尿中のタンパク質が認知症リスクを予測(Protein in urine can predict risk of dementia)

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2025-09-24 カロリンスカ研究所(KI)

カロリンスカ研究所の大規模研究は、尿中のアルブミン濃度(アルブミン尿)が高い高齢者は、将来的に認知症を発症するリスクが有意に高いことを示した。65歳以上の約13万人を平均4年間追跡した結果、7%が認知症を発症。正常値(<30 mg/g)に比べ、30–299 mg/gでは25%、300 mg/g以上では37%リスクが増加した。特に血管性認知症やアルツハイマー病と混合型の発症と関連が強かった。腎臓と脳はいずれも微細血管に依存し、腎障害によるアルブミン漏出は、血液脳関門の損傷や炎症・有害タンパク質の蓄積を引き起こす可能性があるという。研究者は、高血圧・糖尿病・心血管疾患患者などにおけるアルブミン尿の定期的スクリーニングが、認知症予防の早期介入に役立つと強調している。研究成果はJournal of Internal Medicineに掲載された。

<関連情報>

アルブミン尿はeGFRとは独立して認知症リスクの上昇と関連している:SCREAMプロジェクト Albuminuria is associated with increased risk of dementia, independent of eGFR: The SCREAM project

Li Luo, Ron T. Gansevoort, Lyanne M. Kieneker, Yuanhang Yang, Alessandro Bosi, Rudolf A. de Boer, Casper F. M. Franssen, Maria Eriksdotter, Juan-Jesus Carrero, Hong Xu
Journal of Internal Medicine  Published: 23 September 2025
DOI:https://doi.org/10.1111/joim.70022

Graphical Abstract

尿中のタンパク質が認知症リスクを予測(Protein in urine can predict risk of dementia)

Abstract

Background

The association between albuminuria and dementia has been insufficiently studied, possibly due to not considering dementia subtypes, the interplay with estimated glomerular filtration rate (eGFR), and the use of varying albuminuria measurement techniques.

Objectives

This study aimed to investigate the eGFR-independent risk of all-cause and type-specific dementia associated with albuminuria, measured by the urine albumin-creatinine ratio (ACR) and dipstick.

Methods

The main analysis included 132,869 subjects aged ≥65 years without a history of dementia and with at least one ACR test from the Stockholm Creatinine Measurements (SCREAM) project between 2006 and 2019. The primary and secondary outcomes were the incidence of all-cause dementia and type-specific dementia, respectively. Cox regression models were used to calculate hazard ratios (HRs, 95% CIs).

Results

During a median follow-up of 3.9 (interquartile ranges, 1.8–7.1) years, 9435 (7%) subjects developed incident dementia. After multivariable adjustments, including eGFR, an ACR level of 30–299 and ≥300 mg/g was associated with a 25% (HR, 1.25; 95% CI, 1.19–1.31) and a 37% (HR, 1.37; 95% CI, 1.23–1.51) higher risk of developing all-cause dementia, respectively, compared to an ACR level of <30 mg/g. Higher ACR levels were also associated with an increased risk of mixed, vascular, and unspecified dementia, but not with Alzheimer’s disease. These findings were robust in subjects with at least one dipstick proteinuria test.

Conclusion

Increased albuminuria is associated with a higher risk of all-cause dementia, particularly mixed, vascular, and unspecified dementia, independent of baseline eGFR and generalizable across different clinical pathways of albuminuria testing.

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