Table 1.

Supporting evidence for the central role of cerebrovascular disease in cognitive impairment in CKD

Vascular hypothesis

Neurodegenerative hypothesis

Frequently occurring traditional risk factors, including hypertension, smoking, diabetes mellitus and ageing. Positive correlation between haemodynamic and cognitive impairment from TCD studies. Transient ‘cerebral stunning’ in haemodialysis patients associated with accelerated cognitive decline. High burden of subclinical SVD, including silent lacunar infarcts, WML and CMBs. Typical pattern of cognitive impairment with greater deficits in executive function and speed of information processing.

Chronic hypertension, highly prevalent in CKD, is known to lower the pathological threshold at which Alzheimer’s disease features manifest. Chronic cerebral inflammation due to CKD and associated vascular risk factor exposure can increase beta-amyloid production. Higher beta-amyloid levels and impaired clearance in CKD, compounded by SVD and vascular inflammation.

CKD, chronic kidney disease; CMB, cerebral microbleed; SVD, small-vessel disease; TCD, transcranial doppler; WML, white matter lesion.