might indicate that non-vascular related factors (e.g. uremic or inflammatory factors) may play a role in the occurrence of these comorbidities.