Background and purpose
The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and ...motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years.
Methods
Ninety‐eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3–8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2‐year follow‐up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial–temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale.
Results
Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline.
Conclusion
White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid‐stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.
Abstract
Background
Gradual disintegration of white matter (WM) tracts has been observed in Alzheimer’s disease (AD) by postmortem histological analyses and
in‐vivo
neuroimaging. Previous diffusion ...tensor imaging (DTI) studies have shown changes in fractional anisotropy (FA) and radial diffusivity (RD) indicative of microstructural changes in select WM regions in AD and mild cognitive impairment (MCI). However, the precise location of microstructural damage
along
WM tracts at the early stages of cognitive decline is still unknown. In the current study, DTI metrics
along
the major WM tracts were measured and compared in healthy elderly and MCI subjects to localize microstructure changes.
Method
Diffusion tensor images (32 directions, b=1000 s/mm
2
) were acquired on a 3 Tesla Siemens Tim Trio and a 3 Tesla Siemens Prisma Fit MRI scanner in healthy elderly (N=40) and people with MCI (N=44) as part of the Gait and Brain Study in London, Ontario. FA and RD were quantified along 18 major WM tracts in each subject using TRACULA in FreeSurfer. The average FA and RD of each tract were compared between groups using a MANOVA (for FA and RD separately) adjusted for age, sex, education, comorbidity, and MoCA score. If the MANOVA was significant (p<0.05), post‐hoc tests were conducted to identify the tracts on which the DTI metrics differed between the groups. Then, the DTI metrics were examined along these identified tracts to localize observed differences.
Result
The MANOVA detected significant differences in both FA (
p
‐value=0.018) and RD (
p
‐value=0.019) in the 18 tracts studied between controls and MCI subjects. Post‐hoc tests showed that specifically, FA in right cingulum‐cingulate gyrus endings (rh_ccg) (Fig. 1) and in left superior longitudinal fasciculus‐parietal endings (lh_slfp), and RD in rh_ccg and left uncinate fasciculus (lh_unc) (
p
‐value < 0.05) differed between the groups. Comparison along the rh_ccg using t‐test (
p
‐value < 0.05) revealed that FA and RD differed significantly between the groups in the posterior portion of this tract (Figures 2 and 3).
Conclusion
Tract specific white matter disruption in the cingulum gyrus in people with MCI was localized in the posterior part of the rh_ccg tract adjacent to the posterior cingulate (Fig. 1).
Background
Gradual disintegration of white matter (WM) tracts has been observed in Alzheimer’s disease (AD) by postmortem histological analyses and in‐vivo neuroimaging. Previous diffusion tensor ...imaging (DTI) studies have shown changes in fractional anisotropy (FA) and radial diffusivity (RD) indicative of microstructural changes in select WM regions in AD and mild cognitive impairment (MCI). However, the precise location of microstructural damage along WM tracts at the early stages of cognitive decline is still unknown. In the current study, DTI metrics along the major WM tracts were measured and compared in healthy elderly and MCI subjects to localize microstructure changes.
Method
Diffusion tensor images (32 directions, b=1000 s/mm2) were acquired on a 3 Tesla Siemens Tim Trio and a 3 Tesla Siemens Prisma Fit MRI scanner in healthy elderly (N=40) and people with MCI (N=44) as part of the Gait and Brain Study in London, Ontario. FA and RD were quantified along 18 major WM tracts in each subject using TRACULA in FreeSurfer. The average FA and RD of each tract were compared between groups using a MANOVA (for FA and RD separately) adjusted for age, sex, education, comorbidity, and MoCA score. If the MANOVA was significant (p<0.05), post‐hoc tests were conducted to identify the tracts on which the DTI metrics differed between the groups. Then, the DTI metrics were examined along these identified tracts to localize observed differences.
Result
The MANOVA detected significant differences in both FA (p‐value=0.018) and RD (p‐value=0.019) in the 18 tracts studied between controls and MCI subjects. Post‐hoc tests showed that specifically, FA in right cingulum‐cingulate gyrus endings (rh_ccg) (Fig. 1) and in left superior longitudinal fasciculus‐parietal endings (lh_slfp), and RD in rh_ccg and left uncinate fasciculus (lh_unc) (p‐value < 0.05) differed between the groups. Comparison along the rh_ccg using t‐test (p‐value < 0.05) revealed that FA and RD differed significantly between the groups in the posterior portion of this tract (Figures 2 and 3).
Conclusion
Tract specific white matter disruption in the cingulum gyrus in people with MCI was localized in the posterior part of the rh_ccg tract adjacent to the posterior cingulate (Fig. 1).
