Substantial studies have reported the prevalence and the affecting factors of subjective cognitive decline (SCD). The complaints screening scale has also been used for probing. However, little is known in China.To investigate the prevalence and risk factors of SCD, and explore an SCD complaints screening scale in China.Stratified cluster random sampling was conducted. 2,689 residents aged 60-80 years completed questionnaire 1. 814 residents were included for clinical and neuropsychological evaluations. Two standards were used to make the diagnosis of mild cognitive impairment (MCI) and SCD, and a preliminary screening rate comparison was carried out. Finally, we assessed the risk factors of SCD and the correlation between the SCD-questionnaire 9 (SCD-Q9) and the Auditory Verbal Learning Test-Long Delay Free Recall (AVLT-LR).1) Standard 1 (ADNI2): the prevalence of SCD was 18.8% (95% CI = 14.7-22.9%) and zero conformed to six criteria (SCD plus). 2) Standard 2 (Jak/Bondi): the prevalence of SCD was 14.4% (95% CI = 10.7-18.1%). 3) Standard 1 had a relatively higher "false" positive rate, whereas Standard 2 had higher "false" negative rate. 4) Age, low education, fewer close friends, and daily drinking were independent risk factors for SCD progressing to MCI. 5) Total points of SCD-Q9 were negatively correlated to the value of AVLT-LR.The prevalence of SCD is high in the ShunYi District in Beijing, China. Age, low education, less social support, and daily drinking are independent risk factors. The brief SCD-Q9 can be used as a reference.

The success rate of the pharmaceutical research and development (R&D) for dementia drugs has been abysmally low, in the last two decades. Also low has been the number of pipeline drugs in development, compared to other therapy areas. However, the rationale of early terminations has not been reported in the majority of trials. These are key findings of the recently published pharmaceutical pipeline analysis by the UK‐based Office of Health Economics (OHE). Our understanding of main challenges include (1) the significant gaps of knowledge in the nosology and complexity of the underpinning biological mechanisms of the commonest, not familial, forms of late onset dementias; (2) low signal‐to‐noise ratio, notwithstanding the lack of validated biomarkers as entry and/or end‐point criteria; (3) recruitment and retention, particularly in the asymptomatic and early disease stages. A number of current and future strategies aimed at ameliorating drug development are outlined and discussed.

