Abnormalities of CSF flow patterns in the cerebral aqueduct in treatment-resistant late-life depression: a potential biomarker of microvascular angiopathy.

There is growing evidence that microvascular angiopathy (MVA) plays an important role in the development of dementia and affective disorders in older people. At currently available image resolutions it is not possible to image directly the vascular changes associated with MVA, but the effects on blood and cerebrospinal fluid (CSF) flow may be detectable. The aim of this study was to investigate a potential biomarker for MVA based on MRI of abnormalities in CSF flow. Since there is considerable indirect evidence that treatment resistance in late-onset depressive disorder is related to MVA, we assessed the method in a group of 22 normal volunteers and 29 patients with responsive (N=21) or treatment-resistant (N=8) late-onset depressive disorder. Single-slice quantified phase-contrast (PC) images of cerebral blood and CSF flow were collected at 15 points over a cardiac cycle, and the resulting flow curves were parameterized. Significant differences in the CSF flow (width of systolic flow peak and diastolic flow volume, both P<0.01) through the cerebral aqueduct were observed for the group of treatment-resistant patients when compared to age matched controls. No significant difference was observed for a group of 21 patients with treatment-responsive depression. The findings support the hypothesis that MR measurement of CSF flow abnormalities provides a biomarker of MVA, and thus could have application in a wide range of age-related diseases.