Associations of ventriculomegaly and white matter hyperintensities with glymphatic dysfunction in idiopathic normal pressure hydrocephalus

Objectives: To investigate glymphatic function in idiopathic normal pressure hydrocephalus (iNPH) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and to explore the associations of ALPS index with ventriculomegaly and white matter hyperintensities (WMH).

Materials and methods: This study included 41 patients with iNPH and 40 age- and sex-matched normal controls (NCs). All participants underwent brain MRI. Based on DTI, we then calculated the ALPS index to obtain the water diffusivity along the perivascular space. Ventricular volume and WMH were also determined. Differences in the diffusivities and ALPS indexes between the iNPH and NC groups were investigated; associations of the DTI-ALPS index with ventriculomegaly and WMH were analysed.

Results: Patients with iNPH had a lower ALPS index than NCs (p < 0.001). The ALPS index was significantly correlated with the normalised ventricular volume (r = -0.446, p = 0.004), but not with total WMH volume (r = -0.246, p = 0.126). Further regression analyses indicated that the reduced ALPS index was associated with increased ventricular volume (β = -7.158, p = 0.016), but not with normalised WMH volume (β = -2.796, p = 0.161). The receiver operating characteristic analysis demonstrated the ALPS index's excellent diagnostic performance for iNPH (the optimal cut-off point = 1.322; sensitivity, 100.0%; specificity, 87.5%; AUC = 0.980).

Conclusions: Patients with iNPH had a lower ALPS index, which may suggest impaired glymphatic function. This study demonstrated an association of DTI-ALPS index with ventriculomegaly, but not WMH in patients with iNPH.

Key points: Question Glymphatic dysfunction is crucial in idiopathic normal pressure hydrocephalus (iNPH) development, yet its associations with neuroimaging features remains unclear. Findings Diffusion tensor image analysis along the perivascular space (DTI-ALPS) revealed a reduced ALPS index in idiopathic normal pressure hydrocephalus, negatively correlating with ventricular volume. Clinical relevance DTI-ALPS enables non-invasive assessment of glymphatic function and its relationship with neuroimaging characteristics in idiopathic normal pressure hydrocephalus, facilitating the investigation of glymphatic dysfunction in iNPH pathophysiology.