Impaired cerebral blood flow in type 2 diabetes mellitus – A comparative study with subjective cognitive decline, vascular dementia and Alzheimer’s disease subjects

Chau, Anson C.M.; Cheung, Eva Y.W.; Chan, Koon‐Ho; Chow, Wing-Sun; Shea, Yat‐Fung; Chiu, PW; Mak, Henry Ka-Fung

doi:10.1016/j.nicl.2020.102302

Cited by 42 publications

(42 citation statements)

References 49 publications

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“…The decline in CBF values may reflect neuronal dysfunction and synaptic failure (Hays et al, 2016 ). A controversy remains regarding whether the CBF values measured by ASL show hypoperfusion or hyperperfusion patterns in SCD or MCI, and the hypoperfusion/hyperperfusion areas may involve different brain regions simultaneously (Alexopoulos et al, 2012 ; Bron et al, 2014 ; Leeuwis et al, 2017 ; Chau et al, 2020 ; Kim et al, 2020 ). Compared with those of ECs, we found decreased MK values in the bilateral Hip (h), left PCC, left DT (a), and left OLWM and increased MK values in the left Pr in participants with SCD plus.…”

Section: Discussionmentioning

confidence: 99%

Microstructural and Cerebral Blood Flow Abnormalities in Subjective Cognitive Decline Plus: Diffusional Kurtosis Imaging and Three-Dimensional Arterial Spin Labeling Study

Yang

Cao

et al. 2021

Front. Aging Neurosci.

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Objective: To explore microstructural and cerebral blood flow (CBF) abnormalities in individuals with subjective cognitive decline plus (SCD plus) using diffusional kurtosis imaging (DKI) and three-dimensional (3D) arterial spin labeling (ASL).Methods: Twenty-seven patients with SCD plus, 31 patients with amnestic mild cognitive impairment (aMCI), and 33 elderly controls (ECs) were recruited and underwent DKI and 3D ASL using a GE 3.0-T MRI. Mean kurtosis (MK), fractional anisotropy (FA), mean diffusivity (MD), and CBF values were acquired from 24 regions of interest (ROIs) in the brain, including the bilateral hippocampal (Hip) subregions (head, body, and tail), posterior cingulate cortex (PCC), precuneus, dorsal thalamus subregions (anterior nucleus, ventrolateral nucleus, and medial nucleus), lenticular nucleus, caput nuclei caudati, white matter (WM) of the frontal lobe, and WM of the occipital lobe. Pearson's correlation analysis was performed to assess the relationships among the DKI-derived parameters, CBF values, and key neuropsychological tests for SCD plus.Results: Compared with ECs, participants with SCD plus showed a significant decline in MK and CBF values, mainly in the Hip head and PCC, and participants with aMCI exhibited more significant abnormalities in the MK and CBF values than individuals with ECs and SCD plus in multiple regions. Combined MK values showed better discrimination between patients with SCD plus and ECs than that obtained using CBF levels, with areas under the receiver operating characteristic (ROC) curve (AUC) of 0.874 and 0.837, respectively. Similarly, the AUC in discriminating SCD plus from aMCI patients obtained using combined MK values was 0.823, which was also higher than the combined AUC of 0.779 obtained using CBF values. Moreover, MK levels in the left Hip (h) and left PCC positively correlated with the auditory verbal learning test-delayed recall (AVLT-DR) score in participants with SCD plus. By contrast, only the CBF value in the left Hip head positively correlated with the AVLT-DR score.Conclusions: Our results provide new evidence of microstructural and CBF changes in patients with SCD plus. MK may be used as an early potential neuroimaging biomarker and may be a more sensitive DKI parameter than CBF at the very early stage of Alzheimer's disease (AD).

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Section: Discussionmentioning

confidence: 99%

Microstructural and Cerebral Blood Flow Abnormalities in Subjective Cognitive Decline Plus: Diffusional Kurtosis Imaging and Three-Dimensional Arterial Spin Labeling Study

Yang

Cao

et al. 2021

Front. Aging Neurosci.

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“…We believed that the contradiction of GLUT3 expression and glucose uptake maybe resulted from the intensity of intervention that 8 weeks of RH treatment disturbs the adaption caused by 8 days of provocation. It has also been demonstrated that diabetes causes severe cerebrovascular injury, leading to reduced cerebral blood flow and glucose supply to the brain (44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Recurrent moderate hypoglycemia accelerates the progression of Alzheimer’s disease through impairment of the TRPC6/GLUT3 pathway

