Cortical Cerebral Microinfarcts Research Articles

Loss of white matter integrity mediates the association between cortical cerebral microinfarcts and cognitive dysfunction: A longitudinal study.

Cortical cerebral microinfarcts (CMIs) are associated with loss of white matter (WM) integrity and cognitive impairment in cross-sectional studies, while further investigation using longitudinal datasets is required. This study aims to establish the association between cortical CMIs and WM integrity assessed by diffusion-tensor imaging (DTI) measures and to investigate whether DTI measures mediate the relationship between cortical CMIs and cognitive decline. Cortical CMIs were graded on 3T MRI. DTI measures were derived from histogram analysis of mean diffusivity (MD) and fractional anisotropy (FA). Cognitive function was assessed using a neuropsychological test battery. Linear mixed-effect models were employed to examine associations of cortical CMIs with longitudinal changes in DTI measures and cognitive function. Final analysis included 231 patients (71.14 ± 7.60 years). Presence of cortical CMIs at baseline was associated with longitudinal changes in MD median and peak height and FA median and peak height, as well as global cognition (β = -0.50, 95%CI: -0.91, -0.09) and executive function (β = -0.77, 95%CI: -1.25, -0.28). MD median mediated the cross-sectional association between cortical CMIs and global cognition. Further studies are required to investigate whether cortical CMIs and loss of WM integrity are causally related or if they are parallel mechanisms that contribute to cognitive decline.

Retinal parameters, cortical cerebral microinfarcts, and their interaction with cognitive impairment.

Quantitative changes in retinal vessels and thinning of optic nerves have been associated with subclinical (atherosclerosis, inflammation) and clinical age-related brain pathologies (stroke and neurodegeneration). However, data on the association between both retinal vascular and neuronal parameters with cortical cerebral microinfarcts (CMIs) and how these factors jointly influence cognition are lacking. We investigated the association of retinal vascular and neuronal changes with CMIs on 3 T MRI and explored their interaction with cognitive impairment in a memory-clinic population. A total of 538 participants were included. Retinal vascular parameters (caliber, tortuosity, and fractal dimension) were measured from retinal fundus photographs using a semi-automated computer-assisted program. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses were obtained from optical coherence tomography. Cortical CMIs were defined as hypointense on T1-weighted MRI, <5 mm in diameter and restricted to the cortex. Cognition was assessed using Clinical Dementia Rating Sum-of-Boxes (CDR-SoB) score and detailed neuropsychological test. Multivariable regression analysis was conducted adjusting for age, sex, hypertension, hyperlipidemia, diabetes mellitus, smoking, diagnosis, white matter hyperintensities volume, lacunes, and cerebral microbleeds. Larger venular caliber (Rate ratios (RR): 1.15, 95% CI: 1.01-1.38, p = 0.014), increased venular fractal dimension (RR: 1.58, 95% CI: 1.31-1.91, p ⩽ 0.001), increased venular tortuosity (RR: 1.54, 95% CI: 1.35-1.75, p ⩽ 0.001), and thinner GC-IPL (RR: 1.24, 95% CI: 1.13-1.36, p ⩽ 0.001) were associated with CMI counts. Among individuals in highest tertile of retinal parameters, a significant interaction was observed between venular tortuosity (RR: 1.12, 95% CI: 1.02-1.22, p-interaction = 0.014) and GC-IPL (RR: 1.05, 95% CI: 1.01-1.11, p-interaction < 0.001) with CMIs on CDR-SoB. Retinal vascular and neuronal parameters are associated with cortical CMIs, and persons with both pathologies are likely to have cognitive impairment. Further studies may be warranted to evaluate the clinical utility of retinal parameters and CMI in risk prediction for cognitive dysfunction.

The Impact of Cortical Cerebral Microinfarcts on Functional Outcomes in Patients With Ischemic Stroke.

