Emerging roles of PET amyloid tracer in the diagnosis of AD-related neurodegenerative diseases, and assessment of high-risk groups-A comparative study with structural and functional MRI

Abstract

Alzheimer’s disease (AD) is the most common and concerning type of dementia. The incorporation of biomarkers in the diagnosis of AD improves its accuracy and allows for early intervention during AD development. Amyloid-PET tracer aids in detecting the biomarker of amyloid deposition in vivo even at a very stage of AD. In the current thesis, we evaluated the role of amyloid-PET tracer in the diagnosis of AD-related neurodegenerative diseases including AD and other neurodegenerative diseases characteristic of AD pathologies, and in the assessment of populations with a high risk of developing into AD.

In the two studies evaluating the role of amyloid-PET tracer in the diagnosis of AD-related neurodegenerative diseases, one study highlighted real-life clinical application and involved 5 SCD, 41 MCI, and 38 dementia participants based on clinical evaluation. A stepwise study design was applied in this study. The other study incorporated a random forest model using regional amyloid load and/or volume as features when performing the classification of HC, MCI, and AD on a large sample size. A total of 261 participants were included (94 AD, 82 MCI, and 85 HC) in this study, collected from our local dataset and two public datasets. In another two studies aiming at the assessment of high-risk populations, one study compared regional amyloid and local grey matter volume and correlated two events among SCD (n=11), MCI with high amyloid load (MCIp, n=13), MCI with low amyloid load (MCIn, n=21), and AD groups (n=17). The other study combined both amyloid-PET and resting-state fMRI techniques to explore the difference in neural activity measured by the fractional amplitude of low-frequency fluctuations (fALFF) in HC (n=18) vs SCD (n=11) and HC vs T2DM (n=18). The correlation between two events was also performed in SCD and T2DM groups.

The incremental value of amyloid-PET with 18F-Flutemetamol in the diagnosis of AD-related neurodegenerative diseases was proved due to its role in complementing AD-related pathological information. Incorporation of quantitative amyloid load and structural changes to improve the performance of the model was approved and achieved moderate-to-high accuracy. A significant correlation between A and atrophy was shown in MCIp, MCIn, and AD but not SCD. In addition, altered neural activity was found in the superior temporal lobe and motor cortex for the T2DM group and concentrated within the cerebellum for the SCD group. The very early amyloid uptake in both groups was observed to correlate with the neural activity of regions mainly involved in DMN.

The role of amyloid-PET tracer has been proven to aid in the diagnosis of AD-related neurodegenerative diseases by complementing AD-related pathological information in a real-life clinical setting and using a random-forest model based on a large sample size. Furthermore, the incorporation of amyloid-PET techniques helps in exploring the role of A and its correlation with other events in those high-risk populations who may have normal cognition but are affected by the very early A.