Assessment of diffusivity along the perivascular space in early- and late-onset Alzheimer's disease

Abstract

Background

Cerebrospinal fluid (CSF) dynamics plays a key role in clearing soluble amyloid-β from the brain, which may impact Alzheimer's disease (AD) onset.

Objective

This study seeks to differentiate cerebrospinal fluid dysfunction between early-onset AD (EOAD) and late-onset AD (LOAD) subtypes and to examine their associations with brain changes and cognitive function.

Methods

We performed in vivo imaging measurements on 40 EOAD patients, 38 LOAD patients, 69 age-matched young normal controls (YNC), and 60 old normal controls (ONC). Measured variables included diffusion tensor imaging along the perivascular space (DTI-ALPS, subdivided into left, right, and mean), amyloid and tau PET standardized uptake value ratios (SUVR), hippocampus volume, and white matter hyperintensities (WMH) volume. For normally distributed variables, we used ANOVA to assess group differences, followed by Tukey's HSD test for multiple comparison correction. Results without correction are marked. Pearson correlation and linear regression analyzed relationships between the DTI-ALPS index, brain parameters, and cognition within each subgroup.

Results

Both EOAD (p < 0.05, uncorrected) and LOAD (p < 0.05, corrected) showed a lower DTI-ALPS index compared to controls. This lower index was associated with increased disease severity and worsening cognitive performance. In EOAD, the lower DTI-ALPS index was primarily linked to amyloid (Std beta = −0.463, p = 0.008), while in LOAD, it was predominantly associated with age (Std beta = −0.348, p = 0.006) and WMH (Std beta = −0.330, p = 0.009).

Conclusions

This observation suggests that differences in the etiology of cerebrospinal fluid dysfunction may exist between these AD subtypes, warranting further investigation to confirm these hypotheses.