Although the previous studies indicated that impaired cerebrospinal fluid (CSF) dynamics might contribute to the pathophysiology of Alzheimer’s disease (AD), the longitudinal changes of CSF volumes in AD has been still unclear. In this study, using the methodology of quantitative assessment of CSF volumes in idiopathic normal pressure hydrocephalus (iNPH), we assessed longitudinal changes in CSF volumes in AD patients.

The subjects were the patients with mild cognitive impairment and dementia due to AD who visited Osaka University Hospital from November 2009 to October 2018. We excluded the patients with gait disturbances and MRI findings such as Disproportionately enlarged subarachnoid-space hydrocephalus (DESH), which was the suggestive finding of iNPH. For each subject, MRI was performed in the first visit and 1 year later. We quantitatively measured CSF volumes in DESH-related regions, such as ventricle systems (VS), Sylvian fissures (SF), and sulci at high convexity and the midline (SHM)., using an automatic brain volumetric software program (AVSIS) (Ishii et al. 2006, 2013). The ratio of each regional volume to the intracranial volume was calculated and we compared these parameters between two visits.

We enrolled 98 patients with AD (mean (SD) age = 76.0 (5.7)). Wilcoxon signed rank test revealed that, while the ratios of CSF volumes in VS and SF significantly increased during the one-year observation (VS: 4.01 (1.05) % vs 4.14 (1.09) %, p<0.001 ;SF: 1.40 (0.21) % vs 1.42 (0.22) %, p=0.007), those in SHM significantly decreased (4.30 (0.70) % vs 4.23 (0.69) %, p<0.001). The change ratio of relative volumes in VS was correlated with those in SF and SHM (r=0.451, p<0.001; r=-0.350, p<0.001).

In patients with AD, the CSF volumes in VS and SF increased while CSF volumes in SHM decreased. This trend of the longitudinal change was similar to the change in the patients with iNPH. The finding of this study indicates that, in the patients with AD, CSF dynamics may be impaired like the patients with iNPH.