Regional brain atrophy is associated with measures of impaired blood‐CSF barrier in patients with prodromal and overt dementia with Lewy bodies and Alzheimer’s disease dementia

Abstract

AbstractBackgroundAlzheimer’s disease (ADdem) and Lewy body dementia (DLB) are characterized by cholinergic impairment and regional brain atrophy including the medial‐temporal and temporo‐parietal regions. In DLB, the overlapping AD pathology is associated with more prominent atrophy. However, other factors than AD pathology play role in brain atrophy and clinical impairmentl. The choroid plexus (CP), part of blood‐CSF barrier, is central in regulating inflammation and monitoring the CSF synthesis, composition, and circulation. However, association between measures of blood‐CSF barrier impairment and regional brain atrophy, and the effect of AD biomarkers in this association, remain unknown in prodromal and overt AD and DLB.MethodWe included 108 participants from the Czech Brain Aging Study (n = 30 prodromal AD, n = 24 ADdem, n = 10 prodromal DLB, n = 20 overt DLB, n = 24 cognitively unimpaired controls, CN) who underwent clinical/cognitive testing, brain MRI and CSF sampling. FreeSurfer automated algorithm and cholinergic basal forebrain ROIs were used to measure CP volumes and nucleus basalis of Meynert (NBM) and other regional cortical thickness and volumes. From CSF, the established AD biomarkers and an albumin quotient (QAlb), a proxy of blood‐CSF barrier impairment, were derived. Associations were measured using multivariate analysis of variance adjusted for age, sex; mediation analysis was used to assess effect of CSF AD biomarkers on associations between atrophy and blood‐CSF impairment.ResultCP volume was significantly larger and NBM volume was smaller in both DLB and AD compared to CN, and the CP volume increased from prodromal to overt dementia stages. Larger CP volumes were associated with smaller NBM volumes in AD and DLB prodromal and overt stages. Larger CP volumes were associated with abnormal QAlb, and with more abnormal levels of AD biomarkers. More abnormal AD biomarker levels mediated the association between larger CP volumes, abnormal AlbQ and regional atrophy in AD and DLB.ConclusionMeasures of impaired blood‐CSF barrier by enlarged CP and AlbQ are associated with more profound regional atrophy including cholinergic regions from prodromal to overt dementia stages. Whereas AD‐related pathology likely plays role in this, investigating the blood‐CSF barrier as a potential treatment target may be beneficial for AD and DLB patients.