Cortical Microinfarcts Research Articles

Cerebral cortical microinfarcts in patients with internal carotid artery occlusion

Cerebral cortical microinfarcts (CMI) are small ischemic lesions that are associated with cognitive impairment and probably have multiple etiologies. Cerebral hypoperfusion has been proposed as a causal factor. We studied CMI in patients with internal carotid artery (ICA) occlusion, as a model for cerebral hemodynamic compromise. We included 95 patients with a complete ICA occlusion (age 66.2 ± 8.3, 22% female) and 125 reference participants (age 65.5 ± 7.4, 47% female). Participants underwent clinical, neuropsychological, and 3 T brain MRI assessment. CMI were more common in patients with an ICA occlusion (54%, median 2, range 1–33) than in the reference group (6%, median 0; range 1–7; OR 14.3; 95% CI 6.2–33.1; p<.001). CMI were more common ipsilateral to the occlusion than in the contralateral hemisphere (median 2 and 0 respectively; p<.001). In patients with CMI compared to patients without CMI, the number of additional occluded or stenosed cervical arteries was higher (p=.038), and cerebral blood flow was lower (B −6.2 ml/min/100 ml; 95% CI −12.0:–0.41; p=.036). In conclusion, CMI are common in patients with an ICA occlusion, particularly in the hemisphere of the occluded ICA. CMI burden was related to the severity of cervical arterial compromise, supporting a role of hemodynamics in CMI etiology.

Long-term neurobehavioral correlates of brain cortical microinfarcts in a memory clinic cohort in Singapore.

Cortical cerebral microinfarcts are a small vessel disease biomarker underlying cognitive impairment and dementia. However, it is unknown whether cortical cerebral microinfarcts are associated with neuropsychiatric disturbances, and whether its effects are independent of conventional small vessel disease markers. We investigated the associations of cortical cerebral microinfarcts burden with incidence and progression of neuropsychiatric subsyndromes in a memory clinic cohort of elderly in Singapore. In this prospective cohort, 496 subjects underwent detailed neuropsychological and clinical assessments, 3T brain MRI, and Neuropsychiatric Inventory assessment at baseline and two years later. Cortical cerebral microinfarcts and other small vessel disease markers, including white matter hyperintensities, lacunes, and microbleeds, were graded according to established criteria. Neuropsychiatric symptoms (NPS) were clustered into subsyndromes of hyperactivity, psychosis, affective, and apathy following prior findings. Functional decline was determined using the clinical dementia rating (CDR) scale. The presence of multiple cortical cerebral microinfarcts (≥2) was associated with higher total NPS scores (β = 4.19, 95% CI = 2.81-5.58, p < 0.001), particularly hyperactivity (β = 2.01, 95% CI = 1.30-2.71, p < 0.01) and apathy (β = 1.42, 95% CI = 0.65-2.18, p < 0.01) at baseline. Between baseline and year-2, multiple cortical cerebral microinfarcts were associated with accelerated progression in total NPS scores (β = 0.29, 95% CI = 0.06-0.53, p = 0.015), driven by hyperactivity (β = 0.45, 95% CI = 0.17-0.72, p < 0.01). Subjects with multiple cortical cerebral microinfarcts also had a faster functional decline, as measured with the CDR-sum-of-boxes scores, when accompanied with progression (β = 0.31, 95% CI = 0.11-0.51, p < 0.01) or hyperactivity in total NPS (β = 0.34, 95% CI = 0.13-0.56, p < 0.01). Cortical cerebral microinfarcts are associated with incidence and progression of geriatric neurobehavioral disturbances, independent of conventional small vessel disease markers. The impact of incident cortical cerebral microinfarcts on neurocognitive and neuropsychiatric trajectories warrants further investigations.

Micro-MRI improves the accuracy of clinical diagnosis in cerebral small vessel disease.