Demographic changes are increasing the pressure to improve therapeutic strategies against cognitive decline in Alzheimer disease (AD) and mild cognitive impairment (MCI). Besides drug treatment, physical activity seems to be a promising intervention target as epidemiological and clinical studies suggest beneficial effects of exercise training on cognition. Using comparable inclusion and exclusion criteria, we analyzed the efficacy of drug therapy (cholinesterase inhibitors, memantine, and Ginkgo biloba) and exercise interventions for improving cognition in AD and MCI populations.We searched The Cochrane Library, EBSCO, OVID, Web of Science, and U.S Food and Drug Administration data from inception through October 30, 2013. Randomized controlled trials in which at least one treatment arm consisted of an exercise or a pharmacological intervention for AD or MCI patients, and which had either a non-exposed control condition or a control condition that received another intervention. Treatment discontinuation rates and Standardized Mean Change score using Raw score standardization (SMCR) of cognitive performance were calculated.Discontinuation rates varied substantially and ranged between 0% and 49% with a median of 18%. Significantly increased discontinuation rates were found for galantamine and rivastigmine as compared to placebo in AD studies. Drug treatments resulted in a small pooled effect on cognition (SMCR: 0.23, 95% CI: 0.20 to 0.25) in AD studies (N = 45, 18,434 patients) and no effect in any of the MCI studies (N = 5, 3,693 patients; SMCR: 0.03, 95% CI: 0.00 to 0.005). Exercise interventions had a moderate to strong pooled effect size (SMCR: 0.83, 95% CI: 0.59 to 1.07) in AD studies (N = 4, 119 patients), and a small effect size (SMCR: 0.20, 95% CI: 0.11 to 0.28) in MCI (N = 6, 443 patients).Drug treatments have a small but significant impact on cognitive functioning in AD and exercise has the potential to improve cognition in AD and MCI. Head-to-head trials with sufficient statistical power are necessary to directly compare efficacy, safety, and acceptability. Combining these two approaches might further increase the efficacy of each individual intervention.PROSPERO (2013:CRD42013003910).Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Several anti-amyloid monoclonal antibodies have been developed for slowing the progression of Alzheimer disease (AD). Among the furthest developed are aducanumab, which received accelerated approval from the US Food and Drug Administration in 2021, and donanemab, which is currently undergoing phase 3 trials. The cost-effectiveness of these treatments has not been established.To estimate the cost-effectiveness of aducanumab and donanemab relative to standard care for early AD in the US.A decision analytic model was used to estimate the lifetime health and economic outcomes of adults with early AD, from US healthcare sector and societal perspectives. Simulated patients had a mean (SD) age of 75.2 (5.5) years; 65% had mild cognitive impairment and 35% had mild dementia. Analyses were conducted from April 6, 2021, to January 20, 2022.Standard care, aducanumab (selected inputs including disease progression hazard ratio [HR] of 0.89 [95% CI, 0.63-1.15], annual price of $28 000, and twice-yearly monitoring with magnetic resonance imaging [MRI] of the brain), or donanemab (selected inputs including disease progression HR of 0.68 [95% CI, 0.44-0.99], annual price of $28 000, and twice-yearly monitoring with MRI of the brain and amyloid positron emission tomography [PET] monitoring). Donanemab was switched to placebo after substantial amyloid reduction on PET imaging, which occurred in 27% of patients at 6 months and 55% of patients at 12 months.Quality-adjusted life-years (QALYs); costs, in 2020 US dollars; incremental cost-effectiveness ratios (ICERs); and value-based prices, defined as the maximum price at which a treatment would be cost-effective given a cost-effectiveness threshold of ICER of $150 000/QALY.Lifetime QALYs increased by 0.133 with aducanumab and 0.408 with donanemab. Total health care sector and societal costs increased by $130 100 and $127 800, respectively, with aducanumab and by $78 700 and $71 600, respectively, with donanemab, driven largely by drug costs ($119 000 for aducanumab and $44 600 for donanemab). Health care sector and societal ICERs relative to standard care were $981 000/QALY and $964 000/QALY, respectively, for aducanumab and $193 000/QALY and $176 000/QALY, respectively, for donanemab. In sensitivity analysis, aducanumab's value-based price remained less than $50 000/y, even when assuming a 90% reduction in disease progression. Donanemab's value-based price surpassed $50 000/y once its efficacy exceeded 50%.These findings suggest that at current expected prices, neither aducanumab nor donanemab would be cost-effective for early AD in the US. Donanemab's dosing scheme, in which patients suspend treatment on achieving substantial amyloid reductions, may provide a rubric by which sufficiently effective anti-amyloid antibody treatments could be cost-effective even when priced comparably to other biologics.

目的 观察健身气功八段锦对轻度认知障碍(MCI)患者认知水平的影响。方法 2016年1月至6月,社区MCI患者60例随机分为对照组(n=30)和练功组(n=30),练功组予八段锦干预6个月,对照组无干预。干预前后分别采用蒙特利尔认知评估量表(MoCA)进行评估;检测血脂,血清白细胞介素-6 (IL-6)、乙酰胆碱(Ach)、超氧化物歧化酶(SOD)和丙二醛(MDA)水平。结果 6个月后,练功组MoCA总分及视空间与执行功能、抽象思维和延迟回忆评分明显高于对照组(t>3.576, P<0.01)。练功组血清总胆固醇、IL-6和MDA水平低于对照组(t>2.744, P<0.05),高密度脂蛋白胆固醇、Ach和SOD水平明显高于对照组(t>2.922, P<0.01)。结论 健身气功八段锦能改善MCI患者的认知功能,且有降血脂、抗氧化和抗炎作用,两者之间可能有关。

