Dementia is caused by a multitude of neurological disorders. Among the most common are Alzheimer’s disease (AD), frontotemporal dementia (FTD) and normal pressure hydrocephalus (NPH). Multiple overlapping signs and symptoms between the different types of cognitive impairment create diagnostic challenges, and thus, it can be difficult to correctly diagnose the cause of dementia. Therefore, there is a pressing need to identify biomarkers that can accurately differentiate between dementia subtypes. This is important for appropriate patient therapy and clinical trial inclusion ⁽¹⁾. Magnetic Resonance Elastography (MRE) is a noninvasive technique capable of quantitatively measuring tissue stiffness in vivo. Previous studies have investigated the role of brain MRE in AD ^{(2, 3)}, FTD ⁽⁴⁾ and NPH ^{(5, 6)}. The purpose of this study was to report on age and sex bias -corrected brain MRE findings across three dementia cohorts (AD, FTD, and NPH) and to investigate the potential diagnostic role of MRE to help differentiate between dementia subgroups.MRE was performed on 20 NPH patients (age range: 60-86 years), 8 AD patients (78-87 years), 5 FTD patients (54-65 years), and 46 cognitively normal volunteers as controls (56-89 years). Image acquisition was conducted on a 3 Tesla MRI scanner (GE Healthcare, Waukesha, WI). Shear waves with 60 Hz vibration frequency were transmitted into the brain by a pillow-like passive driver. A post-processing technique ⁽⁷⁾ was implemented to determine the median magnitude of the complex shear modulus (|G*|) across different brain regions. Eight regions of interest (ROIs) were examined: cerebrum (entire brain excluding cerebellum), frontal, occipital, parietal, and temporal lobes, deep grey matter/white matter (GM/WM), sensorimotor cortex and cerebellum. All stiffness measurements were age and sex -corrected using a general linear model with the parameters reported in Table 1 as previously described ⁽⁸⁾, with stiffness being defined as |G*| rather than the square of the shear wave speed. The |G*| of each region was compared between dementia subgroups and normal controls using a two-population unpaired t-test for statistical analysis and p<0.05 was considered significant.

The cerebrum of AD and FTD patients showed significant decreases in |G*| compared to cognitively normal controls (p<0.001), while NPH patients showed increased cerebral stiffness that did not reach statistical significance. The NPH group showed significant stiffening of the parietal (p=0.001), occipital and sensorimotor regions (p<0.001), in contrast to softening or no significant stiffness changes in the AD and FTD groups. The temporal lobe in FTD patients showed exclusive significant softening (p=0.003). The frontal lobe and deep grey matter/white matter stiffness values of all three groups (AD, FTD and NPH) were significantly decreased compared to normal controls, and no significant stiffness changes were observed in the cerebellum in any of the groups. A summary of the results is shown in Table 2.

This study demonstrated that AD stiffness changes occurred mostly in the frontal, parietal and temporal lobes in accordance with the known topography of AD pathology. FTD regional differences also occurred most prominently in areas of expected anatomic involvement (the frontal and temporal lobes). NPH, on the other hand, showed increased stiffness of the occipital and parietal lobes, as well as the sensorimotor cortex, possibly due to the low compliance and parenchymal compression of these regions by the enlarged ventricles against the calvarium. (Figures 1, 2)Distinct patterns of regional brain stiffness changes are observed in each of the different dementia groups. MRE offers a potential biomarker to characterize the viscoelastic properties of the brain in dementia patients, and may have a role in the diagnosis and differentiation between common subtypes of dementia.