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

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013140
Author(s):  
Doeschka A. Ferro ◽  
Hugo J. Kuijf ◽  
Saima Hilal ◽  
Susanne J. van Veluw ◽  
Daniëlle van Veldhuizen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Performance ◽  
Sex Education ◽  
Cortical Thickness ◽  
Brain Regions ◽  
Primary Objective ◽  
Cognitive Testing ◽  
Cortical Atrophy ◽  
Intracranial Volume ◽  
3T Mri

Background and objectives: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 establish possible perilesional atrophy surrounding CMIs. Our secondary objective was to examine the role of cortical atrophy in CMI-associated cognitive impairment.Methods:Patients were recruited from two 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’s or vascular dementia. Cortical thickness, chronic cortical microinfarcts 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.Results:Of the 238 patients (mean age 72.5 SD 9.1 years) enrolled, 75 had ≥1 CMIs. Patient with CMIs had a 2.1% lower global cortical thickness (B=-.049 mm, 95% CI [.091; -.007] p=.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=-.048 mm [-.071; -.026] p<.001). In a 20 mm radius area surrounding the CMI-core, cortical thickness was lower than in the area 20-50 mm from the CMI-core (Mean difference -.06 mm 95% CI [-.10; -.02] p=.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=-.12 [-.22; -.01] p=.025).Discussion: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.

scholarly journals Cortical Volume, Thickness, and Surface Area in the Motoric Cognitive Risk Syndrome

2021 ◽  
pp. 1-14
Author(s):  
Helena M. Blumen ◽  
Emily Schwartz ◽  
Gilles Allali ◽  
Olivier Beauchet ◽  
Michele Callisaya ◽  
...  
Keyword(s):  
Surface Area ◽  
Sex Education ◽  
Cortical Thickness ◽  
Clinical Stage ◽  
White Matter Lesions ◽  
Cortical Atrophy ◽  
Intracranial Volume ◽  
Cortical Volume ◽  
Cognitive Risk ◽  
Cognitive Complaint

Background: The motoric cognitive risk (MCR) syndrome is a pre-clinical stage of dementia characterized by slow gait and cognitive complaint. Yet, the brain substrates of MCR are not well established. Objective: To examine cortical thickness, volume, and surface area associated with MCR in the MCR-Neuroimaging Consortium, which harmonizes image processing/analysis of multiple cohorts. Methods: Two-hundred MRIs (M age 72.62 years; 47.74%female; 33.17%MCR) from four different cohorts (50 each) were first processed with FreeSurfer 6.0, and then analyzed using multivariate and univariate general linear models with 1,000 bootstrapped samples (n-1; with resampling). All models adjusted for age, sex, education, white matter lesions, total intracranial volume, and study site. Results: Overall, cortical thickness was lower in individuals with MCR than in those without MCR. There was a trend in the same direction for cortical volume (p = 0.051). Regional cortical thickness was also lower among individuals with MCR than individuals without MCR in prefrontal, insular, temporal, and parietal regions. Conclusion: Cortical atrophy in MCR is pervasive, and include regions previously associated with human locomotion, but also social, cognitive, affective, and motor functions. Cortical atrophy in MCR is easier to detect in cortical thickness than volume and surface area because thickness is more affected by healthy and pathological aging.

scholarly journals Cortical Microstructural Alterations in Mild Cognitive Impairment and Alzheimer’s Disease Dementia

2020 ◽  
Vol 30 (5) ◽  
pp. 2948-2960 ◽  
Author(s):  
Nicholas M Vogt ◽  
Jack F Hunt ◽  
Nagesh Adluru ◽  
Douglas C Dean ◽  
Sterling C Johnson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cortical Thickness ◽  
Gray Matter ◽  
Brain Regions ◽  
Cortical Atrophy ◽  
Microstructural Alterations ◽  
Additional Information

