Cognitive Status Remains Key Predictor of Dementia Risk Alongside p-tau181

The diagnostic framework for Alzheimer disease is shifting toward a biological definition centered on the detection of amyloid and tau pathologies [1]. Blood-based assays for phosphorylated tau 181 (p-tau181) provide a less invasive alternative to lumbar punctures, with data indicating these tests can distinguish Alzheimer dementia from cognitively unimpaired controls with an area under the curve (AUC) of 90.21% to 98.24% [2, 3]. Clinicians must integrate these molecular signals with bedside assessments of mild cognitive impairment and vascular risk factors, such as perivascular spaces (fluid-filled cavities surrounding brain blood vessels that serve as markers of small vessel disease) which correlate with elevated p-tau181 and neurofilament light levels (p < 0.01) [4, 5]. In large prospective cohorts, combining plasma p-tau with brief cognitive tests and apolipoprotein E (APOE) genotyping achieved a prognostic accuracy of 0.91 AUC for predicting progression to dementia within four years [2]. This multidimensional approach clarifies the independent and combined value of biomarkers for long-term risk stratification in primary and secondary care [6, 2].