Background
Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and accurate diagnosis is crucial, including for people with HIV (PWH). Blood-based biomarkers for AD offer a promising, low-cost, non-invasive diagnostic alternative, but data are limited in PWH. Our study measured phosphorylated tau 217 (p-tau217)–the only blood-based biomarker currently recommended for diagnosing AD–and assessed its potential in predicting cognitive decline among virologically suppressed older Thai PWH.
Methods
Blood samples were collected at baseline from virologically suppressed PWH aged 50 years and older, who completed the Thai-validated Montreal Cognitive Assessment (MoCA) at baseline (2015–2017) and a follow-up visit (2021–2024). Cognitive impairment was defined as a MoCA score of less than 25. P-tau217 levels were measured and categorized by quartiles, with a binary comparison between quartile 4 (Q4) and quartile 1–3 (Q1–3). A multivariate linear mixed-effects model, adjusted for sex, education level, baseline MoCA score, HIV duration, nadir CD4 levels (<200 and ≥ 200 cells/mm3), and exposure to efavirenz, with an interaction term for baseline p-tau217 quartile and age, was used to estimate the effect of baseline p-tau217 levels on the changes in cognitive performance overtime.
Results
A total of 255 PWH, with a median interval between MoCA of 5.9 years (IQR: 5.6–6.8), were included: 63.1% were male, median age was 54.3 years (IQR: 51.8–59.1), 76.1% had more than six years of education, median HIV duration was 18.7 years (IQR: 15.3–21.0), and 61.2% had cognitive impairment. There was no significant difference in the proportion of PWH with cognitive impairment at baseline between those in Q4 and those in Q1–3 of p-tau217. However, PWH in Q4 were significantly more likely to have a reduction in MoCA score at follow-up visit than those in Q1–3 (62.5% vs. 49.2%, P=0.01). In the adjusted model, PWH in Q4 showed a significantly greater decline in cognitive performance, with a MoCA score decrease of -4.3 (95% CI -5.8 to -2.7) compared to -1.7 (95% CI -2.6 to -0.8) for Q1–Q3 from age 50 to 80 years (Figure). The association between higher p-tau217 levels (Q4 vs. Q1-Q3) and greater decline in MoCA scores become more pronounced with increasing age (P-interaction=0.02).
Conclusions
Older virologically suppressed Thai PWH with higher baseline p-tau217 levels showed a greater cognitive decline. Measurements of biomarkers for staging and prognostication of AD are ongoing.
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