Aberrant hippocampal subregion networks associated with the classifications of aMCI subjects: a longitudinal resting-state study

Background: Altered hippocampal structure and function is a valuable indicator of possible conversion from amnestic type mild cognitive impairment (aMCI) to Alzheimer’s disease (AD). However, little is known about the disrupted functional connectivity of hippocampus subregional networks in aMCI subjects. Methodology/Principal Findings: aMCI group-1 (n = 26) and controls group-1 (n = 18) underwent baseline and after approximately 20 months follow up resting-state fMRI scans. Integrity of distributed functional connectivity networks incorporating six hippocampal subregions (i.e. cornu ammonis, dentate gyrus and subicular complex, bilaterally) was then explored over time and comparisons made between groups. The ability of these extent longitudinal changes to separate unrelated groups of 30 subjects (aMCI-converters, n = 6; aMCI group-2, n = 12; controls group-2, n = 12) were further assessed. Six longitudinal hippocampus subregional functional connectivity networks showed similar changes in aMCI subjects over time, which were mainly associated with medial frontal gyrus, lateral temporal cortex, insula, posterior cingulate cortex (PCC) and cerebellum. However, the disconnection of hippocampal subregions and PCC may be a key factor of impaired episodic memory in aMCI, and the functional index of these longitudinal changes allowed well classifying independent samples of aMCI converters from non-converters (sensitivity was 83.3%, specificity was 83.3%) and controls (sensitivity was 83.3%, specificity was 91.7%). Conclusions/Significance: It demonstrated that the functional changes in resting-state hippocampus subregional networks could be an important and early indicator for dysfunction that may be particularly relevant to early stage changes and progression of aMCI subjects

Validation and refinement of a predictive nomogram using artificial intelligence: assessing in-hospital mortality in patients with large hemispheric cerebral infarction

BackgroundLarge Hemispheric Infarction (LHI) poses significant mortality and morbidity risks, necessitating predictive models for in-hospital mortality. Previous studies have explored LHI progression to malignant cerebral edema (MCE) but have not comprehensively addressed in-hospital mortality risk, especially in non-decompressive hemicraniectomy (DHC) patients.MethodsDemographic, clinical, risk factor, and laboratory data were gathered. The population was randomly divided into Development and Validation Groups at a 3:1 ratio, with no statistically significant differences observed. Variable selection utilized the Bonferroni-corrected Boruta technique (p < 0.01). Logistic Regression retained essential variables, leading to the development of a nomogram. ROC and DCA curves were generated, and calibration was conducted based on the Validation Group.ResultsThis study included 314 patients with acute anterior-circulating LHI, with 29.6% in the Death group (n = 93). Significant variables, including Glasgow Coma Score, Collateral Score, NLR, Ventilation, Non-MCA territorial involvement, and Midline Shift, were identified through the Boruta algorithm. The final Logistic Regression model led to a nomogram creation, exhibiting excellent discriminative capacity. Calibration curves in the Validation Group showed a high degree of conformity with actual observations. DCA curve analysis indicated substantial clinical net benefit within the 5 to 85% threshold range.ConclusionWe have utilized NIHSS score, Collateral Score, NLR, mechanical ventilation, non-MCA territorial involvement, and midline shift to develop a highly accurate, user-friendly nomogram for predicting in-hospital mortality in LHI patients. This nomogram serves as valuable reference material for future studies on LHI patient prognosis and mortality prevention, while addressing previous research limitations

Specifically Progressive Deficits of Brain Functional Marker in Amnestic Type Mild Cognitive Impairment

Background: Deficits of the default mode network (DMN) have been demonstrated in subjects with amnestic type mild cognitive impairment (aMCI) who have a high risk of developing Alzheimer’s disease (AD). However, no longitudinal study of this network has been reported in aMCI. Identifying links between development of DMN and aMCI progression would be of considerable value in understanding brain changes underpinning aMCI and determining risk of conversion to AD. Methodology/Principal Findings: Resting-state fMRI was acquired in aMCI subjects (n = 26) and controls (n = 18) at baseline and after approximately 20 months follow up. Independent component analysis was used to isolate the DMN in each participant. Differences in DMN between aMCI and controls were examined at baseline, and subsequent changes between baseline and follow-up were also assessed in the groups. Posterior cingulate cortex/precuneus (PCC/PCu) hyper-functional connectivity was observed at baseline in aMCI subjects, while a substantial decrement of these connections was evident at follow-up in aMCI subjects, compared to matched controls. Specifically, PCC/PCu dysfunction was positively related to the impairments of episodic memory from baseline to follow up in aMCI group. Conclusions/Significance: The patterns of longitudinal deficits of DMN may assist investigators to identify and monitor the development of aMCI

Association study of candidate gene polymorphisms with amnestic mild cognitive impairment in a Chinese population.

