Episodic memory decline is a common complication of type 2 diabetes (T2D). To comprehensively explore the neural mechanisms underlying it, we aimed to explore the sequence that episodic memory-related behavioral and brain-imaging biomarkers appear abnormal in the progression of T2D. We enrolled 62 healthy controls and 110 patients with T2D. The California Verbal Learning Test, Montreal cognitive assessment, and Stroop color word test was used to assess the episodic memory, general cognitive function, and executive function. Principal component analysis was applied to extract behavioral biomarkers. Imaging biomarkers included structural and functional MRI features of the entorhinal cortex-hippocampus and hippocampus-anterior cingulate cortex pathways. We used a novel discriminative event-based model to determine the sequence that memory-related biomarkers appear abnormal and estimate the stage of memory decline. T2D patients exhibited poorer memory, general cognitive function, and executive function compared to healthy controls after controlling age, sex, and education level. In the progression of T2D, functional interaction between brain regions showed abnormalities first, followed by memory tests, the cerebral spontaneous neural activity, and finally the gray matter volume. Besides, abnormalities appeared earlier in the entorhinal cortex than in the anterior cingulate cortex. Later stage of memory decline was distributed in older patients with T2D and was associated with higher systolic blood pressure, postprandial blood glucose, and low-density lipoprotein. In T2D, behavioral and brain imaging biomarkers of episodic memory appear abnormal in a specific sequence, and the stage of memory decline was closely associated with old age and vascular risk factors. NCT02420470, ClinicalTrials.gov ( https://www.clinicaltrials.gov/ ).

In this study, functional and structural changes in visual network (VN) of type 2 diabetes mellitus (T2DM) were investigated using multimodal magnetic resonance imaging. We explored degree centrality (DC), amplitude of low frequency fluctuation (ALFF), fractional anisotropy (FA), DC-FA and ALFF-FA in VN. Compared with healthy controls, deteriorated DC, ALFF and DC-FA coefficients in VN were observed in T2DM. These indicators showed positive correlations with cognitive function in T2DM, especially memory and executive function. Functional-structural decoupling may be a potential image biomarker of cognitive function change in T2DM.

Type 2 diabetes mellitus (T2DM) seriously threatens human health and the quality of life, cognitive impairment is considered as a common complication of T2DM. Neuroimaging meta-analysis found brain functional and structural abnormality in patients with T2DM. Therefore, the purpose of the meta-analysis was to identify brain regions of patients with T2DM-related cognitive impairment (T2DM-CI) where functional and structural indicators changed together or could not synchronize. A literature screening of neuroimaging studies on cognitive impairment in T2DM was conducted from 1 January 2007 to 26 May 2023 in PubMed, Web of Science, Cochrane Library, and Medline databases. The functional indicators we studied were amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and degree centrality (DC), while the structural indicator was gray matter (GM), which included gray matter volume (GMV) and cerebral cortical thickness. Studies reporting ALFF, ReHo, DC and GM abnormalities between T2DM-CI and healthy controls (HCs) were selected and their significant peak coordinates (x, y, z) and effect size (t-value) were extracted to perform a meta-analysis using anisotropic effect size sign differential mapping (AES-SDM) 5.15 software. Moreover, the brain regions with significant differences obtained from meta-analysis were saved as masks and then validated in our data. Total 19 studies and 20 datasets were involved in this study. Compared to HCs, combining ALFF, ReHo, and DC measurements, the brain activity of the left anterior cingulate/paracingulate gyri (ACC.L, BA24) in T2DM-CI patients increased significantly, while the brain activity of the left lingual gyrus (LING.L, BA18) in T2DM-CI patients decreased significantly. The GM indicator of the right superior temporal gyrus (STG.R, BA42) and left inferior occipital gyrus (IOG.L, BA19) in T2DM-CI patients decreased significantly. Meta-regression analysis showed the negative relationship between the brain activity reduction in LING.L and the percentage of female patients, as well as the negative relationship between GM reduction in IOG.L and T2DM duration. Furthermore, we validated a decrease in brain activity in the LING.L of T2DM-CI patients in our independent dataset. The decrease of brain activity in LING.L and the decrease of GM in IOG.L were closely related to visual impairment in T2DM-CI patients. These abnormal brain regions may be the main targets for future research, early intervention can delay the further development of cognitive impairment in T2DM patients and improve their quality of life, which also provided early biomarkers for clarifying the mechanism of cognitive impairment in T2DM.

Type 2 diabetes mellitus (T2DM) and cognitive dysfunction are highly prevalent disorders worldwide. Although visual network (VN) alteration and functional-structural coupling are potential warning factors for mild cognitive impairment (MCI) in T2DM patients, the relationship between the three in T2DM without MCI is unclear. Thirty T2DM patients without MCI and twenty-nine healthy controls (HC) were prospectively enrolled. Visual components (VC) were estimated by independent component analysis (ICA). Degree centrality (DC), amplitude of low frequency fluctuation (ALFF) and fractional anisotropy (FA) were established to reflect functional and structural characteristics in these VCs respectively. Functional-structural coupling coefficients were further evaluated using combined FA and DC or ALFF. Partial correlations were performed among neuroimaging indicators and neuropsychological scores and clinical variables. Three VCs were selected using group ICA. Deteriorated DC, ALFF and DC-FA coefficients in the VC1 were observed in the T2DM group compared with the HC group, while FA and ALFF-FA coefficients in these three VCs showed no significant differences. In the T2DM group, DC in the VC1 positively correlated with 2 dimensions in the California Verbal Learning Test, including Trial 4 and Total trial 1–5. The impaired DC-FA coefficients in the VC1 markedly affected the Total perseverative responses % of the Wisconsin Card Sorting Test. These findings indicate that DC and DC-FA coefficients in VN may be potential imaging biomarkers revealing early cognitive deficits in T2DM.

