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Evaluation on acupuncture treatment in mild Alzheimer’s disease by 3D-ASL
MATian, LIHui, FANXiang, NIHong, QIZhigang, LIKuncheng
Chinese Journal of Alzheimer's Disease and Related Disorders ›› 2019, Vol. 2 ›› Issue (4) : 481-487.
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Abbreviation (ISO4): Chinese Journal of Alzheimer's Disease and Related Disorders
Editor in chief: Jun WANG
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Evaluation on acupuncture treatment in mild Alzheimer’s disease by 3D-ASL
Objective: To investigate the changes of cerebral blood flow perfusion in patients with mild Alzheimer’s disease (AD) by three-dimensional arterial spin labeling (3D-ASL), and to evaluate the therapeutic effect of ad acupuncture at “siguan point”. Methods: Twenty mild AD patients (AD group) diagnosed by the neurological memory disorders clinic of Xuanwu Hospital, Capital Medical University from June 2016 to April 2018 and twenty normal volunteers matched with age, gender and education level of AD group were recruited as control group. 20 patients were randomly divided into two groups: “siguan" conventional acupuncture group (10 patients), and “siguan" sham acupuncture group (10 patients). All subjects underwent 3D-ASL scanning to get relative cerebral blood flow data at the time of enrollment, and neuropsychological scale examination was conducted. 3D-ASL scanning was performed again after intervention of acupuncture. The images were processed and analyzed using the software package SPM12. Results: In the “siguan" conventional acupuncture group, 2 cases were excluded because of the significant head movement artifacts. ①There was no statistical difference in age, gender and level of education between the mild AD group and NC group (P> 0.05). The scores of MMSE and MoCA in mild AD group was significantly lower than that of NC group; ② Compared with the NC group, decreased perfusion areas were observed in the bilateral precuneus and posterior cingulate cortex in the mild AD group (cluster number was 878, P< 0.05); (3) ③After 6 months of acupuncture intervention, 3D-ASL was reexamined. It was found that, the perfusion of left anterior cuneiform lobe and posterior cingulate cortex was increased, in addition, the perfusion of bilateral middle frontal cortex, superior frontal cortex, putamen nucleus, caudate nucleus, rectus muscles, left inferior frontal cortex, insula, right thalamus, superior temporal cortex central sulcus were also increased in the conventional acupuncture group. while that of the shallow acupuncture group was decreased in corresponding areas.(cluster number was 11 279, P< 0.05). Conclusion: 3D-ASL discovered that the perfusion of bilateral anterior cuneiform lobe and posterior cingulate cortex was decreased in mild AD and acupuncturing “siguan" point increased the cerebral perfusion (including the original hypoperfusion brain area) in mild AD patients.
Alzheimer’s disease / Three dimensional arterial spin labeling / Acupuncture / “Siguan" point
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Vascular risk factors (e.g. hypertension, dyslipidemia and diabetes) are well known risk factors for Alzheimer' disease. These vascular risk factors lead to vascular brain injuries, which also increase the likelihood of dementia. The advent of amyloid PET imaging has helped establish that vascular risk factors also lead to Alzheimer's disease via pathways that are independent from vascular brain injuries, at least, when vascular brain injuries are measured as white matter lesions and infarcts. While vascular brain injuries (white matter lesions and infarcts) do not seem to influence amyloid pathology, some evidence from amyloid imaging suggests that increased vascular risk is related to increased amyloid burden. Furthermore, while vascular brain injuries and amyloid have an additive and independent impact on brain integrity, vascular risk factors might potentiate the impact of amyloid on cortical thickness on brain regions vulnerable to Alzheimer's disease. New research should further explore and confirm, or refute, possible interactions between amyloid and vascular risk factors on brain integrity and cognition. Neuroimaging tools used to assess vascular brain integrity should also be expanded. Measuring cortical blood flow or damage to the capillary system might, for instance, give insight about how vascular risk factors can be associated to amyloid burden and impact. These findings also stress the need for monitoring vascular risk factors in midlife as a strategy for Alzheimer's disease prevention.