Even with postmortem pathological examination, only limited information is provided of the foci of in vivo clinical information. Cerebral small vessel disease, which is associated with ageing, dementia and stroke, highlights the difficulty in arriving at a definitive diagnosis of the lesions detected on in vivo radiological examination. We performed a radiological−pathological comparative study using ex vivo MRI to examine small cerebral lesions. Four patients with small vessel disease lesions detected on in vivo MRI were studied. Exact pathological findings of in vivo MRI-detected lesions were revealed. The ischaemic lesion after 17 days from onset showed positivity for peroxiredoxin, cluster of differentiation 204 and glial fibrillary acidic protein, indicating sterile inflammation and neuroprotective reaction. Cortical microinfarcts beneath the cortical superficial siderosis were associated with inflammation from the superficial layer in a patient with cerebral amyloid angiopathy; in this patient, a bilinear track-like appearance of the cortical superficial siderosis on the ex vivo MRI was compatible with iron deposition on the pia matter and within cortical layers II–III. An in vivo MRI-detected cerebral microbleed was revealed to be heterogeneous. An in vivo MRI-detected cerebral microbleed was revealed to be a venous angioma. Furthermore, a neuropathologically confirmed embolic cerebral microbleed was firstly detected using this method. Our results suggest that in vivo MRI-detected lobar cerebral microbleeds can be caused by non-cerebral amyloid angiopathy aetiologies, such as microembolism and venous angioma. Venous angioma and embolic microbleeds may mimic cerebral amyloid angiopathy markers on in vivo MRI. To clarify the clinical importance of these lesions, we should investigate their rate and frequency in a large cohort of healthy individuals and patients with cardiac risk factors. Thus, we provide evidence that ex vivo micro-MRI improves the clinical diagnosis of small vessel diseases.

Investigation of hypertensive arteriopathy-related and cerebral amyloid angiopathy-related small vessel disease scores in patients from a memory clinic: a prospective single-centre study

ObjectiveThe severity of cerebral small vessel disease (SVD) is assessed through neuroimaging findings, including hypertensive arteriopathy (HA)-SVD and cerebral amyloid angiopathy (CAA)-SVD. HA-SVD and CAA-SVD have been collectively estimated as...

Aβ (Amyloid Beta) and Tau Tangle Pathology Modifies the Association Between Small Vessel Disease and Cortical Microinfarcts.

There is increasing recognition of the importance of cortical microinfarcts to overall brain health, cognition, and Alzheimer dementia. Cerebral small vessel pathologies are associated with microinfarcts and frequently coexist with Alzheimer disease; however, the extent to which Aβ (amyloid beta) and tau pathology modulates microvascular pathogenesis is not fully understood. Study objective was to examine the relationship of small vessel pathologies, arteriolosclerosis, and cerebral amyloid angiopathy, with cortical microinfarcts in people with differing levels of Aβ or tau tangle burden. Participants were 1489 autopsied older people (mean age at death, 89 years; 67% women) from 1 of 3 ongoing clinical-pathological cohort studies of aging. Neuropathological evaluation identified cortical Aβ and tau tangle burden using immunohistochemistry in 8 brain regions, provided semiquantitative grading of cerebral vessel pathologies, and identified the presence of cortical microinfarcts. Logistic regression models adjusted for demographics and atherosclerosis and examined whether Aβ or tau tangle burden modified relations between small vessel pathologies and cortical microinfarcts. Cortical microinfarcts were present in 17% of older people, moderate-to-severe cerebral amyloid angiopathy pathology in 36%, and arteriolosclerosis in 34%. In logistic regression models, we found interactions with Aβ and tau tangles, reflecting that the association between arteriolosclerosis and cortical microinfarcts was stronger in the context of greater Aβ (estimate, 0.15; SE=0.07; P=0.02) and tau tangle burden (estimate, 0.13; SE=0.06; P=0.02). Interactions also emerged for cerebral amyloid angiopathy, suggesting that the association between cerebral amyloid angiopathy and cortical microinfarcts is more robust in the presence of higher Aβ (estimate, 0.27; SE=0.07; P<0.001) and tangle burden (estimate, 0.16; SE=0.06; P=0.005). These findings suggest that in the presence of elevated Aβ or tangle pathology, small vessel pathologies are associated with greater microvascular tissue injury, highlighting a potential link between neurodegenerative and vascular mechanisms.

