Ventricular anteroposterior ratio is the most reliable feature to differentiate bvFTD from healthy controls and other dementias

Abstract Background Using morphometric analysis, we recently found ventricular expansion to be the most prominent differentiator of behavioural‐variant frontotemporal dementia (bvFTD) from healthy controls and a potentially sensitive marker of disease progression [Manera et al. 2019]. Here, we performed volumetric analysis on the lateral ventricles to find a reliable differentiator of bvFTD from Alzheimer’s Disease (AD), mild cognitive impairment (MCI), the language variants of FTD (Semantic‐Variant, SV, and Progressive‐Nonfluent‐Aphasia, PNFA), and controls. Method We included 825 subjects (59 bvFTD, 28 SV, 30 PNFA, 322 MCI, 127 AD, and 259 controls) with a total of 3800 timepoints from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI). Lateral ventricles were automatically segmented for all timepoints, using a previously validated pipeline. Using a lobe atlas, ventricular volumes (VV) were calculated for frontal, parietal, temporal, and occipital lobes in the left and right hemispheres. Using coronal slice y=120 in the brain atlas, ventricles were also divided into anterior and posterior halves. All volumes were normalized for intracranial volume and log‐transformed to achieve normal distribution. Regression models were used to assess volumetric and ratio differences between cohorts at baseline (Model1:feature∼1+Diagnostic‐Group+Age+Sex). Longitudinal mixed‐effects models were used to assess longitudinal differences in ventricular features (antero‐posterior ventricular ratio and total VV) between bvFTD and other cohorts (Model2:feature∼1+ Diagnostic‐Group +Age+ Diagnostic‐Group:Age+Sex+1|ID). The variables of interest were Diagnostic‐Group (Model 1) and the interaction between Diagnostic‐Group and Age (Diagnostic‐Group:Age, Model 2). ID was considered as a categorical random effect. All results were corrected for multiple comparisons (Bonferroni). Result Figures 1 and 2 show the volumetric and ratio differences between cohorts. Controlling for age and sex, the antero‐posterior ratio was the only feature that was significantly different in bvFTD (Mean±SD:1.37±0.47) compared to all other diagnostic groups (Controls:1.00±0.24,p<0.001; MCI: 0.97±0.22,p<0.001; AD: 0.92±0.22,p<0.001; SV:1.00±0.22,p<0.001; PNFA:1.12±0.48,p=0.004). Total ventricle volume increased with age in all cohorts (p<0.001,Figure 3). bvFTD patients showed a faster increase in the ventricular antero‐posterior ratio compared to all other diagnostic groups (Figure 4, p<0.01). Conclusion The antero‐posterior ratio of the lateral ventricles, in both cross‐sectional and longitudinal analyses, was the most reliable ventricular feature differentiating bvFTD from controls and other dementias.

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