Choroid Plexus Volume, Amyloid Burden, and Cognition in the Alzheimer's Disease Continuum

Abstract

As a part of the glymphatic system, the choroid plexus (CP) is involved in the clearance of harmful metabolites from the brain. We investigated the association between CP volume (CPV), amyloid-β (Aβ) burden, and cognition in patients on the Alzheimer's disease (AD) continuum. We retrospectively reviewed the records of 203 patients on the AD continuum and 82 healthy controls who underwent brain magnetic resonance imaging and ¹⁸F-florbetaben positron emission tomography. Automatic segmentation was performed, and the CPV was calculated. Cognitive function was assessed using detailed neuropsychological tests, and patients on the AD continuum were categorized into the non-dementia and dementia groups. The relationships between CPV, Aβ burden, and cognitive function were assessed using multivariate linear regression and linear mixed model. CPV was greater in the AD group than in the healthy control group (1.50 vs. 1.30, P < 0.001), but was comparable between the AD non-dementia and dementia groups (1.50 vs. 1.48, P = 0.585). After adjusting for age and sex, a larger CPV was significantly associated with greater global Aβ deposition (β = 0.20, P = 0.002). Larger CPV was also associated with worse general cognitive function assessed using the sum of boxes of the clinical dementia rating scale (β = 0.85, P = 0.034) and lower composite scores for memory (β = -0.68, P = 0.002) and frontal/executive function domains (β = -0.65, P < 0.001). In addition, a larger CPV was associated with a more rapid decline in Mini-Mental State Examination scores in the AD dementia group (β = -0.58, P = 0.004). The present study demonstrated that CP enlargement was associated with increased Aβ deposition and impaired memory and frontal/executive function in patients on the AD continuum.

Figure 1.

A representative automatic segmentation results from a patient using FastSurfer. The CP volume labels are highlighted in yellow. For visualization purposes, a 3D rendered CP mask is shown at the bottom right. CP = choroid plexus

Figure 2.

Rain-cloud plots of MR volumetric imaging markers in the normal control, non-dementia AD, and dementia AD groups. MR = magnetic resonance; AD = Alzheimer's disease; CP = choroid plexus; LV = lateral ventricle; WMH = white matter hyperintensity. *Uncorrected P < 0.05; ** uncorrected P < 0.01; *** uncorrected P < 0.001; **** uncorrected P < 0.0001.

Figure 3.

Scatter plot of CP volume and amyloid burden (A) or cognitive function (B) in all participants (normal control, non-dementia AD, and dementia AD groups). CP = choroid plexus