Clinical Relevance of Cortical Cerebral Microinfarcts on 1.5T Magnetic Resonance Imaging in the Late-Adult Population.

Cortical cerebral microinfarcts (CMIs) have been linked with dementia and impaired cognition in cross-sectional studies. However, the clinical relevance of CMIs in a large population-based setting is lacking. We examine the association of cortical CMIs detected on 1.5T magnetic resonance imaging with cardiovascular risk factors, cerebrovascular disease, and brain tissue volumes. We further explore the association between cortical CMIs with cognitive decline and risk of stroke, dementia, and mortality in the general population. Two thousand one hundred fifty-six participants (age: 75.7±5.9 years, women: 55.6%) with clinical history and baseline magnetic resonance imaging (January 2009-December 2013) were included from the Rotterdam Study. Cortical CMIs were graded based on a previously validated method. Markers of cerebrovascular disease and brain tissue volumes were assessed on magnetic resonance imaging. Cognition was assessed using a detailed neuropsychological test at baseline and at 5 years of follow-up. Data on incident stroke, dementia, and mortality were included until January 2016. Two hundred twenty-seven individuals (10.5%) had ≥1 cortical CMIs. The major risk factors of cortical CMIs were male sex, current smoking, history of heart disease, and stroke. Furthermore, presence of cortical CMIs was associated with infarcts and smaller brain volume. Persons with cortical CMIs showed cognitive decline in Stroop tests (color-naming and interference subtasks; β for color-naming, 0.18 [95% CI, 0.04-0.33], P interaction ≤0.001 and β for interference subtask, 1.74, [95% CI, 0.66-2.82], P interaction ≤0.001). During a mean follow-up of 5.2 years, 73 (4.3%) individuals developed incident stroke, 95 (5.1%) incident dementia, and 399 (19.2%) died. People with cortical CMIs were at an increased risk of stroke (hazard ratio, 1.18 [95% CI, 1.09-1.28]) and mortality (hazard ratio, 1.09 [95% CI, 1.00-1.19]). Cortical CMIs are highly prevalent in a population-based setting and are associated with cardiovascular disease, cognitive decline, and increased risk of stroke and mortality. Future investigations will have to show whether cortical CMIs are a useful biomarker to intervene upon to reduce the burden of stroke.

Lacunes, Microinfarcts, and Vascular Dysfunction in Cerebral Amyloid Angiopathy.

To analyze the relationship of lacunes with cortical cerebral microinfarcts (CMIs), to assess their association with vascular dysfunction, and to evaluate their effect on the risk of incident intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA). The count and topography of lacunes (deep/lobar), CMIs, and white matter hyperintensity (WMH) volume were retrospectively analyzed in a prospectively enrolled CAA cohort that underwent high-resolution research MRIs. The relationship of lacunes with CMIs and other CAA-related markers including time to peak (TTP) of blood oxygen level-dependent signal, an established measure of vascular dysfunction, was evaluated in multivariate models. Adjusted Cox regression models were used to investigate the relationship between lacunes and incident ICH. The cohort consisted of 122 patients with probable CAA without dementia (mean age, 69.4 ± 7.6 years). Lacunes were present in 31 patients (25.4%); all but one were located in lobar regions. Cortical CMIs were more common in patients with lacunes compared to patients without lacunes (51.6% vs 20.9%, p = 0.002). TTP was not associated with either lacunes or CMIs (both p > 0.2) but longer TTP response independently correlated with higher WMH volume (p = 0.001). Lacunes were associated with increased ICH risk in univariate and multivariate Cox regression models (p = 0.048 and p = 0.026, respectively). Our findings show a high prevalence of lobar lacunes, frequently coexisting with CMIs in CAA, suggesting that these 2 lesion types may be part of a common spectrum of CAA-related infarcts. Lacunes were not related to vascular dysfunction but predicted incident ICH, favoring severe focal vessel involvement rather than global ischemia as their mechanism.

