The heritability of amyloid burden in older adults: the Older Australian Twins Study

2021 ◽  
pp. jnnp-2021-326677
Author(s):  
Rebecca Koncz ◽  
Anbupalam Thalamuthu ◽  
Wei Wen ◽  
Vibeke S Catts ◽  
Vincent Dore ◽  
...  
Keyword(s):  
Older Adults ◽  
Diffusion Tensor ◽  
Genetic Correlations ◽  
Mean Diffusivity ◽  
Brain Regions ◽  
White Matter Hyperintensity ◽  
Amyloid Pet ◽  
Amyloid Burden ◽  
Environmental Correlations ◽  
Pet Scans

ObjectiveTo determine the proportional genetic contribution to the variability of cerebral β-amyloid load in older adults using the classic twin design.MethodsParticipants (n=206) comprising 61 monozygotic (MZ) twin pairs (68 (55.74%) females; mean age (SD): 71.98 (6.43) years), and 42 dizygotic (DZ) twin pairs (56 (66.67%) females; mean age: 71.14 (5.15) years) were drawn from the Older Australian Twins Study. Participants underwent detailed clinical and neuropsychological evaluations, as well as MRI, diffusion tensor imaging (DTI) and amyloid PET scans. Fifty-eight participants (17 MZ pairs, 12 DZ pairs) had PET scans with 11Carbon-Pittsburgh Compound B, and 148 participants (44 MZ pairs, 30 DZ pairs) with 18Fluorine-NAV4694. Cortical amyloid burden was quantified using the centiloid scale globally, as well as the standardised uptake value ratio (SUVR) globally and in specific brain regions. Small vessel disease (SVD) was quantified using total white matter hyperintensity volume on MRI, and peak width of skeletonised mean diffusivity on DTI. Heritability (h2) and genetic correlations were measured with structural equation modelling under the best fit model, controlling for age, sex, tracer and scanner.ResultsThe heritability of global amyloid burden was moderate (0.41 using SUVR; 0.52 using the centiloid scale) and ranged from 0.20 to 0.54 across different brain regions. There were no significant genetic or environmental correlations between global amyloid burden and markers of SVD.ConclusionAmyloid deposition, the hallmark early feature of Alzheimer’s disease, is under moderate genetic influence, suggesting a major environmental contribution that may be amenable to intervention.

scholarly journals fMRI-guided white matter connectivity in fluid and crystallized cognitive abilities in healthy adults

2020 ◽  
Author(s):  
Yunglin Gazes ◽  
Jayant Sakhardande ◽  
Ashley Mensing ◽  
Qolamreza Razlighi ◽  
Ann Ohkawa ◽  
...  
Keyword(s):  
White Matter ◽  
Episodic Memory ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Brain Regions ◽  
Long Distance ◽  
White Matter Tracts ◽  
Percent Signal Change ◽  
Signal Change ◽  
Fluid Abilities

AbstractThis study examined within-subject differences among three fluid abilities that decline with age: reasoning, episodic memory and processing speed, compared with vocabulary, a crystallized ability that is maintained with age. The data were obtained from the Reference Ability Neural Network (RANN) study from which 221 participants had complete behavioral data for all 12 cognitive tasks, three per ability, along with fMRI and diffusion weighted imaging data. We used fMRI task activation to guide white matter tractography, and generated mean percent signal change in the regions associated with the processing of each ability along with diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), for each cognitive ability. Qualitatively brain regions associated with vocabulary were more localized and lateralized to the left hemisphere whereas the fluid abilities were associated with brain activations that were more distributed across the brain and bilaterally situated. Using continuous age, we observed smaller correlations between MD and age for white matter tracts connecting brain regions associated with the vocabulary ability than that for the fluid abilities, suggesting that vocabulary white matter tracts were better maintained with age. Furthermore, after multiple comparisons correction, the mean percent signal change for the episodic memory showed positive associations with behavioral performance, and the associations between MD and percent signal change differed by age such that, when divided into three age groups to further explore this interaction, only the oldest age group show a significant negative correlation between the two brain measures. Overall, the vocabulary ability may be better maintained with age due to the more localized brain regions involved, which places smaller reliance on long distance white matter tracts for signal transduction. These results support the hypothesis that functional activation and white matter structures underlying the vocabulary ability contribute to the ability’s greater resistance against aging.

scholarly journals Diffusion Tensor Imaging of the Olfactory System in Older Adults With and Without Hyposmia

