Genome-wide genotyping demonstrates a polygenic risk score associated with white matter hyperintensity volume in CADASIL

Background and Purpose—White matter hyperintensities (WMH) on MRI are a quantitative marker for sporadic cerebral small vessel disease and are highly heritable. To date, large-scale genetic studies have identified only a single locus influencing WMH burden. This might in part relate to biological heterogeneity of sporadic WMH. The current study searched for genetic modifiers of WMH volume in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a monogenic small vessel disease. Methods—We performed a genome-wide association study to identify quantitative trait loci for WMH volume by combining data from 517 CADASIL patients collected through 7 centers across Europe. WMH volumes were centrally analyzed and quantified on fluid attenuated inversion recovery images. Genotyping was performed using the Affymetrix 6.0 platform. Individuals were assigned to 2 distinct genetic clusters (cluster 1 and cluster 2) based on their genetic background. Results—Four hundred sixty-six patients entered the final genome-wide association study analysis. The phenotypic variance of WMH burden in CADASIL explained by all single nucleotide polymorphisms in cluster 1 was 0.85 (SE=0.21), suggesting a substantial genetic contribution. Using cluster 1 as derivation and cluster 2 as a validation sample, a polygenic score was significantly associated with WMH burden (P=0.001) after correction for age, sex, and vascular risk factors. No single nucleotide polymorphism reached genome-wide significance. Conclusions—We found a polygenic score to be associated with WMH volume in CADASIL subjects. Our findings suggest that multiple variants with small effects influence WMH burden in CADASIL. The identification of these variants and the biological pathways involved will provide insights into the pathophysiology of white matter disease in CADASIL and possibly small vessel disease in general

Personal familiarity enhances sensitivity to horizontal structure during processing of face identity

What makes identification of familiar faces seemingly effortless? Recent studies using unfamiliar face stimuli suggest that selective processing of information conveyed by horizontally oriented spatial frequency components supports accurate performance in a variety of tasks involving matching of facial identity. Here, we studied upright and inverted face discrimination using stimuli with which observers were either unfamiliar or personally familiar (i.e., friends and colleagues). Our results reveal increased sensitivity to horizontal spatial frequency structure in personally familiar faces, further implicating the selective processing of this information in the face processing expertise exhibited by human observers throughout their daily lives

Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis

Objectives: To establish the frequency of cognitive impairment in a population based sample of patients with recently diagnosed relapsing-remitting multiple sclerosis (RRMS), and to determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage revealed by magnetic resonance imaging (MRI) and magnetisation transfer (MT) imaging. Methods: 58 patients with RRMS consecutively diagnosed in the previous six months in Aquitaine and 70 healthy controls underwent a battery of neuropsychological tests. Lesion load and atrophy indices (brain parenchymal fraction and ventricular fraction) were measured on brain MRI. MT ratio (MTR) histograms were obtained from lesions, normal appearing white matter (NAWM), and normal appearing grey matter (NAGM). Gadolinium enhanced lesions were counted. Results: 44 RRMS patients could be individually matched with healthy controls for age, sex, and education. Patients performed worse in tests of verbal and spatial memory, attention, information processing speed, inhibition, and conceptualisation. Measures of attention and information processing speed were correlated with lesion load, mean NAWM MTR, and the peak location of the NAGM MTR histogram in the patients. Multivariate regression analysis showed that lesion load and mean NAWM MTR were among the MR indices that were most significantly associated with impairment of attention and information processing speed in these early RRMS cases. Conclusions: Cognitive impairment appears to be common in the early stages of RRMS, mainly affecting attention, information processing speed, memory, inhibition, and conceptualisation. The severity of these deficits reflects the extent of the lesions and the severity of tissue disorganisation outside lesions

Correlation between cranial vault size and brain size over time: preliminary MRI evaluation

articleOBJECTIVES: To correlate changes of cranial vault measurements of an adult population during the aging process with brain size using the maximum width of the third ventricle in the axial AC-PC plane. MATERIALS AND METHODS: Prospective study of 126 adult subjects (range: 20 to 80 years) with normal brain MRI and without history of neuropsychiatric disorder. MEASUREMENTS INCLUDED: Cranial vault (Maximum length: Glabella-Opisthocranion, Maximum width: euryon-euryon, and maximum height: Basion-Vertex) measurements and maximum width of the third ventricle in the A C-PC plane. RESULTS: Vault measurements (length, width, high) were similar for every age group, irrespective of gender. The variability of cranial vault measurements between individuals was low (<1 cm). Cranial vault measurements were larger for men, but this was not significant when adjusted for body height Comparatively, a gradual widening of the third ventricle, with an exponential behavior, was observed with advancing age. CONCLUSION: Our results indicate that cranial vault measurements are stable over time (between 20-80 years) comparatively to brain atrophy with advancing age. The low variability of cranial vault measurements and their stability over time should be taken into account during segmentation and normalization of brain parenchymal structures

Evolution de la voute cranienne et du parenchyme cerebral avec l'age : etude preliminaire en IRM

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