The Potential Role of Amyloid Precursor Protein Fragments as a Screening Tool for Mild Cognitive Impairment

Abstract

Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia, in which early detection is essential. Urinary amyloid precursor protein (APP) fragments have been proposed as a non‐invasive biomarker, but their diagnostic value in elderly populations remains uncertain. This study evaluated the diagnostic performance of urinary APP fragments, particularly amyloid‐β protein precursor (AβPP), for MCI screening and examined associated sociodemographic and clinical risk factors among adults aged ≥ 65 years. A single‐center, cross‐sectional, case–control study was conducted at Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia. A total of 140 age‐ and gender‐matched participants were recruited (70 MCI, 70 cognitively normal). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Urinary AβPP was measured using a lateral flow immunochromatography kit. Data on comorbidities, body mass index, education level and smoking status were collected. Diagnostic accuracy and logistic regression analyses were performed. The urinary AβPP test showed a sensitivity of 74.3%, specificity of 27.1%, and overall accuracy of 50.7%, with no significant association with cognitive status ( p  = 0.424). Diabetes mellitus was an independent risk factor predictor for MCI ( p  = 0.007, OR = 5.764, 95% CI 1.615–20.572) along with age ( p  = 0.001, OR = 1.638, 95% CI 1.234–2.175). Urinary AβPP shows high sensitivity but low specificity for MCI screening. Diabetes mellitus is a significant predictor of MCI, highlighting the role of metabolic health in early cognitive decline.