Sweden: In patients with Alzheimer's disease having a mild cognitive impairment or mild dementia, Tau PET imaging provides the best prediction of cognitive function change over two years, Swedish researchers state in the study published in Alzheimer's and Dementia, The Journal of the Alzheimer's Association.

Before this study, many individual biofluids and imaging biomarkers are reported to predict future cognitive decline. However, there needs to be a comprehensive head-to-head study of the individual contribution of the most relevant biomarkers, such as plasma phosphorylated tau (p-tau) and tau PET.

To explain this issue, Oskar Hansson, Memory Clinic, Skåne University Hospital, Malmö, Sweden, and colleagues investigated the ability of tau-PET compared to other potential biomarkers for predicting cognitive decline in patients over two years.

They evaluated the ability of tau-PET, baseline cognition, cortical atrophy on magnetic resonance imaging (MRI), plasma and cerebrospinal fluid (CSF) levels of phosphorylated tau-217, apolipoprotein E gene (APOE) status, neurofilament light (NfL), and amyloid beta (Aβ)42/40 ratio (individually and in combination) for predicting cognitive decline over two years in BioFINDER-2 and Alzheimer's Disease Neuroimaging Initiative (ADNI).

The authors reported the following findings:

• Baseline tau-PET and a composite baseline cognitive score were the strongest independent predictors of cognitive decline.
• Cortical thickness and NfL provided some additional information.
• Using a predictive algorithm to enrich patient selection in a theoretical clinical trial led to a significantly lower required sample size.
• There were more modest, and variable contributions of NfL and cortical thickness, but plasma (or CSF) p-tau, plasma (or CSF) Aβ42/40, and APOE ε4 status were not included in the main models.

To conclude, the researchers found that baseline cognition, tau-PET, p-tau217 levels in blood and CSF, cortical thickness, and CSF NfL can all individually predict future cognitive decline in amnestic MCI or mild dementia patients.

"Models including baseline cognition and tau-PET consistently were the best for predicting a cognitive decline, implying that tau-PET might be an important addition to the diagnostic workup in situations where prognostic information is of importance," the researchers explained.

Further, they found that selecting a study population based on these biomarkers can lead to a decreased number of participants required in clinical trials, for example, anti-tau trials, having cognitive decline as the primary outcome.

Reference:

Smith R, Cullen NC, Pichet Binette A, Leuzy A, Blennow K, Zetterberg H, Klein G, Borroni E, Ossenkoppele R, Janelidze S, Palmqvist S, Mattsson-Carlgren N, Stomrud E, Hansson O; Alzheimer's Disease Neuroimaging Initiative. Tau-PET is superior to phospho-tau when predicting cognitive decline in symptomatic AD patients. Alzheimers Dement. 2022 Dec 14. doi: 10.1002/alz.12875. Epub ahead of print. PMID: 36516028.