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Plasma Proteomic Correlates of Cognitive Function in Older Adults From Central Africa

Year: 2026

Type: preprint

Abstract: Key Points: Plasma markers most closely associated with cognitive phenotype may differ from biomarkers optimized for Alzheimer pathology detection, underscoring the need for population-specific biomarker evaluation. Importance: Blood-based proteomic biomarkers may support scalable dementia research, but their associations with cognitive phenotype remain poorly characterized in sub-Saharan African populations. Objective: To examine associations between selected plasma proteins and multidomain cognitive performance in older adults in the Democratic Republic of Congo. Design: Cross-sectional secondary analysis of baseline data from the Étude du Vieillissement Cognitif et de Démence en République Démocratique du Congo (EVCD-RDC), with participant recruitment and data collection from July 2024 through September 2025. Setting: Community-based prospective cohort in Kinshasa, Democratic Republic of Congo. Participants: The analytic sample included 779 participants: 143 cognitively unimpaired, 218 with mild cognitive impairment, 203 with Alzheimer disease, and 215 with other dementia. Median age was 73 years (IQR, 70-78); 495 participants (63.5%) were female and 284 (36.5%) were male. Exposures: Plasma abundance of 10 candidate proteins measured using the NULISAseq CNS Disease Panel 120. Candidates were selected from an earlier panel-wide analysis based on cognitively unimpaired vs Alzheimer disease discrimination and false-discovery-rate-adjusted significance. Main Outcomes and Measures: Seven cognitive outcomes spanning global cognition, language, working memory, learning, delayed memory, mental abstraction, and problem solving. Separate linear regression models adjusted for age, sex, current smoking, education, and estimated glomerular filtration rate. Benjamini-Hochberg false-discovery-rate correction was applied within each cognitive outcome across the 10 proteins. Results: Eighteen protein-cognition associations were nominally significant, and 6 remained significant after correction. Higher MME was associated with better language (β=0.143; 95% CI, 0.074-0.212), global cognition (β=0.225; 95% CI, 0.071-0.379), and delayed memory (β=0.312; 95% CI, 0.106-0.519). Higher NEFL was associated with poorer global cognition (β=-0.700; 95% CI, -1.080 to -0.319) and delayed memory (β=-0.773; 95% CI, -1.283 to -0.263). Higher ENO2 was associated with better delayed memory (β=0.560; 95% CI, 0.184-0.937). No p-tau217-based measure remained significant after correction. Conclusions and Relevance: MME and NEFL showed the most consistent associations with cognitive performance, whereas p-tau217-based measures did not survive multiple-testing correction. Biomarkers optimized for Alzheimer pathology detection may differ from those most closely associated with cross-sectional cognitive phenotype, supporting population-specific evaluation of plasma proteomic markers.

Source: medRxiv

DOI: 10.64898/2026.10.22.26366214