Dementia risk in renal dysfunction: A systematic review and meta-analysis of prospective studies

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 = 0.015), whereas eGFR <60 mL/min/1.73 m² showed no significant association (OR 1.28, 95% CI 0.99-1.65, p = 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.

Figure 1. Flow diagram

Figure 2. Forest plot of population-based prospective studies assessing the relation between estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² and cognitive impairment or dementia (fully adjusted estimates)

CI = confidence interval; OR = odds ratio.

Figure 3. Forest plot of population-based prospective studies assessing the relation between albuminuria and cognitive impairment or dementia (fully adjusted estimates)

CI = confidence interval; OR = odds ratio.