Association of Kidney Function With Development of Alzheimer Disease and Other Dementias and Dementia-Related Blood Biomarkers

Abstract

ImportancePrevious research has suggested an association of kidney function with risk of Alzheimer disease (AD) or other dementias and dementia-related blood biomarkers, but a distinct association remains unclear.ObjectiveTo evaluate the association of kidney function with risk of diagnosis of incident AD or dementia within 17 years and with the blood biomarkers neurofilament light (NfL), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP).Design, Setting, and ParticipantsIn this prospective, population-based cohort study and nested case-control study, 9940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed up for up to 17 years. Participants were included if information on dementia status and creatinine/cystatin C measurements were available. A subsample of participants additionally had measurements of NfL, p-tau181, and GFAP obtained from blood samples. Statistical analysis was performed from January 3 to November 25, 2022.ExposuresImpaired kidney function, based on estimated glomerular filtration rate less than 60 mL/min/1.73 m2 according to the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine–cystatin C equation.Main Outcomes and MeasuresAll-cause dementia, AD, and vascular dementia diagnosis, as well as log-transformed levels of NfL, p-tau181, and GFAP in blood.ResultsOf 6256 participants (3402 women [54.4%]; mean [SD] age at baseline, 61.7 [6.6] years), 510 received an all-cause dementia diagnosis within 17 years of baseline. The dementia-related blood biomarker nested case-control sample included 766 participants. After adjusting for age and sex, impaired kidney function at baseline was not associated with a higher risk of all-cause dementia (hazard ratio [HR], 0.95; 95% CI, 0.69-1.29), AD (HR, 0.94; 95% CI, 0.55-1.63), or vascular dementia diagnosis (HR, 1.06; 95% CI, 0.65-1.70) within 17 years. In the cross-sectional analysis, after adjusting for age and sex, impaired kidney function was significantly associated with NfL and p-tau181 levels in blood (NfL: β = 0.47 and P < .001; p-tau181: β = 0.21 and P = .003). After adjusting for age and sex, significant associations with GFAP levels were evident only among men (men: β = 0.31 and P = .006; women: β = −0.12 and P = .11).Conclusions and RelevanceIn this population-based study of community-dwelling adults, reduced kidney function was associated with increased levels of dementia-related blood biomarkers but not increased dementia risk. Kidney function might influence the accuracy of dementia-related blood biomarkers and should be considered in clinical translation.

Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease

“…Alternatively, our findings may be specific to autosomal dominant AD. These findings warrant further investigation in other autosomal dominant and sporadic AD cohorts to clarify the effect of sex on plasma biomarkers, potential sex‐specific confounding measurement factors 73 (e.g., medical comorbidities), and underlying mechanisms and pathology clearance pathways 74 that may explain differences between biomarker modalities and prior findings in sporadic AD. Of note, very few PSEN1 mutation carriers in our sample had medical comorbidities (i.e., history of cardiovascular, renal, or hepatic conditions), as expected given their young age of symptom onset.…”

Biomarkers of neurodegeneration and neural injury as potential predictors for delirium

“…Studies examining plasma NfL have found increased NfL to be associated with delirium 24,25 . Reduced kidney function has been associated with increased levels of dementia‐related blood biomarkers including GFAP but not increased dementia risk 51 …”

“…24,25 Reduced kidney function has been associated with increased levels of dementia-related blood biomarkers including GFAP but not increased dementia risk. 51 A major strength of this study is the use of matched delirium cases and controls without delirium. This is a powerful study design, which maximizes efficiency for evaluating potential biomarkers.…”

Alzheimer’s Disease cerebrospinal fluid Biomarkers and kidney function in normal and cognitively impaired older adults

“…This is to our knowledge one of the few first large studies that reported the association of kidney function with CSF AD biomarkers and its interaction with cognitive status. This study highlights the need to incorporate kidney function in studies of AD risk factors and the need to consider renal health when interpreting the results of AD biomarkers 33,34 within clinical evaluations and trials particularly during the early symptomatic stages of AD. This also adds an additional factor to our understanding of the complex multifactorial processes contributing to AD and its biomarkers.…”