In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer’s disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.

Background: The challenge of differentiating, at an early stage, Parkinson’s disease from parkinsonism caused by other disorders remains unsolved. We proposed using an artificial neural network (ANN) to process images of dopamine transporter single-photon emission computed tomography (DAT-SPECT). Methods: Abnormal DAT-SPECT images of subjects with Parkinson’s disease and parkinsonism caused by other disorders were divided into training and test sets. Striatal regions of the images were segmented by using an active contour model and were used as the data to perform transfer learning on a pre-trained ANN to discriminate Parkinson’s disease from parkinsonism caused by other disorders. A support vector machine trained using parameters of semi-quantitative measurements including specific binding ratio and asymmetry index was used for comparison. Results: The predictive accuracy of the ANN classifier (86%) was higher than that of the support vector machine classifier (68%). The sensitivity and specificity of the ANN classifier in predicting Parkinson’s disease were 81.8% and 88.6%, respectively. Conclusions: The ANN classifier outperformed classical biomarkers in differentiating Parkinson’s disease from parkinsonism caused by other disorders. This classifier can be readily included into standalone computer software for clinical application.

This work presents a fall detection system that is worn on the head, where the acceleration and posture are stable such that everyday movement can be identified without disturbing the wearer. Falling movements are recognized by comparing the acceleration and orientation of a wearer’s head using prespecified thresholds. The proposed system consists of a triaxial accelerometer, gyroscope, and magnetometer; as such, a Madgwick’s filter is adopted to improve the accuracy of the estimation of orientation. Moreover, with its integrated Wi-Fi module, the proposed system can notify an emergency contact in a timely manner to provide help for the falling person. Based on experimental results concerning falling movements and activities of daily living, the proposed system achieved a sensitivity of 96.67% in fall detection, with a specificity of 98.27%, and, therefore, is suitable for detecting falling movements in daily life.

Background: This study was to evaluate the correlation of the hypoperfusion intensity ratio (HIR) with the collateral score from multiphase computed tomography angiography (mCTA) among patients with large vessel stroke. Method: From February 2019 to May 2020, we retrospectively reviewed the patients with large vessel strokes (intracranial carotid artery or proximal middle cerebral artery occlusion). HIR was defined as a Tmax > 10 s lesion volume divided by a Tmax > 6 s lesion volume, which was calculated by automatic software (Syngo.via, Siemens). The correlation between the HIR and mCTA score was evaluated by Pearson’s correlation. The cutoff value predicting the mCTA score was evaluated by receiver operating characteristic analysis. Result: Ninety-four patients were enrolled in the final analysis. The patients with good collaterals had a smaller core volume (37.3 ± 24.7 vs. 116.5 ± 70 mL, p < 0.001) and lower HIR (0.51 ± 0.2 vs. 0.73 ± 0.13, p < 0.001) than those with poor collaterals. A higher HIR was correlated with a poorer collateral score by Pearson’s correlation. (r = −0.64, p < 0.001). The receiver operating characteristic (ROC) analysis suggested that the best HIR value for predicting a good collateral score was 0.68 (area under curve: 0.82). Conclusion: HIR is a good surrogate of collateral circulation in patients with acute large artery occlusion.

Chemotherapy-induced cognitive impairment (CICI) is an adverse side effect of cancer treatment with increasing awareness. Hippocampal damage and related neurocognitive impairment may mediate the development of CICI, in which altered neurogenesis may play a role. In addition, increased inflammation may be related to chemotherapy-induced hippocampal damage. Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that may enhance neurogenesis and modulate inflammation, may be useful for treating CICI. To test this hypothesis, paclitaxel was administered to eight-week-old male B6 mice to demonstrate the relationship between CICI and impaired neurogenesis, and then, we evaluated the impact of different memantine regimens on neurogenesis and inflammation in this CICI model. The results demonstrated that both the pretreatment and cotreatment regimens with memantine successfully reversed impaired neurogenesis and spatial memory impairment in behavior tests. The pretreatment regimen unsuccessfully inhibited the expression of peripheral and central TNF-$\mathsf{\alpha }$ and IL-1$\mathsf{\beta }$ and did not improve the mood alterations following paclitaxel treatment. However, the cotreatment regimen led to a better modulatory effect on inflammation and restoration of mood disturbance. In conclusion, this study illustrated that impaired neurogenesis is one of the mechanisms of paclitaxel-induced CICI. Memantine may serve as a potential treatment for paclitaxel-induced CICI, but different treatment strategies may lead to variations in the treatment efficacy.

Background: Angiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)–modulating effects, has additional benefits compared to other ARBs remains unclear.Methods and findings: Between 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set atp< 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19% versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97;p= 0.030). They also had lower risk of dementia diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95;p= 0.022) and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97;p= 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%; HR, 0.79; 95% CI, 0.67 to 0.94;p= 0.008) during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data.Conclusions: The current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population.