Alcohol Intake Differentiates AD and LATE: A Telltale Lifestyle from Two Large-Scale Datasets

TL;DR

This study identifies alcohol consumption as a key differentiating lifestyle factor between AD and LATE, revealing that light-to-moderate drinking may offer protective effects, especially in APOE e4 carriers, based on analysis of large datasets.

Contribution

It introduces an integrated feature selection approach to distinguish risk factors for AD and LATE, highlighting alcohol intake's differential impact in specific subpopulations.

Findings

Light-to-moderate alcohol intake is protective against AD and LATE.

Protective effects are stronger for AD than LATE.

APOE e4 carriers show notable associations with alcohol consumption effects.

Abstract

Alzheimer's disease (AD), as a progressive brain disease, affects cognition, memory, and behavior. Similarly, limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently defined common neurodegenerative disease that mimics the clinical symptoms of AD. At present, the risk factors implicated in LATE and those distinguishing LATE from AD are largely unknown. We leveraged an integrated feature selection-based algorithmic approach, to identify important factors differentiating subjects with LATE and/or AD from Control on significantly imbalanced data. We analyzed two datasets ROSMAP and NACC and discovered that alcohol consumption was a top lifestyle and environmental factor linked with LATE and AD and their associations were differential. In particular, we identified a specific subpopulation consisting of APOE e4 carriers. We found that, for this subpopulation, light-to-moderate alcohol intake was a protective factor against both AD and LATE, but its protective role against AD appeared stronger than LATE. The codes for our algorithms are available at https://github.com/xinxingwu-uk/PFV.