Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients

Finsterwalder, Sofia; Vlegels, Naomi; Gesierich, Benno; Caballero, Miguel Ángel Araque; Weaver, Nick A.; Franzmeier, Nicolai; Georgakis, Marios K.; Konieczny, M.; Koek, Huiberdina L.; Karch, Celeste M.; Graff‐Radford, Neill R.; Salloway, Stephen; Oh, Hwamee; Allegri, Ricardo; Chhatwal, Jasmeer P.; Jessen, Frank; Düzel, Emrah; Dobisch, Laura; Metzger, Coraline D.; Peters, Oliver; Incesoy, Enise I.; Priller, Josef; Spruth, Eike Jakob; Schneider, Anja; Fließbach, Klaus; Büerger, Katharina; Janowitz, Daniel; Teipel, Stefan J.; Kilimann, Ingo; Laske, Christoph; Buchmann, Martina; Heneka, Michael T.; Brosseron, Frederic; Spottke, Annika; Roy, Nina; Ertl‐Wagner, Birgit; Scheffler, Klaus; Seo, Sang Won; Kim, Yeshin; Na, Duk L.; Kim, Hee Jin; Ewers, Michael; Levin, Johannes; Schmidt, Reinhold; Pasternak, Ofer; Dichgans, Martin; Biessels, Geert Jan; Duering, Marco

doi:10.1002/alz.12150

Cited by 40 publications

(51 citation statements)

References 49 publications

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“…Notably, after adjusting for WMH, our results show that the FBA results remained mostly unchanged in both ZJU and ADNI datasets, but the significance level somehow lowered. Our results suggested that WMH did contribute to part of the microstructural alterations in AD patients, which is in accordance with previous results [ 22 ]. Thus, it is necessary to take CSVD burden into account in future AD studies.…”

Section: Discussionsupporting

confidence: 93%

“…Besides, AD is a multifactorial disease with multiple contributors to its pathophysiology, including cerebral small vascular disease (CSVD) [ 21 ]. Recent work suggested that the effects of CSVD on WM integrity should also be accounted for [ 22 ]. After adjusting for WMH, we repeated the same analyses in both ZJU and ADNI datasets and the results we yielded remained mostly unchanged despite of a lower but statistically sound significance level ( Supplementary Material 3 ).…”

Section: Resultsmentioning

confidence: 99%

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Distinct fiber-specific white matter reductions pattern in early- and late-onset Alzheimer’s disease

Luo

Wang

Jiaerken

et al. 2021

Aging

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Distinct fiber-specific white matter reductions pattern in early- and late-onset Alzheimer’s disease

Luo

Wang

Jiaerken

et al. 2021

Aging

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“…In DIAN the other bundle where Aβ and white matter measures were related was the anterior cingulum, another bundle connecting key regions where Aβ accumulates. In line with these results similar associations have been found in DIAN using CSF Aβ (Finsterwalder et al, 2020). On the other hand, in PREVENT-AD, the strongest associations with Aβ were detected in the uncinate fasciculus.…”

Section: Discussionsupporting

confidence: 89%

Bundle-specific associations between white matter microstructure and Aβ and tau pathology in preclinical Alzheimer’s disease

Binette

Theaud

Rheault

et al. 2021

eLife

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Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer's disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focussed on free-water corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau burden in both cohorts. Associations were found in the posterior cingulum and uncinate fasciculus in preclinical sporadic AD, and in the anterior and posterior cingulum in presymptomatic mutation carriers. These results suggest that microstructural alterations accompany pathological accumulation as early as the preclinical stage of both sporadic and autosomal dominant AD.

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“…13,36 PSMD, like other DTI metrics, appears to be more sensitive to cSVD-related white matter abnormalities than to neurodegenerative pathology. 13,42 The low burden of cSVD pathology observed in our non-CAA sample might explain the absence of association between PSMD and processing speed.…”

Section: Discussionmentioning

confidence: 88%

Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy

Raposo

Zotin

Schoemaker

et al. 2021

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Whole-brain network connectivity has been shown to be a useful biomarker of cerebral amyloid angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in cerebral amyloid angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS: We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable cerebral amyloid angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to cerebral amyloid angiopathy (non-cerebral amyloid angiopathy-mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with cerebral amyloid angiopathy-mild cognitive impairment and non-cerebral amyloid angiopathy-mild cognitive impairment and explored its associations with cognitive functions and conventional markers of cerebral small-vessel disease, using linear regression models. RESULTS: Subjects with Cerebral amyloid angiopathy-mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-cerebral amyloid angiopathy-mild cognitive impairment (P , .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with cerebral amyloid angiopathy, after adjusting for other MRI markers of cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-cerebral amyloid angiopathy-mild cognitive impairment. CONCLUSIONS: Peak width of skeletonized mean diffusivity is altered in cerebral amyloid angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in cerebral amyloid angiopathy and could be a useful biomarker for cognition in this population. ABBREVIATIONS: CAA ¼ cerebral amyloid angiopathy; CMB ¼ cerebral microbleeds; CSO-PVS ¼ perivascular spaces in the centrum semiovale; cSS ¼ cortical superficial siderosis; cSVD ¼ cerebral small vessel disease; ICH ¼ intracerebral hemorrhage; IQR ¼ interquartile range; MCI ¼ mild cognitive impairment; MD ¼ mean diffusivity; MMSE ¼ Mini-Mental State Examination; PSMD ¼ peak width of skeletonized mean diffusivity; nTBV ¼ normalized total brain volume; nWMHV ¼ normalized white matter hyperintensity volume; WMH ¼ white matter hyperintensities S poradic cerebral amyloid angiopathy (CAA) is a highly prevalent cerebral small-vessel disease (cSVD) in the elderly. 1 CAA is a well-known cause of lobar intracerebral hemorrhage (ICH) and is also increasingly recognized as a major contributor to vascular cognitive impairment and dementia. 2,3 Although underlying

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Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients

Cited by 40 publications

References 49 publications

Distinct fiber-specific white matter reductions pattern in early- and late-onset Alzheimer’s disease

Distinct fiber-specific white matter reductions pattern in early- and late-onset Alzheimer’s disease

Bundle-specific associations between white matter microstructure and Aβ and tau pathology in preclinical Alzheimer’s disease

Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy

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