To examine whether combined center- and home-based Tai Chi training can improve cognitive ability and reduce physiological fall risk in older adults with amnestic mild cognitive impairment (a-MCI).Randomized controlled trial.Chiang Mai, Thailand.Adults aged 60 and older who met Petersen's criteria for multiple-domain a-MCI (N = 66).Three weeks center-based and 12 weeks home-based Tai Chi (50 minutes per session, 3 times per week).Cognitive tests, including Logical Memory (LM) delayed recall, Block Design, Digit Span forward and backward, and Trail-Making Test Part B-A (TMT B-A), and fall risk index using the Physiological Profile Assessment (PPA).At the end of the trial, performance on LM, Block Design, and TMT B-A were significantly better for the Tai Chi group than the control group after adjusting for baseline test performance. The Tai Chi group also had significantly better composite PPA score and PPA parameter scores: knee extension strength, reaction time, postural sway, and lower limb proprioception.Combined center- and home-based Tai Chi training three times per week for 15 weeks significantly improved cognitive function and moderately reduced physiological fall risk in older adults with multiple-domain a-MCI. Tai Chi may be particularly beneficial to older adults with this condition.© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

While effective therapies for preventing or slowing cognitive decline in at-risk populations remain elusive, evidence suggests mind-body interventions may hold promise.In this study, we assessed the effects of Kirtan Kriya meditation (KK) and music listening (ML) on cognitive outcomes in adults experiencing subjective cognitive decline (SCD), a strong predictor of Alzheimer's disease.Sixty participants with SCD were randomized to a KK or ML program and asked to practice 12 minutes/day for 3 months, then at their discretion for the ensuing 3 months. At baseline, 3 months, and 6 months we measured memory and cognitive functioning [Memory Functioning Questionnaire (MFQ), Trail-making Test (TMT-A/B), and Digit-Symbol Substitution Test (DSST)].The 6-month study was completed by 53 participants (88%). Participants performed an average of 93% (91% KK, 94% ML) of sessions in the first 3 months, and 71% (68% KK, 74% ML) during the 3-month, practice-optional, follow-up period. Both groups showed marked and significant improvements at 3 months in memory and cognitive performance (MFQ, DSST, TMT-A/B; p's≤0.04). At 6 months, overall gains were maintained or improved (p's≤0.006), with effect sizes ranging from medium (DSST, ML group) to large (DSST, KK group; TMT-A/B, MFQ). Changes were unrelated to treatment expectancies and did not differ by age, gender, baseline cognition scores, or other factors.Findings of this preliminary randomized controlled trial suggest practice of meditation or ML can significantly enhance both subjective memory function and objective cognitive performance in adults with SCD, and may offer promise for improving outcomes in this population.

轻度认知障碍（MCI）是一种介于正常和痴呆的过渡状态。目前MCI尚无有效的治疗药物，常采用认知训练、体育锻炼、心理干预等非药物治疗措施。早期对MCI患者进行非药物治疗干预，可以改善患者的认知功能，提高生活质量，延缓其向痴呆进展。本文对目前MCI的非药物治疗进行总结，以期为痴呆的预防和早期干预提供有益的补充手段。

The glymphatic movement of fluid through the brain removes metabolic waste1–4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer’s disease5–8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer’s disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.

