Deep Learning-Based MRI Analysis Reveals Lewy Body Co-Pathology Accelerates Brain Aging in Alzheimer's Disease.

Area of Science:

• Neuroscience
• Neurology
• Biomarker Discovery

Background:

• Alzheimer's disease (AD) and Lewy body (LB) pathology often coexist in the brain.
• Cerebrospinal fluid (CSF) α-synuclein seed amplification assays (SAA) now allow in vivo detection of LB pathology.
• Understanding the combined impact of AD and LB pathology on neurodegeneration is critical.

Purpose of the Study:

• To investigate the synergistic effects of co-existing Alzheimer's disease and Lewy body pathology on brain aging and neurodegeneration.
• To utilize a deep learning model for brain age estimation in individuals with varying AD and LB pathology profiles.

Main Methods:

• Trained a deep learning model on MRI scans from 4,355 individuals to estimate brain age.
• Applied the model to 803 cognitively impaired participants classified into four AD/LB pathology subgroups.
• Utilized p-tau181/Aβ42 ratio for AD pathology and SAA status for LB pathology determination.

Main Results:

• The Alzheimer's disease + Lewy body pathology (AD+LB+) subgroup showed the most accelerated brain aging.
• Saliency maps indicated more pronounced neurodegeneration in the AD+LB+ group.
• This group also exhibited steeper longitudinal atrophy and greater cognitive deficits.

Conclusions:

• Lewy body pathology synergistically amplifies Alzheimer's disease-related neurodegeneration.
• Combined biomarker assays are essential for identifying individuals with co-existing AD and LB pathology.
• Targeted interventions are needed for patients with combined AD and LB pathology.