Blood Test May Predict Future Risk of Cognitive Impairment in Alzheimer's Disease: JAMA
USA: A JAMA study presented at the Alzheimer's Association International Conference has revealed that a blood test measuring plasma phosphorylated tau 217 (P-tau217) can help predict an individual's risk of developing cognitive impairment over the next 2, 5, and 10 years. The findings suggest that P-tau217 could serve as a valuable biomarker for early risk assessment and timely intervention in Alzheimer's disease.
The study, led by Rachel F. Buckley from the Department of Neurology, Mass General Brigham, Boston, Massachusetts, and colleagues, found that higher plasma P-tau217 levels in cognitively healthy older adults were consistently associated with a greater likelihood of progressing to mild cognitive impairment or dementia, as well as faster cognitive decline over time. The researchers noted that blood-based biomarkers could offer a practical, less invasive approach for identifying individuals at increased risk before clinical symptoms emerge.
To assess the prognostic value of plasma P-tau217, researchers analyzed harmonized data from 2,684 cognitively unimpaired older adults across six longitudinal cohorts in North America, Japan, and Australia. The primary outcome was progression to cognitive impairment—defined as mild cognitive impairment, dementia, or two consecutive global Clinical Dementia Rating scores of 0.5 or higher—while the secondary outcome was cognitive decline measured using the Preclinical Alzheimer Cognitive Composite (PACC).
Participants had a median age of 69.6 years, 63% were women, and 478 individuals developed cognitive impairment during a median follow-up of 5.4 years (maximum 13.5 years).
Key findings of the study include:
- Each 1-standard deviation (SD) increase in baseline plasma P-tau217 was associated with a 38% higher risk of progression to cognitive impairment (hazard ratio [HR], 1.38).
- The association remained significant even after adjustment for β-amyloid PET imaging findings (HR, 1.32).
- Participants with high P-tau217 levels (1.1–2.4 SD) had an estimated 24% absolute risk of developing cognitive impairment within five years.
- Those with very high P-tau217 levels (>2.5 SD) had an estimated 38% five-year risk, with substantially higher estimated risk over 10 years, although long-term estimates were limited by fewer participants with extended follow-up.
- Elevated P-tau217 levels were also linked to more rapid cognitive decline, with the very high P-tau217 group showing an annual decline of −0.07 latent PACC units, compared with an annual improvement of 0.03 units in the low P-tau217 group.
The researchers noted that differences in cohort design and biomarker platforms, along with limited racial, ethnic, and socioeconomic diversity, may limit the generalizability of the findings. They also cited the absence of clinically validated P-tau217 thresholds, lack of adjustment for comorbidities and competing risks such as death, and limited follow-up beyond 10 years as key limitations.
The authors concluded that plasma P-tau217 shows promise as a long-term prognostic biomarker for cognitively unimpaired older adults and could aid the development of individualized risk prediction models. However, they emphasized that validation in broader, population-based cohorts is essential before its use in routine clinical practice.
Reference:
Buckley RF, Townsend DL, Birkenbihl CJ, et al. Prognostic Value of Blood-Based P-Tau217 Levels for Progression to Cognitive Impairment. JAMA. Published online July 14, 2026. doi:10.1001/jama.2026.12556
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