Dementia causes a substantial global economic burden, but effective treatment is lacking. Recently, studies have revealed that gamma-band waves of electrical brain activity, particularly 40 Hz oscillations, are closely associated with high-order cognitive functions and can activate microglia to clear amyloid-β deposition. Here, we found that compared with sham stimulation, applying 40-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) over the bilateral angular gyrus in patients with probable Alzheimer’s disease (AD; n = 37) resulted in up to 8 weeks of significantly improved cognitive function. Power spectral density analysis of the resting-state electroencephalography (EEG) demonstrated that 40-Hz rTMS modulated gamma-band oscillations in the left posterior temporoparietal region. Further testing with magnetic resonance imaging and TMS-EEG revealed the following: 40-Hz rTMS 1) prevented gray matter volume loss, 2) enhanced local functional integration within bilateral angular gyrus, as well as global functional integration in bilateral angular gyrus and the left middle frontal gyrus, 3) strengthened information flow from the left posterior temporoparietal region to the frontal areas and strengthened the dynamic connectivity between anterior and posterior brain regions. These findings demonstrate that modulating gamma-band oscillations effectively improves cognitive function in patients with probable AD by promoting local, long-range, and dynamic connectivity within the brain.

Transcranial alternating current stimulation (tACS)-a noninvasive brain stimulation technique that modulates cortical oscillations through entrainment-has been demonstrated to alter oscillatory activity and enhance cognition in healthy adults. TACS is being explored as a tool to improve cognition and memory in patient populations with mild cognitive impairment (MCI) and Alzheimer's disease (AD).To review the growing body of literature and current findings obtained from the application of tACS in patients with MCI or AD, highlighting the effects of gamma tACS on brain function, memory, and cognition. Evidence on the use of brain stimulation in animal models of AD is also discussed. Important parameters of stimulation are underscored for consideration in protocols that aim to apply tACS as a therapeutic tool in patients with MCI/AD.The application of gamma tACS has shown promising results in the improvement of cognitive and memory processes that are impacted in patients with MCI/AD. These data demonstrate the potential for tACS as an interventional stand-alone tool or alongside pharmacological and/or other behavioral interventions in MCI/AD.While the use of tACS in MCI/AD has evidenced encouraging results, the effects of this stimulation technique on brain function and pathophysiology in MCI/AD remains to be fully determined. This review explores the literature and highlights the need for continued research on tACS as a tool to alter the course of the disease by reinstating oscillatory activity, improving cognitive and memory processing, delaying disease progression, and remediating cognitive abilities in patients with MCI/AD.Copyright © 2023. Published by Elsevier Inc.

Cognitive-enhancing effects of vagus nerve stimulation (VNS) have been reported during 6 months of treatment in a pilot study of patients with Alzheimer's disease (AD). Data through 1 year of VNS (collected from June 2000 to September 2003) are now reported.All patients (N = 17) met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD. Responder rates for the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Mini-Mental State Examination (MMSE) were measured as improvement or absence of decline from baseline. Global change, depressive symptoms, and quality of life were also assessed. Cerebrospinal fluid (CSF) levels for total tau, tau phosphorylated at Thr181 (phosphotau), and Abeta42 were measured by standardized enzyme-linked immunosorbent assay (ELISA).VNS was well tolerated. After 1 year, 7 (41.2%) of 17 patients and 12 (70.6%) of 17 patients improved or did not decline from baseline on the ADAS-cog and MMSE, respectively. Twelve of 17 patients were rated as having no change or some improvement from baseline on the Clinician Interview-Based Impression of Change (CIBIC+). No significant decline in mood, behavior, or quality of life occurred during 1 year of treatment. The median change in CSF tau at 1 year was a reduction of 4.8% (p =.057), with a 5.0% increase in phosphotau (p =.040; N = 14).The results of this study support long-term tolerability of VNS among patients with AD and warrant further investigation.