White matter network damage mediates association between cerebrovascular disease and cognition

To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores. Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers. Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.

Significance of Cortical Micro-Infarcts in the Human Brain

Cortical micro-infarcts are due to cerebral small vessel disease. In contrast to the arteriosclerotic type of cerebral small vessel disease, cortical micro-infarcts are mainly related and due to cerebral amyloid angiopathy. Alzheimer’s disease is the most frequent neurodegenerative dementia disease associated to cerebral amyloid angiopathy and cortical micro-infarcts. Vascular dementia cannot only be due to lacunar infarcts and ischemic white matter changes, but can also be caused by cortical micro-infarcts. The latter are a frequent cause of vascular dementia and decrease globally the cerebral blood flow.

Cerebral amyloid angiopathy, comorbid atrial fibrillation

Cerebral amyloid angiopathy (CAA) is caused by the deposition of β-amyloid in small vessels in the cerebral cortex and leptomeninges. Nowadays, CAA is recognized more often due to the development of neuroimaging technologies. The frequency of CAA increases in old age that explains its frequent association with cardiovascular diseases. Combination of CAA with atrial fibrillation (AF) causes particular difficulties in managing of the patients, since antithrombotic drugs prescribed to patients with AF mostly contraindicated in CAA because of increased risk of intracerebral hemorrhages. The article presents a case report of the patient with AF who was admitted to the stroke center with acute ischemic stroke. According to MRI, the focus of acute ischemia was small and localized in the cerebellum. This stroke was regarded as having an undetermined etiology according TOAST classification. Small-vessel occlusion subtype was not diagnosed because the TOAST criteria do not attribute an ischemic focus in the cerebellum to a lacunar stroke, while cardioembolic subtype was rejected due to a small (less than 1.5 cm in diameter) size of the focus. Probable CAA in the patient was diagnosed on the basis of the following MRI data: multiple cortical-subcortical micro-hemorrhages (T2*GRE); a single cortical focus with features of the hemorrhage at the stage of intracellular methemoglobin deposition (T1- weighted MR images); bilateral enlargement of perivascular spaces in semioval centers (FLAIR); a negative fronto-occipital gradient (T2-weighted MR images). A diagnosis of CAA was made in accordance with the 2010 Boston criteria and 2019 recommendations of the International CAA Association. The article discusses the hemorrhagic and non-hemorrhagic MRI features of CAA. Frequency of occurrence of cortical microinfarcts in CAA is discussed as well as their differences from small cardioembolic infarcts in AF. Algorithms for antithrombotic therapy for secondary prevention of ischemic stroke in patients with CAA and AF are considered.

Post-Mortem 7.0-Tesla Magnetic Resonance Imaging of the Hippocampus in Progressive Supranuclear Palsy with and without Cerebral Amyloid Angiopathy

Introduction and Purpose: Cerebral amyloid angiopathy (CAA) can be observed in patients with progressive supranuclear palsy (PSP), though to a lesser degree than in Alzheimer’s disease. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) evaluates whether CAA has an influence on the degree of hippocampal atrophy (HA) and on the incidence of associated micro-infarcts (HMIs) and cortical micro-bleeds (HMBs). Material and Methods: Eight brains with PSP-CAA were compared to 20 PSP brains without CAA. In addition to the neuropathological examination, the hippocampus was evaluated on the most representative coronal section with T2 and T2*-weighted MRI sequences. The average degree of HA was determined in both groups. The incidence of HMIs and HMBs was also compared as well as the frequency of cortical micro-infarcts (CoMIs) and cortical micro-bleeds (CoMBs) in the hemispheric neocortex. Results: The neuropathological examination showed a higher incidence of lacunar infarcts in the PSP-CAA brains compared to the PSP ones. With magnetic resonance imaging (MRI), the severity of HA and the incidence of HMIs and HMBs was similar between both groups. Additionally, the frequency of CoMIs and CoMBs in the neocortex was comparable. Conclusions: The association of CAA in PSP brains has no influence on the degree of HA and on the incidence of the small cerebrovascular lesions in the hippocampus as well as in the neocortex.