Abstract In Alzheimer’s disease (AD), neurodegenerative processes are ongoing for years prior to the time that cortical atrophy can be reliably detected using conventional neuroimaging techniques. Recent advances in diffusion-weighted imaging have provided new techniques to study neural microstructure, which may provide additional information regarding neurodegeneration. In this study, we used neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion model, in order to investigate cortical microstructure along the clinical continuum of mild cognitive impairment (MCI) and AD dementia. Using gray matter-based spatial statistics (GBSS), we demonstrated that neurite density index (NDI) was significantly lower throughout temporal and parietal cortical regions in MCI, while both NDI and orientation dispersion index (ODI) were lower throughout parietal, temporal, and frontal regions in AD dementia. In follow-up ROI analyses comparing microstructure and cortical thickness (derived from T1-weighted MRI) within the same brain regions, differences in NODDI metrics remained, even after controlling for cortical thickness. Moreover, for participants with MCI, gray matter NDI—but not cortical thickness—was lower in temporal, parietal, and posterior cingulate regions. Taken together, our results highlight the utility of NODDI metrics in detecting cortical microstructural degeneration that occurs prior to measurable macrostructural changes and overt clinical dementia.

scholarly journals Cognitive impairment in schizophrenia: relationships with cortical thickness in fronto-temporal regions, and dissociability from symptom severity

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Erkan Alkan ◽  
Geoff Davies ◽  
Simon L. Evans
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Performance ◽  
Cortical Thickness ◽  
Symptom Severity ◽  
Visual Learning ◽  
Brain Regions ◽  
Antipsychotic Treatment ◽  
Neural Basis ◽  
Cognitive Domains ◽  
Attention Performance

AbstractCognitive impairments are a core and persistent characteristic of schizophrenia with implications for daily functioning. These show only limited response to antipsychotic treatment and their neural basis is not well characterised. Previous studies point to relationships between cortical thickness and cognitive performance in fronto-temporal brain regions in schizophrenia patients (SZH). There is also evidence that these relationships might be independent of symptom severity, suggesting dissociable disease processes. We set out to explore these possibilities in a sample of 70 SZH and 72 age and gender-matched healthy controls (provided by the Center of Biomedical Research Excellence (COBRE)). Cortical thickness within fronto-temporal regions implicated by previous work was considered in relation to performance across various cognitive domains (from the MATRICS Cognitive Battery). Compared to controls, SZH had thinner cortices across most fronto-temporal regions and significantly lower performance on all cognitive domains. Robust relationships with cortical thickness were found: visual learning and attention performance correlated with bilateral superior and middle frontal thickness in SZH only. Correlations between attention performance and right transverse temporal thickness were also specific to SZH. Findings point to the importance of these regions for cognitive performance in SZH, possibly reflecting compensatory processes and/or aberrant connectivity. No links to symptom severity were observed in these regions, suggesting these relationships are dissociable from underlying psychotic symptomology. Findings enhance understanding of the brain structural underpinnings and possible aetiology of cognitive impairment in SZH.

scholarly journals Executive, language and fluency dysfunction are markers of localised TDP-43 cerebral pathology in non-demented ALS

2019 ◽  
Vol 91 (2) ◽  
pp. 149-157 ◽  
Author(s):  
Jenna M Gregory ◽  
Karina McDade ◽  
Thomas H Bak ◽  
Suvankar Pal ◽  
Siddharthan Chandran ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Executive Functions ◽  
Cognitive Deficits ◽  
Regional Distribution ◽  
Brain Regions ◽  
Cognitive Testing ◽  
Functional Deficits ◽  
Language Functions ◽  
Cerebral Pathology ◽  
Lateral Sclerosis