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To compare quantitative cerebral blood flow (CBF) values in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and subjects with subjective complaints by using a whole-brain three-dimensional (3D) pseudocontinuous arterial spin-labeling (ASL) technique at 3.0 T.The local institutional review board approved the study. All subjects provided informed consent. Whole-brain 3D fast spin-echo pseudocontinuous ASL images were acquired at 3.0 T in 71 patients with AD (mean age, 65 years ± 7; 55% women), 35 patients with MCI (mean age, 65 years ± 8; 42% women), and 73 subjects with subjective complaints (mean age, 60 years ± 9; 39% women) who visited a memory clinic. Analyses were performed by using both uncorrected maps and maps corrected for partial volume effects. Regional CBF was compared by using analyses of variance; permutation tests were used for voxel-wise comparisons. Associations with cognition (Mini-Mental State Examination) were investigated by using linear regression analyses. All analyses were corrected for age and sex.Uncorrected CBF was decreased in patients with AD compared with subjects with subjective complaints (27 mL/100 g/min ± 5 vs 33 mL/100 g/min ± 5; P <.001), with strongest reductions in the parietal lobes (22 mL/100 g/min ± 6 vs 30 mL/100 g/min ± 5; ie, decrease of 27%). Corrected cortical CBF showed similar results. In patients with MCI, CBF was decreased in the precuneus and the parietal and occipital lobes compared with subjects with subjective complaints. Voxel-wise comparisons confirmed the region of interest-based findings, showing the largest CBF differences in the precuneus and bilateral parietal cortex. Uncorrected and corrected cortical CBF were associated with cognition across diagnostic groups (β = 0.46 and β = 0.42, P <.001) and within the AD group (β = 0.41 and β = 0.42, P <.001).CBF measured with 3D pseudocontinuous ASL MR imaging helps detect functional changes in the prodromal and more advanced stages of AD and is a marker for disease severity.RSNA, 2012
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According to the so-called disconnection hypothesis, the loss of synaptic inputs from the medial temporal lobes (MTL) in Alzheimer's disease (AD) may lead to reduced activity of target neurons in cortical areas and, consequently, to decreased cerebral blood flow (CBF) in those areas. The aim of this study was to assess whether hypoperfusion in parietotemporal and frontal cortices of patients with mild cognitive impairment who converted to AD (MCI-c) and patients with mild AD is associated with atrophy in the MTL and/or microstructural changes in the white matter (WM) tracts connecting these areas. We assessed these relationships by investigating correlations between CBF in hypoperfused areas, mean cortical thickness in atrophied regions of the MTL, and fractional anisotropy (FA) in WM tracts. In the MCI-c group, a strong correlation was observed between CBF of the superior parietal gyri and FA in the parahippocampal tracts (left: r = 0.90, p < 0.0001; right: r = 0.597, p = 0.024), and between FA in the right parahippocampal tract and the right precuneus (r = 0.551, p = 0.041). No significant correlations between CBF in hypoperfused regions and FA in the WM tract were observed in the AD group. These results suggest an association between perfusion deficits and altered WM tracts in prodromal AD, while microvasculature impairments may have a greater influence in more advanced stages. We did not find correlations between cortical thinning in the medial temporal lobes and decreased FA in the WM tracts of the limbic system in either group.
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The utility of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in Alzheimer's disease (AD) diagnosis has been well established. Recently, measurement of cerebral blood flow using arterial spin labeling magnetic resonance imaging (ASL-MRI) has shown diagnostic potential in AD, although it has never been directly compared with FDG-PET.We used a novel imaging protocol to obtain FDG-PET and ASL-MRI images concurrently in 17 AD patients and 19 age-matched control subjects. Paired FDG-PET and ASL-MRI images from 19 control subjects and 15 AD patients were included for qualitative analysis, and paired images from 18 control subjects and 13 AD patients were suitable for quantitative analyses.The combined imaging protocol was well tolerated. Both modalities revealed similar regional abnormalities in AD, as well as comparable sensitivity and specificity for the detection of AD after visual review by two expert readers. Interobserver agreement was better for FDG-PET (κ: 0.75, standard error: 0.12) than ASL-MRI (κ: 0.51, standard error: 0.15); intermodality agreement was moderate to strong (κ: 0.45-0.61); and readers were more confident of FDG-PET reads. Simple quantitative analysis of global cerebral fluorodeoxyglucose uptake (FDG-PET) or whole-brain cerebral blood flow (ASL-MRI) showed excellent diagnostic accuracy for both modalities, with area under receiver operating characteristic curves of 0.90 for FDG-PET (95% confidence interval: 0.79-0.99) and 0.91 for ASL-MRI (95% confidence interval: 0.80-1.00).Our results demonstrate that FDG-PET and ASL-MRI identify similar regional abnormalities and have comparable diagnostic accuracy in a small population of AD patients, and support the further study of ASL-MRI in dementia diagnosis.Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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To investigate the reliability and accuracy of two pseudo-continuous arterial spin labeling (pCASL) sequences, using two-dimensional (2D) gradient-echo echo planar imaging (EPI) and 3D gradient and spin echo (GRASE) as the readout, respectively.Each sequence was performed twice 4 weeks apart on six normal control subjects, six elderly subjects with mild cognitive impairment (MCI), and one participant with Alzheimer's disease (AD). Eight of these subjects also underwent H2 (15) O positron emission tomography (PET) scans on the same day or proximal to their second MRI scan. The longitudinal repeatability of EPI and GRASE pCASL were evaluated with the intraclass correlation coefficient (ICC) and within-subject coefficient of variation (wsCV).The ICCs of global perfusion measurements were 0.697 and 0.413 for GRASE and EPI based pCASL respectively. GRASE pCASL also demonstrated a higher longitudinal repeatability for regional perfusion measurements across 24 regions-of-interests (ICC = 0.707; wsCV = 10.9%) compared with EPI pCASL (ICC = 0.362; wsCV = 15.3%). When compared with PET, EPI pCASL showed a higher degree of spatial correlation with PET than GRASE pCASL, although the difference was not statistically significant.The 3D GRASE pCASL offers better repeatability than 2D EPI pCASL, thereby may provide a reliable imaging marker for the evaluation of disease progression and treatment effects in MCI and early AD subjects.Copyright © 2013 Wiley Periodicals, Inc.
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To investigate arterial spin-labelling (ASL) cerebral blood flow (CBF) changes in predementia stages of Alzheimer's disease (AD).Data were obtained from 177 patients with subjective complaints, mild cognitive impairment and AD from the Amsterdam Dementia Cohort. AD stages were based on diagnosis and cerebrospinal fluid biomarkers amyloid-β (Aβ) and total-tau (tau). General-linear-models were used to assess relationships between AD stages and total and regional CBF, correcting for age and sex.Decreasing CBF was related to more advanced AD stages in all supratentorial regions (p for trend < 0.05). Post-hoc testing revealed that CBF was lower in AD compared to controls and stage-1 predementia patients (i.e. abnormal Aβ and normal tau) in temporal and parietal regions, and compared to stage-2 predementia patients (i.e. abnormal Aβ and tau) in temporal regions. CBF values of stage-2 predementia patients were numerically in between those of stage-1 predementia patients and AD.The continuing decrease of CBF along the continuum of AD indicates the potential of ASL-CBF as a measure for disease progression.• Decreasing CBF relates to more advanced AD stages in all supratentorial regions. • The reduction of CBF does not reach a bottom level. • ASL-CBF has potential as a measure for disease progression in AD.
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To investigate arterial spin labeling (ASL)-MRI for the early diagnosis of and differentiation between the two most common types of presenile dementia: Alzheimer's disease (AD) and frontotemporal dementia (FTD), and for distinguishing age-related from pathological perfusion changes.Thirteen AD and 19 FTD patients, and 25 age-matched older and 22 younger controls underwent 3D pseudo-continuous ASL-MRI at 3 T. Gray matter (GM) volume and cerebral blood flow (CBF), corrected for partial volume effects, were quantified in the entire supratentorial cortex and in 10 GM regions. Sensitivity, specificity and diagnostic performance were evaluated in regions showing significant CBF differences between patient groups or between patients and older controls.AD compared with FTD patients had hypoperfusion in the posterior cingulate cortex, differentiating these with a diagnostic performance of 74 %. Compared to older controls, FTD patients showed hypoperfusion in the anterior cingulate cortex, whereas AD patients showed a more widespread regional hypoperfusion as well as atrophy. Regional atrophy was not different between AD and FTD. Diagnostic performance of ASL to differentiate AD or FTD from controls was good (78-85 %). Older controls showed global hypoperfusion compared to young controls.ASL-MRI contributes to early diagnosis of and differentiation between presenile AD and FTD.ASL-MRI facilitates differentiation of early Alzheimer's disease and frontotemporal dementia. Posterior cingulate perfusion is lower in Alzheimer's disease than frontotemporal dementia. Compared to controls, Alzheimer's disease patients show hypoperfusion in multiple regions. Compared to controls, frontotemporal dementia patients show focal anterior cingulate hypoperfusion. Global decreased perfusion in older adults differs from hypoperfusion in dementia.
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