Predicting the efficacy of donepezil intervention in Alzheimer's disease patients using regional homogeneity in the inferior orbitofrontal cortex.

BACKGROUND: Although donepezil is a commonly used drug for treating Alzheimer's disease (AD), the mechanisms by which it affects patients' functional brain activity, and thus modulates clinical symptoms, remain unclear. METHODS: In the present study, we used resting-state functional magnetic resonance imaging (MRI) and regional homogeneity (ReHo) to investigate the effects of donepezil on local brain activity in AD patients. Resting-state functional MRI data were collected from 32 subjects: 16 healthy controls and 16 AD patients. All 16 AD patients underwent 6 months of donepezil treatment and received two MRI scans (pre- and post-intervention). Analysis of covariance and post hoc analyses were used to compare ReHo differences among the healthy controls, pre-intervention AD patients, and post-intervention AD patients. Pearson correlation analysis was used to examine relationships between ReHo values in differential brain regions and clinical symptoms. RESULTS: Compared with healthy controls, post-intervention AD patients had reduced ReHo in the orbital part of the inferior frontal gyrus, and pre-intervention AD patients had reduced ReHo in the orbital part of the right inferior frontal gyrus. Pattern recognition models revealed that pre-intervention ReHo values in abnormal brain regions of AD patients were 76% accurate for predicting the efficacy of donepezil on cognitive function and 65% accurate for predicting its efficacy on depressive symptoms. CONCLUSIONS: These findings deepen our understanding of the brain mechanisms underlying the clinical efficacy of donepezil in AD patients, and provide a novel way to predict its clinical efficacy in such patients.

Abnormal functional connectivity of the habenula in mild cognitive impairment patients with depression symptoms revealed by resting-state functional magnetic resonance imaging.

BACKGROUND: Recent research suggests that abnormalities in the habenula (HB), a core area of the brain that transmits reward information, may be a determinant of depression. However, it is not clear whether the functional connectivity (FC) pattern of the mild cognitive impairment (MCI) with and without depression symptoms is abnormal. METHODS: In this study, we used resting-state functional magnetic resonance imaging (fMRI) to examine the FC pattern of the HB in MCI patients with depression symptoms (D-MCI). We acquired fMRI data from 54 subjects on a 3T MRI. Subjects collected included 16 patients with D-MCI, 18 patients with MCI with no depression, and 20 healthy controls. One way ANCOVA and post hoc t-test were used to compare the difference in FC strength between the three groups. RESULTS: The D-MCI group had altered FC between the left HB and the right superior temporal gyrus, right inferior frontal gyrus/opercular part, and right middle frontal gyrus. The D-MCI group had increased FC between the right HB and precuneus. CONCLUSIONS: These results suggest that the dysfunction of the HB-Default model network might be involved in the neural mechanism underlying depression in MCI.

The role of lipid species in Alzheimer's disease onset: A comprehensive Mendelian randomization analysis.

BACKGROUND: Alzheimer's disease (AD) remains a significant global health challenge, with its etiology intricately linked to a variety of genetic and environmental factors. Among these, lipid metabolism has been hypothesized to play a crucial role, though the causal pathways remain inadequately elucidated. This study aims to employ Mendelian Randomization (MR) to unravel the potential causal relationships between a comprehensive array of lipid species and the risk of developing AD. METHODS: Utilizing a two-sample MR framework, we analyzed data from genome-wide association studies (GWAS) encompassing 487,511 individuals of European descent. A total of 179 lipid species across 13 lipid categories were investigated for their causal association with AD. Genetic variants serving as instrumental variables (IVs) were carefully selected based on stringent criteria to ensure validity. The statistical analyses, including inverse variance weighting (IVW), weighted median-based estimation, and sensitivity analyses, were conducted using the R software environment. RESULTS: Our findings reveal a significant causal relationship between ten specific lipid species and the risk of AD. Notably, certain lipids such as Sterol ester (27:1/15:0) and Phosphatidylcholine (16:0_22:4) exhibited a protective effect against AD, as evidenced by their inverse correlation with the disease's risk. Additionally, a reciprocal analysis suggested a negative causal impact of AD on the levels of certain Triacylglycerol species. The integrity of our results was reinforced by sensitivity analyses, including the MR Egger intercept test, indicating the absence of horizontal pleiotropy and confirming the reliability of our findings. CONCLUSIONS: This study substantiates the causal link between specific lipid species and Alzheimer's disease, highlighting the complex interplay between lipid metabolism and AD pathogenesis. The identified lipid biomarkers offer new insights into the disease's etiology and potential therapeutic targets. Furthermore, our rigorous methodological approach demonstrates the utility of MR in disentangling the causal relationships in complex diseases.

[Effect of ginsenoside Rb1 on cerebral infarction volume and IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion injury model rats].

OBJECTIVE: To investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats. METHODS: The I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R. RESULTS: In the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05). CONCLUSION: Ginsenoside Rb1 (20, 40, 80 mg/kg) might effectively release local cerebral ischemia by down-regulating the IL-1 beta expression.