ObjectiveApproximately 35% of patients with amyotrophic lateral sclerosis (ALS) exhibit mild cognitive deficits in executive functions, language and fluency, without dementia. The precise pathology of these extramotor symptoms has remained unknown. This study aimed to determine the pathological correlate of cognitive impairment in patients with non-demented ALS.MethodsIn-depth neuropathological analysis of 27 patients with non-demented ALS who had undergone cognitive testing (Edinburgh Cognitive and Behaviour ALS Screen (ECAS)) during life. Analysis involved assessing 43 kDa Tar-DNA binding protein (TDP-43) accumulation in brain regions specifically involved in executive functions, language functions and verbal fluency to ascertain whether functional deficits would relate to a specific regional distribution of pathology.ResultsAll patients with cognitive impairment had TDP-43 pathology in extramotor brain regions (positive predictive value of 100%). The ECAS also predicted TDP-43 pathology with 100% specificity in brain regions associated with executive, language and fluency domains. We also detected a subgroup with no cognitive dysfunction, despite having substantial TDP-43 pathology, so called mismatch cases.ConclusionsCognitive impairment as detected by the ECAS is a valid predictor of TDP-43 pathology in non-demented ALS. The profile of mild cognitive deficits specifically predicts regional cerebral involvement. These findings highlight the utility of the ECAS in accurately assessing the pathological burden of disease.

scholarly journals Cortical atrophy and transcallosal diaschisis following isolated subcortical stroke

2019 ◽  
Vol 40 (3) ◽  
pp. 611-621 ◽  
Author(s):  
Bastian Cheng ◽  
Philipp Dietzmann ◽  
Robert Schulz ◽  
Marlene Boenstrup ◽  
Lutz Krawinkel ◽  
...  
Keyword(s):  
White Matter ◽  
Cortical Thickness ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
White Matter Integrity ◽  
Cortical Atrophy ◽  
Fiber Tractography ◽  
Stroke Patients ◽  
Fiber Tracts ◽  
One Year

Following acute ischemic stroke, isolated subcortical lesions induce gray matter atrophy in anatomically connected, yet distant cortical brain regions. We expand on previous studies by analyzing cortical thinning in contralesional, homologous regions indirectly linked to primary stroke lesions via ipsilesional cortical areas. For this purpose, stroke patients were serially studied by magnetic resonance imaging (diffusion tensor imaging and high-resolution anatomical imaging) in the acute (days 3–5) and late chronic stage one year after stroke. We analyzed changes of gray and white matter integrity in 18 stroke patients (median age 68 years) with subcortical stroke. We applied probabilistic fiber tractography to identify brain regions connected to stroke lesions and contralesional homologous areas. Cortical thickness was quantified by semi-automatic measurements, and fractional anisotropy was analyzed. One year after stroke, significant decrease of cortical thickness was detected in areas connected to ischemic lesions (mean −0.15 mm; 95% CI −0.23 to −0.07 mm) as well as homologous contralateral brain regions (mean −0.13 mm; 95% CI −0.07 to −0.19 mm). We detected reduced white matter integrity of inter- and intrahemispheric fiber tracts. There were no significant associations with clinical recovery. Our results indicate that impact of subcortical lesions extends to homologous brain areas via transcallosal diaschisis.

scholarly journals Relationships between Cognitive Performance, Neuroimaging and Vascular Disease: The DHS-MIND Study

2015 ◽  
Vol 45 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Fang-Chi Hsu ◽  
Laura M. Raffield ◽  
Christina E. Hugenschmidt ◽  
Amanda Cox ◽  
Jianzhao Xu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vascular Disease ◽  
Cognitive Performance ◽  
Gray Matter Volume ◽  
Cognitive Testing ◽  
Intracranial Volume ◽  
Semantic Fluency ◽  
Total Brain Volume ◽  
Subclinical Cvd

