Aug 2026· Neurology and Clinical Neuroscience· 0 citations· 29 references
TL;DR
Urinary AβPP shows high sensitivity but low specificity for MCI screening, highlighting the role of metabolic health in early cognitive decline.
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.
BACKGROUND AND PURPOSE
Subjective cognitive decline (SCD) may precede mild cognitive impairment (MCI) and dementia. However, the prognosis of patients with amyloid-negative (A-) SCD remains unclear. We investigated whether baseline plasma and imaging biomarkers predict four-year clinical progression in A-SCD.
METHODS
Sixty-five individuals with A-SCD were followed for four years. Baseline plasma biomarkers-phosphorylated tau 181 (pTau181), glial fibrillary acidic protein, neurofilament light chain (NfL), and pTau181/Aβ42 ratio-and MRI markers (hippocampal volume and white matter hyperintensity [WMH] grade) were assessed. Outcomes included MCI conversion and cognitive progression defined as ≥1-point (Prog-1) or ≥2-point (Prog-2) decline in Korean Mini-Mental State Examination. Predictive performance was evaluated using multivariable logistic regression and bootstrap-validated receiver operating characteristic analyses.
RESULTS
Fourteen participants (21.5%) converted to MCI, and 24 (36.9%) were classified as Prog-1. Plasma biomarkers did not show consistent predictive performance across predefined endpoints (all p>0.05), although NfL demonstrated modest discrimination for MCI conversion (area under the curve [AUC] 0.686, p=0.008). Hippocampal volume demonstrated significant discriminative performance for MCI conversion (AUC 0.765, p=0.016) and Prog-1 (AUC 0.933, p<0.001). For Prog-2, hippocampal volume showed high discrimination (AUC 0.952, p<0.001). WMH grade also demonstrated significant discrimination for MCI conversion (AUC 0.835, p<0.001) and Prog-1 (AUC 0.857, p<0.001). Bootstrap analyses (1,000 iterations) tended to show higher AUC estimates for imaging markers compared with plasma biomarkers.
CONCLUSIONS
In this A-SCD cohort, hippocampal atrophy demonstrated more consistent prognostic performance than Alzheimer's disease-focused plasma biomarkers for predicting four-year conversion to MCI and cognitive decline, suggesting a potential role for MRI-based neurodegeneration markers in clinical risk stratification.
Bora Yoon, Hyuk-je Lee, Y. Hong et al.· Journal of Clinical Neurolog...· 1 citation
BackgroundHearing impairment (HI) has been identified as a potentially modifiable risk factor for dementia, yet its relationship with Alzheimer's disease (AD) neuropathology and the temporal directionality remain unclear, particularly in late life.ObjectiveTo examine cross-sectional and longitudinal associations between HI, clinical cognitive status, and AD biomarkers in community-dwelling older adults.MethodsWe included 474 DRIVES Project participants (mean age 73.5 ± 5.2 years). Hearing was assessed using the NIH Toolbox Words-in-Noise (WIN) test. Clinical cognitive status was assessed using Clinical Dementia Rating (CDR). AD biomarkers included cerebrospinal fluid (CSF) Aβ42/Aβ40, t-tau/Aβ42, and p-tau/Aβ42 ratios and amyloid PET imaging. Multivariable linear, logistic, Cox proportional hazards, and Fine-Gray competing-risk models were used.ResultsHI was more prevalent among participants with mild cognitive impairment (MCI; defined as CDR = 0.5) than cognitively normal individuals (50% versus 24%, p < 0.001), and MCI status was independently associated with worse baseline WIN thresholds (β = 1.55 dB SNR; 95% CI 0.72-2.37). HI was not cross-sectionally associated with CSF amyloid or tau ratios or amyloid PET positivity. Longitudinally, baseline MCI was associated with a higher risk of incident HI (Cox HR = 2.63, 95% CI 1.48-4.67; Fine-Gray sHR = 2.79, 95% CI 1.06-7.40), whereas baseline HI was not associated with subsequent CDR progression.ConclusionsIn older adults, HI was associated with MCI but not core AD biomarkers or future CDR progression, suggesting that late-life HI may reflect cognitive vulnerability or broader brain aging rather than independently driving AD pathology.