The present study examined cortical cerebral microinfarcts (CMIs) on a 3T magnetic resonance imaging and investigated the impact of CMIs on the comprehensive functional outcomes during the post-stroke rehabilitation period. Patients with acute phase of first-ever ischemic stroke were retrospectively recruited (n = 62) and divided into 2 groups with and without CMIs. Clinical parameters including age, sex, stroke lesion laterality, location, the National Institutes of Health Stroke Scale score, as well as history of hypertension, dyslipidemia, diabetes mellitus, and smoking were obtained. Functional outcomes were assessed twice at baseline and one month later with the Korean version of the Mini-Mental State Examination, the Berg balance scale (BBS), and the functional independence measure. Partial correlation and multiple linear regression analyses were used to examine the relationship between the presence of CMIs and the change in functional outcomes. At least one CMI was reported in 27 patients, who were older (p = 0.043). The presence of CMIs was significantly associated with functional impairment in all 3 functional outcomes, after controlling for confounding factors (p < 0.05). CMIs might contribute to poor functional outcomes during the post-stroke rehabilitation period. These results suggest that CMIs should be considered when establishing rehabilitation treatment strategies or making a prognosis.

Association Between Cerebral Cortical Microinfarcts and Perilesional Cortical Atrophy on 3T MRI.

Cerebral cortical microinfarcts (CMIs) are a novel MRI marker of cerebrovascular disease (CeVD) that predicts accelerated cognitive decline. Presence of CMIs is known to be associated with global cortical atrophy, although the mechanism linking the two is unclear. Our primary objective was to examine the relation between CMIs and cortical atrophy and to establish possible perilesional atrophy surrounding CMIs. Our secondary objective was to examine the role of cortical atrophy in CMI-associated cognitive impairment. Patients were recruited from 2 Singapore memory clinics between December 2010 and September 2013 and included if they received the diagnosis no objective cognitive impairment, cognitive impairment (with or without a history of stroke), or Alzheimer or vascular dementia. Cortical thickness, chronic CMIs, and MRI markers of CeVD were assessed on 3T MRI. Patients underwent cognitive testing. Cortical thickness was compared globally between patients with and without CMIs, regionally within individual patients with CMIs comparing brain regions with CMIs to the corresponding contralateral region without CMIs, and locally within individuals patients in a 50-mm radius of CMIs. Global cortical thickness was analyzed as mediator in the relation between CMI and cognitive performance. Of the 238 patients (mean age 72.5 years, SD 9.1 years) enrolled, 75 had ≥1 CMIs. Patient with CMIs had a 2.1% lower global cortical thickness (B = -0.049 mm, 95% confidence interval [CI] 0.091 to -0.007, p = 0.022) compared to patients without CMIs, after correction for age, sex, education, and intracranial volume. In patients with CMIs, cortical thickness in brain regions with CMIs was 2.2% lower than in contralateral regions without CMIs (B = -0.048 mm [95% CI -0.071 to -0.026], p < 0.001). In a 20-mm radius area surrounding the CMI core, cortical thickness was lower than in the area 20 to 50 mm from the CMI core (mean difference -0.06 mm [-0.10 to -0.02], p = 0.002). Global cortical thickness was a significant mediator in the relationship between CMI presence and cognitive performance as measure with the Mini-Mental State Examination (B = -0.12 [-0.22 to -0.01], p = 0.025). We found cortical atrophy surrounding CMIs, suggesting a perilesional effect in a cortical area many times larger than the CMI core. Our findings support the notion that CMIs affect brain structure beyond the actual lesion site.