Background:Parkinson's disease (PD) is a neurodegenerative disease with high incidence rate. Resting state functional magnetic resonance imaging (rs-fMRI), as a widely used method for studying neurodegenerative diseases, has not yet been combined with two important indicators, amplitude low-frequency fluctuation (ALFF) and cerebral blood flow (CBF), for standardized analysis of PD.Methods:In this study, we used seed-based d-mapping and permutation of subject images (SDM-PSI) software to investigate the changes in ALFF and CBF of PD patients. After obtaining the regions of PD with changes in ALFF or CBF, we conducted a multimodal analysis to identify brain regions where ALFF and CBF changed together or could not synchronize.Results:The final study included 31 eligible trials with 37 data sets. The main analysis results showed that the ALFF of the left striatum and left anterior thalamic projection decreased in PD patients, while the CBF of the right superior frontal gyrus decreased. However, the results of multimodal analysis suggested that there were no statistically significant brain regions. In addition, the decrease of ALFF in the left striatum and the decrease of CBF in the right superior frontal gyrus was correlated with the decrease in clinical cognitive scores.Conclusion:PD patients had a series of spontaneous brain activity abnormalities, mainly involving brain regions related to the striatum-thalamic-cortex circuit, and related to the clinical manifestations of PD. Among them, the left striatum and right superior frontal gyrus are more closely related to cognition.Systematic review registration:https://www.crd.york.ac.uk/ PROSPERO (CRD42023390914).

Disturbance of neurovascular coupling (NVC) is suggested to be one potential mechanism in type 2 diabetes mellitus (T2DM) associated mild cognitive impairment (MCI). However, NVC evidence derived from functional magnetic resonance imaging ignores the relationship of neuronal activity with vascular injury. Twenty-seven T2DM patients without MCI and thirty healthy controls were prospectively enrolled. Brain regions with changed susceptibility detected by quantitative susceptibility mapping (QSM) were used as seeds for functional connectivity (FC) analysis. NVC coefficients were estimated using combined degree centrality (DC) with susceptibility or cerebral blood flow (CBF). Partial correlations between neuroimaging indicators and cognitive decline were investigated. In T2DM group, higher susceptibility values in right hippocampal gyrus (R.PHG) were found and were negatively correlated with Naming Ability of Montreal Cognitive Assessment. FC increased remarkably between R.PHG and right middle temporal gyrus (R.MTG), right calcarine gyrus (R.CAL). Both NVC coefficients (DC-QSM and DC-CBF) reduced in R.PHG and increased in R.MTG and R.CAL. Both NVC coefficients in R.PHG and R.MTG increased with the improvement of cognitive ability, especially for executive function. These demonstrated that QSM and DC-QSM coefficients can be promising biomarkers for early evaluation of cognitive decline in T2DM patients and help to better understand the mechanism of NVC.

BackgroundAlzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are aging related diseases with high incidence. Because of the correlation of incidence rate and some possible mechanisms of comorbidity, the two diseases have been studied in combination by many researchers, and even some scholars call AD type 3 diabetes. But the relationship between the two is still controversial.MethodsThis study used seed-based d mapping software to conduct a meta-analysis of the whole brain resting state functional magnetic resonance imaging (rs-fMRI) study, exploring the differences in amplitude low-frequency fluctuation (ALFF) and cerebral blood flow (CBF) between patients (AD or T2DM) and healthy controls (HCs), and searching for neuroimaging evidence that can explain the relationship between the two diseases.ResultsThe final study included 22 datasets of ALFF and 22 datasets of CBF. The results of T2DM group showed that ALFF increased in both cerebellum and left inferior temporal gyrus regions, but decreased in left middle occipital gyrus, right inferior occipital gyrus, and left anterior central gyrus regions. In the T2DM group, CBF increased in the right supplementary motor area, while decreased in the middle occipital gyrus and inferior parietal gyrus. The results of the AD group showed that the ALFF increased in the right cerebellum, right hippocampus, and right striatum, while decreased in the precuneus gyrus and right superior temporal gyrus. In the AD group, CBF in the anterior precuneus gyrus and inferior parietal gyrus decreased. Multimodal analysis within a disease showed that ALFF and CBF both decreased in the occipital lobe of the T2DM group and in the precuneus and parietal lobe of the AD group. In addition, there was a common decrease of CBF in the right middle occipital gyrus in both groups.ConclusionBased on neuroimaging evidence, we believe that T2DM and AD are two diseases with their respective characteristics of central nervous activity and cerebral perfusion. The changes in CBF between the two diseases partially overlap, which is consistent with their respective clinical characteristics and also indicates a close relationship between them.Systematic review registrationPROSPERO [CRD42022370014].