Among patients with transient ischemic attack (TIA) and stroke, predialysis chronic kidney disease (CKD) does not appear to be independently associated with either pre- or post-stroke dementia, according to study findings published in Neurology.
Patients with CKD have a higher probability for cognitive impairment, with vascular and neurodegenerative mechanisms believed to play a key role. One previous study, using brain imaging, found CKD to be predictive of all-cause dementia independent of both previous symptomatic cerebrovascular disease and small vessel disease, the researchers stated. In an effort to explore whether vascular and neurodegenerative mechanisms are associated with an increased risk for cognitive impairment in individuals with CKD, the researchers sought to investigate this vascular theory by exploring the link between CKD and dementia both prior to and following TIA and stroke.
A prospective, population-based cohort study of transient ischemic attack (TIA) and stroke (Oxford Vascular [OxVasc] Study) was conducted in Oxfordshire, United Kingdom. In OXVASC, pre-event and post-event dementia were determined via direct patient evaluation and follow-up for 5 years, supplemented by review of hospital/primary care records.
Logistic regression was used to examine the relationship between pre-event dementia and CKD, which was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2. Cox and competing risk regression models were utilized to assess the association between post-event dementia and CKD. All analyses accounted to adjustments for sex, age, education, stroke severity, previous stroke, white matter disease, dysphasia, and diabetes.
A total of 2305 participants were recruited for the OxVasc study. Overall, 49% (1133 of 2305) of the patients were male, 30% (688 of 2305) of the participants had experienced a TIA, and 70% (1617 of 2305) of patients had experienced a stroke—with 1482 cases of ischemic stroke and 135 cases of primary intracerebral hemorrhagic (PICH) stroke reported. Median participant age was 76.9 years. Hypertension was the most common risk factor, which was reported in 61% (1405 of 2305) of patients.
The median eGFR was 59.5 mL/min/1.73 m2. Overall, 50.9% (1174 of 2305) of the patients had CKD (eGFR of 30 to 59 mL/min/1.73 m2 in 1040 individuals [45.2%] and eGFR of <30 mL/min/1.73 m2 in 134 individuals [5.8%]). Only 12 patients were dialysis-dependent. The CKD group was older, and had a greater burden of vascular risk factors and comorbidities, including hypertension, diabetes, hyperlipidemia, ischemic heart disease, atrial fibrillation, prior stroke, and peripheral vascular disease, compared with those with normal renal function. Those in the CKD group were also more likely to have moderate to severe white matter disease, to have low baseline cognitive scores, and to be less well educated.
Pre-event dementia was reported in 9.8% (225 of 2305) of patients. Per unadjusted analysis, compared with participants with normal renal function, CKD was strongly associated with pre-event dementia (odds ratio [OR], 2.04; 95% CI, 1.52 to 2.72; P <.001)—particularly in those with an eGFR of <30 mL/min/1.73 m2 (OR, 3.21; 95% CI, 1.96 to 5.26; P <.001). All of these associations became nonsignificant after adjusting for sex, age, and education. Following additional adjustment for other factors linked to pre-event dementia, further reduction in any association with CKD was observed (OR, 0.92; 95% CI, 0.92 to 0.65; P=.65). Exclusion of PICH strokes did not affect the study results.
Additionally, CKD was associated with post-event dementia (hazard ratio [HR], 2.01; 95% CI, 1.65 to 2.72; P <.001). This association decreased, however, following adjustment for covariates (HR, 1.09; 95% CI, 0.85 to 1.39; P =.50). CKD was more strongly associated with late (>1 year) post-event dementia (subdistribution HR [SHR], 2.32; 95% CI, 1.70 to 3.17; P <.001), especially following TIA and minor stroke (SHR, 3.08; 95% CI, 2.05 to 4.64; P <.001), which was not statistically significant following adjustment (SHR, 1.53; 95% CI, 0.90 to 2.60; P =.12).
The study has several limitations, including TIA/stroke and dementia diagnoses were given by a senior vascular neurologist and experienced consultant physician with subspecialty interest in dementia instead of a consensus panel, pre-event dementia was retrospectively diagnosed, and lastly, the relationship between CKD and specific subtypes of dementia were not studied.
The researchers concluded, “In patients with TIA and stroke, CKD was not independently associated with either pre- or post-event dementia, suggesting that renal-specific mechanisms are unlikely to play an important role in etiology.”
Additional studies are warranted, in order to determine whether other unique mechanisms or pathways exist that can lead to late-onset dementia in individuals with CKD who experience minor stroke events.
Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.
Kelly DM, Pendlebury ST, Rothwell PM. Associations of chronic kidney disease with dementia before and after transient ischemic attack and stroke: population-based cohort study. Neurology. Published online January 7, 2022. doi:10.1212/WNL.0000000000013205