Retinal parameters, cortical microinfarcts and functional cognitive impairment

AbstractBackgroundQuantitative changes in retinal vessels and thinning of optic nerves have been associated with subclinical and clinical age‐related brain pathologies. However, data on the association between both retinal vascular and neuronal parameters with cortical cerebral microinfarcts and how these factors jointly contribute to functional cognitive impairment is lacking. We investigate the association of retinal vascular and neuronal changes with cortical CMIs on 3T MRI and to explore their interaction in relation to functional cognitive impairment in a memory‐clinic population.MethodA total of 538 participants (mean age:72.6±7.8 years) were included. Retinal vascular parameters (caliber, tortuosity, fractal dimension) were measured from retinal fundus photographs using a semi‐automated computer‐assisted program. Retinal nerve fiber layer (RNFL) and ganglion cell‐inner plexiform layer (GC‐IPL) thicknesses were obtained from spectral domain‐optical coherence tomography. Cortical CMIs were defined as hypointense lesions on T1‐weighted images, &lt;5mm in diameter, restricted to the cortex, and perpendicular to the cortical surface. Functional cognitive impairment was assessed on Clinical Dementia Rating Sum‐of‐Boxes (CDR‐SoB) score.ResultLarger venular caliber (Rate ratios (RR):1.21, 95%CI:1.03‐1.42), increased venular fractal dimension (RR:1.25, 95%CI:1.07‐1.46), increased venular tortuosity (RR:1.08, 95%CI:1.02‐1.15) and thinner GC‐IPL (RR:1.22, 95%CI:1.12‐1.32) were associated with increasing CMI counts. A significant interaction term was found between venular fractals, venular tortuosity, thinner GC‐IPL and RNFL and cortical CMIs (p&lt;0.05) on CDR‐SoB scores. Among individuals in highest tertile of retinal parameters, a significant interaction was observed between venular tortuosity (RR:1.14, 95%CI:1.09‐1.19, p‐interaction&lt;0.001), GC‐IPL (RR:1.23, 95%CI:1.13‐1.34, p‐interaction&lt;0.001) and RNFL (RR:1.48, 95%CI:1.31‐1.68, p‐interaction=0.002) with CMIs on CDR‐SoB scores.ConclusionWe showed that retinal vascular and neuronal parameters are associated with cortical CMIs independent of risk factors. Moreover, there was an interaction between retinal parameters and cortical CMIs on CDR‐SoB. Further studies may be warranted to evaluate the potential clinical utility of retinal parameters in risk prediction for CMIs.

Assessing cortical cerebral microinfarcts on iron-sensitive MRI in cerebral small vessel disease

Recent studies suggest that a subset of cortical microinfarcts may be identifiable on T2* but invisible on T1 and T2 follow-up images. We aimed to investigate whether cortical microinfarcts are associated with iron accumulation after the acute stage. The RUN DMC – InTENse study is a serial MRI study including individuals with cerebral small vessel disease (SVD). 54 Participants underwent 10 monthly 3 T MRIs, including diffusion-weighted imaging, quantitative R1 (=1/T1), R2 (=1/T2), and R2* (=1/T2*) mapping, from which MRI parameters within areas corresponding to microinfarcts and control region of interests (ROIs) were retrieved within 16 participants. Finally, we compared pre- and post-lesional values with repeated measures ANOVA and post-hoc paired t-tests using the mean difference between lesion and control ROI values. We observed 21 acute cortical microinfarcts in 7 of the 54 participants (median age 69 years [IQR 66–74], 63% male). R2* maps demonstrated an increase in R2* values at the moment of the last available follow-up MRI (median [IQR], 5 [5–14] weeks after infarction) relative to prelesional values (p = .08), indicative of iron accumulation. Our data suggest that cortical microinfarcts are associated with increased R2* values, indicative of iron accumulation, possibly due to microhemorrhages, neuroinflammation or neurodegeneration, awaiting histopathological verification.

