Delusional Severity Is Associated with Abnormal Texture in FLAIR MRI

Area of Science:

• Neuroimaging
• Neurology
• Biomarkers

Background:

• Cognitive impairment in adults, including mild cognitive impairment (MCI) and Alzheimer's Disease (AD), can be associated with delusions.
• Quantifying brain changes in normal appearing brain matter (NABM) may offer insights into delusion severity.

Purpose of the Study:

• To investigate the relationship between brain imaging biomarkers in NABM and the severity of delusions in cognitively impaired adults.
• To explore potential associations with cerebrospinal fluid (CSF) tau and APOE4 status.

Main Methods:

• Analysis of FLAIR MRI data from 42 participants (24 MCI, 18 AD) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
• Automated segmentation of NABM (gray and white matter) and computation of volume, Integrity, and Damage biomarkers.
• Multivariable regression analysis correlating biomarkers with delusion severity (mild, moderate, severe), adjusting for covariates like age, sex, education, APOE4, and CSF tau.

Main Results:

• All three NABM biomarkers were significantly associated with the difference between severe (level 3) and mild (level 1) delusions.
• The Integrity biomarker also differentiated between mild (level 1) and moderate (level 2) delusions.
• Significant interactions were found between severe delusions, CSF tau, and all imaging biomarkers. APOE4 homozygotes also showed significant relationships with biomarkers.

Conclusions:

• More severe delusions in cognitively impaired older adults are linked to a greater global brain disease burden in NABM, as measured by FLAIR MRI.
• Tissue degeneration in NABM is more pronounced in individuals with higher delusional symptom severity, with a notable association with CSF tau.
• Further research is needed to elucidate the tau-associated mechanisms underlying increased delusion severity.