Comparing cerebral perfusion in Alzheimer's disease and Parkinson's disease dementia: an ASL-MRI study.
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SUBMITTER: Le Heron CJ
PROVIDER: S-EPMC4050238 | biostudies-literature | 2014 Jun
REPOSITORIES: biostudies-literature
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Comparing cerebral perfusion in Alzheimer's disease and Parkinson's disease dementia: an ASL-MRI study.
Le Heron Campbell J CJ Wright Sarah L SL Melzer Tracy R TR Myall Daniel J DJ MacAskill Michael R MR Livingston Leslie L Keenan Ross J RJ Watts Richard R Dalrymple-Alford John C JC Anderson Tim J TJ
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20140312 6
Emerging evidence suggests that Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer's disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to ...[more]
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Project description:ObjectivesAlzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [(18)F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD.MethodsNormalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed.ResultsVoxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68).ConclusionsSimilar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET.Key points• Similar patterns of hypoperfusion and hypometabolism were observed in patients with dementia. • For both imaging modalities, parietal abnormalities were found in Alzheimer's disease. • For both imaging modalities, prefrontal abnormalities were found in frontotemporal dementia.
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Project description:Age-related hearing loss (HL) can be related to brain dysfunction or structural damage and may result in cerebral metabolic/perfusion abnormalities. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) allows investigating noninvasively brain perfusion changes. Pseudocontinuous ASL and T1-weighted MRI (at 3 T) and neuropsychological testing (Montreal Cognitive Assessment) were performed in 31 HL (age range?=?47-77 years, mean age?±?SD = 63.4?±?8.4?years, pure-tone average [PTA] HL?>?50?dB) and 28 normal hearing (NH; age range?=?48-78 years, mean age?±?SD?=?59.7?±?7.4?years) subjects. Cerebral blood flow (CBF) and gray matter volume (GMV) were analyzed in the cortical volume to assess perfusion and structural group differences. Two HL subjects showing cognitive impairment were excluded from group comparisons. No significant differences in either global or local atrophy were detected between groups but the HL group exhibited significant regional effects of reduced perfusion within the bilateral primary auditory cortex, with maximal CBF difference (-17.2%) in the right lateral Heschl's gyrus. For the whole sample of HL and NH subjects (n?=?59?=?31 HL?+?28 NH), the regional CBF was correlated positively to the regional GMV (p?=?0.020). In HL subjects (n?=?31), the regional CBF was correlated negatively to the audiogram steepness (frequency range: 2-4 kHz, right ear: p?=?0.022, left ear: p?=?0.015). The observed cortical pattern of perfusion reduction suggests that neuronal metabolism can be related to HL before the recognition of brain structural damage. This also illustrates the potential of ASL-MRI to contribute early functional markers of reduced central processing associated with HL.
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Project description:PurposeClinical applicability of renal arterial spin labeling (ASL) MRI is hampered because of time consuming and observer dependent post-processing, including manual segmentation of the cortex to obtain cortical renal blood flow (RBF). Machine learning has proven its value in medical image segmentation, including the kidneys. This study presents a fully automatic workflow for renal cortex perfusion quantification by including machine learning-based segmentation.MethodsFully automatic workflow was achieved by construction of a cascade of 3 U-nets to replace manual segmentation in ASL quantification. All 1.5T ASL-MRI data, including M0 , T1 , and ASL label-control images, from 10 healthy volunteers was used for training (dataset 1). Trained cascade performance was validated on 4 additional volunteers (dataset 2). Manual segmentations were generated by 2 observers, yielding reference and second observer segmentations. To validate the intended use of the automatic segmentations, manual and automatic RBF values in mL/min/100 g were compared.ResultsGood agreement was found between automatic and manual segmentations on dataset 1 (dice score = 0.78 ± 0.04), which was in line with inter-observer variability (dice score = 0.77 ± 0.02). Good agreement was confirmed on dataset 2 (dice score = 0.75 ± 0.03). Moreover, similar cortical RBF was obtained with automatic or manual segmentations, on average and at subject level; with 211 ± 31 mL/min/100 g and 208 ± 31 mL/min/100 g (P < .05), respectively, with narrow limits of agreement at -11 and 4.6 mL/min/100 g. RBF accuracy with automated segmentations was confirmed on dataset 2.ConclusionOur proposed method automates ASL quantification without compromising RBF accuracy. With quick processing and without observer dependence, renal ASL-MRI is more attractive for clinical application as well as for longitudinal and multi-center studies.
