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ABSTRACT Background and hypothesis It remains unclear whether the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD), and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring Cohort participants. Methods We included Framingham Offspring participants free of dementia, attending an examination during midlife (exam cycle 6, baseline) for ascertainment of kidney function status, with brain magnetic resonance imaging late in life (exam cycles 7–9), cognitive outcome data, and available interim hypertension and BP assessments. We related CKD (estimated glomerular filtration rate 60 ml/min/1.73 m2) and albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) to CSVD markers and cognitive outcomes using multivariable regression analyses. Results Among 2604 participants (mean age 67.4 ± 9.2, 64% women, 7% had CKD, and 9% albuminuria), albuminuria was independently associated with covert infarcts adjusted OR, 1.55 (1.00–2.38); P = 0.049 and incident MCI and dementia adjusted hazard ratio (HR), 1.68 (1.18–2.41); P = 0.005 and 1.71, (1.11–2.64); P = 0.015, respectively. CKD was not associated with CSVD markers but was associated with a higher risk of incident dementia HR, 1.53 (1.02–2.29); P = 0.041. While albuminuria was predictive of the Alzheimer's disease subtype adjusted HR = 1.68, (1.03–2.74); P = 0.04), CKD was predictive of vascular dementia [adjusted HR, 2.78 (1.16–6.68); P = 0.023. Conclusions Kidney disease was associated with CSVD and cognitive disorders in asymptomatic community dwelling participants. The relation was independent of premorbid BP, suggesting that the link between kidney and brain disease may involve additional mechanisms beyond BP-related injury.
Kelly et al. (Mon,) studied this question.