Tau-positive positron emission tomography (PET) may play a significant role in forecasting progression to dementia and Alzheimer’s disease, according to new research.
For the longitudinal study, recently published in the Journal of the American Medical Association (JAMA), the researchers assessed the frequency of tau PET positive findings in a cohort of 6,514 participants (mean age of 69.5) drawn from 13 countries. The cohort included people with no cognitive impairment, those with mild cognitive impairment (MCI), people with Alzheimer’s disease (AD) dementia, and participants with other neurodegenerative disorders, according to the study.
The study authors found that participants with a combination of MCI, positive amyloid-β (Aβ) PET and positive tau PET had a 69.9 percent risk of progressing to dementia within five years in contrast to 30.4 percent for people with MCI, positive Aβ PET and negative tau PET. Participants with MCI and negative findings on Aβ and tau PET had a 15.3 percent risk for dementia progression in five years, according to the researchers.
Positive tau PET findings in participants with AD dementia and positive Aβ PET were associated with over double the risk of a progressing Clinical Dementia Rating Global (CDR-G) score in three years (67.2 percent) in comparison to participants with AD dementia and negative tau PET (33.9 percent with negative amyloid PET and 32.4 percent with positive Aβ PET).
“An Aβ PET–positive/tau PET–positive profile was associated with increased incidence of clinically relevant outcomes in both participants with MCI and early AD dementia. These results suggest that tau PET positivity is a reliable indicator of AD pathology being a dominant contributor to clinical symptoms,” wrote lead study author Alexis Moscoso, Ph.D., who is affiliated with the Department of Psychiatry and Neurochemistry at the Institute of Neuroscience and Physiology and Sahlgrenska Academy at the University of Gothenburg in Gothenburg, Sweden, and colleagues.
The researchers also found that positive tau PET significantly elevated 5-year risks for MCI and dementia progression for study participants with no initial cognitive impairment.
The combination of positive tau PET and positive Aβ PET was associated with a 57.4 percent risk of MCI or dementia progression in comparison to 16.6 percent with positive Aβ PET/negative tau PET and 6.4 percent for negative Aβ PET/negative tau PET, according to the study authors.
“ … An Aβ PET–positive/tau PET–positive profile in cognitively unimpaired individuals was associated with higher rates of progression to MCI or dementia over the following 5 years compared with their Aβ PET–positive/tau PET–negative and Aβ PET–negative/tau PET–negative counterparts,” noted Moscoso and colleagues.
Three Key Takeaways
1. Tau PET positivity significantly enhances prognostic accuracy. In individuals with mild cognitive impairment (MCI), the combination of tau PET and amyloid-β (Aβ) PET positivity was associated with a 69.9 percent risk of dementia progression over five years, much higher than with Aβ PET positivity alone (30.4 percent).
2. Tau PET is a key indicator of Alzheimer’s disease pathology. Among participants with early AD dementia, positive tau PET more than doubled the likelihood of clinical deterioration (as measured by Clinical Dementia Rating Global scores) over three years compared to those without tau PET positivity.
3. Early tau PET findings predict future cognitive decline. In cognitively unimpaired individuals, dual positivity on tau and Aβ PET scans was linked to a 57.4 percent five-year risk of developing MCI or dementia, highlighting tau PET’s potential for early detection and risk stratification even before clinical symptoms arise.
The study authors acknowledged a lack of clarity with respect to cases in which positive tau PET occurs in patients with negative Aβ PET findings.
“ … Explanations include flortaucipir F 18 binding to AD-like tau aggregates present in tangle-dominant forms of dementia, binding to targets other than tau, and false-positive Aβ PET and/or tau PET scans,” added Moscoso and colleagues. “It is also important to note that tau PET radiotracers other than flortaucipir F 18 may have different off-target binding profiles, and the frequency of positivity in Aβ-negative conditions with these radiotracers may differ from the estimates derived in this study.”
(Editor’s note: For related content, see “A Closer Look at the New Appropriate Use Criteria for Brain PET: An Interview with Phillip Kuo, MD, Part 2,” “FDA Grants Fast Track Designation to Emerging Agent for PET Imaging” and “FDA Clears New Centiloid Scoring and Tau PET Quantification Tools.”)
In regard to study limitations, the authors conceded possible bias due to the pooling of data from independent studies with different study designs and the inclusion of cognitively unimpaired people from research cohorts that may not be representative of a broader population. The researchers also noted small sample sizes for Aβ PET-negative/tau PET-positive participants and participants over 90 years of age.