Background
Spoken discourse (language beyond single words or sentences) performance can be used to detect cognitive impairment in cerebrovascular disease (CVD) Roberts A, et al. (2021). Top Lang ...Disord 41(1):73‐98. However, the neurological basis for altered spoken discourse in CVD is poorly defined. This study examined the association between spoken discourse and indicators of white matter microstructural integrity provided by diffusion tensor imaging (DTI) to better define the link between CVD‐related neurodegeneration and altered spoken discourse.
Method
Spoken discourse and 3T DTI data (30‐32 directions, b=1000) were obtained from the CVD cohort of the Ontario Neurodegenerative Disease Research Initiative (n=133). Spoken discourse analyses were completed previously Roberts, 2021. A DTI analysis pipeline Hassan SMH, et al. (2019) PLoS One 14(12):e0226715 was used to generate brain maps of fractional anisotropy (FA) and mean diffusivity (MD) and calculate mean FA and MD values for the inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus – parietal (SLFp) and temporal (SLFt) endings, and uncinate fasciculi (UNC) in each hemisphere. Canonical correlation analyses examined associations between DTI metrics and 10 spoken discourse measures separately for FA in left hemisphere, MD in left hemisphere, FA in right hemisphere, MD in right hemisphere.
Result
Canonical correlations were significant in the left hemisphere (FA: r=0.47, p<0.05; MD: r=0.51, p<0.01) but not the right (FA: r=0.34, p=0.90; MD: r=0.40, p=0.15)(Figure 1). Among the white matter tracts, the strongest canonical loadings were seen for the SLFp (FA: 0.81; MD: ‐0.59) and SLFt (FA: 0.71; MD: ‐0.40) compared to the ILF (FA: 0.44; MD: 0.03) and UNC (FA: ‐0.34; MD: 0.10). Higher FA in the SLFp and SLFt was associated with better performance on measures of fluency and information content. Lower MD in these tracts was associated with better performance on measures of fluency, information content, and syntax.
Conclusion
Spoken discourse performance was associated with white matter microstructural integrity in the left hemisphere of the brain. Of the white matter tracts investigated in this study, impaired spoken discourse performance in CVD was most strongly linked to altered tissue microstructure in the parietal and temporal endings of the superior longitudinal fasciculus.
Background
Spoken discourse (language beyond single words or sentences) performance can be used to detect cognitive impairment in cerebrovascular disease (CVD) Roberts A, et al. (2021). Top Lang ...Disord 41(1):73‐98. However, the neurological basis for altered spoken discourse in CVD is poorly defined. This study examined the association between spoken discourse and indicators of white matter microstructural integrity provided by diffusion tensor imaging (DTI) to better define the link between CVD‐related neurodegeneration and altered spoken discourse.
Method
Spoken discourse and 3T DTI data (30‐32 directions, b=1000) were obtained from the CVD cohort of the Ontario Neurodegenerative Disease Research Initiative (n=133). Spoken discourse analyses were completed previously Roberts, 2021. A DTI analysis pipeline Hassan SMH, et al. (2019) PLoS One 14(12):e0226715 was used to generate brain maps of fractional anisotropy (FA) and mean diffusivity (MD) and calculate mean FA and MD values for the inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus – parietal (SLFp) and temporal (SLFt) endings, and uncinate fasciculi (UNC) in each hemisphere. Canonical correlation analyses examined associations between DTI metrics and 10 spoken discourse measures separately for FA in left hemisphere, MD in left hemisphere, FA in right hemisphere, MD in right hemisphere.
Result
Canonical correlations were significant in the left hemisphere (FA: r=0.47, p<0.05; MD: r=0.51, p<0.01) but not the right (FA: r=0.34, p=0.90; MD: r=0.40, p=0.15)(Figure 1). Among the white matter tracts, the strongest canonical loadings were seen for the SLFp (FA: 0.81; MD: ‐0.59) and SLFt (FA: 0.71; MD: ‐0.40) compared to the ILF (FA: 0.44; MD: 0.03) and UNC (FA: ‐0.34; MD: 0.10). Higher FA in the SLFp and SLFt was associated with better performance on measures of fluency and information content. Lower MD in these tracts was associated with better performance on measures of fluency, information content, and syntax.
Conclusion
Spoken discourse performance was associated with white matter microstructural integrity in the left hemisphere of the brain. Of the white matter tracts investigated in this study, impaired spoken discourse performance in CVD was most strongly linked to altered tissue microstructure in the parietal and temporal endings of the superior longitudinal fasciculus.