Vagus nerve stimulation (VNS) is used for treating refractory epilepsy and major depression. While the impact of this treatment on seizures has been established, its impact on human cognition remains equivocal. The goal of this study is to elucidate the immediate effects of vagus nerve stimulation on attention, cognition, and emotional reactivity in patients with epilepsy. Twenty patients (12 male and 8 female; 45 ± 13 years old) treated with VNS due to refractory epilepsy participated in the study. Subjects performed a computer-based test of executive functions embedded with emotional distractors while their brain activity was recorded with electroencephalography. Subjects' cognitive performance, early visual event-related potential N1, and frontal alpha asymmetry were studied when cyclic vagus nerve stimulation was on and when it was off. We found that vagus nerve stimulation improved working memory performance as seen in reduced errors on a subtask that relied on working memory, odds ratio (OR) = 0.63 (95% confidence interval, CI [0.47, 0.85]) and increased N1 amplitude, F(1, 15) = 10.17, p = .006. In addition, vagus nerve stimulation resulted in longer reaction time, F(1, 16) = 8.23, p = .019, and greater frontal alpha asymmetry, F(1, 16) = 11.79, p = .003, in response to threat-related distractors. This is the first study to show immediate improvement in working memory performance in humans with clinically relevant vagus nerve stimulation. Furthermore, vagus nerve stimulation had immediate effects on emotional reactivity evidenced in behavior and brain physiology.

Vagus nerve stimulation (VNS) is an established treatment method for therapy-refractory epilepsy and, in Europe, for treatment-resistant depression also. Clinical and experimental investigations have also shown positive effects of VNS on cognition in epilepsy and depression. The purpose of the present pilot study was to investigate the effect of VNS on cognition in patients with Alzheimer's disease.All the included patients (N = 10) met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for the diagnosis of Alzheimer's disease. Before the implantation of the vagus stimulator (NeuroCybernetic Prosthesis), the patients underwent neuropsychological tests (e.g., Alzheimer's Disease Assessment Scale-cognitive subscale [ADAS-cog] and Mini-Mental State Examination [MMSE]), computerized tomography of the brain, medical/neurologic and psychological examinations (status evaluation), and lumbar puncture with investigation of the cerebrospinal fluid. The presence of depressive symptoms was rated using the Montgomery-Asberg Depression Rating Scale. The VNS was initiated 2 weeks after the implantation, and the patients were followed up with regular investigations and tests over 6 months. Response was defined as improvement or absence of impairment in ADAS-cog and MMSE scores after 3 and 6 months.After 3 months of treatment, 7 of 10 patients were responders according to the ADAS-cog (median improvement of 3.0 points), and 9 of 10 patients were responders according to the MMSE (median improvement of 1.5 points). After 6 months of treatment, 7 patients were responders on the ADAS-cog (median improvement of 2.5 points), and 7 patients were responders on the MMSE (median improvement of 2.5 points). VNS was well tolerated, and its side effects were mild and transient.The results of this open-label pilot study suggest a positive effect of VNS on cognition in patients with Alzheimer's disease. Further studies are warranted.

The pathogenesis of insomnia is related to the dysfunction of the thalamus. Transcutaneous auricular vagus nerve stimulation (taVNS) has proved to be effective in treating insomnia. However, whether taVNS alleviates insomnia through modulating thalamus-related functional connectivity remains unclear. To elucidate the instant modulating effects of taVNS on the resting state functional connectivity (RSFC) of the thalamus, 20 patients with insomnia disorder were recruited to receive taVNS treatment and their resting state functional magnetic resonance imaging (fMRI) data were collected immediately before and after stimulation. The fMRI data were compared with 20 age- and gender-matched healthy subjects who received no stimulation and had RSFC fMRI data collected once. RSFC analyses of the thalamus were performed in both groups. In addition to assessing the group differences between ID patients and healthy controls regarding the RSFC of the thalamus, we examined the taVNS-induced changes of RSFC of the thalamus in ID patients. Before taVNS treatment, the ID patients showed increased RSFC of the thalamus with the right insula and inferior frontal gyrus than healthy controls. After taVNS treatment, the RSFC between the thalamus and the right angular gyrus, left anterior cingulate gyrus, and precuneus were significantly decreased in patients. This study provides insights into the instant brain effects involving the thalamus-related functional connectivity of taVNS performed on insomnia disorder patients.

