Contextual variability in under-diagnosed cardiometabolic disease and cognitive vulnerability among populations at high risk for Alzheimer's disease and related dementias.

Underdiagnosis of cardiometabolic risk factors (CMRFs) may represent an unrecognised biological pathway contributing to dementia risk; yet remains poorly characterised in African and African diaspora populations. We quantified the prevalence and determinants of underdiagnosed hypertension and abnormal glycaemia across four cohorts comprising up to 7,000 adults aged ≥ 40 years from Nigeria, Kenya, and The United States: Indianapolis, and North Texas. Underdiagnosis was defined as absence of self-reported diagnosis despite elevated systolic blood pressure (≥ 130 mmHg) or fasting blood glucose (≥ 100 mg/dL). Cohort-stratified analyses examined demographic, socioeconomic, cognitive, Alzheimer's genetic, and blood-based biomarker correlates. Underdiagnosis was pervasive in African cohorts. Elevated fasting glucose was associated with cognitive impairment in Kenya and North Texas, while severe hypertension and diabetes were linked to Alzheimer's disease-related biomarkers [pTau217/181, NFL and Aβ42/40] in North Texas (all p ≤ 0.05). These findings identify context-specific diagnostic gaps in populations at high dementia risk and highlight cardiometabolic detection as a mechanistic target for prevention.