Brain Imaging Abnormalities in Mixed Alzheimer’s and Subcortical Vascular Dementia

Abstract

Background: A large proportion of Alzheimer’s disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity. Objective: To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD. Methods: We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures. Results: Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD). Conclusion: These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.

Towards in vivo MRI-based diagnostics and tracking of dementia

“…Considering an exhaustive set of neuropathologies, we found a significant association between cerebrovascular and tau pathology severity with WMH burden. This supports the previously reported link between AD and WMHs independently of comorbid vascular pathology [259][260][261].…”

“…AD neuropathology, as well as disease severity in patients presenting it, are also associated with WMH burden [259]. This relation cannot be explained solely by comorbid vascular disease, as higher WMH volumes have been found in individuals with clinically-defined mixed AD and VaD compared to patients presenting only one of the two [260]. Exploring the separate effects of AD hallmarks on WMHs, some studies found these lesions are associated with amyloid-β but not to tau [261][262][263], while others reported the opposite [264,265].…”

Neuroimaging in Dementia

“…Patients with mixed AD and vascular pathologies show greater levels of white matter hyperintensities and more advanced white matter degeneration on structural MRI and DWI relative to those with AD only or vascular cognitive impairment only. 62 Mixed dementia cases have also been shown to have more rapid degeneration in motor function, such as gait and grip strength. 63 Cerebrovascular risk factors in both cognitively impaired patients and cognitively normal patients provide additive risk for cognitive decline, although this may vary by ethnicity, as well as more prominent perivascular spaces and white matter hyperintensities on MRI.…”

“…At this time, only AD and vascular pathologies can be visualized in vivo, because other notable pathologies (eg, α-synuclein, TDP-43, fused in sarcoma [FUS]) can be assessed only at autopsy. Patients with mixed AD and vascular pathologies show greater levels of white matter hyperintensities and more advanced white matter degeneration on structural MRI and DWI relative to those with AD only or vascular cognitive impairment only 62 . Mixed dementia cases have also been shown to have more rapid degeneration in motor function, such as gait and grip strength 63 .…”