Cortical cerebral microinfarcts on 7T MRI: Risk factors, neuroimaging correlates and cognitive functioning – The Medea-7T study

We determined the occurrence and association of cortical cerebral microinfarcts (CMIs) at 7 T MRI with risk factors, neuroimaging markers of small and large vessel disease, and cognitive functioning. Within the Medea-7T study, a diverse cohort of older persons with normal cognition, patients with vascular disease, and memory clinic patients, we included 386 participants (68 ± 9 years) with available 7 T and 1.5 T/3T brain MRI, and risk factor and neuropsychological data. CMIs were found in 10% of participants and were associated with older age (RR = 1.79 per +10 years, 95%CI 1.28–2.50), history of stroke or TIA (RR = 4.03, 95%CI 2.18–7.43), cortical infarcts (RR = 5.28, 95%CI 2.91–9.55), lacunes (RR = 5.66, 95%CI 2.85–11.27), cerebellar infarcts (RR = 2.73, 95%CI 1.27–5.84) and decreased cerebral blood flow (RR = 1.35 per −100 ml/min, 95%CI 1.00–1.83), after adjustment for age and sex. Furthermore, participants with >2 CMIs had 0.5 SD (95%CI 0.05–0.91) lower global cognitive performance, compared to participants without CMIs. Our results indicate that CMIs on 7 T MRI are observed in vascular and memory clinic patients with similar frequency, and are associated with older age, history of stroke or TIA, other brain infarcts, and poorer global cognitive functioning.

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.

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.

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.

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.

Last haircut in Amwaj: COVID-19 in Bahrain.

<h3>Objective:</h3> We examined the risk factors of cortical cerebral microinfarcts (CMIs) on 3T MRI and their association with cognitive impairment. <h3>Methods:</h3> Participants (aged 60 years and older) from the multiethnic Epidemiology of Dementia In Singapore Study underwent detailed neuropsychological testing and 3T brain MRI. Cortical CMIs were graded using a previously validated protocol. Cognitive impairment was categorized into cognitive impairment, no dementia (CIND)-mild, CIND-moderate, and dementia. Cognitive function was summarized as composite and domain-specific <i>z</i> scores. <h3>Results:</h3> Among 861 participants, 54 (6.3%) had ≥1 cortical CMI. In multivariate-adjusted models, the risk factors of cortical CMIs were increasing age, Malay ethnicity, hypertension, diabetes, history of stroke, and markers of both large (cortical infarcts and intracranial stenosis) and small (lacunar infarcts, white matter hyperintensities, cerebral microbleeds) vessel disease. Presence of cortical CMIs was associated with CIND-moderate (odds ratio: 3.12; 95% confidence interval [CI]: 1.18–8.58), dementia (odds ratio: 16.92; 95% CI: 3.37–85.05), and poorer cognitive function (mean difference in composite <i>z</i> score: −0.42; 95% CI: −0.62 to −0.21). Additional adjustments for vascular risk factors and other MRI markers did not alter these associations. <h3>Conclusions:</h3> Cortical CMIs are a novel MRI marker of cerebrovascular disease and are independently associated with cognitive impairment and dementia. These findings provide new insights into the burden of cerebrovascular disease in cognitive impairment. Future research is needed to establish the additional etiologic and prognostic significance of cortical CMIs.

Cerebral cortical microinfarcts: A novel MRI marker of vascular brain injury in patients with heart failure

BackgroundPatients with heart failure (HF) are at risk for vascular brain injury. Cerebral cortical microinfarcts (CMIs) are a novel MRI marker of vascular brain injury. This study aims to determine the occurrence of CMIs in patient with HF and their clinical correlates, including haemodynamic status. MethodsFrom the Heart-Brain Study, a multicenter prospective cohort study, 154 patients with clinically stable HF without concurrent atrial fibrillation (mean age 69.5 ± 10.1, 32% female) and 124 reference participants without HF (mean age 65.6 ± 7.4, 47% females) were evaluated for CMIs on 3 T MRI. CMI presence in HF was tested for associations with vascular risk profile, cardiac function and history, MRI markers of vascular brain injury and cognitive profile. ResultsCMI occurrence was higher in patient with HF (17%) than reference participants (7%); after correction for age and sex OR 2.5 [95% CI 1.1–6.0] p = .032; after additional correction for vascular risk factors OR 2.7 [1.0–7.1] p = .052. In patients with HF, CMI presence was associated with office hypertension (OR 2.7 [1.2–6.5] p = .021) and a lower cardiac index (B = -0.29 [−0.55−−0.04] p = .023 independent of vascular risk factors), but not with cause or duration of HF. Presence of CMIs was not associated with cognitive performance in patients with HF. ConclusionsCMIs are a common occurrence in patients with HF and related to an adverse vascular risk factor profile and severity of cardiac dysfunction. CMIs thus represent a novel marker of vascular brain injury in these patients.

