EP Visualization of Perivascular Spaces on 3T MR Images of Alzheimer Patients: University Hospital-based Dementia Cohort Study Toshinori Hirai 1,4, Hiroyuki Uetani 1, Mamoru Hashimoto 2, Manabu Ikeda 2, Minako Azuma 1, Mika Kitajima 1, Yasuyuki Yamashita 1 Departments of Diagnostic Radiology 1 and Psychiatry and Neuropathobiology 2, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Department of Radiology 4, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

☑ The author has no conflict of interest to disclose with respect to this presentation.

INTRODUCTION Alzheimer’s disease (AD) is the commonest dementia. One major characteristic of its pathology is accumulation of amyloid-b (Ab) as insoluble deposits in brain parenchyma and in blood vessel walls [cerebral amyloid angiopathy (CAA)]. The distribution of Ab deposits in the basement membranes of cerebral capillaries and arteries corresponds to the perivascular drainage pathways by which interstitial fluid (ISF) and solutes are eliminated from the brain—effectively the lymphatic drainage of the brain. Failure of perivascular drainage of Ab and deposition of Ab in the arterial walls has two major consequences: (i) intracerebral hemorrhage associated with rupture of Ab-laden arteries in CAA; and (ii) AD in which failure of elimination of ISF, Ab and other soluble metabolites from the brain alters homeostasis and the neuronal environment resulting in cognitive decline and dementia. Weller RO, et al. Brain Pathology 2008;18: 253–266

PURPOSE Although conventional MRI can show the perivascular spaces (PVS) of the brain, there are no systematic studies investigating PVS of the brain in AD patients. The aim of this study was to investigate changes in the visualization of PVS in AD patients in a university hospital-based dementia cohort study.

MATERIALS AND METHODS 35 patients with AD (16 men, 19 women, mean age 75±8.9 years), MMSE: 11-26, mean age-matched patients with subjective complaints (SC) (6 men, 9 women, mean age 73±7.7 years) When all clinical findings were normal we recorded SC All underwent baseline and follow-up 3T MRI at least 9 months apart 2 senior neuropsychiatrists diagnosed on the basis of pre- established criteria for probable AD of the National Institute of Neurologic Disorders and Stroke/Alzheimer Disease and Related Disorders (NINCDS-ADRDA)

3T unit (Magnetom Trio, Siemens, Germany) MR protocol: MPRAGE, T2WI, FLAIR, SWI, MRA TR/TE eff (ms) Matrix FOV (mm) Section thickness (mm) T2WI MPRAGE 3600/ x mm MRI 1900/ x mm

Evaluation of PVS Independent analysis by 2 neuroradiologists Parenchymal hyperintensity areas on axial T2-weighted images with an effective diameter of <3 mm, no FLAIR hyperintensity, and T1 hypointensity were considered to represent PVS Assessment of the baseline and follow-up MR images for the visualization of PVS in the gyri above the centrum semiovale using a 4-point system: grade 3 = visualization of PVS in more than two-thirds of the gyri grade 2 = visualization of PVS in one- to two-thirds of the gyri grade 1 = visualization of PVS in less than one-third of the gyri grade 0 = no visualization of PVS in any gyri

Statistical analysis Interobserver agreement was determined with the κ coefficient Differences in the mean scores of the 2 patient groups were as assessed with the Mann-Whitney test and Fisher’s exact test Significant difference: p < 0.05

RESULTS For the PVS grading score on baseline and follow-up MR images interobserver agreement was very good (κ = 0.86 and κ = 0.82, respectively). The mean score for the baseline MRI study was 1.60 ± 0.77 for AD- and 1.93 ± 0.83 for SC patients; the difference was not statistically significant. On follow-up MR studies the PVS score fell in 11 of 35 (31%) AD patients (Fig 1); it rose in 1 of 15 (7%) SC- but not in any AD patients. In AD patients there was a significant difference between the baseline and follow-up MR studies (p < 0.05), whereas no significant difference was found for SC group (Fig 2).

Fig 1. A 77-year-old woman with AD Baseline T2WI Grade 2 2-year follow-up T2WI Grade 1

AD patient group SC group Fig 2. Change of PVS visualization between the baseline and follow-up MR studies

DISCUSSION The association between age and the severity of PVS was consistently detected in previous studies. Although our study was a relatively short-period follow-up study, the PVS score fell in 11 of 35 (31%) AD patients and rose in 1 of 15 (7%) SC- but not in any AD patients. These results indicate that AD and aging differently affects the size of PVS: decreasing effect for AD and increasing effect for aging. In AD, the distribution of Ab deposits in the basement membranes of cerebral capillaries and arteries corresponds to the perivascular drainage pathways. This phenomenon may explain our results.

CONCLUSION Our pilot study showed that PVS visualization on follow-up 3T MRI decreased in about one-third of patients with AD. A change in the visualization of PVS on 3T MRI may be a useful diagnostic marker for AD.

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