The link between age-related kidney dysfunction and cognitive impairment is an interesting one, particularly in the context of research into klotho, which has functions in both the kidney and the brain, and has been shown to extend life and improve cognitive function in animal studies. It isn't completely clear as to which of these areas of the body is most important to the noted benefits to cognitive function in animal models, produced via various strategies for klotho overexpression. The most recent research on this topic tends to suggest that the mechanisms are indirect, involving many organ systems, rather than being a direct effect in the brain. Klotho in the brain might not be as important as initially thought.
The link between brain dysfunction and chronic kidney disease (CKD) was first noted in 1930, so it is not a new finding. Experts spoke of "dialysis dementia" or "uremic encephalopathy". What is new, however, is the finding that mild cognitive impairment (MCI) may already be present in earlier stages of CKD, affecting approximately one in two CKD patients (prevalence varies in studies between 30% and 60%). In contrast to "normal" dementia, CKD-related MCI is not age-related, meaning the cognitive impairment exceeds that expected of the normal aging process. It usually worsens with declining glomerular filtration rate (GFR) of patients - the lower the GFR, the higher the risk of being affected by cognitive impairments.
The pathogenesis appears complex, involving a variety of factors besides vascular disease - the most frequent trigger for "standard" dementia in elderly people. Dialysis does not help or stop the process of cognitive decline, thus experts believe that factors which are not corrected completely by dialysis, for example the clearance of middle molecules, uncontrolled secondary hyperparathyroidism and anemia, may further the process of cognitive impairment. One interesting finding, though, is that kidney transplantation appears to slow cognitive decline.
The paucity of intervention strategies is the reason why there is no routine screening for MCI in CKD patients. Cognitive decline is one of many manifestations of brain damage that clearly accompany the decline of kidney function. Other manifestations include sleep disorders and depression, both of which are also common in CKD patients. "Chronic kidney disease is an illness that obviously affects the body and the brain. The latter has been neglected by research, but new tools in neuroscience, such as tractography or two-photon microscopy hold out the promise of gaining further insights in the pathogenesis of MCI so that we might identify therapy targets and be able to treat it one day. Until then, we have to be aware that CKD is a severe disease which affects not only the kidneys, but also other organs systems and the brain - even in early stages. This is why we should strengthen CKD prevention strategies and raise awareness for this illness that is much more severe than most people think."