Associations of white matter hyperintensities with cerebrovascular architecture in Alzheimer’s disease and related dementias

Abstract

AbstractBackgroundMRI‐detected white matter hyperintensities (WMHs), a marker of cerebrovascular‐pathology, are common in Alzheimer’s disease (AD) and related dementias (ADRDs). In stroke, WMH‐volume was found to correlate most with stroke risk‐factors in the anterior cerebral arterial‐territory. Since the relationship between WMHs and arterial‐territories remains unexplored in the ADRDs, we systematically investigated WMHs’ spatial distribution (1) in 8 ADRDs relative to cognitively unimpaired (CU), and (2) across arterial‐territories per ADRD.MethodsThe extensive CCNA‐COMPASS‐ND cohort (N = 927) allowed us to investigate 9 clinical categories: CU, subjective (SCI) and mild (MCI) cognitive impairment, vascular MCI (V‐MCI), AD, vascular AD (V‐AD), Lewy‐body dementia (LBD), fronto‐temporal dementia (FTD), and Parkinson’s disease (PD) (Fig.1A). FLAIR and T1w MRI‐scans were used to segment WMHs (Dadar et al.,2017). Following registration to standard space, an arterial‐territory atlas (Schirmer et al.,2019) was used to calculate WMH‐volumes in 10 regions (Fig.1B). Statistical analyses were run on whole‐brain‐WMH‐volume and regional‐WMH‐ratios (region‐size‐normalized‐WMH‐volume/whole‐brain‐WMH‐volume). Data‐analyses used a series of linear models accounting for clinical category, age, and sex – followed by pairwise group‐comparisons corrected for multiple comparisons.Results 1) Relative to CU: Whole‐brain‐WMH‐volumes were higher for V‐MCI, V‐AD, and FTD. WMH‐ratios were higher in MCA and LMCA for 2 ADRDs (SCI;V‐MCI) and lower in PCA, LPCA, and RPCA for SCI. WMH‐ratios were higher in ACA or LACA and lower in PCA, LPCA, or RPCA for 4 ADRDs (V‐MCI;V‐AD;FTD;PD) (Fig.1C). Sex‐analyses: Men’s WMH‐volumes were higher in whole‐brain (CU;V‐MCI;FTD), while their WMH‐ratios were higherin LMCA (CU), but lower in ACA (SCI;MCI), LACA (MCI), and RACA (SCI). 2) MCA contained higher WMH‐ratios than ACA and PCA in all clinical categories. Relative to PCA, ACA’s WMH‐ratio was higher in 2 ADRDs (V‐MCI;V‐AD) and lower in 4 (CU;MCI;AD;PD). Pairwise‐group comparisons between all left/right arterial‐territories demonstrated consistent results (Fig.2). Asymmetry‐analyses: The right arterial side had higher WMH‐ratios in ACA (CU;V‐MCI), MCA (CU;SCI;MCI;V‐MCI;AD;V‐AD;PD), and PCA (MCI;AD).ConclusionWe identified arterial‐territories of increased susceptibility to WMH‐formation per ADRD. The two most prevalent ADRDs (AD;V‐AD) were found to accumulate WMHs in a territory‐specific manner – higher WMH‐ratios in ACA for V‐AD and PCA for AD. Overall, the arterial‐territory‐specific WMH‐signatures identified may improve ADRD‐diagnosis accuracy.