Post-mortem 7.0-Tesla Magnetic Resonance Imaging of the Hippocampus in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is reported to be probably linked to frontotemporal lobar degeneration (FTLD). Since FTLD is characterized by severe frontotemporal degeneration along with hippocampal atrophy (HA), the present study used post-mortem 7.0-tesla magnetic resonance imaging to investigate whether a certain degree of HA occurs in the ALS brains as well. The examined post-mortem brain samples comprised 9 from the ALS cases and 17 from the age-matched controls. The hippocampus samples were examined on the most representative coronal section using T2 and T2* MRI sequences, and the average degree of HA was determined for both groups. The occurrence of hippocampal micro-infarcts (HMIs) and hippocampal micro-bleeds (HMBs), as well as the frequency of cortical micro-infarcts (CoMIs) and cortical micro-bleeds (CoMBs) in the neocortex, were compared between the groups. Considerable HA was observed in the ALS group compared to the control group. The incidence of HMIs and HMBs was low and comparable in the ALS and control groups. Moreover, the frequency of CoMIs and CoMBs in the neocortex was relatively comparable in the two groups. This post-mortem observation of HA is an additional argument in favor of the link between ALS and FTLD. Furthermore, both ALS and FTLD share a low vascular risk profile.

Comparison of Post-mortem 7.0-Tesla Magnetic Resonance Imaging of the Brains of Alzheimer Patients with and without Cerebral Amyloid Angiopathy

Purpose: The influence of cerebral amyloid angiopathy (CAA) in Alzheimer’s disease (AD) remains unexplored. The present post-mortem study investigated possible differences in the degree of hippocampal atrophy (HA) between AD patients with and without CAA using 7.0-tesla magnetic resonance imaging (MRI). Also, the incidence of the hippocampal cortical micro-infarcts (HCoMIs) and hippocampal cortical micro-bleeds (HCoMBs) is compared to those in the neocortex. Methods: The examined post-mortem brains included 30 AD-CAA cases and 20 AD without CAA cases. The samples of the hippocampus were evaluated on the most representative coronal section with T2 and T2* MRI sequences. The average degree of HA was determined in both groups. The incidences of HCoMIs and HCoMBs, along with the frequency of CoMIs and CoMBs in the neocortex were compared in both groups: AD-with CAA and AD without CAA cases. Results: No significant differences were observed in the degree of HA and the incidence of hippocampal micro-infarcts (HMIs) and hippocampal micro-bleeds (HMBs) between the AD-CAA and the AD brains in contrast to the higher incidence of these cerebrovascular lesions in the neocortex of AD-CAA brains. The incidence of CoMIs and CoMBs in the neocortex showed similarity to that in the hippocampus of AD patients without CAA. Conclusions: CAA does not influence the degree of HA and the incidence of micro-infarcts (MIs) and micro-bleeds (MBs) in the hippocampus, in contrast to the high contribution of the latter with CAA in the neocortex. The hippocampus seems to be more spared from cerebrovascular involvement than the other parts of the brain.

Does cerebral hemodynamic compromise contribute to cerebral cortical microinfarcts: A proof of concept study in patients with internal carotid artery occlusion

