Plasma Insulin Predicts Early Amyloid-ß Pathology Changes in Alzheimer's Disease.

Background: Evidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD), sharing similar pathophysiological traits like impaired insulin signaling. Objective: To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology. Methods: A total of 304 participants were included in the Alzheimer's Disease Neuroimaging Initiative, assessing plasma insulin and CSF AD pathology. We explored the cross-sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages. Results: In the non-demented group, amyloid-ß (Aß)+ participants (e.g., as reflected by CSF Aß42) exhibited significantly lower plasma insulin levels compared to non-demented Aß-participants (p < 0.001). This reduction in plasma insulin was more evident in the A+T+ group (as shown by CSF Aß42 and pTau181 levels) when compared to the A-T- group within the non-dementia group (p = 0.002). Additionally, higher plasma insulin levels were consistently associated with more normal CSF Aß42 levels (p < 0.001) across all participants. This association was particularly significant in the Aß-group (p = 0.002) and among non-demented individuals (p < 0.001). Notably, baseline plasma insulin was significantly correlated with longitudinal changes in CSF Aß42 (p = 0.006), whereas baseline CSF Aß42 did not show a similar correlation with changes in plasma insulin over time. Conclusions: These findings suggest an association between plasma insulin and early Aß pathology in the early stages of AD, indicating that plasma insulin may be a potential predictor of changes in early Aß pathology.

Sex differences in the relationship between depression and Alzheimer's disease-mechanisms, genetics, and therapeutic opportunities.

Depression and Alzheimer's disease (AD) are prevalent neuropsychiatric disorders with intriguing epidemiological overlaps. Their interrelation has recently garnered widespread attention. Empirical evidence indicates that depressive disorders significantly contribute to AD risk, and approximately a quarter of AD patients have comorbid major depressive disorder, which underscores the bidirectional link between AD and depression. A growing body of evidence substantiates pervasive sex differences in both AD and depression: both conditions exhibit a higher incidence among women than among men. However, the available literature on this topic is somewhat fragmented, with no comprehensive review that delineates sex disparities in the depression-AD correlation. In this review, we bridge these gaps by summarizing recent progress in understanding sex-based differences in mechanisms, genetics, and therapeutic prospects for depression and AD. Additionally, we outline key challenges in the field, holding potential for improving treatment precision and efficacy tailored to male and female patients' distinct needs.

Long-term efficacy, prognostic factors, and safety of deep brain stimulation in patients with refractory Tourette syndrome: A single center, single target, retrospective study.

BACKGROUND: To evaluate the long-term efficacy, prognostic factors, and safety of posteroventral globus pallidus internus deep brain stimulation (DBS) in patients with refractory Tourette syndrome (RTS). METHODS: This retrospective study recruited 61 patients with RTS who underwent posteroventral globus pallidus internus (GPi) DBS from January 2010 to December 2020 at the Chinese People's Liberation Army General Hospital. The Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive-Compulsive Scale (YBOCS), Beck Depression Inventory (BDI), Gilles de la Tourette Syndrome Quality-of-Life Scale (GTS-QOL) were used to evaluate the preoperative and postoperative clinical condition in all patients. Prognostic factors and adverse events following surgery were analyzed. RESULTS: Patient follow up was conducted for an average of 73.33 ± 28.44 months. The final postoperative YGTSS (32.39 ± 22.34 vs 76.61 ± 17.07), YBOCS (11.26 ± 5.57 vs 18.31 ± 8.55), BDI (14.36 ± 8.16 vs 24.79 ± 11.03) and GTS-QOL (39.69 ± 18.29 vs 78.08 ± 14.52) scores at the end of the follow-up period were significantly lower than those before the surgery (p < 0.05). While age and the duration of follow-up were closely related to prognosis, the disease duration and gender were not. No serious adverse events were observed and only one patient exhibited symptomatic deterioration. CONCLUSIONS: Posteroventral-GPI DBS provides long-term effectiveness, acceptable safety and can improve the quality of life in RTS patients. Moreover, DBS is more successful among younger patients and with longer treatment duration.

Partial improvement in performance of patients with severe Alzheimer's disease at an early stage of fornix deep brain stimulation.

