Differential dementia diagnosis using event‐based modelling: Alzheimer’s disease versus Dementia with Lewy Bodies

Abstract

AbstractBackgroundDifferential diagnosis of dementias in the clinic is challenging, especially in the prodromal phase where early symptoms overlap. Here we prototype a differential diagnosis system based on event‐based modeling of MRI atrophy in two dementias.MethodPublic data from ADNI, NACC, PPMI, PDBP (N = 1978). Inclusion criteria: baseline T1w‐MRI successfully processed by FreeSurfer 7.1.1, CN/AD/DLB/MCI diagnosis. A nearest‐neighbour approach matched disease‐specific control groups to AD and DLB by Age/Sex/scanner (field strength), and Desikan‐Killiany volumes were adjusted for normal trends in Age/Sex/field‐strength/intracranial volume. The final analysis dataset consisted of 91 DLB, 298 AD, and 786 MCI (N = 1175), with matched control groups for each.One event‐based model (EBM) of regional brain atrophy was fit per disease, using Kernel Density Estimation mixture models to quantify biomarker abnormality. Input features were brain volumes having disease signal in both AD and DLB.The EBM patient‐staging tool was adapted to perform differential diagnosis. The tool converts individual data into a probability distribution over stages — stage likelihood — for each model. We define EBM diagnosis as the model having the maximum stage likelihood.ResultFigure 1 shows the event‐based model posterior (positional variance diagram) for AD (left) and DLB (right). AD atrophy starts in a subset of limbic regions before progressing to the temporal cortex and beyond. The DLB atrophy pattern diverges considerably (off‐diagonal density in Figure 1), including involvement of additional limbic regions early on. Figure 2 shows patient staging results for each model, with MCI individuals earlier than patients as expected. Differential diagnosis accuracy was 63%, which is comparable to previous studies.ConclusionWe successfully adapted event‐based modeling of MRI atrophy for differential diagnosis of AD vs DLB. More data for other dementias, especially in the prodromal phase, is needed to test and deploy such a tool in memory clinics.