Clinical Manifestations.

Area of Science:

• Neurology
• Neuroimaging
• Psychiatry

Background:

• Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD) and may indicate early disease stages.
• Previous studies link NPS to increased amyloid-beta (Aβ) and tau pathology, particularly in vulnerable brain regions like the amygdala.
• White matter hyperintensity (WMH) volume and sex differences are also implicated in AD progression and NPS severity.

Purpose of the Study:

• To investigate the associations between NPS and key AD biomarkers: Aβ burden, amygdala tau deposition, and frontal white matter hyperintensity (WMH) volume.
• To explore potential sex-based differences in these associations, hypothesizing stronger links in females due to their higher reported NPS prevalence.

Main Methods:

• Utilized PET imaging (amyloid and tau) and MRI (WMH volume) in 208 cognitively unimpaired participants from the PREVENT-AD cohort.
• Employed linear regression models with sex as an interaction term to analyze the relationship between NPS (apathy, anxiety, depression, stress, perseverative thinking, neuroticism) and biomarkers.
• Controlled for age, education, APOE4 status, and cardiovascular risk factors in all analyses.

Main Results:

• Found significant associations between NPS and AD markers, particularly WMH volume, which were more pronounced in males than females.
• Observed associations between stress and depression with amyloid and amygdala tau in males.
• Identified an association between perseverative thinking and amygdala tau in females.

Conclusions:

• Confirmed associations between NPS and AD biomarkers (MRI and PET) in at-risk, cognitively unimpaired individuals.
• Contradicted the initial hypothesis by revealing stronger associations in males for certain markers, despite females' higher NPS prevalence.
• Highlights the complex interplay between NPS, sex, and AD pathology, warranting further investigation into sex-specific mechanisms.