The Role of Dialysis in the Pathogenesis and Treatment of Dementia

Dearbhla M. Kelly

Disclosures

Nephrol Dial Transplant. 2019;34(7):1080-1083. 

In This Article

Dialysis-induced Brain Injury

HD is associated with significant circulatory stress that can produce recurrent acute ischaemic brain insults. These longitudinal effects of HD on the white matter microstructure were eloquently demonstrated in one study with diffusion tensor magnetic resonance imaging (DTI) at baseline and follow-up on 38 incident dialysis patients.[16] Patients were randomized to dialyse with a dialysate temperature of either 37°C or 0.5°C below the core body temperature and followed-up for 1 year. On follow-up DTI, HD patients displayed increased fractional anisotropy and reduced radial diffusivity consistent with established white matter (ischaemic) damage. In the group exposed to a cooler dialysate, there were no changes in brain white matter associated with haemodynamic instability. Improving the haemodynamic tolerance may therefore preserve the white matter microstructure, though whether this would also abrogate the deleterious effects of dialysis on cognition is unclear.

Retention of uraemic metabolites is another proposed mechanism for cognitive impairment in patients with ESKD. Metabolic profiling using liquid chromatography/mass spectrometry was performed in 321 maintenance HD patients, and executive function was assessed with the Trail Making Test Part B and the Digit Symbol Substitution test.[17] Four metabolites–4-hydroxyphenylacetate, phenylacetylglutamine, hippurate and prolylhydroxyproline–were associated with impaired executive function.

Dialysis is a state of chronic inflammation resulting from exogenous factors such as HD membranes and central venous catheters, cellular factors such as oxidative stress, tissue factors such as hypoxia, salt and fluid overload, microbial factors such as immune dysfunction, and from the retention of uraemic toxins.[18] There is increasing recognition that the 'amyloid-cascade hypothesis' cannot fully explain the neuronal damage in AD, and that neuroinflammation plays an important role in the pathogenesis of AD and other neurodegenerative diseases.[19] Since dialysis induces oxidative stress and chronic inflammation, it could be hypothesized that the pro-inflammatory effects of dialysis could also have a negative effect on brain amyloid deposition.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....