Clinical associations of T2-weighted lesion load and lesion location in small vessel disease: Insights from a large prospective cohort study

Aprile, Anna; Gaetano, Laura; Magon, Stefano; Bauer, Lorena; Feurer, Regina; Gnahn, Hans; Hartmann, Julia; Seifert, Christian L.; Poppert, Holger; Wuerfel, Jens; Radue, Ernst‐Wilhelm; Kappos, Ludwig; Sprenger, Till

doi:10.1016/j.neuroimage.2019.01.052

Cited by 18 publications

(18 citation statements)

References 33 publications

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“…Previously, a comparable voxel‐based analyses on patients with cerebral small vessel disease demonstrated that cerebrovascular risk profiles promote T2‐weighted subcortical (white matter) lesion formation most severely at specific, well‐defined locations. 26 The current study based on diffusion‐weighted MRI data of a consecutive 1‐year sample of patients also demonstrated that symptomatic, small cortical infarcts are indeed not equally distributed across the brain. Rather, they are predominantly located along specific brain structures associated with motor control and sensory function (Figure 3A ).…”

Section: Discussionsupporting

confidence: 50%

Distribution Pattern Analysis of Cortical Brain Infarcts on Diffusion‐Weighted Magnetic Resonance Imaging: A Hypothesis‐Generating Approach to the Burden of Silent Embolic Stroke

Schaller‐Paule

Fritz

Schaefer

et al. 2022

JAHA

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Background In patients with covert cerebrovascular disease or proximal source of embolism, embolic silent brain infarction may precede major stroke events. Therefore, characterization of particularly cortical silent brain infarction is essential for identifying affected patients and commencing adequate secondary prevention. This study aimed to investigate differences in the distribution pattern of cortical ischemic stroke lesions to assess potential predilection sites of cortical silent brain infarction. Methods and Results We prospectively included all consecutive patients with stroke presenting from January 1 to December 31, 2018. Diffusion‐weighted imaging lesions were used to generate voxel‐based lesion maps and assigned to atlas‐based cortical regions of interest in middle cerebral artery territories. Each region‐of‐interest lesion frequency was related to the respective region‐of‐interest volume to identify frequently affected and underrepresented cerebral cortex areas. Diffusion‐weighted imaging data for voxel‐based lesion maps were available in 334 out of 633 patients. Primary analysis revealed that small‐ (<0.24 cc) and medium‐sized (0.24–2640 cc) lesions distributed predominantly along regions associated with sensorimotor or language function. Detailed analysis within middle cerebral artery territories showed an approximated frequency of missed cortical stroke lesions of up to 67% in the right and 69% in the left hemisphere. In particular, the frontal, temporal, and occipital cortices were underrepresented. Larger lesion size and areas associated with higher cortical function led to hospital admission. Conclusions Cortical brain infarcts in hospitalized patients are not dispersed equally but are predominantly located in brain structures associated with motor control and sensory and language function. Matching underrepresented cerebral cortex regions to symptoms not yet associated with stroke warrants further exploration.

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Section: Discussionsupporting

confidence: 50%

Distribution Pattern Analysis of Cortical Brain Infarcts on Diffusion‐Weighted Magnetic Resonance Imaging: A Hypothesis‐Generating Approach to the Burden of Silent Embolic Stroke

Schaller‐Paule

Fritz

Schaefer

et al. 2022

JAHA

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“…[ 50 ] Nevertheless, the language disorder of the scattered CSVD is often manifested as less speech, but the understanding and expression ability are generally intact. Previous study [ 51 , 52 ] has compared the language functions of patients with AD and CSVD, and it has been found that the AD group only has showed impairment of semantic fluency, while the CSVD group has showed impaired semantic fluency and speech fluency, which may be related to the reduction of executive function and processing speed.…”

Section: Discussionmentioning

confidence: 99%

The cognitive dysfunction related to Alzheimer disease or cerebral small vessel disease

Liang

Gong

et al. 2021

Medicine

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Alzheimer disease (AD) and sporadic cerebral small vessel disease (CSVD) are common cognitive disorders. Both AD and CSVD have mental symptoms including chronic progressive cognitive impairment, dysfunction, and behavioral abnormalities. However, the differences on the cognitive dysfunction of AD and CSVD remain unclear. It is necessary to elucidate the cognitive dysfunction differences of AD and CSVD, and to identify the potential risk factors. AD or sporadic CSVD patients treated in our hospital from December 1, 2018 to May 31, 2019 were included. And we selected healthy participants as controls. The mini-mental state examination and Montreal Cognitive Assessment Scale were used for neuropsychological assessment, and related medical information were collected and compared. A total of 190 patients were included. The total mini-mental state examination scores in AD, CSVD group were significantly less than that of control group, there were significant differences in the domains of directional ability, attention and computing ability, delayed recall, and visual perception (all P < .05); the total Montreal Cognitive Assessment Scale scores in AD, CSVD group were significantly less than that of control group. There were significant differences in the domains of visual space and execution, immediate remember, attention and computing ability, language, delayed recall, and directional ability (all P < .05); diabetes was a risk factor both for AD (hazard ratio = 1.63, 95% confidence interval: 1.35–1.97) and CSVD (hazard ratio = 1.15, 95% confidence interval: 1.08–1.27). The cognitive dysfunctions of AD are difference to that of CSVD patients, and diabetes is the risk factor both for AD and CSVD, future studies are needed to further identify the prevention and treatment of AD and CSVD.