AbstractBackgroundCerebral cortical microinfarcts (CMI) are small ischemic lesions that are associated with cognitive impairment and are often detected in patients with dementia, also in patients with a clinical diagnosis of Alzheimer’s disease (AD). CMI probably have multiple etiologies. Cerebral hypoperfusion has also been proposed as a causal factor. We studied CMI in patients with internal carotid artery (ICA) occlusion, as a model for cerebral hemodynamic compromise, addressing CMI presence and spatial distribution, also in relation to the condition of the remaining arterial supply.MethodsWe included 95 patients with a complete ICA occlusion (age 66.2±8.3, 22% female) and a reference group of 125 participants (age 65.5±7.4, 47% female) from the Heart‐Brain Study. Participants underwent an extensive evaluation including clinical and neuropsychological assessment, and 3T brain MR, on which CMI were rated according to standardized criteria.ResultsCMI were more common in patients with an ICA occlusion (54%, median 2, range 1‐33) than in the reference group (6%, median 0; range 1‐7) (OR 14.3; 95% CI 6.2‐33.1; p&lt;.001). Among patients with a unilateral ICA occlusion, CMI were more common ipsilateral to the occlusion than in the contralateral hemisphere (median 2 and 0 respectively; p&lt;.001). In patients with CMI the number of (other) occluded or stenosed cervical arteries was higher (p=.038), and cerebral blood flow tended to be lower (B ‐6.2 ml/min/100ml; 95% CI ‐12.4‐0.02; p=.05) than in patients without CMI.ConclusionCMI are very common in patients with an ICA occlusion, preferably in the hemisphere of the occluded ICA and CMI burden was related to the severity of cervical arterial compromise. Supporting the etiological role of hemodynamics in the occurrence of CMI. Given the common occurrence of CMI in patients with AD and known effects of AD on cerebral perfusion, further studies on the interplay between AD pathologies, cerebral perfusion and CMIs in relation to clinical outcomes, in particular cognitive decline, are warranted.

Novel MRI markers of small vessel disease in relation to Alzheimer’s disease

AbstractBackgroundVascular brain injury, particularly small vessel disease (SVD), is a common cause of cognitive decline and is detected on brain MRI in the majority of patients with dementia, including Alzheimer’s disease (AD). Established MRI markers of SVD related brain injury are white matter hyperintensities, lacunar infarcts, microbleeds and enlarged perivascular spaces. Yet, these MRI markers clearly do not cover the full extent of SVD related injury. Also, these lesions represent an end‐stage of injury to the parenchyma, rather than the actual abnormalities that occur in the small vessels themselves. In my presentation I will address a novel marker of more subtle parenchymal injury, cortical microinfarcts (CMI), and emerging markers of cerebral small vessel function.MethodsEstimates from autopsy studies are that 100s to 1000s of CMI may be present in the brain of a single affected individual. High field strength imaging on 7Tesla MRI and further developments onto 3Tesla MRI has enabled in vivo detection of the largest CMI, and MRI rating criteria have been published. 7Tesla MRI is also used to zoom in on the small vessels themselves, and markers of cerebral small vessel function are emerging.ResultsMRI studies in patients with a clinical diagnosis of AD observe a CMI prevalence ranging between 8‐55%. These studies allow to investigate potential causes and consequences of CMI for the first time in vivo. It appears that CMI relate with worse clinical outcome and may be caused by various etiologies, including hypoperfusion, microemboli, and SVD pathology, in particular cerebral amyloid angiopathy. The novel measures of small vessel function that will be reviewed include measures of small vessel reactivity, and measures of blood flow velocity and pulsatility in individual penetrating arteries (diameter 100‐800 µm). Initial studies show abnormalities of these measures in patients when compared with healthy controls. I will review ongoing studies in patients with hereditary and sporadic SVD that aim to establish the value of these small vessel function markers in clinical research.ConclusionWith these efforts we aim to advance insight into disease processes in SVD to help better understand the mechanisms underlying cognitive impairment and dementia.

Cortical cerebral microinfarcts and risk of stroke, dementia and mortality: The Rotterdam study