Background: Type 2 diabetes mellitus increases the risk of cognitive decline and dementia, and elevated burdens of vascular disease are hypothesized to contribute to this risk. These relationships were examined in the Diabetes Heart Study-MIND using a battery of cognitive tests, neuroimaging measures and subclinical cardiovascular disease (CVD) burden assessed by coronary artery calcified (CAC) plaque. We hypothesized that CAC would attenuate the association between neuroimaging measures and cognition performance. Methods: Associations were examined using marginal models in this family-based cohort of 572 European Americans from 263 families. All models were adjusted for age, gender, education, type 2 diabetes and hypertension, with some neuroimaging measures additionally adjusted for intracranial volume. Results: Higher total brain volume was associated with better performance on the Digit Symbol Substitution Task and Semantic Fluency (both p ≤ 7.0 × 10-4). Higher gray matter volume was associated with better performance on the Modified Mini-Mental State Examination and Semantic Fluency (both p ≤ 9.0 × 10-4). Adjusting for CAC caused minimal changes to the results. Conclusions: Relationships exist between neuroimaging measures and cognitive performance in a type 2 diabetes-enriched European American cohort. Associations were minimally attenuated after adjusting for subclinical CVD. Additional work is needed to understand how subclinical CVD burden interacts with other factors and impacts relationships between neuroimaging and cognitive testing measures.

scholarly journals Interactions between plasma concentrations of folate and markers of vitamin B12status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study

2013 ◽  
Vol 111 (6) ◽  
pp. 1085-1095 ◽  
Author(s):  
Esmée L. Doets ◽  
Per M. Ueland ◽  
Grethe S. Tell ◽  
Stein Emil Vollset ◽  
Ottar K. Nygård ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Folic Acid ◽  
Cognitive Performance ◽  
Sex Education ◽  
Plasma Concentrations ◽  
Health Study ◽  
Vitamin B ◽  
Plasma Vitamin ◽  
Folic Acid Fortification ◽  
Plasma Folate

A combination of high folate with low vitamin B12plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72–74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-ɛ4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0·009) between plasma concentrations of folate and vitamin B12in relation to cognitive performance. Plasma vitamin B12concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12concentrations in the lower range, the association between plasma folate and cognitive performance was strongest.

Problem-solving abilities and frontal lobe cortical thickness in healthy aging and mild cognitive impairment

2010 ◽  
Vol 16 (5) ◽  
pp. 836-845 ◽  
Author(s):  
G. SÁNCHEZ-BENAVIDES ◽  
B. GÓMEZ-ANSÓN ◽  
M. QUINTANA ◽  
Y. VIVES ◽  
R.M. MANERO ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Problem Solving ◽  
Frontal Lobe ◽  
Cortical Thickness ◽  
Healthy Aging ◽  
Cortical Atrophy ◽  
Control Group ◽  
Left Frontal Lobe ◽  
Transitional State

AbstractMild cognitive impairment (MCI) is considered a transitional state between normal aging and Alzheimer disease. Most MCI subjects present disturbances in multiple neuropsychological domains, including executive function. This study aimed at exploring frontal lobe cortical thinning in MCI and healthy controls, and its relationship with problem-solving abilities. Twenty-three MCI patients and 30 elderly controls underwent MRI and neuropsychological assessment. Cortical thickness was measured by means of FreeSurfer. Problem-solving was assessed by means of the Tower of London (TOL) task. MCI showed a global thinning of the cortex. With regard to specific regions of interest, a thinning in the left frontal lobe and the bilateral posterior cingulate gyri was found. Partial correlations, after controlling for age, education, Mini-Mental Status Examination, and non-frontal mean thickness revealed negative significant correlations between frontal lobe thickness and executive outcomes in the control group. This counterintuitive relationship was not observed in the MCI group, suggesting that the frontal cortical atrophy observed in MCI entails a specific pathology-related relationship with high-level executive outcomes that is qualitatively different from that observed in healthy aging. (JINS, 2010, 16, 836–845.)

scholarly journals Cardiac autonomic function and cognitive performance in patients with atrial fibrillation

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
P Haemmerle ◽  
S Aeschbacher ◽  
A Springer ◽  
C Eken ◽  
M Coslovsky ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Rate ◽  
Cognitive Impairment ◽  
Cognitive Performance ◽  
Autonomic Function ◽  
Cognitive Testing ◽  
Cardiac Autonomic Function ◽  
Multicenter Cohort Study ◽  
Funding Sources ◽  
Cardiac Autonomic Dysfunction