Histological correlates of postmortem ultra-high-resolution single-section MRI in cortical cerebral microinfarcts

The identification of cerebral microinfarctions with magnetic resonance imaging (MRI) and histological methods remains challenging in aging and dementia. Here, we matched pathological changes in the microvasculature of cortical cerebral microinfarcts to MRI signals using single 100 μm-thick histological sections scanned with ultra-high-resolution 11.7 T MRI. Histologically, microinfarcts were located in superficial or deep cortical layers or transcortically, compatible with the pattern of layer-specific arteriolar blood supply of the cerebral cortex. Contrary to acute microinfarcts, at chronic stages the core region of microinfarcts showed pallor with extracellular accumulation of lipofuscin and depletion of neurons, a dense meshwork of collagen 4-positive microvessels with numerous string vessels, CD68-positive macrophages and glial fibrillary acidic protein (GFAP)-positive astrocytes. In MRI scans, cortical microinfarcts at chronic stages, called chronic cortical microinfarcts here, gave hypointense signals in T1-weighted and hyperintense signals in T2-weighted images when thinning of the tissue and cavitation and/or prominent iron accumulation were present. Iron accumulation in chronic microinfarcts, histologically verified with Prussian blue staining, also produced strong hypointense T2*-weighted signals. In summary, the microinfarct core was occupied by a dense microvascular meshwork with string vessels, which was invaded by macrophages and astroglia and contained various degrees of iron accumulation. While postmortem ultra-high-resolution single-section imaging improved MRI-histological matching and the structural characterization of chronic cortical cerebral microinfarcts, miniscule microinfarcts without thinning or iron accumulation could not be detected with certainty in the MRI scans. Moreover, string vessels at the infarct margin indicate disturbances in the microcirculation in and around microinfarcts, which might be exploitable in the diagnostics of cortical cerebral microinfarcts with MRI in vivo.

Influence of Comorbidity of Cerebrovascular Disease and Amyloid-β on Alzheimer's Disease.

Quantifying the contribution of cerebrovascular disease to the clinical and pathological profile of Alzheimer's disease is challenging. We aimed to determine the influence of cerebrovascular disease, amyloid-β (Aβ), and their comorbidity on cognitive decline, hippocampal atrophy, and Aβ deposition, by evaluating data from the Australian Imaging, Biomarker and Lifestyle Study of Ageing. Two-hundred and eighteen participants underwent Aβ PET, MRI, and cognitive assessment at 18-month intervals for up to 90 months. Aβ status was determined on baseline PET. Participants were also classified as V+ on baseline MRI if they had≥1 large cortical infarcts, subcortical infarcts, or cortical cerebral microinfarcts; or white matter hyperintensity volume greater than the 90th percentile of healthy controls. Linear mixed models were conducted comparing slopes of change in cognition, hippocampal volume, and Aβ load between the four resultant groups. Mean age at baseline was 74 years (range 59-96). One-hundred and fifteen participants were cognitively normal, 54 had mild cognitive impairment, and 49 had Alzheimer's disease. Compared to the Aβ-/V- group, the Aβ+/V- and Aβ+/V+ groups showed significantly faster cognitive decline and hippocampal atrophy over 90 months. V+ status was associated with greater cognitive decline (Cohen's d = 0.85, p < 0.001) and hippocampal atrophy (d = 2.05, p < 0.001) in the Aβ+ group but not in the Aβ- group. V+ status was not associated with Aβ accumulation in any group. Comorbidity of cerebrovascular disease and Aβ was associated with cognitive decline and neurodegeneration. Cerebrovascular disease was not associated with the rate of Aβ accumulation.