AbstractBackgroundCortical cerebral microinfarcts (CMIs) –a novel MRI marker of cerebral vascular pathology have been linked with dementia and impaired cognition in cross‐sectional studies. However, it is unknown if cortical CMIs are an indicator of further cognitive decline and incident clinical outcomes. We examine the risk factors of CMIs on 1.5T MRI and their association with cognitive decline and risk of stroke, dementia and mortality.Method2156 participants (median age: 74.6 (range: 70.7‐79.3 years, women 55.6%) with baseline MRI (acquired between January 2009‐December 2013) and no prevalent dementia were included. Data on incident clinical outcomes were available (until January 2016) were included. CMIs on 1.5T were graded based on a previously validated criterion on 3T and were defined as the hypointense lesions on T1‐weighted images, &lt;5mm in diameter, restricted to cortex and perpendicular to the cortical surface Markers of cerebrovascular disease (cortical infarcts, white matter hyperintensities, lacunes, cerebral microbleeds) and neurodegeneration (volumes of total brain and hippocampus) were collected. Cognition was assessed using a detailed neuropsychological test at baseline and at follow‐up after five years.Result227 individuals (10.5%) had one or more cortical CMIs. The main risk factors of cortical CMIs were male sex (OR: 1.86, 95%CI: 1.23‐2.82), heart disease (OR: 1.81, 95%CI:1.24‐2.63), cortical infarcts (OR: 6.03, 95%CI:3.79‐9.58) and lacunes (OR: 1.12, 95%CI: 1.03‐2.29). Persons with cortical CMIs showed cognitive decline albeit non‐significant. During a mean follow‐up of 5.2 years, 14 (6.5%) individuals with cortical CMIs developed incident stroke, 10 (4.6%) incident dementia and 76 (3.5%) died. People with cortical CMIs at baseline had an increased risk of strokes (Risk Ratio (RR): 1.66, 95%CI:0.8‐3.11), mortality (RR: 1.18, 95%CI:0.97‐1.43) compared to individuals with no CMIs, unlike the risk of dementia (RR: 0.72, 95%CI: 0.27‐1.30) albeit non‐significant.ConclusionCortical CMIs are highly prevalent in a population‐based setting and are associated with cardiovascular risk factors and increased risk of stroke and mortality albeit non‐significant. These findings provide new insights into the etiologic and prognostic significance of cortical CMIs. Future investigations will have to show whether screening and treating persons with cortical CMIs can effectively reduce the burden of stroke.

Association between cortical microinfarcts and total small vessel disease burden in cerebral amyloid angiopathy on 3-Tesla magnetic resonance imaging.

Cortical microinfarcts (CMIs) are frequently found in the brains of patients with advanced cerebral amyloid angiopathy (CAA) at autopsy. The small vessel disease (SVD) score for CAA (i.e., the CAA-SVD score) has been proposed to evaluate the severity of CAA-associated vasculopathic changes by a combination of magnetic resonance imaging (MRI) markers. The aim of this study was to examine the association between total CAA-SVD score and features of CMIs on in vivo 3-Tesla MRI. Eighty patients with probable CAA were retrospectively analyzed. Lobar cerebral microbleeds, cortical superficial siderosis, enlargement of perivascular space in the centrum semiovale and white matter hyperintensity were collectively assessed, and the total CAA-SVD score was calculated. The presence of CMI was also examined. Of the 80 patients, 13 (16.25%) had CMIs. CMIs were detected more frequently in the parietal and occipital lobes. A positive correlation was found between total CAA-SVD score and prevalence of CMI (ρ=0.943; p=0.005). Total CAA-SVD score was significantly higher in patients with CMIs than in those without (p=0.009). In a multivariable logistic regression analysis, the presence of CMIs was significantly associated with total CAA-SVD score (odds ratio 2.318 [95% confidence interval 1.228-4.376]; p=0.01, per each additional point). The presence of CMIs with a high CAA-SVD score could be an indicator of more severe amyloid-associated vasculopathic changes in patients with probable CAA.

