Diffusion Imaging Biomarkers of Regional White Matter Injury Correlate With Change in Executive Function and Processing Speed After Brain Radiation Therapy

Neurosurgical resection is one of the few opportunities researchers have to image the human brain both prior to and following focal damage. One of the challenges associated with studying brains undergoing surgical resection is that they often do not fit the brain templates most image-processing methodologies are based on, so manual intervention is required to reconcile the pathology and the most extreme cases must be excluded. Manual intervention requires significant time investment and introduces reproducibility concerns. We propose an automatic longitudinal pipeline based on High Angular Resolution Diffusion Imaging acquisitions to facilitate a Pathway Lesion Symptom Mapping analysis relating focal white matter injury to functional deficits. This two-part approach includes (i) automatic segmentation of focal white matter injury from anisotropic power differences, and (ii) modeling disconnection using tractography on the single-subject level, which specifically identifies the disconnections associated with focal white matter damage. The advantages of this approach stem from (1) objective and automatic lesion segmentation and tractogram generation, (2) objective and precise segmentation of affected tissue likely to be associated with damage to long-range white matter pathways (defined by anisotropic power), (3) good performance even in the cases of anatomical distortions by use of nonlinear tensor-based registration in the patient space, which aligns images using white matter contrast. Mapping a system as variable and complex as the human brain requires sample sizes much larger than the current technology can support. This pipeline can be used to execute large-scale, sufficiently powered analyses by meeting the need for an automatic approach to objectively quantify white matter disconnection.

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Associations of the Lifestyle for Brain Health Index With Structural Brain Changes and Cognition: Results From the Maastricht Study

Neurology ◽

10.1212/wnl.0000000000012572 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012572

Author(s):

Irene S Heger ◽

Kay Deckers ◽

Miranda T Schram ◽

Coen DA Stehouwer ◽

Pieter C Dagnelie ◽

...

Keyword(s):

Cognitive Impairment ◽

Information Processing ◽

Executive Function ◽

White Matter ◽

Processing Speed ◽

Grey Matter ◽

White Matter Hyperintensities ◽

Information Processing Speed ◽

Brain Health ◽

Dementia Risk

Background and Objectives:Observational research has shown that a substantial proportion of all dementia cases worldwide is attributable to modifiable risk factors. Dementia risk scores might be useful to identify high-risk individuals and monitor treatment adherence. The objective of this study was to investigate whether a dementia risk score, the LIfestyle for BRAin health (LIBRA) index, is associated with MRI markers and cognitive functioning/impairment in the general population.Methods:Cross-sectional data was used from the observational population-based cohort of The Maastricht Study.. The weighted compound score of LIBRA (including twelve dementia risk and protective factors, e.g. hypertension, physical inactivity) was calculated, with higher scores indicating higher dementia risk. Standardized volumes of white matter, grey matter, CSF (as proxy for general brain atrophy), white matter hyperintensities, and presence of cerebral small vessel disease were derived from 3T MRI. Cognitive functioning was tested in three domains: memory, information processing speed, and executive function and attention. Values ≤1.5 SD below the average were defined as cognitive impairment. Multiple regression analyses and structural equation modelling were used, adjusted for age, sex, education, intracranial volume and type-2 diabetes.Results:Participants (n=4,164; mean age 59y; 49.7% men) with higher LIBRA scores (mean=1.19, range=-2.7 to +9.2), denoting higher dementia risk, had higher volumes of white matter hyperintensities (β=0.051, p=.002), and lower scores on information processing speed (β=-0.067, p=.001) and executive function and attention (β=-0.065, p=.004). Only in men, associations between LIBRA and volumes of grey matter (β=-0.093, p<.001), CSF (β=0.104, p<.001) and memory (β=-0.054, p=.026) were found. White matter hyperintensities and CSF volume partly mediated the association between LIBRA and cognition.Discussion:Higher health- and lifestyle-based dementia risk is associated with markers of general brain atrophy, cerebrovascular pathology and worse cognition, suggesting that LIBRA meaningfully summarizes individual lifestyle-related brain health. Improving LIBRA factors on an individual level might improve population brain health. Sex differences in lifestyle-related pathology and cognition need to be further explored.Classification of Evidence:This study provides Class II evidence that higher LIBRA scores are significantly associated with lower scores on some cognitive domains and a higher risk of cognitive impairment.

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Cognitive Correlates of MRI-defined Cerebral Vascular Injury and Atrophy in Elderly American Indians: The Strong Heart Study

Journal of the International Neuropsychological Society ◽

10.1017/s1355617719001073 ◽

2019 ◽

Vol 26 (3) ◽

pp. 263-275 ◽

Cited By ~ 1

Author(s):

Astrid Suchy-Dicey ◽

Dean Shibata ◽

Brenna Cholerton ◽

Lonnie Nelson ◽

Darren Calhoun ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Magnetic Resonance ◽

Cerebrovascular Disease ◽

Cognitive Functioning ◽

American Indians ◽

Processing Speed ◽

Brain Volume ◽

Hippocampal Volume ◽

White Matter Disease

AbstractObjective:American Indians experience substantial health disparities relative to the US population, including vascular brain aging. Poorer cognitive test performance has been associated with cranial magnetic resonance imaging findings in aging community populations, but no study has investigated these associations in elderly American Indians.Methods:We examined 786 American Indians aged 64 years and older from the Cerebrovascular Disease and its Consequences in American Indians study (2010–2013). Cranial magnetic resonance images were scored for cortical and subcortical infarcts, hemorrhages, severity of white matter disease, sulcal widening, ventricle enlargement, and volumetric estimates for white matter hyperintensities (WMHs), hippocampus, and brain. Participants completed demographic, medical history, and neuropsychological assessments including testing for general cognitive functioning, verbal learning and memory, processing speed, phonemic fluency, and executive function.Results:Processing speed was independently associated with the presence of any infarcts, white matter disease, and hippocampal and brain volumes, independent of socioeconomic, language, education, and clinical factors. Other significant associations included general cognitive functioning with hippocampal volume. Nonsignificant, marginal associations included general cognition with WMH and brain volume; verbal memory with hippocampal volume; verbal fluency and executive function with brain volume; and processing speed with ventricle enlargement.Conclusions:Brain-cognition associations found in this study of elderly American Indians are similar to those found in other racial/ethnic populations, with processing speed comprising an especially strong correlate of cerebrovascular disease. These findings may assist future efforts to define opportunities for disease prevention, to conduct research on diagnostic and normative standards, and to guide clinical evaluation of this underserved and overburdened population.

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