Auswahl der wissenschaftlichen Literatur zum Thema „Peak width of skeletonized mean diffusivity (PSMD)“

Post-stroke cognitive impairment is common and can have major impact on life after stroke. Peak-width of Skeletonized Mean Diffusivity (PSMD) is a diffusion imaging marker of white matter microstructure and is also associated with cognition. Here, we examined associations between PSMD and post-stroke global cognition in an ongoing study of mild ischemic stroke patients. We studied cross-sectional associations between PSMD and cognition at both 3-months (N = 229) and 1-year (N = 173) post-stroke, adjusted for premorbid IQ, sex, age, stroke severity and disability, as well as the association between baseline PSMD and 1-year cognition. At baseline, (mean age = 65.9 years (SD = 11.1); 34% female), lower Montreal Cognitive Assessment (MoCA) scores were associated with older age, lower premorbid IQ and higher stroke severity, but not with PSMD (βstandardized = −0.116, 95% CI −0.241, 0.009; p = 0.069). At 1-year, premorbid IQ, older age, higher stroke severity and higher PSMD (βstandardized = −0.301, 95% CI −0.434, −0.168; p < 0.001) were associated with lower MoCA. Higher baseline PSMD was associated with lower 1-year MoCA (βstandardized = −0.182, 95% CI −0.308, −0.056; p = 0.005). PSMD becomes more associated with global cognition at 1-year post-stroke, possibly once acute effects have settled. Additionally, PSMD in the subacute phase after a mild stroke could help predict long-term cognitive impairment.

Despite associations of regular coffee consumption with fewer neurodegenerative disorders, its association with microstructural brain alterations is unclear. To address this, we examined the association of coffee consumption with brain MRI parameters representing vascular brain damage, neurodegeneration, and microstructural integrity in 2316 participants in the population-based Hamburg City Health Study. Cortical thickness and white matter hyperintensity (WMH) load were measured on FLAIR and T1-weighted images. Microstructural white matter integrity was quantified as peak width of skeletonized mean diffusivity (PSMD) on diffusion-weighted MRI. Daily coffee consumption was assessed in five groups (<1 cup, 1–2 cups, 3–4 cups, 5–6 cups, >6 cups). In multiple linear regressions, we examined the association between brain MRI parameters and coffee consumption (reference group <1 cup). After adjustment for covariates, 3–4 cups of daily coffee were associated with lower PSMD (p = 0.028) and higher cortical thickness (p = 0.015) compared to <1 cup. Moreover, 1–2 cups per day was also associated with lower PSMD (p = 0.022). Associations with WMH load or other groups of coffee consumption were not significant (p > 0.05). The findings indicate that regular coffee consumption is positively associated with microstructural white matter integrity and cortical thickness. Further research is necessary to determine longitudinal effects of coffee on brain microstructure.

Background and objectivePeak width of skeletonized mean diffusivity (PSMD), a fully automated diffusion tensor imaging (DTI) biomarker of white matter (WM) microstructure damage, has been shown to be associated with cognition in various WM pathologies. However, its application in schizophrenic disease remains unexplored. This study aims to investigate PSMD along with other DTI markers in first-episode schizophrenia patients compared to healthy controls (HCs), and explore the correlations between these metrics and clinical characteristics.MethodsA total of 56 first-episode drug-naive schizophrenia patients and 64 HCs were recruited for this study. Participants underwent structural imaging and DTI, followed by comprehensive clinical assessments, including the Positive and Negative Syndrome Scale (PANSS) for patients and cognitive function tests for all participants. We calculated PSMD, peak width of skeletonized fractional anisotropy (PSFA), axial diffusivity (PSAD), radial diffusivity (PSRD) values, skeletonized average mean diffusivity (MD), average fractional anisotropy (FA), average axial diffusivity (AD), and average radial diffusivity (RD) values as well as structural network global topological parameters, and examined between-group differences in these WM metrics. Furthermore, we investigated associations between abnormal metrics and clinical characteristics.ResultsCompared to HCs, patients exhibited significantly increased PSMD values (t = 2.467, p = 0.015), decreased global efficiency (Z = −2.188, p = 0.029), and increased normalized characteristic path length (lambda) (t = 2.270, p = 0.025). No significant differences were observed between the groups in the remaining metrics, including PSFA, PSAD, PSRD, average MD, FA, AD, RD, local efficiency, normalized cluster coefficient, small-worldness, assortativity, modularity, or hierarchy (p &gt; 0.05). After adjusting for relevant variables, both PSMD and lambda values exhibited a significant negative correlation with reasoning and problem-solving scores (PSMD: r = −0.409, p = 0.038; lambda: r = −0.520, p = 0.006). No statistically significant correlations were observed between each PANSS score and the aforementioned metrics in the patient group (p &gt; 0.05). Multivariate linear regression analysis revealed that increased PSMD (β = −0.426, t = −2.260, p = 0.034) and increased lambda (β = −0.490, t = −2.994, p = 0.007) were independently associated with decreased reasoning and problem-solving scores respectively (Radj2 = 0.295, F = 2.951, p = 0.029). But these significant correlations did not withstand FDR correction (p_FDR &gt; 0.05).ConclusionPSMD can be considered as a valuable neuroimaging biomarker that complements conventional diffusion measurements for investigating abnormalities in WM microstructural integrity and cognitive functions in schizophrenia.