Background Cerebral small vessel disease is associated with higher ratios of soluble-epoxide hydrolase derived linoleic acid diols (12,13-dihydroxyoctadecenoic acid DiHOME and 9,10-DiHOME) to their ...parent epoxides (12(13)-epoxyoctadecenoic acid EpOME and 9(10)-EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra-high-performance liquid chromatography-mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13-DiHOME/12(13)-EpOME ratio (β=0.251,
=0.023). The 12,13-DiHOME/12(13)-EpOME ratio was associated with more lacunes (β=0.266,
=0.028) but not with large vessel stroke volumes. Ratios of 12,13-DiHOME/12(13)-EpOME and 9,10-DiHOME/9(10)-EpOME were associated with greater volumes of white matter hyperintensities (β=0.364,
<0.001; β=0.362,
<0.001) and white matter MRI-visible perivascular spaces (β=0.302,
=0.011; β=0.314,
=0.006). In small vessel stroke, the 12,13-DiHOME/12(13)-EpOME ratio was associated with higher white matter free water diffusion (β=0.439,
=0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10-DiHOME/9(10)-EpOME ratio was associated with temporal lobe atrophy (β=-0.277,
=0.031). Conclusions Linoleic acid markers of cytochrome P450/soluble-epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular-glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.
Background
Neuronal activity (NA) and metabolism are impaired in the early stages of Alzheimer’s Disease (AD) and Frontotemporal Dementia (FTD) leading to specific patterns of cognitive decline. ...Detailed disease models elucidating how and where in brain these NA disturbances commence and how they gradually progress remain incomplete. Recently, we introduced several NA metrics quantified based on fluctuations of the resting‐state fMRI (rs‐fMRI) signal. NA was significantly lower in AD and mild cognitive impairment compared to normal elderly controls (NEC). Here we extend this work using the most sensitive metric to examine NA profile differences between people with AD and FTD.
Method
3T MRI rs‐fMRI data (TR=∼2.4 Sec, 250 volumes) were obtained from the Ontario Neurodegenerative Disease Research Initiative (AD group: N=40, aged 71.8 ± 8.1, 42% female; and FTD group: N=50, aged 67.8 ± 7.3, 36% female), and Gait and Brain Study (NEC group: N=46, aged 71.0 ± 5.5, 33% female). The rs‐fMRI signal was pre‐processed and decomposed into independent components (ICs) using IC analysis. The ICs were classified into neuronal and non‐neuronal sources using a support vector machine classifier. Voxelwise NA was quantified based on the magnitude of neuronal ICs in the rs‐fMRI signal composition. This metric was utilized to create resting‐state NA maps in each subject, which were compared between groups voxel by voxel using a multiple comparisons permutation test (MCPT) with 1000 permutations.
Result
Group average NA maps are provided in Fig. 1. Average NA was lower in FTD (24%) and AD (40%) compared to NEC. There was a significant difference (adjusted p‐values from MCPT) between NEC and FTD (p<0.001), NEC and AD (p<0.001), and FTD and AD (p<0.05). Difference NA maps comparing the groups and associated significance maps are shown in Fig. 2. The FTD group had significantly higher NA compared to AD in ∼53% of brain voxels (Fig. 2).
Conclusion
Significantly lower NA was detected in AD and FTD compared to NEC. Localized significant NA differences between AD and FTD were detected emerging mostly as clusters in occipital and subcortical areas that are known to be less affected by FTD.
Objectives
To investigate whether a history of traumatic brain injury (TBI) is associated with greater long-term grey-matter loss in patients with mild cognitive impairment (MCI).
Methods
85 patients ...with MCI were identified, including 26 with a previous history of traumatic brain injury (MCITBI-) and 59 without (MCITBI+). Cortical thickness was evaluated by segmenting T1-weighted MRI scans acquired longitudinally over a 2-year period. Bayesian multilevel modelling was used to evaluate group differences in baseline cortical thickness and longitudinal change, as well as group differences in neuropsychological measures of executive function.
Results
At baseline, the MCITBI+ group had less grey matter within right entorhinal, left medial orbitofrontal and inferior temporal cortex areas bilaterally. Longitudinally, the MCITBI+ group also exhibited greater longitudinal declines in left rostral middle frontal, the left caudal middle frontal and left lateral orbitofrontal areas sover the span of 2 years (median = 1–2%, 90%HDI −0.01%: −0.001%, probability of direction (PD) = 90–99%). The MCITBI+ group also displayed greater longitudinal declines in Trail-Making-Test (TMT)-derived ratio (median: 0.737%, 90%HDI: 0.229%: 1.31%, PD = 98.8%) and differences scores (median: 20.6%, 90%HDI: −5.17%: 43.2%, PD = 91.7%).