To investigate the relationship between amnestic mild cognitive impairment (aMCI) and candidate gene polymorphisms in a Chinese population, 116 aMCI patients and 93 normal controls were recruited. Multi-dimensional neuropsychological tests were used to extensively assess the cognitive functions of the subjects. MassARRAY and iPLEX systems were used to measure candidate single nucleotide polymorohisms (SNPs) and analyse allelic, genotypic or haplotypic distributions. The scores of the neuropsychological tests were significantly lower for the aMCI patients than for the normal controls. The distributions of SNPs relating to the amyloid cascade hypothesis (TOMM40 rs157581 G and TOMM40 rs2075650 G), to the cholesterol metabolism hypothesis (ApoE rs429358 C, LDLR rs11668477 G and CH25H rs7091822 T and PLAU rs2227564 CT) and to the tau hypothesis (MAPT/STH rs242562 GG) in aMCI were significantly different than those in normal controls. Interactions were also found in aMCI amongst SNPs in LDLR rs11668477, PLAU rs2227564, and TOMM40 rs157581, between SNPs in TOMM40 rs157580 and BACE2 rs9975138. The study suggests that aMCI is characterised by memory impairment and associated with SNPs in three systems relating to the pathogenesis of AD--those of the amyloid cascade, tau and cholesterol metabolism pathways. Interactions were also observed between genes in the amyloid pathway and between the amyloid and cholesterol pathways

Groups × time points ANOVA of DMN IC functional connectivity.

<p>Note: A corrected threshold by Monte Carlo simulation at <i>P</i><0.05. R =  right; L =  left; B =  Bilateral; BA =  Brodmann’s area; Cluster size is in mm³; MNI: Montreal Neurological Institute.</p

Validation of the ICA approach in aMCI subjects and healthy controls.

<p>Images showed the DMN in aMCI group and controls group at baseline and follow up, separately. Significant consistency between these studies is demonstrated across the majority of clusters including the posterior cingulated cortex, precuneus, inferior parietal lobule, prefrontal cortex, ventral anterior cingulate cortex, lateral temporal cortex. Thresholds were set at a corrected <i>P</i><0.05, determined by Monte Carlo simulation.</p

Figure 3

<p>(1). Comparison to controls group at baseline, aMCI group showed increased functional connectivity of DMN IC in a  =  bilateral PCC/PCu. (2). A comparison between the longitudinal changes between aMCI group and controls group, showing a greater decrement in functional connectivity of DMN IC in the aMCI group, particularly in PCC/PCu, and another region was d  =  right anterior cingulate/ medial frontal gyrus. In addition, the longitudinal increased functional connectivity of the prefrontal cortex was observed at follow up in aMCI subjects compared with controls, including b  =  left superior frontal gyrus/ middle frontal gyrus, c  =  right superior frontal gyrus/ middle frontal gyrus, e  =  left middle frontal gyrus and f  =  left inferior frontal gyrus. Thresholds were set at a corrected <i>P</i><0.05, determined by Monte Carlo simulation. (3) Overlap regions (PCC/Pcu) between baseline changes and longitudinal changes of DMN IC were observed in aMCI group compared to controls. (4) Hyper-functional connectivity between the PCC/PCu (overlap regions) and mean DMN IC in baseline aMCI subjects, and significant hypo-connections of these regions were in follow-up aMCI subjects, whilst controls only showed a light decreases at the longitudinal period. * <i>P</i><0.05 (0.046); ** <i>P</i><0.001(0.000). (5) Correlative analysis: within the aMCI group, the decreases of functional connectivity between PCC/PCu and mean DMN IC were positively related to the impairments of episodic memory (AVLT-delayed recall scores, r = 0.462, <i>P</i> = 0.018, two-tailed) from baseline to follow up. It should be noted that the raw scores of AVLT-delayed recall for each subject was transformed to z scores.</p