Clinical effect of white matter network disruption related to amyloid and small vessel disease

Kim, Hee Jin; Im, Kiho; Kwon, Hyuk-Min; Lee, Jong Min; Kim, Chang-Soo; Kim, Yeo Jin; Jung, Na-Yeon; Cho, Hanna; Ye, Byoung Seok; Noh, Young; Kim, Geon Ha; Ko, En Da; Kim, Jae Seung; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Lee, Jae Hong; Ewers, Michael; Weiner, Michael W.; Na, Duk L.; Seo, Sang Won

doi:10.1212/wnl.0000000000001705

Cited by 77 publications

(60 citation statements)

References 39 publications

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“…Also, we found that NAWM FA was associated with mRS without being mediated by GM volume. This observation has already been raised in patients with subcortical and/or neurodegenerative cognitive impairment (4,34). Indeed, Kim et al demonstrated an association between decreased FA in specific regions and gait performances (4) or executive functions (34), that was not mediated by brain atrophy, suggesting that white matter microstructural integrity explained a substantial part of clinical performances on top of brain atrophy.…”

Section: Nawm Integrity and Post-stroke Outcome The Hypothesis Of Anmentioning

confidence: 88%

Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke

Sagnier

Catheline

Dilharreguy

et al. 2020

Stroke

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Objective. To evaluate the relationship between normal appearing white matter (NAWM) integrity and post-ischemic stroke recovery in four main domains including, cognition, mood, gait, and dependency. Methods. A prospective study was conducted, including patients diagnosed for an ischemic supratentorial stroke on a 3T-brain MRI performed 24-72 hours after symptoms onset. Clinical assessment one-year after stroke included a Montreal Cognitive Assessment, an Isaacs set test (IST), a Zazzo's cancellation task, a Hospital anxiety and depression scale, a 10-m walking test, a modified Rankin scale (mRS). DTI parameters in the NAWM were computed using FMRIB's Diffusion Toolbox. The relationships between mean NAWM DTI parameters and the clinical scores were assessed using linear and ordinal regression analyses, including the volumes of white matter hyperintensities (WMH), grey matter and ischemic stroke as radiological covariates. Results. 207 subjects were included (66 ± 13 y.o, 67% men, median NIHSS 3, interquartile range 2-6). In the models including only radiological variables, NAWM fractional anisotropy (FA) was associated with the mRS and the cognitive scores. After adjusting for demographic confounders, NAWM FA remained a significant predictor of mRS (β =-0.24, p = 0.04). Additional path analysis showed that NAWM FA had a direct effect on mRS (β =-0.241, p = 0.001), and a less important indirect effect mediating WMH burden. Similar results were found with mean diffusivity, axial and radial diffusivity. In further subgroup analyses, a relationship between NAWM integrity in widespread white matter tracts, mRS and IST was found in right-hemispheric strokes. Conclusion. NAWM DTI parameters measured early after an ischemic stroke are independent predictors of functional outcome and may be additional markers to include in studies evaluating poststroke recovery.

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Section: Nawm Integrity and Post-stroke Outcome The Hypothesis Of Anmentioning

confidence: 88%

Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke

Sagnier

Catheline

Dilharreguy

et al. 2020

Stroke

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“…In CAA, microstructural white matter damage seems to affect the temporal lobe , while in DPA it is found more extensively (internal/external capsule, periventricular frontal white matter) . In CAA, brain network alterations are predominantly found in the occipital and posterior temporal lobes progressing over the course of time , while in DPA frontal and lateral temporal networks seem to be rather affected . Microstructural white matter integrity is further influenced by APOEε4 carriage and aHTN , and interactions between those factors and CSVD burden have thus to be taken into account.…”

Section: Neuroimaging Biomarkers Of Sporadic Csvdmentioning

confidence: 99%

Invited Review: The spectrum of age‐related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathies

Schreiber

Wilisch‐Neumann

Schreiber

et al. 2019

Neuropathology Appl Neurobio

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Invited Review: The spectrum of age-related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathiesDeep perforator arteriopathy (DPA) and cerebral amyloid angiopathy (CAA) are the commonest known cerebral small vessel diseases (CSVD), which cause ischaemic stroke, intracebral haemorrhage (ICH) and vascular cognitive impairment (VCI). While thus far mainly considered as separate entities, we here propose that DPA and CAA share similarities, overlap and interact, so that 'pure' DPA or CAA are extremes along a continuum of age-related small vessel pathologies. We suggest blood-brain barrier (BBB) breakdown, endothelial damage and impaired perivascular b-amyloid (Ab) drainage are hallmark common mechanisms connecting DPA and CAA. We also suggest a need for new biomarkers (e.g. high-resolution imaging) to deepen understanding of the complex relationships between DPA and CAA.

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“…This supports the suggestion that cognitive impairment in CAA is not only due to the disruption of eloquent cortical areas by direct lobar ICH damage, but also because of more widespread underlying CAA-related SVD damage. Structural markers of SVD are associated with disruptions of network efficiency [16,17], and it has been hypothesised that SVD damage may specifically impact tasks that require integration of different brain areas, as these are particularly susceptible to "disconnection" [18]. The concept of acute or early cognitive impairment following ICH (in contrast to late or delayed onset) is recognised [1,6], and thought to be due to direct consequences of the haemorrhage (for example, haematoma size and location), whereas delayed or late impairment, is thought to be driven predominantly by the small vessel processes [1]; this is supported by evidence that the presence of imaging markers of CAA at the time of ICH increases the risk of subsequent dementia [2].…”

Section: Jns-d-18-00113 13mentioning

confidence: 99%

Domain-specific characterisation of early cognitive impairment following spontaneous intracerebral haemorrhage

Banerjee

Summers

Chan

et al. 2018

Journal of the Neurological Sciences

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Cognitive deficits after spontaneous intracerebral haemorrhage (ICH) are common and result in functional impairment, but few studies have examined deficits across cognitive domains in the subacute phase. This study aims to describe the cognitive profile following acute ICH and explore how cerebral amyloid angiopathy (CAA) may impact performance. We retrospectively reviewed 187 consecutive patients with ICH (mean age 58.9 years, 55.6% male) with available imaging and neuropsychological data (median 12 days after stroke). In our cohort, 84% (n = 158) were impaired in at least one cognitive domain and 65% (n = 122) in two or more domains. Deficits in non-verbal IQ (76.6%), information processing speed (62.4%) and executive functions (58.1%) were most common. Patients with lobar ICH (n = 92) had more deficits in naming and visual perception than those with non-lobar ICH, but not in adjusted analyses. Patients with probable CAA (n = 21) had more deficits in verbal IQ, visual perception and executive functions than those without probable CAA; in adjusted analyses, probable CAA predicted impairment in verbal IQ (OR 38.6, 95% CI 3.2 to 465.4, p = 0.004) and executive function (OR 3.4, 95% CI 1.0 to 11.7, p = 0.050). We conclude that cognitive deficits following ICH are common across domains, and that those with CAA appear to have a different cognitive profile. Replication of this work in larger cohorts will be important for confirming and further quantifying these observations.

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Clinical effect of white matter network disruption related to amyloid and small vessel disease

Abstract: Background: We tested our hypothesis that the white matter network might mediate the effect of

Cited by 77 publications

References 39 publications

Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke

Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke

Invited Review: The spectrum of age‐related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathies

Domain-specific characterisation of early cognitive impairment following spontaneous intracerebral haemorrhage

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