Distinct patterns of microstructural brain changes in Alzheimer's disease subtypes: Diffusion MRI metrics in braak stage-related regions

BackgroundAlzheimer's disease (AD) is pathologically defined by the accumulation of amyloid-β and phosphorylated tau and subsequent neuronal death. These neuropathological changes typically accumulate in the medial temporal lobe before spreading to other cortical regions (Braak staging pattern). Recent studies using postmortem brain tissue and neuroimaging data have revealed AD subtypes with distinct neuropathological patterns. Hippocampal-sparing (HpSp) subtype of AD shows the preservation of medial temporal lobe volume, compared to typical AD; however, underlying changes in the brain microstructure remain largely unclear.ObjectiveWe used Neurite Orientation Dispersion and Density Imaging (NODDI) to investigate the microstructural signatures in each AD subtype.MethodsWe defined typical and HpSp AD based on visual assessment scales of brain MRI, among individuals with mild cognitive impairment who were positive for core AD cerebrospinal fluid markers. We set regions of interest in Braak stage (BS)-related areas (hippocampus (BS II), precuneus (BS V), and postcentral gyrus (BS VI)) and compared NODDI metrics, including intracellular volume fraction, orientation dispersion index, and isotropic volume fraction (Viso), among typical AD, HpSp AD, and non-AD control groups.ResultsNODDI metrics in the hippocampus were significantly different between the typical and HpSp AD groups. Notably, the hippocampal NODDI values in the HpSp AD group were comparable to those of the control group. Viso values in the precuneus were significantly higher in HpSp AD, compared to typical AD.ConclusionsThis suggests that AD subtypes have distinct patterns of microstructural changes in BS-related brain regions.