Impaired kidney function significantly elevated circulating levels of most Alzheimer disease blood biomarkers yet did not independently increase dementia risk, according to findings from a 16-year population-based study published in Neurology. Instead, kidney impairment appeared to accelerate clinical expression of underlying neurodegenerative pathology.
Among 2,279 dementia-free patients (median age 72 years; 62% female) from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), researchers found that lower estimated glomerular filtration rate (eGFR) was associated with higher median levels of all examined Alzheimer disease blood biomarkers except amyloid beta 42/40 ratio, following a nonlinear relationship.
At an eGFR of 30 mL/min/1.73 m², neurofilament light chain showed the strongest elevation at approximately one standard deviation above baseline, while phosphorylated tau 181, phosphorylated tau 217, total tau, and glial fibrillary acidic protein showed smaller increases ranging from 0.1 to 0.24 standard deviations above baseline. The study used the amyloid beta 42/40 ratio rather than amyloid beta 42 alone, as ratios have shown higher diagnostic accuracy for Alzheimer disease.
During mean follow-up of approximately 8 years, 362 patients developed dementia. In multivariable-adjusted models accounting for age, sex, education, APOE ε4 carrier status, anemia, cardiovascular and cerebrovascular disease, and body mass index, impaired kidney function (eGFR less than 60 mL/min/1.73 m²) showed no association with increased dementia hazard compared with preserved kidney function (eGFR greater than or equal to 60 mL/min/1.73 m²).
However, although no statistically significant interaction was detected between kidney function and biomarkers overall, stratified analyses revealed that kidney function modified the biomarker-dementia relationship. Patients with impaired kidney function and elevated neurofilament light chain had nearly four times the likelihood of developing dementia, while those with preserved kidney function and elevated neurofilament light chain had approximately twice the likelihood. Similarly, increased total tau levels were associated with dementia only among patients with impaired kidney function, whereas no significant association emerged in those with preserved kidney function.
The associations of phosphorylated tau 181, phosphorylated tau 217, and glial fibrillary acidic protein with dementia remained similar across kidney function groups, while amyloid beta 42/40 showed no association with dementia risk in either group.
Kidney function was assessed using eGFR based on serum creatinine via the 2009 Chronic Kidney Disease-Epidemiology Collaboration equation. Alzheimer disease biomarkers—including amyloid beta 42/40, phosphorylated tau 181, phosphorylated tau 217, total tau, neurofilament light chain, and glial fibrillary acidic protein—were measured from peripheral blood samples using the Simoa platform. Dementia was diagnosed according to DSM-IV criteria through a three-step procedure involving examining physician assessment, reviewing physician evaluation, and neurologist determination when disagreement occurred.
Results remained largely unchanged after excluding patients who developed dementia during the 16-year follow-up period and when adjusting for calf circumference instead of body mass index. Time-varying analyses incorporating longitudinal eGFR measurements and chronic conditions similarly showed no higher dementia hazard at more severe kidney impairment levels compared with the reference group.
Overall, 557 patients (24%) had impaired kidney function (eGFR less than 60 mL/min/1.73 m²); these patients were older and mostly female and had a higher comorbidity burden compared with patients with preserved kidney function.
The study included randomly selected patients aged 60 years or older from 11 age cohorts living in the Kungsholmen district in central Stockholm. Of 5,111 invited patients, 3,363 (73%) completed baseline assessment between 2001 and 2004.
Study limitations included single-time-point biomarker measurements, potential overestimation of true glomerular filtration rate in patients with low muscle mass using creatinine-based equations, and a predominantly highly educated White urban population limiting generalizability. The authors note that the paucity of dementia cases and low number of patients with severely impaired renal function may have prevented detection of associations between lower eGFR and higher dementia risk.
Researchers concluded that impaired kidney function acts as a modifier and booster of disease expression rather than a risk factor per se, potentially influencing the timing of clinical dementia onset in the presence of brain pathology.
Disclosures can be found in the study.
Source: Neurology
