To Predict Dementia, Should We Be Mindful of the Kidneys?

Abstract

Dementia is a growing public health problem, expected to affect more than 8 million Americans by the year 2050 at a cost of more than $100 billion annually (1). Therapies aimed at slowing dementia progression have thus far proved disappointing, prompting a shift in research emphasis from development of dementiamodifying therapies to dementia-prevention strategies. The shift in emphasis to disease prevention has in turn fueled the search for biomarkers that can identify earlier stages of cognitive decline or high-risk individuals.At the same time, a growing body of research points to brain microvascular disease as playing a key role in the development of cognitive decline and dementia. Using newer magnetic resonance imaging (MRI) techniques, the prevalence of microvascular (lacunar) infarcts among community-dwelling adults with no history of stroke is estimated to be approximately 30%. Beyond these subclinical infarcts, white matter hyperintensities, described by some as "incomplete infarcts" related to arteriolosclerosis of penetrating vessels, are also common in asymptomatic individuals. These lesions are present in 20% of adults aged Ն64 and up to 95% of adults aged Ն80 years (2). In numerous studies in clinical and community-based cohorts, the presence of small vessel infarcts or white matter hyperintensities doubled the risk for dementia (2).The vascular beds of the brain and kidney have similar hemodynamic properties as high-flow, lowresistance end organs with tightly autoregulated perfusion, so it seems logical that microvascular disease in the kidney and brain might travel together. The relations among estimated GFR (eGFR), a biomarker of kidney filtration function, albuminuria, a biomarker of glomerular permeability, and macrovascular events has now been well described. Albuminuria and eGFR each correlate with microvascular lesions in the brain (3,4), independent of traditional vascular risk factors. How do albuminuria and eGFR relate to microvascular outcomes such as cognitive impairment?The study by Joosten et al. (5) in this issue of CJASN addresses this question. Using data from the Prevention of Renal and Vascular End-stage Disease (PRE-VEND) study, a community-based cohort study in the Netherlands, Joosten et al. evaluated the association between baseline and longitudinal measurements of albuminuria and eGFR with cognitive function in 4095 participants with a mean age of 55 years. Albuminuria was measured using the average of two 24-hour urine collections, and GFR was estimated using the Modification of Diet in Renal Disease (MDRD) equation at baseline and 6 years later. Cognitive function was measured at the follow-up assessment using a single cognitive test. Higher levels of albuminuria at baseline and worsening albuminuria over time were associated with poorer cognitive function, independent of measured demographic and vascular risk factors. The association varied by age, such that it was present in younger individuals (35 to 48 years) but not in older individuals. Among younger individuals, th...

Relationship Between Longitudinal Measures of Renal Function and Onset of Dementia in a Community Cohort of Older Adults

“…Similar relationships have been described for urinary albumin excretion, with several studies demonstrating greater loss of cognitive function in individuals with higher levels of albuminuria, even after accounting for baseline level of kidney function . Collectively, the results of these studies suggest that measures of kidney disease severity are associated with an increased risk of cognitive impairment …”

Kidney Disease and Cognitive Function: African American-Diabetes Heart Study MIND

“…[24,25] The present analyses contain results of the most extensive cognitive battery employed in the understudied AA population with T2D and kidney disease to date. Greater albuminuria was associated with statistically significant worse performance on measures of global cognitive function (3MSE and MoCA), as well as speed of processing and executive function measured by DSC, Stroop 3 time, Stroop 3 errors and Stroop interference.…”

“…Kurella Tamura and colleagues reported CRIC baseline cognitive function based on the 3MSE; 3MSE scores >1 standard deviation below the mean defined cognitive impairment. [24] Among 3,591 CRIC participants with mean MDRD eGFR 43.4±13.5 ml/min/1.73m 2 , 13% had cognitive impairment. After multivariate adjustment, participants with eGFR <30 ml/min/1.73m 2 had a 47% higher odds of cognitive impairment than did those with an eGFR 45–59 ml/min/1.73m 2 ; however, anemia was felt to be an important contributor.…”

Cerebral hemodynamics in peritoneal dialysis versus intermittent hemodialysis: A transcranial Doppler pilot study

“…Hypoperfusion and hyperperfusion is common during iHD. 2,9,12 –14 Repeated impaired cerebral perfusion creates vascular damage, leading to changes in cerebral structure and blood flow. 2,3,9,14,15…”

“…2,9,[12][13][14] Repeated impaired cerebral perfusion creates vascular damage, leading to changes in cerebral structure and blood flow. 2,3,9,14,15 TCD ultrasonography uses cerebral hemodynamics as a surrogate for cerebral perfusion (MFV for blood flow velocity; PI for distal vessel resistance to flow). 8 Prior TCD studies focused on declines in MCA MFV during iHD.…”