Working memory (WM) is one of the core components of higher cognitive functions. There exists debate regarding the extent to which current techniques can enhance human WM capacity. Here, we examined the WM modulation effects of a previously less studied technique, transcutaneous auricular vagus nerve stimulation (taVNS). In experiment 1, a within-subject study, we aimed to investigate whether and which stimulation protocols of taVNS can modulate spatial WM performance in healthy adults. Forty-eight participants performed baseline spatial n-back tasks (1, 3-back) and then received online taVNS, offline taVNS, or sham stimulation before or during (online group) the posttest of spatial n-back tasks in random order. Results showed that offline taVNS could significantly increase hits in spatial 3-back task, whereas no effect was found in online taVNS or sham group. No significant taVNS effects were found on correct rejections or reaction time of accurate trials (aRT) in both online and offline protocols. To replicate the results found in experiment 1 and further investigate the generalization effect of offline taVNS, we carried out experiment 2. Sixty participants were recruited and received offline taVNS or offline earlobe stimulation in random order between baseline and posttests of behavioral tests (spatial/digit 3-back tasks). Results replicated the findings; offline taVNS could improve hits but not correct rejections or aRT in spatial WM performance, which were found in experiment 1. However, there were no significant stimulation effects on digit 3-back task. Overall, the findings suggest that offline taVNS has potential on modulating WM performance.

Direct vagus nerve stimulation (dVNS) is known to improve mood, epilepsy, and memory. Memory improvements have been observed in Alzheimer's disease patients after long-term stimulation. The potential of transcutaneous vagus nerve stimulation (tVNS), a noninvasive alternative to dVNS, to alter memory performance remains unknown. We aimed to investigate the effect of a single-session tVNS on associative memory performance in healthy older individuals. To investigate this, we performed a single-blind sham-controlled randomized crossover pilot study in healthy older individuals (n = 30, 50% female). During the stimulation or sham condition, participants performed an associative face-name memory task. tVNS enhanced the number of hits of the memory task, compared with the sham condition. This effect was specific to the experimental task. Participants reported few side effects. We conclude that tVNS is a promising neuromodulatory technique to improve associative memory performance in older individuals, even after a single session. More research is necessary to investigate its underlying neural mechanisms, the impact of varying stimulation parameters, and its applicability in patients with cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.

Postoperative cognitive dysfunction (POCD) is a decline in cognitive function for weeks or months after surgery. It may affect the patients' length of hospital stay, quality of life, the rehabilitation process, and work performance. Prolonged POCD occurs frequently after cardiac surgery, and the risk of POCD increases with age. The pathophysiology of POCD has not been well understood. However, emerging evidences indicate that various inflammatory mediators are involved in the pathophysiology of POCD and inflammatory response may a potential pathogenic factor. The vagus nerve stimulation has been shown to decrease production and release of pro-inflammatory cytokines through the cholinergic anti-inflammatory pathway (CAP) in both animal model and human. Considering that the inflammation plays a definite role in the pathogenesis of POCD and the vagus nerve can mediate inflammation via CAP, we hypothesize that the transcutaneous vagus nerve stimulation may attenuate POCD by decreasing inflammatory response in elderly patients.

This study investigated the impact of transcutaneous auricular vagus nerve stimulation (taVNS) on working memory (WM) in refractory temporal lobe epilepsy (rTLE) and the underlying mechanisms.