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“…With the exception of the external capsule, we found rather substantial evidence for associations between WMH and worse cognitive performance, likewise affecting memory and executive function, and outcomes (Table 3). Intriguingly, hypertension was associated with executive, memory, and baseline and longitudinal global cognitive function only via splenial WMH, a white matter structure responsible for cognitive processing and a hub where distinct pathologies impact the neural circuitries interconnecting the temporal and occipital regions of both cerebral hemispheres [7,[49][50][51]. White matter damage in this region, as associated with cardiovascular risk, could be expected to translate to lower cognitive functioning in global cognition but also in discrete domains [7].…”

Section: Discussionmentioning

confidence: 99%

Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: A cross-sectional study

Bernal

Schreiber

Menze

et al. 2022

Preprint

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Background Posterior white matter hyperintensities (WMH) in subjects across the Alzheimer's disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathology—not just arterial hypertension—impacts WMH, adversely influencing cognition. Here we seek to determine the effect of both hypertension and Aβ positivity on WMH, and their impact on cognition. Methods We analysed data from subjects with a low vascular profile and normal cognition (NC), subjective cognitive decline (SCD), and amnestic mild cognitive impairment (MCI) enrolled in the ongoing observational multicentre DZNE Longitudinal Cognitive Impairment and Dementia Study (n = 375, median age 70.2 [IQR 66.0-74.4] years; 176 female; NC/SCD/MCI 127/162/86). All subjects underwent a rich neuropsychological assessment. We focused on baseline memory and executive function—derived from multiple neuropsychological tests using confirmatory factor analysis—, baseline preclinical Alzheimer’s cognitive composite 5 (PACC5) scores, and changes in PACC5 scores over course of three years (ΔPACC5). Results Subjects with hypertension or Aβ positivity presented the largest WMH volumes (pFDR<0.05), with spatial overlap in the frontal (hypertension: 0.42 ± 0.17; Aβ: 0.46 ± 0.18), occipital (hypertension: 0.50 ± 0.16; Aβ: 0.50 ± 0.16), parietal lobes (hypertension: 0.57 ± 0.18; Aβ: 0.56 ± 0.20), corona radiata (hypertension: 0.45 ± 0.17; Aβ: 0.40 ± 0.13), optic radiation (hypertension: 0.39 ± 0.18; Aβ: 0.74 ± 0.19), and splenium of the corpus callosum (hypertension: 0.36 ± 0.12; Aβ: 0.28 ± 0.12). Hypertension, Aβ positivity, and WMH were connected to cognition. First, WMH coincided with worse cognitive performance and outcomes (pFDR<0.05), regardless of Aβ and hypertension. Accelerated cognitive decline was associated with WMH in the genu of the corpus callosum and segments of the forceps major and inferior fronto-occipital longitudinal fasciculus (pFDR<0.05). Second, hypertension was indirectly linked to cognitive performance at baseline and over time via splenial WMH (indirect-only effect; memory: -0.05 ± 0.02, pFDR=0.029; executive: -0.04 ± 0.02, pFDR=0.067; PACC5: -0.05 ± 0.02, pFDR=0.030; ΔPACC5: -0.09 ± 0.03, pFDR=0.043). Third, the relationship between Aβ positivity and baseline and longitudinal cognitive performance was independent of WMH burden. Conclusions Posterior white matter is susceptible to hypertension and Aβ accumulation and it mediates the association between hypertension and cognitive dysfunction. Posterior WMH could be a promising target to tackle the downstream damage related to the potentially interacting and potentiating effects of the two pathologies. Trial Registration German Clinical Trials Register (DRKS00007966, 04/05/2015)

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Clinical associations of T2-weighted lesion load and lesion location in small vessel disease: Insights from a large prospective cohort study

Cited by 18 publications

References 33 publications

Distribution Pattern Analysis of Cortical Brain Infarcts on Diffusion‐Weighted Magnetic Resonance Imaging: A Hypothesis‐Generating Approach to the Burden of Silent Embolic Stroke

Distribution Pattern Analysis of Cortical Brain Infarcts on Diffusion‐Weighted Magnetic Resonance Imaging: A Hypothesis‐Generating Approach to the Burden of Silent Embolic Stroke

The cognitive dysfunction related to Alzheimer disease or cerebral small vessel disease

Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: A cross-sectional study

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