Tau deposition and structural connectivity demonstrate differential association patterns with neurocognitive tests

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Tau neurofibrillary tangles are central to Alzheimer's Disease (AD) pathogenesis.
• Brain connectivity and white-matter integrity influence tau propagation.
• Advances in tau positron emission tomography (PET) and diffusion MRI enable in vivo visualization of tau pathology and structural connectivity.

Purpose of the Study:

• To investigate the association between tau deposition, structural brain connectivity, and memory function in prodromal AD.
• To determine how tau accumulation and network metrics relate to each other and to neurocognitive performance.
• To explore the synergistic effects of tau deposition and dysconnectivity on memory recall.

Main Methods:

• Studied 83 participants (57 cognitively normal, 26 mild cognitive impairment) using tau PET and diffusion MRI.
• Analyzed data from 70 cortical/subcortical brain regions.
• Correlated tau accumulation and network metrics with neurocognitive test scores, including delayed memory recall.

Main Results:

• Tau accumulation correlated with network metrics in early deposition regions.
• Increased tau was linked to poorer performance across most neurocognitive tests.
• Decreased network connectivity specifically impacted delayed memory recall.
• Tau deposition and dysconnectivity showed a synergistic negative effect on delayed recall.

Conclusions:

• Both tau deposition and structural brain dysconnectivity are associated with neurocognitive dysfunction in prodromal AD.
• Tau PET may be more sensitive than diffusion MRI in detecting neurocognitive performance decline.
• These findings highlight the complex interplay between tau pathology, connectivity, and cognitive impairment in early AD.