There are 9.9 million new cases of dementia in the world every year. Short-term conversion rate from mild cognitive impairment (MCI) to dementia is between 20% and 40%, but long-term in 5-10 years ranges from 60% to 100%. It is particularly important to prevent or prolong the development of MCI into dementia. Both auriculotherapy and vagus nerve stimulation are effective on improving cognitive functions. However, there is no double blinded randomized clinical trial to support the effectiveness of transcutaneous electrical stimulation of auricular acupoints in patients with MCI.This randomized controlled trial involved patients with MCI, aged from 55 to 75 years old. Patients were randomly allocated to transcutaneous auricular vagus nerve stimulation (taVNS) group or sham taVNS group. In the taVNS group, two auricular acupoints were stimulated, including heart (concha, CO) and kidney (CO), which are in the distribution of vagus nerve. While in the sham taVNS group, two other auricular acupoints were stimulated, including elbow (scaphoid fossa, SF) and shoulder (SF), which are out of the distribution of vagus nerve. The primary outcome was the Montreal cognitive assessment-basic, MOCA-B. The secondary outcomes included auditory verbal learning test-HuaShan version (AVLT-H), shape trails test A&B (STT-A&B), animal fluence test (AFT), Boston naming test (BNT), Pittsburgh sleep quality index (PSQI), rapid eye movement sleep behavior disorder screening questionnaire (RBDSQ), Epworth sleepiness scale (ESS) and functional activities questionnaire (FAQ). These outcome measures were taken at baseline, 24 weeks later.After 24 weeks of intervention, the data of 52 patients were intended for analysis. After intervention, there was significant difference in the overall scores of MoCA-B between taVNS group and sham taVNS group (p = 0.033 < 0.05). In taVNS group, compared with before intervention, the overall scores of MOCA-B increased significantly after intervention (p < 0.001). As for N5 and N7, the two sub-indicators of AVLT-H, in taVNS group, compared with before intervention, both N5 and N7 increased significantly after intervention (both ps < 0.001). As for STTB, in taVNS group, compared with before intervention, STTB was significantly reduced after intervention (p = 0.016). For BNT, in taVNS group, compared with before intervention, BNT increased significantly after intervention (p < 0.001). In taVNS group, compared with before intervention, PSQI, RBDSQ, ESS and FAQ decreased significantly after intervention (p = 0.002, 0.025, <0.001, 0.006 respectively). 1 patient with a history of tympanic membrane perforation in taVNS group was reported with mild adverse reactions which disappeared a week after termination of taVNS. The intervention of taVNS is effective on increasing the overall scores of MoCA-B, N5 and N7.The clinical trial demonstrated that taVNS can improve cognitive performance in patients with MCI. This inexpensive, effective and innovative method can be recommended as a therapy for more patients with MCI in the prevention or prolonging of its development into dementia, but it is still required to be further investigated.http://www.chictr.org.cn. (ID: ChiCTR2000038868).Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

The current model of the basal ganglia system based on the 'direct', 'indirect' and 'hyperdirect' pathways provides striking predictions about basal ganglia function that have been used to develop deep brain stimulation approaches for Parkinson's disease and dystonia. The aim of this review is to challenge this scheme in light of new tract tracing information that has recently become available from the human brain using MRI-based tractography, thus providing a novel perspective on the basal ganglia system. We also explore the implications of additional direct pathways running from cortex to basal ganglia and between basal ganglia and cerebellum in the pathophysiology of movement disorders.© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Many suggestions have been made as to the functions of the prefrontal (PF) cortex. However, they involve labelling areas using psychological terminology. But what we need to know is how the PF cortex operates. We argue that understanding this must start with describing the flow of information. We illustrate this argument by considering three PF areas. Each has a unique pattern of inputs and outputs, and we suggest that the implication is that each performs a unique transformation from the inputs to the outputs. The caudal PF cortex transforms input that is maintained by attention or short-term memory into the target of the appropriate eye movement. The mid-dorsal PF cortex transforms input concerning the order of objects or actions into the target of the appropriate eye and hand movements, thus supporting sequences of action. The ventral PF cortex transforms input concerning an object or sound into prospective activity that encodes the associated object or sound. However, it is important to appreciate that the mid-dorsal and ventral PF cortex are specialized for encoding abstract transformations, irrespective of the specific actions or objects. The advantage is that this enables generalization to novel problems that have the same underlying logic. We account for the difference between fast learning and slow learning in this way. The human brain has co-opted these mechanisms so as to support intelligence. Non-verbal tests of IQ typically use sequences of letters, numbers or designs. These test the ability to understand the abstract rules that apply. Here the activations lie in the mid-dorsal PF cortex. Verbal tests typically assess the ability to understand semantic associations. These can be presented either in pictorial or verbal form. Here the activations lie in the ventral PF cortex.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