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Project description:Fibrinogen is reportedly associated with neurodegenerative diseases (NDs), but the underlying causality remains controversial. Using Mendelian randomization (MR), this study aimed to assess the causal association between fibrinogen and Alzheimer's disease (AD), Parkinson's disease (PD), and Lewy body dementia (LBD). Genetic variants associated with fibrinogen and γ-fibrinogen were selected and used as instrumental variables. The effect estimates of the main analysis were obtained by inverse-variance weighting (IVW), complemented by sensitivity analyses to verify model assumptions, and multivariable MR was conducted to control for potential pleiotropic effect. Two-step MR was performed to assess the causal association through mediators. The main analysis suggested no causal association between genetically predicted plasma fibrinogen and γ-fibrinogen levels and the risk of AD, PD, and LBD. The effect estimates did not change in the follow-up sensitivity analyses and MVMR. However, the two-step MR analysis provides evidence that fibrinogen may contribute to the risk of AD via CRP levels. There was an inverse effect of adult height levels on the risk of AD. Our results support the effects of fibrinogen on the risk of AD through increasing plasma CRP levels. Our study found no evidence to support the effects of genetically determined fibrinogen and γ-fibrinogen levels on the risk of PD and LBD. Additionally, our findings suggested an inverse association between genetically determined adult height levels and the risk of AD. Future studies are needed to elucidate the underlying mechanisms and their clinical applications.
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Project description:BACKGROUND:With the disappointing outcomes of clinical trials on patients with Alzheimer's disease or mild cognitive impairment (MCI), there is increasing attention to understanding cognitive decline in normal elderly individuals, with the goal of identifying subjects who are most susceptible to imminent cognitive impairment. PURPOSE/HYPOTHESIS:To evaluate the potential of cerebral blood flow (CBF) as a biomarker by investigating the relationship between CBF at baseline and cognition at follow-up. STUDY TYPE:Prospective longitudinal study with a 4-year time interval. POPULATION:309 healthy subjects aged 20-89 years old. FIELD STRENGTH/SEQUENCE:3T pseudo-continuous-arterial-spin-labeling MRI. ASSESSMENT:CBF at baseline and cognitive assessment at both baseline and follow-up. STATISTICAL TESTS:Linear regression analyses with age, systolic blood pressure, physical activity, and baseline cognition as covariates. RESULTS:Linear regression analyses revealed that whole-brain CBF at baseline was predictive of general fluid cognition at follow-up. This effect was observed in the older group (age ?54 years, ??=?0.221, P?=?0.004), but not in younger or entire sample (??=?0.018, P?=?0.867 and ??=?0.089, P?=?0.098, respectively). Among major brain lobes, frontal CBF had the highest sensitivity in predicting future cognition, with a significant effect observed for fluid cognition (??=?0.244 P?=?0.001), episodic memory (??=?0.294, P?=?0.001), and reasoning (??=?0.186, P?=?0.027). These associations remained significant after accounting for baseline cognition. Voxelwise analysis revealed that medial frontal cortex and anterior cingulate cortex, part of the default mode network (DMN), are among the most important regions in predicting fluid cognition. DATA CONCLUSION:In a healthy aging cohort, CBF can predict general cognitive ability as well as specific domains of cognitive function. LEVEL OF EVIDENCE:1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:449-458.
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Project description:Micro- or macro-circulatory insufficiency has a negative impact in patients with Alzheimer's disease (AD). This study used arterial spin-labeled magnetic resonance imaging (ASL-MRI) and ethylcysteinate dimer single-photon emission computed tomography (ECD-SPECT) in 50 patients with AD and 30 age-matched controls to investigate how hypoperfusion patterns were associated with gray matter atrophy and clinical data. All participants completed 3DT1-MRI, ECD-SPECT and ASL-MRI examinations. Medial temporal cortex (MTC) volumes were correlated with regional signals showing significantly lower relative cerebral blood flow (rCBF) in ASL-MRI or perfusion index (PI) in ECD-SPECT. Neurobehavioral scores served as the outcome measures. Regions with lower PI showed spatial similarities with atrophy in the medial, anterior and superior temporal lobes, posterior cingulate cortex and angular gyrus, while regions showing lower rCBF were localized to the distal branches of posterior cerebral artery territories (posterior parietal and inferior temporal lobe) and watershed areas (angular gyrus, precuneus, posterior cingulate gyrus and middle frontal cortex). rCBF values in watershed areas correlated with MTC volumes and language composite scores. Precuneus and angular gyrus hypoperfusion were associated with the corresponding cortical atrophy. Macro- or micro-vasculature perfusion integrities and cortical atrophy determined the overall perfusion imaging topography and contributed differently to the clinical outcomes.
