Fig. 5: Exploratory analysis of vascular, α-synuclein (Lewy body) and TDP-43 copathology features in T/N_M susceptible groups.

a Representative ¹⁸F-FDG SUVR images from six patients. Susceptible patients shown here have imaging findings consistent with copathology (sagittal views are slices through the right hemisphere). Vascular pathology features in susceptible groups included greater (b) vascular risk factors and (c) subcortical infarcts. The cortical susceptible group had participants with (a) cingulate island sign, the sparing of posterior cingulate cortex (white arrowheads) relative to cuneus (black arrowheads) in representative ¹⁸F-FDG images, quantified by higher (d) cingulate island ratio across groups. The cortical susceptible group had (e) significantly worse clock drawing scores and trended toward greater (f) proportion of participants with hallucinations on the Neuropsychiatric Inventory (NPI) item B and worse (g) ADNI visuospatial z-scores than the other groups. The limbic susceptible group had participants with (a) medial temporal lobe (MTL) and frontal supraorbital (FSO) ¹⁸F-FDG hypometabolism (white arrowheads) relative to inferior temporal gyrus (I, black arrowheads) in representative ¹⁸F-FDG images, quantified by larger (h) I/MTL/FSO ¹⁸F-FDG ratio and worse MTL asymmetry in (i) ¹⁸F-FDG SUVR and (j) thickness. The limbic susceptible group had the significantly worse (k) categorical fluency, (l) language and (m) memory z-scores. Box plots show data points as dots, mean as an X symbol, median as the middle box line, first quartile (Q1) and third quartiles (Q3) as box edges (denoting the interquartile range, IQR), whiskers as the minimum/maximum points and outliers based on thresholds <Q1 − 1.5(IQR) or >Q3 + 1.5(IQR). Cognitive test comparisons included A status, education, sex and age as covariates. Significant differences in pairwise comparisons by two-tailed likelihood ratio tests are denoted by *p < 0.05, **p < 0.005. These results were not corrected for multiple comparisons due to their exploratory nature. Sample sizes and p values are provided in Supplementary Data 1. Source data are provided as a Source Data file.