Impact of age on the cerebrospinal fluid spaces: high-convexity and medial subarachnoid spaces decrease with age

Abstract

Abstract Background: Impaired cerebrospinal fluid (CSF) dynamics may contribute to the pathophysiology of neurodegenerative diseases. CSF dynamics may play a crucial role in brain health in older people; nonetheless, such age-related changes have not been well elucidated. Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a neuroimaging phenotype of idiopathic normal-pressure hydrocephalus, which originates from impaired CSF dynamics. DESH is closely associated with aging; therefore, this study aimed to investigate the pathophysiology of DESH and determine age-related changes in CSF dynamics.Methods: Using magnetic resonance imaging, we investigated the pathophysiology of DESH by quantitatively evaluating the volumes of DESH-related regions (ventricles [VS], Sylvian fissure [SF], and subarachnoid spaces at high convexity and midline [SHM]) and brain parenchyma in community-dwelling individuals aged ≥65 years. DESH-related regions were assessed using a visual rating scale, and their volumes were measured using voxel-based morphometry. The brain parenchyma volumes were measured using FreeSurfer software.Results: The data of 1,356 individuals were analyzed, and 25 (1.8%) individuals had DESH. Regarding the relationships between the volume of each CSF space and age, VS and SF volumes increased with age, whereas SHM volume decreased with age. The VS and SF volumes increased as the whole brain volume decreased, whereas SHM volume decreased as the whole brain volume decreased; that is, SHM narrowed as brain atrophy progressed. Moreover, lower Mini-Mental State Examination scores were significantly associated with lower SHM volume and higher VS volume. These associations remained significant even when individuals with DESH were excluded.Conclusions: This study showed that the volume of high-convexity and medial subarachnoid spaces decreases with age; the human brain continuously progresses toward a “DESH-like” morphology with aging in community-dwelling older persons (i.e., DESH is an “accelerated aging stage” but not an “age-related disorder”). Our results indicated that brain atrophy is associated with the development of “DESH-like” morphology. In addition, this morphological change, as well as brain atrophy, is an important condition that can cause cognitive decline in older adults. Our findings highlight the importance of investigating the aging process of CSF dynamics in the human brain to preserve brain health in older people.