Conclusions
Our findings support the notion that patients with MCI and a history of TBI are at risk of accelerated neurodegeneration, displaying greatest evidence for cortical atrophy within the left middle frontal and lateral orbitofrontal frontal cortex. Importantly, these results suggest that long-term TBI-mediated atrophy is more pronounced in areas vulnerable to TBI-related mechanical injury, highlighting their potential relevance for diagnostic forms of intervention in TBI.
Abstract
Background
Early pathological changes in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) gradually decrease neuronal metabolism and function measured by PET and functional MRI ...(fMRI). These changes are often associated with cognitive decline and can help in the diagnosis of AD. However more sensitive indicators of the earliest stages of disease must be developed to detect disease prior to cognitive impairment. Recently, a novel
neuronal activity
(NA) metric was introduced based on resting‐state fMRI (rs‐fMRI) signal oscillations, which showed dramatically lower NA in AD. Here we introduced a more sophisticated and potentially more sensitive NA metric to identify subtle NA differences between three groups: normal elderly controls (NEC), MCI, and AD.
Method
The rs‐fMRI scans (TR=∼2400, ∼10 minute acquisition) were acquired at 3T from 8 MRI scanners in the Ontario Neurodegenerative Disease Research Initiative (AD group, N=40, aged 71.8 ± 8.1, 42% female; and MCI groups, N=80, aged 70.3 ± 8.3, 46% female), and the Gait and Brain Study (NEC group, N=30, aged 71.3 ± 6.0, 23.33% female). The rs‐fMRI signal was pre‐processed using FMRIB Software Library (FSL) and decomposed into independent components (ICs) using IC analysis. The ICs were classified into neuronal and non‐neuronal using a support vector machine classifier. The proposed voxel‐wise NA metric was defined based on similarity (
cross covariance
) between rs‐fMRI signal and neuronal ICs. This metric was utilized to create resting‐state NA map in each subject, which were compared between groups.
Result
Single subject and group average NA maps are provided in Fig. 1. The % difference maps between each group are shown in Fig. 2. The average voxelwise % difference in NA between groups was 38% between NEC and MCI, 38% between NEC and AD, and 10% between MCI and AD. Average NA in whole gray matter, hippocampus, posterior cingulate cortex, and precuneus, in each group are also provided in Fig. 3.
Conclusion
Lower NA was clearly detected in AD and MCI groups compared to NEC. The large decrease in NA detected in MCI subjects compared to NEC suggests this metric is highly sensitive to early changes in neuronal function.
Background
Early pathological changes in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) gradually decrease neuronal metabolism and function measured by PET and functional MRI (fMRI). ...These changes are often associated with cognitive decline and can help in the diagnosis of AD. However more sensitive indicators of the earliest stages of disease must be developed to detect disease prior to cognitive impairment. Recently, a novel neuronal activity (NA) metric was introduced based on resting‐state fMRI (rs‐fMRI) signal oscillations, which showed dramatically lower NA in AD. Here we introduced a more sophisticated and potentially more sensitive NA metric to identify subtle NA differences between three groups: normal elderly controls (NEC), MCI, and AD.
Method
The rs‐fMRI scans (TR=∼2400, ∼10 minute acquisition) were acquired at 3T from 8 MRI scanners in the Ontario Neurodegenerative Disease Research Initiative (AD group, N=40, aged 71.8 ± 8.1, 42% female; and MCI groups, N=80, aged 70.3 ± 8.3, 46% female), and the Gait and Brain Study (NEC group, N=30, aged 71.3 ± 6.0, 23.33% female). The rs‐fMRI signal was pre‐processed using FMRIB Software Library (FSL) and decomposed into independent components (ICs) using IC analysis. The ICs were classified into neuronal and non‐neuronal using a support vector machine classifier. The proposed voxel‐wise NA metric was defined based on similarity (cross covariance) between rs‐fMRI signal and neuronal ICs. This metric was utilized to create resting‐state NA map in each subject, which were compared between groups.
Result
Single subject and group average NA maps are provided in Fig. 1. The % difference maps between each group are shown in Fig. 2. The average voxelwise % difference in NA between groups was 38% between NEC and MCI, 38% between NEC and AD, and 10% between MCI and AD. Average NA in whole gray matter, hippocampus, posterior cingulate cortex, and precuneus, in each group are also provided in Fig. 3.
Conclusion
Lower NA was clearly detected in AD and MCI groups compared to NEC. The large decrease in NA detected in MCI subjects compared to NEC suggests this metric is highly sensitive to early changes in neuronal function.
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