Body Mass Index Decrease Has a Distinct Association with Alzheimer's Disease Pathophysiology in APOE ɛ4 Carriers and...

Area of Science:

• Neuroscience
• Genetics
• Gerontology

Background:

• Body mass index (BMI) changes are potentially linked to Alzheimer's disease (AD) pathology.
• The influence of the apolipoprotein E ɛ4 (APOE ɛ4) allele on this association remains unclear.

Purpose of the Study:

• To investigate the relationship between BMI changes and AD pathologies.
• To differentiate these associations based on APOE ɛ4 carrier status.

Main Methods:

• Analysis of 862 non-demented participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with at least two BMI measurements.
• Examined associations between BMI slopes and longitudinal changes in amyloid-beta (Aβ) accumulation, neurodegeneration, cognition, and tau deposition.
• Stratified analyses by Aβ and APOE ɛ4 status.

Main Results:

• In individuals with amyloid-beta plaques and without the APOE ɛ4 allele, faster BMI declines were associated with increased Aβ accumulation, brain hypometabolism, memory decline, and executive dysfunction.
• Among individuals without amyloid-beta plaques, faster BMI decreases correlated with faster Aβ accumulation in APOE ɛ4 carriers.
• Faster BMI declines were linked to cognitive decline (memory and executive function) in both APOE ɛ4 carriers and non-carriers without amyloid-beta plaques.

Conclusions:

• Body weight fluctuations, particularly declines, are significantly associated with Alzheimer's disease progression.
• The APOE ɛ4 genotype modulates the relationship between BMI changes and AD biomarkers and cognitive decline.
• Monitoring BMI in older adults offers valuable insights into AD risk and progression, especially when considering genetic factors.