He¹,

Li²,

Cui³

et al. 2022

JCI Insight

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Currently, the most effective strategy for dealing with Alzheimer's disease (AD) is delaying the onset of dementia. Severe hypoglycemia is strongly associated with dementia; however, the effects of recurrent moderate hypoglycemia (RH) on progression of cognitive deficits in diabetic patients with genetic susceptibility to AD remain unclear. Here, we report that insulin-controlled hyperglycemia only slightly aggravated AD-type pathologies and cognitive impairment; however, RH significantly increased neuronal hyperactivity and accelerated the progression of cognitive deficits in streptozotocin(STZ)-induced diabetic APP/PS1 mice. GLUT3-mediated neuronal glucose uptake was not significantly altered under hyperglycemia, but was markedly reduced by RH, which induced excessive mitochondrial fission in the hippocampus.Overexpression of GLUT3 specifically in DG area of hippocampus enhanced mitochondrial function and improved cognitive deficits induced by RH. Activation of TRPC6 increased GLUT3-mediated glucose uptake in brain and alleviated RH-induced cognitive deficits, and inactivation of Ca 2+ /AMPK pathway was responsible for TRPC6-induced GLUT3 inhibition. Taken together, RH impairs brain GLUT3-mediated glucose uptake and further provokes neuronal mitochondrial dysfunction by inhibiting TRPC6 expression, which then accelerates progression of cognitive deficits in diabetic APP/PS1 mice. Avoiding RH is essential for glycemic control in diabetic patients, and TRPC6/GLUT3 represent potent targets for delaying the onset of dementia in diabetic patients.

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“…As described in our previous study [ 27 ], dementia or cognitive impaired subjects were referred by the geriatricians from the memory clinic of the Queen Mary Hospital, Hong Kong for a prospective study during June 2017 to June 2019. A multi-disciplinary panel with two geriatricians (Y.F.S., P.K.C.C.)…”

Section: Methodsmentioning

confidence: 99%

“…and a neuroradiologist (H.K.F.M) confirmed the final diagnosis for each subject, with the support from the findings from clinical (baseline and follow-up), neuropsychological assessment, i.e., Montreal Cognitive Assessment—Hong Kong version (HK-MoCA), and neuroimaging (structural MRI, PCASL-MR perfusion, MRA, and amyloid PET-CT). The diagnostic criteria were detailed in the prior study [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

Diagnostic Efficacy of Voxel-Mirrored Homotopic Connectivity in Vascular Dementia as Compared to Alzheimer’s Related Neurodegenerative Diseases—A Resting State fMRI Study

Shea

Chiu

Kwan

et al. 2021

Life

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Previous studies have demonstrated that functional connectivity (FC) of different brain regions in resting state function MRI were abnormal in patients suffering from mild cognitive impairment (MCI) and Alzheimer’s disease (AD) when comparing to healthy controls (HC) using seed based, independent component analysis (ICA) or small world network techniques. A new technique called voxel-mirrored homotopic connectivity (VMHC) was used in the current study to evaluate the value of interhemispheric functional connectivity (IFC) as a diagnostic tool to differentiate vascular dementia (VD) from other Alzheimer’s related neurodegenerative diseases. Eighty-three participants were recruited from the university hospital memory clinic. A multidisciplinary panel formed by a neuroradiologist and two geriatricians classified the participants into VD (13), AD (16), MCI (29), and HC (25) based on clinical history, Montreal Cognitive Assessment Hong Kong version (HK‑MoCA) neuropsychological score, structural MRI, MR perfusion, and 18-F Flutametamol (amyloid) PET-CT findings of individual subjects. We adopted the calculation method used by Kelly et al. (2011) and Zuo et al. (2010) in obtaining VMHC maps. Specific patterns of VMHC maps were obtained for VD, AD, and MCI to HC comparison. VD showed significant reduction in VMHC in frontal orbital gyrus and gyrus rectus. Increased VMHC was observed in default mode network (DMN), executive control network (ECN), and the remaining salient network (SN) regions. AD showed a reduction of IFC in all DMN, ECN, and SN regions; whereas MCI showed VMHC reduction in vSN, and increased VMHC in DMN and ECN. When combining VMHC values of relevant brain regions, the accuracy was improved to 87%, 92%, and 83% for VD, AD, and MCI from HC, respectively, in receiver operating characteristic (ROC) analysis. Through studying the VMHC maps and using VMHC values in relevant brain regions, VMHC can be considered as a reliable diagnostic tool for VD, AD, and MCI from HC.

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Impaired cerebral blood flow in type 2 diabetes mellitus – A comparative study with subjective cognitive decline, vascular dementia and Alzheimer’s disease subjects

Cited by 42 publications

References 49 publications

Microstructural and Cerebral Blood Flow Abnormalities in Subjective Cognitive Decline Plus: Diffusional Kurtosis Imaging and Three-Dimensional Arterial Spin Labeling Study

Microstructural and Cerebral Blood Flow Abnormalities in Subjective Cognitive Decline Plus: Diffusional Kurtosis Imaging and Three-Dimensional Arterial Spin Labeling Study

Recurrent moderate hypoglycemia accelerates the progression of Alzheimer’s disease through impairment of the TRPC6/GLUT3 pathway

Diagnostic Efficacy of Voxel-Mirrored Homotopic Connectivity in Vascular Dementia as Compared to Alzheimer’s Related Neurodegenerative Diseases—A Resting State fMRI Study

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