November 3, 2024

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Tau PET: Best Tool for Predicting MCI Progression to Dementia

Tau PET: Best Tool for Predicting MCI Progression to Dementia



Tau PET: Best Tool for Predicting MCI Progression to Dementia

Accurate, timely, and personalized prognosis is crucial for patients with Alzheimer’s disease (AD) to plan interventions, reduce uncertainty, and support medical decisions, especially during the mild cognitive impairment (MCI) stage. Among the numerous biomarkers of AD pathology and neurodegenerative changes, neuroimaging excels in predicting cognitive decline.

MRI-measured brain atrophy is one of the most widely used clinical markers for predicting dementia progression. However, MRI is less sensitive to subtle cognitive changes compared to PET. Although β-amyloid (Aβ) PET has been shown to predict cognitive impairment, it typically requires long follow-up periods due to a significant delay between amyloid deposition and clinical symptoms.

Researchers have now focused on another pathological protein, tau. Although tau PET is not yet widely used clinically, studies indicate that tau PET can accurately distinguish AD patients from healthy controls and has a close spatial and temporal correlation with clinical symptoms.

A research team from Amsterdam University Medical Center in the Netherlands and Skåne University Hospital in Sweden conducted a study revealing that among tau PET, Aβ PET, and MRI, only the tau PET model outperformed the basic model (based on age, sex, education level, and Mini-Mental State Examination scores) in predicting the progression of MCI to dementia. This suggests that tau PET might be the best available neuroimaging biomarker for predicting MCI prognosis. The study results were published in JAMA Neurology.

 

Tau PET: Best Tool for Predicting MCI Progression to Dementia

 

Researchers included 331 MCI patients from memory clinics and clinical trials in Korea, Sweden, the United States, and Switzerland between June 1, 2014, and January 15, 2024, as the discovery cohort. The validation cohort consisted of 117 MCI patients from the Alzheimer’s Disease Neuroimaging Initiative.

In the discovery cohort, 165 individuals (52%) carried the APOEε4 allele, with an average MMSE score of 27.1 and an average clinical follow-up time of 1.9 years. During the follow-up, 110 individuals (33%) progressed to dementia, of which 71 cases were AD-related.

In the discovery cohort, for predicting all-cause dementia, only the tau PET model outperformed the basic model (AUC: 0.75 vs. 0.71). For predicting AD-related dementia, the tau PET model, tau PET visual read, and Aβ Centiloids quantitative model all outperformed the basic model (AUC: 0.84 vs. 0.83 vs. 0.83 vs. 0.75).

In the validation cohort, for predicting all-cause dementia, both the tau PET and tau PET visual read models outperformed the basic model (AUC: 0.85 vs. 0.85 vs. 0.73). For predicting AD-related dementia, tau PET and tau PET visual read also performed better (AUC: 0.85 vs. 0.85 vs. 0.70).

Both in the discovery and validation cohorts, positive quantitative and visual read results of tau PET, Aβ PET, and MRI indicated an increased risk of MCI progressing to all-cause dementia and AD-related dementia, with AD-related dementia posing a higher risk.

According to the AD ATN (Aβ, tau, and neurodegeneration) biomarker framework, individuals with multiple positive neuroimaging biomarkers had a higher risk of progressing to dementia compared to those with a single positive biomarker. The highest risk was observed when all ATN biomarkers were positive for progressing to AD-related dementia.

In summary, this study shows that tau PET is the best neuroimaging biomarker for predicting the clinical progression of MCI, outperforming Aβ PET and MRI.

Researchers emphasize that from a clinical and practical perspective, physicians need to know which imaging tests to order when estimating whether an MCI patient’s condition will remain stable or progress rapidly. This prognostic assessment is crucial for patients and caregivers, as reflected in a survey where the most important question for them was, “How fast will the patient’s (my) memory decline?”

The researchers hope their findings will make a significant step towards achieving accurate and personalized prognoses for MCI patients, reducing uncertainty and lowering the disease burden.

**References:**

1. Groot C, Smith R, Collij LE, et al. Tau Positron Emission Tomography for Predicting Dementia in Individuals With Mild Cognitive Impairment. JAMA Neurology. Published online June 10, 2024. doi:10.1001/jamaneurol.2024.1612

2. Mank A, van Maurik IS, Bakker ED, et al. Identifying relevant outcomes in the progression of Alzheimer’s disease; what do patients and care partners want to know about prognosis? Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 2021, 7(1): e12189.

Tau PET: Best Tool for Predicting MCI Progression to Dementia

[1] Groot C, Smith R, Collij LE, et al. Tau Positron Emission Tomography for Predicting Dementia in Individuals With Mild Cognitive Impairment. JAMA Neurology. Published online June 10, 2024. doi:10.1001/jamaneurol.2024.1612

[2] Mank A, van Maurik I S, Bakker E D, et al. Identifying relevant outcomes in the progression of Alzheimer’s disease; what do patients and care partners want to know about prognosis?[J]. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 2021, 7(1): e12189.


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