Kidney Function and Cognitive Decline in Older Adults: Examining the Role of Neurodegeneration

Abstract

BACKGROUND/OBJECTIVES Cognitive decline associated with impaired kidney function might involve neurodegeneration. Our objectives were to evaluate the longitudinal association between kidney function and cognitive decline in older adults and to assess the involvement of cortical beta‐amyloid and hippocampal atrophy (features of Alzheimer's disease (AD)) in this association. DESIGN Secondary analysis of the randomized controlled Multidomain Alzheimer Preventive Trial (MAPT). SETTINGS Thirteen memory centers (France and Monaco, 2008–2016). PARTICIPANTS A total of 1,334 community‐dwellers >70 years old without dementia at baseline. MEASUREMENTS We estimated glomerular filtration rate (eGFR) from serum creatinine using CKD‐Epi equation. Cognition was assessed at baseline, 6, 12, 24, 36, 48, and 60 months using a composite Z‐score designed for MAPT. The Clinical Dementia Rating (CDR) score was used to assess cognition and functional independence. We examined the association between eGFR and (1) evolution of the composite cognitive Z‐score using mixed‐effect models and (2) progression on CDR using Cox models and mixed‐effect models. Adjustments were made for age, sex, education, ApoE genotype, cardiovascular risk factors and disease, hippocampal volume (measured with magnetic resonance), and cortical beta‐amyloid (measured with positron emission tomography). RESULTS Median (IQR) eGFR was 73(60–84) mL/min/1.73 m2. Two hundred sixty‐nine participants experienced progression on CDR score during follow‐up. eGFR<60 was significantly associated with progression on CDR score (adjusted hazard ratio (aHR) = 1.35, 95% CI 1.01–1.80) and with both the cognitive and functional independence components of CDR, but not with the evolution of the composite cognitive Z‐score (adjusted β‐coefficient −0.004, 95% CI −0.014; 0.006). Associations were not modified after further adjustment for beta‐amyloid (subsample: n = 252) and hippocampal volume (subsample: n = 270). CONCLUSIONS We did not find a mild to moderate renal insufficiency to be associated with brain imaging features of AD, and our results do not support the involvement of AD mechanisms in the incidence of cognitive impairment and functional decline associated with chronic kidney disease.

Kidney Function Is Not Related to Brain Amyloid Burden on PET Imaging in The 90+ Study Cohort

“…In the current study we found no relationship between CKD and brain amyloid-β burden, assessed non-invasively. Similarly, in a French cohort of community-dwellers >70 years old where eGFR was relatively preserved (median eGFR 73 with interquartile range 60-84 ml/min/1.73 m 2 ), CKD was associated with cognitive decline over time but was not associated with imaging features of Alzheimer's disease (cortical amyloid-β and hippocampal atrophy) ( 29 ). A strength of the current study is the use of cystatin C eGFR measurements, which are not modified by diet or muscle mass and thus are more valid than creatinine-based eGFR in elderly individuals ( 9 , 10 ).…”

Performance of dialysis patients on the standard and basic Arabic versions of the Montreal Cognitive Assessments

“…We performed cognitive assessments using the Arabic version of the standard MoCA (MoCA-A) and the Arabic basic version (MoCA-B). 18 , 25 These tests are available in Arabic from the MoCA website, and permission to use the tests in research, with minor modification 27 to follow the local Arabic accent, was obtained from http://mocatest.org . Both scales are scored from 0–30, with lower scores indicating worse cognitive function.…”

“…For reliability analysis, repeat testing was done after 2 to 4 weeks in 18 patients with the MoCA-A and in 18 patients with the MoCA-B. Considering that various cutoffs for impairment have been proposed in the literature, 6,9,25,[27][28][29][30] and considering the absence of validated cutoffs in the Saudi population, it was determined to analyze the total MoCA score results as a continuous variable for the primary analysis. To provide the reader with a comparison to other work on the topic, we identified four potential cutoffs, determined by reviewing the literature, at 26, 24, 22, and 20 out of 30 for both scales, 6,27,30,31 and the prevalence of impairment according to each cutoff was estimated.…”

“… 18 In addition to the standard MoCA tool, a separate version was designed to detect impairments in those with significantly lower levels of education. This newer tool is known as the MoCA-Basic 25 and has not yet been widely used in dialysis patients.…”

Intra-Brain and Plasma Levels of L-Serine Are Associated with Cognitive Status in Patients with Chronic Kidney Disease

“…Also, cognitive impairment and dementia are significant comorbidities. The prevalence of these diseases is 2–7 times higher in CKD patients as compared to the general population [ 2 , 3 , 4 ]. Therefore, to understand the mechanisms and develop novel biomarkers are highly required.…”