2021 ◽  
Vol 13 ◽  
Author(s):  
Cynthia Felix ◽  
Lana M. Chahine ◽  
James Hengenius ◽  
Honglei Chen ◽  
Andrea L. Rosso ◽  
...  
Keyword(s):  
Older Adults ◽  
Diffusion Tensor Imaging ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Cognitive Status ◽  
Olfactory Cortex ◽  
P Value ◽  
Body Composition Study ◽  
Orbital Part ◽  
Normal Cognition

Objectives: To compare gray matter microstructural characteristics of higher-order olfactory regions among older adults with and without hyposmia.Methods: Data from the Brief Smell Identification Test (BSIT) were obtained in 1998–99 for 265 dementia-free adults from the Health, Aging, and Body Composition study (age at BSIT: 74.9 ± 2.7; 62% White; 43% male) who received 3T diffusion tensor imaging in 2006–08 [Interval of time: mean (SD): 8.01 years (0.50)], Apolipoprotein (ApoEε4) genotypes, and repeated 3MS assessments until 2011–12. Cognitive status (mild cognitive impairment, dementia, normal cognition) was adjudicated in 2011–12. Hyposmia was defined as BSIT ≤ 8. Microstructural integrity was quantified by mean diffusivity (MD) in regions of the primary olfactory cortex amygdala, orbitofrontal cortex (including olfactory cortex, gyrus rectus, the orbital parts of the superior, middle, and inferior frontal gyri, medial orbital part of the superior frontal gyrus), and hippocampus. Multivariable regression models were adjusted for total brain atrophy, demographics, cognitive status, and ApoEε4 genotype.Results: Hyposmia in 1998–99 (n = 57, 21.59%) was significantly associated with greater MD in 2006–08, specifically in the orbital part of the middle frontal gyrus, and amygdala, on the right [adjusted beta (p value): 0.414 (0.01); 0.527 (0.01); respectively].Conclusion: Older adults with higher mean diffusivity in regions important for olfaction are more likely to have hyposmia up to ten years prior. Future studies should address whether hyposmia can serve as an early biomarker of brain microstructural abnormalities for older adults with a range of cognitive functions, including those with normal cognition.

scholarly journals Tract Specificity of Age Effects on Diffusion Tensor Imaging Measures of White Matter Health

2021 ◽  
Vol 13 ◽  
Author(s):  
Stephanie Matijevic ◽  
Lee Ryan
Keyword(s):  
Older Adults ◽  
Diffusion Tensor Imaging ◽  
Individual Differences ◽  
White Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
White Matter Integrity ◽  
White Matter Tracts ◽  
Apoe Ε4 ◽  
Age Related

Well-established literature indicates that older adults have poorer cerebral white matter integrity, as measured through diffusion tensor imaging (DTI). Age differences in DTI have been observed widely across white matter, although some tracts appear more sensitive to the effects of aging than others. Factors like APOE ε4 status and sex may contribute to individual differences in white matter integrity that also selectively impact certain tracts, and could influence DTI changes in aging. The present study explored the degree to which age, APOE ε4, and sex exerted global vs. tract specific effects on DTI metrics in cognitively healthy late middle-aged to older adults. Data from 49 older adults (ages 54–92) at two time-points separated by approximately 2.7 years were collected. DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD), were extracted from nine white matter tracts and global white matter. Results showed that across timepoints, FA and MD increased globally, with no tract-specific changes observed. Baseline age had a global influence on both measures, with increasing age associated with lower FA and higher MD. After controlling for global white matter FA, age additionally predicted FA for the genu, callosum body, inferior fronto-occipital fasciculus (IFOF), and both anterior and posterior cingulum. Females exhibited lower global FA on average compared to males. In contrast, MD was selectively elevated in the anterior cingulum and superior longitudinal fasciculus (SLF), for females compared to males. APOE ε4 status was not predictive of either measure. In summary, these results indicate that age and sex are associated with both global and tract-specific alterations to DTI metrics among a healthy older adult cohort. Older women have poorer white matter integrity compared to older men, perhaps related to menopause-induced metabolic changes. While age-related alterations to white matter integrity are global, there is substantial variation in the degree to which tracts are impacted, possibly as a consequence of tract anatomical variability. The present study highlights the importance of accounting for global sources of variation in DTI metrics when attempting to investigate individual differences (due to age, sex, or other factors) in specific white matter tracts.