AbstractBackgroundCerebral small vessel disease (CSVD) is common in Alzheimer’s disease (AD), but it is unclear how CSVD affects cognition and disease progression. Peak width of Skeletonized Mean Diffusivity (PSMD) is a Magnetic Resonance Imaging (MRI) marker of global white matter integrity, believed to reflect both total vascular burden and the cognitive impact of CSVD. We examined the relationship between PSMD and memory, processing speed and executive function, and to assess the predictive value of PSMD on clinical progression.Method265 cases and controls between 40‐80 years old were recruited from the Norwegian multi‐center study DDI (Dementia Disease Initiation), with 2‐5 follow ups (0.7‐8 years). Subjects were according to the Clinical Dementia Rating (CDR), with 0 as cognitively unimpaired (CU) if, 0,5 as mild cognitive impairment (MCI) if CDR, and ≥ 1 as dementia. Amyloid status was determined from Amyloid‐PET or from amyloid‐β42/40. PSMD was obtained from 6 MRI scanners and harmonized for scanner effects in R using ComBat, with age, sex, staging and amyloid status at baseline as covariates.The relationship between PSMD and cognitive scores was assessed using a general linear model, with age, sex, education and an PSMD‐amyloid interaction variable as covariates. Subjects were classified into the following groups: A‐ low PSMD, A+ low PSMD, A‐ low PSMD, A+ high PSMD high, where PSMD high or low signifies above or below the group median. Survival analysis was performed in 195 subjects, using the “survival” package from R, with progression from CU to MCI/dementia or from MCI to dementia as the events of interest. Hazard ratios were assessed with the Cox proportional‐hazards model with age and A status/PSMD at baseline and sex as covariates.ResultThere was a significant relationship (p<0.01) between PSMD and TMT A and B, but not with CERAD recall. PSMD low A+ subjects had 5.5 times higher risk of cognitive decline (p<0.01) than PSMD low A‐, while PSMD high A+ had 14.3 times higher risk.ConclusionWe found that high PSMD load increases the risk of AD disease progression, but is not significantly associated with delayed recall, the core cognitive biomarker of AD.