Semere Bekena, R. Singh, Subrata Pal et al.· Journal of Alzheimer's Disea...· 0 citations
Increased serum p-tau217 and decreased ApoE levels were significantly associated with greater AD severity, suggesting that both biomarkers may serve as complementary noninvasive indicators of disease severity in Alzheimer’s disease.
Ahmed Kadom Kalaf, Khawla A. Shemran, Waleed Azeez AlAmeedy· International Journal of Nut...· 0 citations
Background: Mild cognitive impairment (MCI) represents an intermediate state between normal cognitive ageing and dementia. Given the increasing dementia burden in the country, there is a critical need for early detection through the assessment of MCI. However, studies that comprehensively examined the associations between micronutrients, neuronal markers, and cognitive impairment are scarce. Methods: A community-based cross-sectional study was conducted among 184 adults aged 55–85 years in Hyderabad between January 2024 and March 2025. Sociodemographic, anthropometric, biochemical, nutritional, and neuronal biomarkers were estimated. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) tool. Results: The study reported an MCI prevalence of 36.4% among older adults, significantly associated with higher HbA1c and systolic blood pressure, and elevated neuronal markers such as β-Amyloid, T tau, and Nfl. Vitamin D, B1, B2, B6, and B9 levels were significantly lower in the MCI group, with a higher burden of deficiency. Higher vitamin levels were correlated with better MoCA scores and a lower predicted probability of MCI, especially vitamins D and B6. In particular, B2 and B6 have shown associations with BDNF, tau, and Nfl markers. Conclusions: Lower levels of circulatory vitamins were significantly associated with a higher probability of MCI. Also, neuronal biomarkers were significantly associated with micronutrient deficiencies. These findings suggest that micronutrient deficiencies may be associated with MCI in older adults, highlighting the potential importance of maintaining adequate micronutrient status to support healthy cognitive aging and possibly reduce the risk of dementia. However, given the cross-sectional design of the present study, causal relationships cannot be established. Future longitudinal studies are warranted to validate these associations and further clarify the temporal relationship between micronutrient status and cognitive decline.
BackgroundAmyloid-negative tau-related neurodegeneration represents a non-Alzheimer biomarker-defined profile; however, its clinical heterogeneity and prognostic relevance remain unclear within Alzheimer's disease-related frameworks.ObjectiveTo characterize the clinical spectrum and identify predictors of mortality in patients with this profile.MethodsIn this retrospective cohort study, 1280 patients evaluated at a tertiary neurology center were screened, and 130 with an amyloid-negative cerebrospinal fluid (CSF) pattern [amyloid-β (Aβ)42 normal, phosphorylated tau (pTau), and total tau (tTau) elevated] were included. Survival was assessed using Kaplan-Meier analysis, and predictors of mortality were evaluated using Cox models.ResultsThe cohort (mean age 68.8 ± 10.1 years; 45.4% female) showed heterogeneous diagnoses, mainly mild cognitive impairment and frontotemporal dementia (each 30%). Survival differed across diagnostic groups (log-rank p = 0.037), with more favorable outcomes in mild cognitive impairment. Male sex was more frequent among non-survivors (88.9% versus 45.6%, p < 0.001). Higher CSF tTau levels were associated with mortality in the joint Cox model (HR 1.003, 95% CI 1.001-1.006, p = 0.006) and faster clinical progression (r = 0.22, p = 0.011). When modeled separately, neither tTau nor pTau was independently associated with mortality; however, both became significant in opposite directions when included jointly.ConclusionsThe amyloid-negative A-T + N + profile represents a clinically heterogeneous subgroup with prognostic relevance. CSF tTau was associated with mortality and faster clinical progression, but the joint-model findings involving tTau and pTau should be interpreted cautiously as hypothesis-generating. Further studies are needed to clarify the prognostic value of tau-related biomarkers in this population.
Aslı Aksoy Gündoğdu, B. Samancı, M. Alaylıoğlu et al.· Journal of Alzheimer's Disea...· 0 citations
Serial biomarker assessment provided stronger prognostic information than baseline measurements alone in clinically stable patients with chronic HF, and longitudinal increases in circulating amyloid-β peptides associated with cognitive decline, structural brain changes, and mortality.
J. Traub, Anna Frey, G. Homola et al.· ESC Heart Failure· 0 citations
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