Gradient of Tissue Injury after Stroke: Rethinking the Infarct versus Noninfarcted Dichotomy

2020 ◽  
Vol 49 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Felix Ng ◽  
Vijay Venkatraman ◽  
Mark Parsons ◽  
Andrew Bivard ◽  
Gagan Sharma ◽  
...  
Keyword(s):  
Diffusion Tensor ◽  
Tissue Injury ◽  
Ct Perfusion ◽  
Mean Diffusivity ◽  
Brain Regions ◽  
Homologous Region ◽  
Anterior Circulation ◽  
Prospective Longitudinal Study ◽  
Fluid Attenuated Inversion Recovery ◽  
Prospective Longitudinal

Aim: To evaluate the degree of variability in microstructural injury within and adjacent to regions identified as infarcted tissue using diffusion tensor imaging (DTI). Methods: In this prospective longitudinal study, 18 patients presenting within 12 h of anterior circulation acute ischemic stroke who underwent CT perfusion (CTP) at baseline followed by fluid-attenuated inversion recovery (FLAIR) and DTI 1-month were analyzed. Four regions of interest (ROI) corresponding to the severity of hypoperfusion on CTP within and beyond the radiological infarct lesion defined on FLAIR were segmented. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified for each ROI and compared to a mirror homologue in the contralateral hemisphere. Ipsilateral to contralateral FA and MD ratios were compared across ROIs. Results: Lower FA and higher MD values were observed within both the infarct lesion and the peri-infarct tissue compared with their homologous contralateral brain regions (all comparisons p ≤ 0.01). No difference was observed in FA and MD between remote nonhypoperfused tissue and its contralateral homologous region (FA p = 0.42, MD p ≥ 0.99). The magnitude of asymmetry (ipsilateral/contralateral ratios) of FA and MD was greater with increasing severity of hypoperfusion in a dose-response pattern. Asymmetry greatest in the area of infarction with severe hypoperfusion, followed by infarction with moderate hypoperfusion, the peri-infarct hypoperfused tissue, and lastly the remote nonhypoperfused normal tissue (median on clustered quantile regression p ≤ 0.01). Conclusion: A gradient of microstructural injury corresponding to the severity of ischemic insult is present within and beyond conventionally defined infarct boundaries. The traditional dichotomized notion of infarcted versus noninfarcted tissue widely adopted in clinical research and in practice warrants reexamination.

scholarly journals Characteristics of mental health implications and plasma metabolomics in patients recently recovered from COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lian Yang ◽  
Mei Zhou ◽  
Lingli Li ◽  
Ping Luo ◽  
Wenliang Fan ◽  
...  
Keyword(s):  
Mental Health ◽  
Metabolic Profiling ◽  
Diffusion Tensor ◽  
Demographic Data ◽  
Mean Diffusivity ◽  
Brain Regions ◽  
Cerebral White Matter ◽  
Radial Diffusivity ◽  
Amine Metabolism ◽  
Diffusion Tensor Imaging Dti

AbstractThis study aimed to explore the associations between cerebral white matter (WM) alterations, mental health status, and metabolism in recovered COVID-19 patients. We included 28 recovered COVID-19 patients and 27 healthy controls between April 2020 and June 2020. Demographic data, the mental health scores, diffusion-tensor imaging (DTI) data, and plasma metabolomics were collected and compared between the two groups. Tract-based spatial statistics and graph theory approaches were used for DTI data analysis. Untargeted metabolomics analysis of the plasma was performed. Correlation analyses were performed between these characteristics. Recovered COVID-19 patients showed decreased fractional anisotropy, increased mean diffusivity and radial diffusivity values in widespread brain regions, and significantly lower global efficiency, longer shortest path length, and less nodal local efficiency in superior occipital gyrus (all, P < 0.05, Bonferroni corrected). Our results also demonstrated significantly different plasma metabolic profiling in recovered COVID-19 patients even at 3 months after their hospital discharge, which was mainly related to purine pathways, amino acids, lipids, and amine metabolism. Certain regions with cerebral WM alterations in the recovered patients showed significant correlations with different metabolites and the mental health scores. We observed multiple alterations in both WM integrity and plasma metabolomics that may explain the deteriorated mental health of recovered COVID-19 patients. These findings may provide potential biomarkers for the mental health evaluation for the recovered COVID-19 patients and potential targets for novel therapeutics.