Intracranial vessel wall lesions on 7T MRI and MRI features of cerebral small vessel disease: The SMART-MR study

The etiology of cerebral small vessel disease (CSVD) is the subject of ongoing research. Although intracranial atherosclerosis (ICAS) has been proposed as a possible cause, studies on their relationship remain sparse. We used 7 T vessel wall magnetic resonance imaging (MRI) to study the association between intracranial vessel wall lesions—a neuroimaging marker of ICAS—and MRI features of CSVD. Within the SMART-MR study, cross-sectional analyses were performed in 130 patients (68 ± 9 years; 88% male). ICAS burden—defined as the number of vessel wall lesions—was determined on 7 T vessel wall MRI. CSVD features were determined on 1.5 T and 7 T MRI. Associations between ICAS burden and CSVD features were estimated with linear or modified Poisson regression, adjusted for age, sex, vascular risk factors, and medication use. In 125 patients, ≥1 vessel wall lesions were found (mean 8.5 ± 5.7 lesions). ICAS burden (per + 1 SD) was associated with presence of large subcortical and/or cortical infarcts (RR = 1.65; 95%CI: 1.12–2.43), lacunes (RR = 1.45; 95% CI: 1.14–1.86), cortical microinfarcts (RR = 1.48; 95%CI: 1.13–1.94), and total white matter hyperintensity volume (b = 0.24; 95%CI: 0.02–0.46). Concluding, patients with a higher ICAS burden had more CSVD features, although no evidence of co-location was observed. Further longitudinal studies are required to determine if ICAS precedes development of CSVD.

Single Cortical Microinfarcts Lead to Widespread Microglia/Macrophage Migration Along the White Matter

Loss of cognitive function with aging is a complex and poorly understood process. Recently, clinical research has linked the occurrence of cortical microinfarcts to cognitive decline. Cortical microinfarcts form following the occlusion of penetrating vessels and are considered to be restricted to the proximity of the occluded vessel. Whether and how such local events propagate and affect remote brain regions remain unknown. To this end, we combined histological analysis and longitudinal diffusion tensor imaging (DTI), following the targeted-photothrombotic occlusion of single cortical penetrating vessels. Occlusions resulted in distant tissue reorganization across the mouse brain. This remodeling co-occurred with the formation of a microglia/macrophage migratory path along subcortical white matter tracts, reaching the contralateral hemisphere through the corpus callosum and leaving a microstructural signature detected by DTI-tractography. CX3CR1-deficient mice exhibited shorter trail lengths, differential remodeling, and only ipsilateral white matter tract changes. We concluded that microinfarcts lead to brain-wide remodeling in a microglial CX3CR1-dependent manner.

Cortical Microinfarcts Associated With Worse Outcomes in Patients With Acute Ischemic Stroke Receiving Endovascular Treatment.

We aimed to evaluate the impact of cortical microinfarcts (CMIs) on functional outcome after endovascular treatment in patients with acute ischemic stroke. In a multicenter registration study for RESCUE-RE (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization), eligible patients with large vessel occlusion stroke receiving endovascular treatment, who had undergone 3T magnetic resonance imaging on admission or within 24 hours after endovascular treatment were analyzed. We evaluated the presence and numbers of CMIs with assessment of axial T1, T2-weighted images, and fluid-attenuated inversion recovery images. The primary outcome was functional dependence or death defined as modified Rankin Scale scores of 3 to 6 at 90 days. Secondary outcomes included early neurological improvement, any intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality. We investigated the independent associations of CMIs with the outcomes using multivariable logistic regression in overall patients and in subgroups. Among 414 patients (enrolled from July 2018 to May 2019) included in the analyses, 96 (23.2%) patients had at least one CMI (maximum 6). Patients with CMI(s) were more likely to be functionally dependent or dead at 90 days, compared with those without (55.2% versus 37.4%; P<0.01). In multivariable logistic regression analyses, presence of CMI(s) (adjusted odds ratio, 1.78 [95% CI, 1.04-3.07]; P=0.04) and multiple CMIs (CMIs ≥2; adjusted odds ratio, 7.41 [95% CI, 2.48-22.17]; P<0.001) were independently, significantly associated with the primary outcome. There was no significant difference between subgroups in the associations between CMI presence and the primary outcome. Acute large vessel occlusion stroke patients receiving endovascular treatment with CMI(s) were more likely to have a poor functional outcome at 90 days, independent of patients' characteristics. Such associations may be dose-dependent. Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.