MRI Markers of Mixed Pathology and Cognitive Impairment in Multiethnic Asians.

There is a need to elucidate the combined influence of neurodegeneration and cerebrovascular disease (CeVD) on cognitive impairment, especially in diverse populations. Here, we evaluated 840 multiethnic individuals (mean age = 70.18) across the disease spectrum from the Epidemiology of Dementia in Singapore study. First, we determined whether a validated quantitative MRI score of mixed pathology is associated with clinical diagnosis and whether the score differed between ethnicities (Chinese, Malays, and Indians). We then evaluated whether the score was associated with multidomain cognitive impairment and if additional measures of CeVD were further associated with cognitive impairment. We found that lower quantitative MRI scores were associated with severity of clinical diagnosis and Chinese individuals had the highest quantitative MRI scores, followed by Indians and Malays. Lower quantitative MRI scores were also associated with lower performance in attention, language, visuoconstruction, visuomotor, visual, and verbal memory domains. Lastly, the presence of intracranial stenosis and cortical cerebral microinfarcts, but not cerebral microbleeds, were associated with memory performance beyond quantitative MRI scores. Taken together, our results demonstrate the utility of using multiple MRI markers of neurodegeneration and CeVD for identifying multiethnic Asians with the greatest cognitive impairment due to mixed pathology.

Cortical microinfarcts in memory clinic patients are associated with reduced cerebral perfusion

Cerebral cortical microinfarcts (CMIs) are small ischemic lesions associated with cognitive impairment and dementia. CMIs are frequently observed in cortical watershed areas suggesting that hypoperfusion contributes to their development. We investigated if presence of CMIs was related to a decrease in cerebral perfusion, globally or specifically in cortex surrounding CMIs. In 181 memory clinic patients (mean age 72 ± 9 years, 51% male), CMI presence was rated on 3-T magnetic resonance imaging (MRI). Cerebral perfusion was assessed from cortical gray matter of the anterior circulation using pseudo-continuous arterial spin labeling parameters cerebral blood flow (CBF) (perfusion in mL blood/100 g tissue/min) and spatial coefficient of variation (CoV) (reflecting arterial transit time (ATT)). Patients with CMIs had a 12% lower CBF (beta = −.20) and 22% higher spatial CoV (beta = .20) (both p < .05) without a specific regional pattern on voxel-based CBF analysis. CBF in a 2 cm region-of-interest around the CMIs did not differ from CBF in a reference zone in the contralateral hemisphere. These findings show that CMIs in memory clinic patients are primarily related to global reductions in cerebral perfusion, thus shedding new light on the etiology of vascular brain injury in dementia.

The new insights into human brain imaging after stroke.

Over the last two decades, developments of human brain stroke imaging have raised several questions about the place of new MRI biomarkers in the acute management of stroke and the prediction of poststroke outcome. Recent studies have demonstrated the main role of perfusion-weighted imaging in the identification of the best cerebral perfusion profile for a better response after reperfusion therapies in acute ischemic stroke. A major issue remains the early prediction of stroke outcome. While voxel-based lesion-symptom mapping emphasized the influence of stroke location, the analysis of the brain parenchyma underpinning the stroke lesion showed the relevance of prestroke cerebral status, including cortical atrophy, white matter integrity, or presence of chronic cortical cerebral microinfarcts. Moreover, besides the evaluation of the visually abnormal brain tissue, the analysis of normal-appearing brain parenchyma using diffusion tensor imaging and magnetization transfer imaging or spectroscopy offered new biomarkers to improve the prediction of the prognosis and new targets to follow in therapeutic trials. The aim of this review was to depict the main new radiological biomarkers reported in the last two decades that will provide a more thorough prediction of functional, motor, and neuropsychological outcome following the stroke. These new developments in neuroimaging might be a cornerstone in the emerging personalized medicine for stroke patients.