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation OnBehalf Swiss-AF Investigators Background Atrial fibrillation (AF) is associated with loss of cognition and dementia. Cardiac autonomic dysfunction has been linked to cognitive decline. We aimed to investigate if reduced cardiac autonomic function (CAF) is associated with cognitive impairment in AF patients.  Methods Patients with paroxysmal, persistent and permanent AF were enrolled from a multicenter cohort study if they presented in AF ("AF group") or in sinus rhythm ("SR group") on a baseline 5-minute ECG recording. Parameters quantifying CAF (heart rate variability triangular index (HRVI), mean heart rate (MHR), the root mean square of successive differences (RMSSD) and the standard deviation of the normal-to-normal intervals (SDNN)) were calculated. We used the Montreal Cognitive Assessment (MoCA) to assess global cognitive function. Results 1,685 AF patients with a mean age of 73 ± 8 years, 29% females, were included. The MoCA score was 24.5 ± 3.2 in the AF group (n = 710 patients) and 25.4 ± 3.2 in the SR group (n = 975 patients). After adjusting for multiple confounders, lower HRVI was associated with lower MoCA scores, both in the SR group (β=0.049; 95% confidence interval (CI): 0.016 to 0.081; p = 0.003) and in the AF group (β=0.068; 95% CI: 0.020 to 0.116; p = 0.006). In the AF group, higher MHR was associated with a poorer performance in the MoCA (β=-0.008; 95% CI: -0.014 to -0.002; p = 0.014 ). Other parameters of CAF were not associated with cognition. Conclusion Our data suggest that impaired CAF is associated with worse cognitive performance in patients with AF. Elderly AF patients with impaired HRVI might undergo cognitive testing in order to screen for cognitive impairment.

Abstract P56: Diffusion Tensor Imaging at the Time of Stroke is Associated With Cognitive Performance 4 Months Later

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Kyle C Kern ◽  
Clinton B Wright ◽  
Richard Leigh
Keyword(s):  
Cognitive Impairment ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Linear Regression ◽  
Cognitive Performance ◽  
Diffusion Tensor ◽  
Cognitive Status ◽  
Cognitive Testing ◽  
Brain Health

Introduction: Cognitive impairment after stroke is associated with stroke severity and baseline brain health. We hypothesized that acute diffusion tensor imaging (DTI) metrics would identify patients at risk for post-stroke cognitive impairment. Methods: Patients were enrolled prospectively in an observational study that involves serial MRI and cognitive testing in patients with recent stroke and moderate white matter disease on MRI but without dementia. DTI was performed at the time of stroke; cognitive testing with the MOCA and the Telephone Interview for Cognitive Status (TICS) were performed 3 months later. DTI was used to calculate Peak Skeletonized Mean Diffusivity (PSMD), a measure of global white matter microstructural integrity previously validated in cerebral small vessel disease. Fractional anisotropy maps were skeletonized (figure panel A) and a histogram of the corresponding MD values was used to calculate the peak width in the non-stroke hemisphere (panel B). Linear regression was used to test whether acute PSMD in the non-stroke hemisphere, acute stroke volume, or baseline NIHSS predicted cognitive performance 3 months later. Results: Fourteen patients followed-up at a median of 123 days. Patients had a median age of 73 years, mean baseline NIHSS of 1.2 (IQR 0-1.75), mean infarct volume of 4cc (range 0-16cc), mean MOCA of 25 (range 19-30), mean TICS of 33 (range 23-41), and 50% were women. Using multivariable linear regression, only acute PSMD predicted follow-up MOCA (std beta= -0.64, adj R 2 = 0.37, p= 0.013) while compared to baseline NIHSS, PSMD showed a stronger association with follow-up TICS score (std beta= -0.57 vs -0.44, p= 0.017; model adj R 2 = 0.476, p= 0.011)(Panel C). Conclusions: In this cohort of patients with small strokes we found that acute contralateral PSMD provided a measure of brain health that appears to predict cognitive performance at 3 months better than stroke size or severity. These are preliminary findings from an ongoing study.

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