scholarly journals Hyposmia and Neuroimaging Signature in Community-Dwelling Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 530-530
Author(s):  
Cynthia Felix ◽  
Lana Chahine ◽  
Honglei Chen ◽  
Zichun Cao ◽  
Caterina Rosano
Keyword(s):  
Older Adults ◽  
Gray Matter ◽  
Orbitofrontal Cortex ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Community Dwelling ◽  
Intracranial Volume ◽  
Total Brain ◽  
Identification Test ◽  
Community Dwelling Older Adults

Abstract Olfaction declines with aging, and hyposmia, or impaired sense of smell, is associated with neurodegenerative disorders including Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). Neuroimaging studies of hyposmia in AD/PD patients have often examined pathology-specific brain regions. Our knowledge of neural correlates in regions that mediate olfaction in community-dwelling older adults, is limited. We quantified mean diffusivity (MD) of the gray matter (GM) using diffusion tensor imaging in a community-dwelling sample of 308 older adults (mean age: 82.9 years, 58% women, 40% black). We focused on total brain and these regions involved in olfaction- olfactory bulb, amygdala, entorhinal cortex, orbitofrontal cortex, and hippocampus. Smell was tested with a scratch-and-sniff validated odor identification test, the Brief Smell Identification Test (BSIT). Hyposmia was defined as BSIT score of ≤8, assessed about 7 years prior to neuroimaging. In our sample, 23% had hyposmia, more in in men (30%) than in women (19%). Hyposmia was not significantly associated with cardiovascular risk factors such as hypertension; diseases such as stroke; age; race; cognitive or mobility functions (all p&gt;0.1). In linear regression models adjusted for demographics and brain atrophy (total brain gray matter volume divided by intracranial volume), hyposmia was significantly associated with higher GM MD (lower microstructural integrity) of the left orbitofrontal cortex (standardized beta: 0.142, t=2.56, p=0.011). Understanding the neural substrates involved in hyposmia in aging is an important step towards advancing research on hyposmia in non-clinic-based, community-dwelling populations.

scholarly journals Diffusion tensor imaging revealed different pathological processes of white matter hyperintensities

2019 ◽  
Author(s):  
Zhigang Min ◽  
Hairong Shan ◽  
Long Xu ◽  
Daihai Yuan ◽  
Xuexia Sheng ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Brain Regions ◽  
Periventricular White Matter ◽  
Frontal Horn ◽  
Fazekas Scale ◽  
Normal White Matter

Abstract Background The purpose of this study was to verify the pathological heterogeneity of white matter hyperintensities (WMHs). We compared diffusion tensor imaging (DTI) metrics within different brain regions using identical grading protocols, and subsequently investigated the microstructural changes in these areas as the WMH progressed. Methods Seventy-three patients with WMH and 18 healthy controls who received DTI were included in this study. We measured fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR) of periventricular and deep WMH in six brain regions and grouped these measures according to the Fazekas scale. We then compared the DTI metrics of different regions with the same Fazekas scale grade. Results Significantly lower FA values (all p<0.001), and higher MD (all p<0.001) and DR values (all p<0.001) were associated with WMH observed within the periventricular white matter around the frontal horn (pFH) and the frontal lateral ventricle (pFLV) compared to other regions with the same Fazekas grades. However, in the normal white matter of the pFH and pFLV, FA was not significantly lower than all other regions. Furthermore, in these areas, MD, DA, and DR were not significantly higher than in all other regions. Conclusion Distinct pathological processes occurred within frontal periventricular WMH and other regions; these processes may represent the effects of severe demyelination within the frontal periventricular white matter.

Abstract WP71: Gradient of Tissue Injury on Diffusion Tensor Imaging After Stroke: Rethinking the Infarct vs Non-infarcted Dichotomy

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Felix Ng ◽  
Vijay Venkatraman ◽  
Mark Parsons ◽  
Andrew Bivard ◽  
Gagan Sharma ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Diffusion Tensor ◽  
Tissue Injury ◽  
Ct Perfusion ◽  
Mean Diffusivity ◽  
Brain Regions ◽  
Homologous Region ◽  
Fluid Attenuated Inversion Recovery ◽  
Infarcted Tissue ◽  
Diffusion Tensor Imaging Dti