Au cours des dernières années l’espérance de vie accrue a conduit à une augmentation majeure du nombre de nouveaux patients atteints de maladies neurologiques communes, notamment AVC et démence. Des preuves croissantes suggèrent que des déterminants précoces tout au long de la vie, y compris des facteurs génétiques, jouent un rôle crucial dans l'apparition de ces maladies. La maladie des petits vaisseaux cérébraux (MPVC) est une cause majeure d'AVC, de déclin cognitif et de démence. La MPVC est le plus souvent « occulte », détectable en imagerie cérébrale en l'absence de manifestations cliniques. Les marqueurs en IRM cérébrale de la MPVC, qui peuvent être mesurés de manière non invasive dans de grandes cohortes, peuvent fournir des informations cruciales sur les mécanismes physiopathologiques sous-tendant AVC et démences. Les hypersignaux de la substance blanche (HSB), les lacunes, les microhémorragies cérébrales et les espaces périvasculaires sont les marqueurs de MPVC les plus souvent étudiés en IRM, tandis que l'imagerie par tenseur de diffusion (DTI) offre de nouvelles opportunités pour explorer la susceptibilité à la MPVC tout au long de la vie. Déchiffrer ces facteurs de risque génétiques de la MPVC, y compris à des stades précoces de la vie, est un outil puissant pour comprendre les mécanismes moléculaires menant à cette maladie. Dans cette thèse, nous avons exploré les déterminants génétiques des marqueurs d'IRM de la MPVC dans la population générale tout au long de la vie, en réalisant de grandes métaanalyses collaboratives d'études d'association génétiques pangénomiques (GWAS), incluant jusqu'à 58,403 participants de la population générale. Tout d'abord, nous avons réalisé une GWAS des HSB stratifiée sur la présence ou absence d'hypertension artérielle. Nos résultats apportent un nouvel éclairage sur les effets modificateurs de l'hypertension artérielle sur la susceptibilité génétique aux HSB. Deuxièmement, nous avons examiné les déterminants génétiques d'un nouveau marqueur en DTI, la « peak width of skeletonized mean diffusivity » (PSMD), en réalisant une première GWAS de PSMD, tout au long de la vie. Nous avons identifié 25 nouveaux loci associés à un PSMD plus élevé, avec une bonne corrélation de la taille d’effets entre des populations européennes et asiatiques. De plus, dans une étude d'association sur l'exome entier à partir de données de séquençage panexomique, des variants rares et la combinaison de variants rares avec perte de fonction ou de variants « singleton » dans 4 gènes différents étaient associés au PSMD. Un volume d’HSB déterminé génétiquement était associé significativement à un PSMD plus élevé non seulement à tous les âges de la vie adulte mais également chez l’enfant. Par ailleurs, les variants communs associés à un PSMD élevé étaient enrichis en gènes exprimés dans les cellules endothéliales cérébrales foetales, suggérant des effets développementaux. En conclusion, ce travail fournit de nouvelles informations sur la génomique des formes complexes de MPVC, tout au long de la vie, dans différents groupes ethniques, et en tenant compte de la présence d'hypertension artérielle, le facteur de risque le plus courant de MPVC. Ces résultats sont informatifs pour le développement de stratégies préventives et thérapeutiques pour la MPVC et ses complications, un enjeu majeur de santé publique
Over the last century, life expectancy has increased dramatically, contributing to a sharp increase in the number of patients with common neurological disease, especially stroke and dementia. Mounting evidence suggests that early life factors, including genetic factors, play a crucial role in the occurrence of such diseases. Cerebral small vessel disease (cSVD) is a major cause of stroke, cognitive decline and dementia. cSVD is most often covert, detectable on brain images in the absence of clinical manifestations. Brain magnetic resonance imaging (MRI) markers of cSVD, which can be measured non-invasively in large population, can provide crucial insights into the cause of late-life neurological diseases. White matter hyperintensities (WMH), lacunes, cerebral microbleeds, and perivascular spaces are the most commonly studied MRI-markers of cSVD, while diffusion tensor imaging (DTI) offers new opportunity to explore susceptibility to cSVD across the lifespan. Deciphering these genetic risk factors of cSVD, including in early life, is a powerful tool to decipher molecular mechanisms leading to this disease. In this thesis, we explored the genetic determinants of MRI-markers of cSVD in the general population across the lifespan, by conducting large collaborative meta-analyses of genome-wide association studies (GWAS) in up to 58,403 participants from the general population. First, we conducted a GWAS of WMH stratified on hypertension status. Our results shed new light into modifying effects of high blood pressure on genetic susceptibility to WMH. Second, we examined the genetic underpinnings of an emerging DTI marker, peak width of skeletonized mean diffusivity (PSMD), by conducting the first GWAS of PSMD, across the lifespan. We identified up to 25 novel genetic risk loci for PSMD, with good effect size correlation across European and East-Asian ancestries. Additionally, in a whole-exome association study (derived from whole exome sequencing), rare variants and burden of rare loss-of-function or singleton variants in 4 different genes were associated with PSMD. Genetically determined larger volume of WMH was associated with higher PSMD from early childhood to older age. Moreover, common PSMD risk loci were enriched in genes expressed in fetal brain endothelial cells. In conclusion, this work provides new insights into complex genomics of cSVD across the lifespan, across ancestries, and in interaction with hypertension, the most common risk factor of cSVD. These results are informative for the development of efficient preventive and therapeutic strategies for cSVD and its complications, a major public health challenge