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Project description:As the differential diagnosis of dementias based on established clinical criteria is often difficult, biomarkers for applicable diagnostic testing are currently under intensive investigation. Amyloid plaques deposited in the brain of patients suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated forms of amyloid-beta (Abeta) peptides, such as Abeta1-42. Absolute Abeta1-42 levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor. A recently established quantitative urea-based Abeta-sodium-dodecylsulphate-polyacrylamide-gel-electrophoresis with Western immunoblot (Abeta-SDS-PAGE/immunoblot) revealed a highly conserved Abeta peptide pattern of the carboxy-terminally truncated Abeta peptides 1-37, 1-38, 1-39 in addition to 1-40 and 1-42 in human CSF. We used the Abeta-SDS-PAGE/immunoblot to investigate the CSF of 23 patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented disease controls (NDC) for disease-specific alterations of the Abeta peptide patterns in its absolute and relative quantities. The diagnostic groups were matched for age and severity of dementia. The present study is the first attempt to evaluate the meaning of Abeta peptide patterns in CSF for differential diagnosis of the three neurodegenerative diseases--Alzheimer's disease, DLB and PDD. The Abeta peptide patterns displayed disease-specific variations and the ratio of the differentially altered Abeta1-42 to the Abeta1-37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD. Additionally, a novel peptide with Abeta-like immunoreactivity was observed constantly in the CSF of all 88 investigated patients. The pronounced percentage increase of this peptide in DLB allowed a highly significant discrimination from PDD. Using a cut-off point of 0.954%, this marker yielded a diagnostic sensitivity and specificity of 81 and 71%, respectively. From several lines of indication, we consider this peptide to represent an oxidized alpha-helical form of Abeta1-40 (Abeta1-40*). The increased abundance of Abeta1-40* probably reflects a disease-specific alteration of the Abeta1-40 metabolism in DLB. We conclude that Abeta peptide patterns reflect disease-specific pathophysiological pathways of different dementia syndromes as distinct neurochemical phenotypes. Although Abeta peptide patterns failed to fulfil the requirements for a sole biomarker, their combined evaluation with other biomarkers is promising in neurochemical dementia diagnosis. It is noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite their similar neuropathological appearance. Their distinct molecular phenotypes support the view of different pathophysiological pathways for each of these neurodegenerative diseases.
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Project description:Cortical dysfunction in Parkinson's disease (PD) may be caused by disruption to ascending systems or by intrinsic cortical neuropathology. We introduce and conduct a joint analysis of metabolism and atrophy capable of identifying whether metabolic disruption occurs in mild PD without cortical atrophy, to determine the extent and spatial pattern of cortical involvement in mild PD. The design was observational, studying 23 cognitively normal participants with mild PD (mean Hoehn & Yahr stage 2) and 21 healthy controls. Cortical thickness (obtained from analysis of structural magnetic resonance imaging [MRI] with FreeSurfer) and cerebral perfusion measures (obtained from arterial spin labeling [ASL]) analyzed independently and then together in a joint multiple factorial analysis to identify spatial patterns of perfusion and cortical thickness. We identify a pattern of changes in perfusion and cortical thickness characterized by symmetric parietal cortical thinning and reduced precuneus perfusion, with relative preservation of thickness and perfusion in the anterior cingulate cortex (ACC), right prefrontal gyrus, and medial frontal gyrus. The expression of this pattern is correlated with motor system symptoms and speed of processing. A spatial pattern of joint parietal cortical thinning and disproportionate reduction in perfusion occurs in our nondemented PD sample. We found no PD-related components of reduced perfusion without cortical thinning. This suggests that PD affects the cortex itself, even when symptoms are relatively mild.
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