Objective: To evaluate the degree of variability in microstructural injury within and adjacent to regions identified as infarcted tissue using Diffusion Tensor Imaging (DTI). Methods: Perfusion CT was performed in 18 patients within 12 hours of ischemic stroke onset followed by Fluid-attenuated Inversion recovery (FLAIR) and DTI one month after stroke. Four regions of interest (ROIs) corresponding to the severity of hypoperfusion on CT perfusion within and beyond the radiological infarct lesion defined on FLAIR were segmented. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified for each ROI and compared to a mirror homologue in the contralateral hemisphere. Ipsilateral to contralateral FA and MD ratios were compared across ROIs. Results: Lower FA and higher MD values were observed within both the infarct lesion and the peri-infarct tissue compared with their homologous contralateral brain regions (all comparisons p≤0.01). No difference was observed in FA and MD between remote non-hypoperfused tissue and its contralateral homologous region (FA p=0.42, MD p≥0.99). The magnitude of asymmetry (ipsilateral/contralateral ratios) of FA and MD was greater with increasing severity of hypoperfusion in a dose-response pattern. Asymmetry greatest in the area of infarction with severe hypoperfusion, followed by infarction with moderate hypoperfusion, the peri-infarct hypoperfused tissue and lastly the remote non-hypoperfused normal tissue (median on clustered quantile regression p≤0.01). Conclusion: A gradient of microstructural injury corresponding to the severity of ischemic insult is present within and beyond conventionally-defined infarct boundaries. The traditional dichotomized notion of infarcted versus non-infarcted tissue widely adopted in clinical research and in practice warrants re-examination.

scholarly journals White matter microstructural abnormalities in euthymic bipolar disorder

2010 ◽  
Vol 196 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Karine A. N. Macritchie ◽  
Adrian J. Lloyd ◽  
Mark E. Bastin ◽  
Kamini Vasudev ◽  
Peter Gallagher ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Substance Use ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Mean Diffusivity ◽  
Brain Regions ◽  
White Matter Hyperintensity ◽  
Sign Test ◽  
Periventricular White Matter ◽  
Diffusion Parameters

BackgroundAbnormal diffusion parameters are reported in specific brain regions and white matter tracts in bipolar disorder.AimsTo investigate whether these abnormalities are generalised, and thus evident in large regions of white matter.MethodDiffusion parameters were measured at several regions in the corpus callosum and in deep/periventricular white matter in 28 currently euthymic patients with bipolar disorder and controls. White matter hyperintensity loads were assessed.ResultsComparing the whole data-sets using the sign test, in the group with bipolar disorder, mean diffusivity was greater at all 15 sites (P<0.001) and fractional anisotropy was reduced at 13 (P<0.01). The effect of diagnosis was significant for callosal mean diffusivity and fractional anisotropy and for deep/periventricular mean diffusivity (MANCOVA). Comparing individual regions (Mann–Whitney U-test), prefrontal and periventricular mean diffusivity were significantly increased; callosal and occipital fractional anisotropy were significantly reduced. Former substance use and lithium were possible confounding factors. Periventricular white matter hyperintensities were associated with significantly increased periventricular mean diffusivity in individuals with bipolar disorder.ConclusionsGeneralised white matter microstructural abnormalities may exist in bipolar disorder, possibly exacerbated by past substance use and ameliorated by lithium.

scholarly journals Alterations in Diffusion Measures of White Matter Integrity Associated with Healthy Aging

2019 ◽  
Author(s):  
Ciara J Molloy ◽  
Sinead Nugent ◽  
Arun L W Bokde
Keyword(s):  
White Matter ◽  
Healthy Aging ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
B Value ◽  
White Matter Hyperintensity ◽  
Normal Appearing White Matter ◽  
Age Related ◽  
Aging Adults ◽  
The Impact

Abstract This study aimed to characterize age-related white matter changes by evaluating patterns of overlap between the linear association of age with fractional anisotropy (FA) with mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Specifically, we assessed patterns of overlap between diffusion measures of normal appearing white matter by covarying for white matter hyperintensity (WMH) load, as WMHs are thought to increase with age and impact diffusion measures. Seventy-nine healthy adults aged between 18 and 75 years took part in the study. Diffusion tensor imaging (DTI) data were based on 61 directions acquired with a b-value of 2,000. We found five main patterns of overlap: FA alone (15.95%); FA and RD (31.90%); FA and AD (12.99%); FA, RD, and AD (27.93%); and FA, RD, and MD (8.79%). We showed that cognitively healthy aging adults had low WMH load, which subsequently had minimal effect on diffusion measures. We discuss how patterns of overlap may reflect underlying biological changes observed with aging such as loss of myelination, axonal damage, as well as mild microstructural and chronic white matter impairments. This study contributes to understanding the underlying causes of degeneration in specific regions of the brain and highlights the importance of considering the impact of WMHs in aging studies of white matter.

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