Interactive versus additive relationships between regional cortical thinning and amyloid burden in predicting...

Area of Science:

• Neuroscience
• Neurology
• Biomarkers

Background:

• The link between Beta-amyloid (Aβ) plaque deposition, neurodegeneration, and Alzheimer's disease (AD) clinical decline remains unclear.
• Understanding these mechanisms is crucial for early diagnosis and intervention in mild cognitive impairment (MCI) and mild AD dementia.

Purpose of the Study:

• To investigate if amyloid accumulation and neurodegeneration independently or interactively predict clinical decline in individuals with memory impairment.
• To identify specific brain regions vulnerable to amyloid pathology and their association with disease progression.

Main Methods:

• Studied a cohort of older individuals diagnosed with amnestic MCI or mild AD dementia.
• Assessed baseline Aβ-associated cortical thinning and its relationship with Clinical Dementia Rating Sum-of-Boxes (CDR-SB) scores over time.
• Examined the influence of Aβ burden on the association between cortical thickness and clinical decline.

Main Results:

• Baseline Aβ-associated cortical thinning in temporal and parietal regions correlated with higher baseline CDR-SB.
• Aβ-associated cortical thinning predicted future CDR-SB changes.
• Regions outside the medial temporal lobe (MTL), including the lateral temporo-parietal cortex and precuneus, were significantly affected in individuals with high Aβ burden.
• Amyloid pathology was a stronger predictor of clinical decline than MTL thickness.
• These relationships were observed even in the prodromal stage of AD.

Conclusions:

• Cortical thinning in specific regions, particularly outside the MTL, is a significant predictor of clinical decline in AD, driven by amyloid pathology.
• Amyloid burden plays a critical role in AD progression, exceeding the predictive power of MTL neurodegeneration alone.
• These findings highlight the potential of targeting amyloid pathology and monitoring extra-MTL regions for early detection and management of AD, even at the MCI stage.