Dementia risk in renal dysfunction

Abstract

Objective: Renal dysfunction has been linked with increased risk for cognitive impairment and dementia, but studies are conflicting. For that reason, the aim of the present systematic review and meta-analysis is to summarize the best available evidence on the prospective association between potential markers of renal dysfunction and development of cognitive impairment or dementia.Methods: Medline, Embase, and Cochrane Database of Systematic Reviews were searched for potential publications until August 1, 2016. Studies were eligible if they fulfilled the following criteria: population-based study, prospective design, $100 participants, aged $45 years, $1 year follow-up, and cognition/dementia outcomes. Where appropriate, random effects meta-analyses were conducted yielding pooled odds ratios (OR) and 95% confidence intervals (CI).Results: Twenty-two out of 8,494 abstracts fulfilled the eligibility criteria. Sufficient evidence was found for albuminuria, mixed results for estimated glomerular filtration rate (eGFR), insufficient support for cystatin C, and tentative evidence for serum creatinine and creatinine clearance. Meta-analyses of 5 studies representing 27,805 persons showed a 35% increased risk of cognitive impairment or dementia in those with albuminuria (OR 1.35, 95% CI 1.06-1.73, p 5 0.015), whereas eGFR ,60 mL/min/1.73 m 2 showed no significant association (OR 1.28, 95% CI 0.99-1.65, p 5 0.063). No meta-analyses could be done for serum creatinine, creatinine clearance, or cystatin C. Conclusions:The overall evidence for an association between renal dysfunction and cognitive impairment or dementia is modest. Evidence suggests that albuminuria is associated with higher odds of developing cognitive impairment or dementia. Renal dysfunction has been considered a candidate risk factor for cognitive impairment and dementia.1-3 The kidneys and the brain, both being end organs, are susceptible to vascular damage due to broadly similar anatomic and hemodynamic features. 4 Chronic kidney disease (CKD) and dementia share a similar risk factor profile including hypertension, diabetes mellitus, or hyperlipidemia, and in both conditions a high prevalence of small vessel disease, silent brain infarcts, white matter pathology, and microbleeds was reported.2,3,5-8 Hence, several pathways may underlie the association between CKD and cognitive impairment, including shared vascular factors or a direct neurotoxic effect of uremia. 2,9 Worldwide, the number of people with dementia has increased.

Hypertensive organ damage predicts future cognitive performance: A 9‐year follow‐up study in patients with hypertension

“…We could not show an association between renal damage (determined by either eGFR or UAE) and cognitive performance. This is contradicting with the results of previous studies,10, 11 which might be caused by the small sample size of our study.…”

“…These imaging markers of cSVD are strongly associated with cognitive function 3, 4, 5, 6. Other types of hypertensive organ damage, such as cardiac and renal damages, have also been linked to lower cognitive function or increased risk of cognitive impairment 7, 8, 9, 10, 11…”

Diet‐Related Metabolites Associated with Cognitive Decline Revealed by Untargeted Metabolomics in a Prospective Cohort

“…The findings regarding glucose and creatinine are in accordance with previous literature, with a strong relation between diabetes and a greater risk of dementia. With respect to arginine, a few untargeted metabolomics studies reported an increased serum concentration in cognitively impaired older persons and a lower plasma arginine was one of the most significant metabolic differences in older adults with superior memory performance compared to subjects with normal performance or cognitive disorders .…”

Urine dicarboxylic acids change in pre-symptomatic Alzheimer’s disease and reflect loss of energy capacity and hippocampal volume

“…To account for kidney function and hydration levels [41][42][43], we analyzed the urine concentration of total protein, creatinine, albumin, and the urinary albumin to creatinine ratio (UACR). Individuals with AD showed evidence of kidney function impairment through higher mean concentrations of total protein, albumin, and UACR compared to controls (Table 1), consistent with the higher level of albuminuria recognized with cognitive decline [44][45][46].…”

“…Distinguishing AD from physiological variations in urine lipids is a challenge, since variation in urine composition can arise from many factors, in particular diet, hydration, time of collection, and kidney disease, for which a number of correction approaches have been used [52]. Further, microalbuminuria is known to occur with cognitive decline [44][45][46]. We chose to collect "spot" urine samples rather than the 24-hour collections that average changes throughout the day, because we intend that any future test in clinical practice must implement a simple collection process.…”