Deep brain stimulation is a therapy for Alzheimer's disease (AD) that has previously been used for mainly mild to moderate cases. This study provides the first evidence of early alterations in performance induced by stimulation targeted at the fornix in severe AD patients. The performance of the five cases enrolled in this study was scored with specialized assessments including the Mini-Mental State Examination and Clinical Dementia Rating, both before and at an early stage after deep brain stimulation. The burden of caregivers was also evaluated using the Zarit Caregiver Burden Interview. As a whole, the cognitive performance of patients remained stable or improved to varying degrees, and caregiver burden was decreased. Individually, an improved mental state or social performance was observed in three patients, and one of these three patients showed remarkable improvement in long-term memory. The conditions of another patient deteriorated because of inappropriate antipsychotic medications that were administered by his caregivers. Taken together, deep brain stimulation was capable of improving some cognitive aspects in patients with severe AD, and of ameliorating their emotional and social performance, at least at an early stage. However, long-term effects induced by deep brain stimulation in patients with severe AD need to be further validated. More research should focus on clarifying the mechanism of deep brain stimulation. This study was registered with ClinicalTrials.gov (NCT03115814) on April 14, 2017.

In vivo visualization of connections among revised Papez circuit hubs using full q-space diffusion spectrum imaging tractography.

Structural connections among the hubs of the revised Papez circuit remain to be elucidated in the human brain. As the original Papez circuit failed to explain functional imaging findings, a more detailed investigation is needed to delineate connections among the circuit's key hubs. Here we acquired diffusion spectrum imaging (DSI) from eight normal subjects and used data from the Human Connectome Project (HCP) to elucidate connections among hubs in the retrosplenial gyrus, hippocampus, mammillary bodies, and anterior thalamic nuclei. Our results show that the ventral hippocampal commissure (VHC) was visualized in all eight individual DSI datasets, as well as in the DSI and HCP group datasets, but a strictly defined VHC was only visualized in one individual dataset. Thalamic fibers were observed to connect with both the posterior cingulate cortex (PCC) and retrosplenial cortex (RSC). The RSC was mainly responsible for direct hippocampal connections, while the PCC was not. This indicates that the RSC and PCC represent separate functional hubs in humans, as also shown by previous primate axonal tracing studies and functional magnetic resonance imaging observations.

Connection between bilateral temporal regions: Tractography using human connectome data and diffusion spectrum imaging.

Temporal lobe epilepsy often propagates inter-hemispherically. Although the pathway of the propagation was verified by electrophysiology, the trajectory remains poorly defined. DTI can depict fiber trajectory but it has limited angular resolution and cannot adequately assess cortical regions. We visualized potential pathways of bitemporal epilepsy propagation using diffusion spectrum imaging (DSI) with data consisting of 8 groups of 514 directions and diffusion templates of 842 subjects from the human connectome project (HCP). We verified the results with reference to the axonal-tracing literature. Both the large population overall and individual connection properties were investigated. In both the HCP 842 atlas and DSI individual data, the bilateral temporal pole was found to connect via the anterior commissure. The splenium of the corpus callosum was divided into 3 subregions (CS1, CS2, CS3) according to the form of connections. CS1 was predominately located at the rostral third and the dorsal part of middle third of the splenium; it communicated with the bilateral parietal lobe. SC2 was predominately located at the ventral middle third of the splenium. Fibers passed through the lateral wall of the lateral ventricle and connected to regions lateral of the occipitotemporal sulci. CS3 was located at the caudal third of the splenium. Together with the hippocampal commissure, its fibers constituted the medial wall of the lateral ventricle and distributed medially to the occipitotemporal sulci. The trajectory of bilateral temporal connections was visualized in this study; the results might help in the understanding and treatment of inter-hemispherical propagation of temporal-lobe epilepsy.

[Relationship between muscle motor evoked potentials and hindlimbs motor function in rabbits with spinal cord injury].

OBJECTIVE: To study the relationship between muscle motor evoked potentials (MEP) and hindlimbs motor function in rabbits with spinal cord injury. METHODS: Forty-five rabbits were randomly divided into 9 groups, including one control group and 8 injured groups (receiving Allen's injury of 0, 50, 75, 100, 125, 150, 175, 200, or 250 gcf). Hindlimb strength and muscle MEP were recorded at the 1st day and 4th week postoperatively. At 4 weeks after spinal section, the spinal cord tissue was sampled for histological examination with HE staining and immunohistochemistry with anti-NF antibody of the corticospinal tract fibers. RESULTS: During the operation, MEP showed an all-or-none pattern with significant correlations to postoperative optical density of NF and postoperative hindlimb motor function. The latency prolongation of the muscle MEP at the 4th week showed a linear correlation to the hindlimb Tarlov's score, whereas the MEP amplitude was not correlated to postoperative hindlimb motor function. CONCLUSIONS: The all-or-none pattern of muscle MEP can be used to evaluate the severity of spinal cord injury.