FIGURE 1
Figure 1. Flowchart of patient inclusion.
Data Acquisition
The PC-MRI was performed using a 1.5-T machine. Conventional morphologic image sequences were first acquired in the sagittal and axial planes. The CSF flow acquisition planes were then selected perpendicular to the presumed direction of flow through the Sylvius aqueduct [representing the ventricular flow (Jacobson et al., 1996)] and the spinal C2-C3 sub-arachnoid spaces (representing the spinal flow). Flow images were acquired using a velocity-encoded phase-contrast pulse sequence with peripheral gating, as previously described (Baledent et al., 2001, 2004). Velocity sensitization was set at 10 cm/s for the ventricular flow and 5 cm/s for the spinal flow.
Data Analysis
Phase-contrast magnetic resonance imaging data were transferred to a Sparc 10 workstation (SUN Microsystems) and analyzed using an in-house image processing software with Interactive Data Language (Baledent et al., 2001). This software automatically measures the CSF flow curve over the cardiac cycle for a given region of interest. Cranial–caudal flows were positive (CSF flush), whereas caudal–cranial flows were negative (CSF fill). The difference between CSF fill and flush flows is the net CSF flow, which reflects the volume of CSF produced (Nilsson et al., 1994). For technical reasons, intracranial sub-arachnoid CSF flow was not investigated.
Neurocognitive Assessment
All patients underwent a battery of neurocognitive tests that assessed global cognitive status, memory, executive functions, praxis, as well as depression and anxiety (Table 2). Global cognitive efficiency was assessed by the Mini-Mental State Examination (MMSE) (Folstein et al., 1975), standard of Kalafat et al. (2003), following the GRECO standardization and calibration, and the Mattis Dementia Rating scale (MDRS) (Hersch, 1979; Gardner et al., 1981). The memory domain was assessed using the Wechsler Adult Intelligence Scale (WAIS-III) – Digit Span task (Iverson and Tulsky, 2003; Hill et al., 2010) and the Grober-Buschke (GB) test (French version of the Free and Cued Selective Reminding Test) (Buschke, 1984; Grober et al., 1988; Grober and Kawas, 1997; Van der Linden and Juillerat, 2004). Instrumental cognition was assessed with Signoret’s Battery of Cognitive Efficacy (BEC 96) (visuo-constructive subscale) (Jacus et al., 2001). Attention and executive domains were assessed using the Stroop Color and Words Test (Comalli et al., 1962), as well as two categoric and semantic verbal fluency tests, as impaired semantic fluency is a predictor of progression to AD (Vaughan et al., 2018) and categoric fluency may be impaired in amnesic MCI (Balthazar et al., 2007). In addition, the patients were evaluated with the Montgomery-Asberg Depression rating scale (MADRS) (Montgomery and Asberg, 1979), on 60 points, and the Goldberg anxiety scale (Goldberg et al., 1987; Huber et al., 1999) on 9 points, to rule out effects of depression or anxiety on cognitive test results.
Mild cognitive impairment was diagnosed based on the criteria of Petersen et al. (Petersen et al., 2001), while AD and AD-like diseases were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) and the recommendations of the National Institute on Aging – Alzheimer’s Association workgroups (McKhann et al., 2011).
Vascular risk factors were diagnosed based on a comprehensive geriatric assessment performed at our geriatric unit. Blood samples were obtained after a minimum of 10 h of fasting. The diagnosis of diabetes was attributed with blood glucose levels above 7 mmol/L, anemia with hemoglobin levels below 12 (women) or 13 (men) g/dL and inflammation with CRP levels above 10 mg/L. Likewise, the reference range was 4.1–6.5 mmol/L for total cholesterol, 0.6–1.8 mmol/L for triglycerides and 35–50 g/L for Albumin. Malnutrition was defined by Albumin levels