The basal ganglia play a central role in cognition and are involved in such general functions as action selection and reinforcement learning. Here, we present a model exploring the hypothesis that the basal ganglia implement a conditional information-routing system. The system directs the transmission of cortical signals between pairs of regions by manipulating separately the selection of sources and destinations of information transfers. We suggest that such a mechanism provides an account for several cognitive functions of the basal ganglia. The model also incorporates a possible mechanism by which subsequent transfers of information control the release of dopamine. This signal is used to produce novel stimulus-response associations by internalizing transferred cortical representations in the striatum. We discuss how the model is related to production systems and cognitive architectures. A series of simulations is presented to illustrate how the model can perform simple stimulus-response tasks, develop automatic behaviors, and provide an account of impairments in Parkinson's and Huntington's diseases.PsycINFO Database Record (c) 2010 APA, all rights reserved.

Delineation of functional topography is critical to the evolving understanding of the cerebellum's role in a wide range of nervous system functions. We used data from the Human Connectome Project (n = 787) to analyze cerebellar fMRI task activation (motor, working memory, language, social and emotion processing) and resting-state functional connectivity calculated from cerebral cortical seeds corresponding to the peak Cohen's d of each task contrast. The combination of exceptional statistical power, activation from both motor and multiple non-motor tasks in the same participants, and convergent resting-state networks in the same participants revealed novel aspects of the functional topography of the human cerebellum. Consistent with prior studies there were two distinct representations of motor activation. Newly revealed were three distinct representations each for working memory, language, social, and emotional task processing that were largely separate for these four cognitive and affective domains. In most cases, the task-based activations and the corresponding resting-network correlations were congruent in identifying the two motor representations and the three non-motor representations that were unique to working memory, language, social cognition, and emotion. The definitive localization and characterization of distinct triple representations for cognition and emotion task processing in the cerebellum opens up new basic science questions as to why there are triple representations (what different functions are enabled by the different representations?) and new clinical questions (what are the differing consequences of lesions to the different representations?).Copyright © 2018 Elsevier Inc. All rights reserved.

Emotional information is better remembered than neutral information. Extensive evidence indicates that the amygdala and its interactions with other cerebral regions play an important role in the memory-enhancing effect of emotional arousal. While the cerebellum has been found to be involved in fear conditioning, its role in emotional enhancement of episodic memory is less clear. To address this issue, we used a whole-brain functional MRI approach in 1,418 healthy participants. First, we identified clusters significantly activated during enhanced memory encoding of negative and positive emotional pictures. In addition to the well-known emotional memory–related cerebral regions, we identified a cluster in the cerebellum. We then used dynamic causal modeling and identified several cerebellar connections with increased connection strength corresponding to enhanced emotional memory, including one to a cluster covering the amygdala and hippocampus, and bidirectional connections with a cluster covering the anterior cingulate cortex. The present findings indicate that the cerebellum is an integral part of a network involved in emotional enhancement of episodic memory.

Microglia were first recognized as a distinct cell population in the CNS one century ago. For a long time, they were primarily considered to be phagocytes responsible for removing debris during CNS development and disease. More recently, advances in imaging and genetics and the advent of single-cell technologies provided new insights into the much more complex and fascinating biology of microglia. The ontogeny of microglia was identified, and their functions in health and disease were better defined. Although many questions about microglia and their roles in human diseases remain unanswered, the prospect of targeting microglia for the treatment of neurological and psychiatric disorders is tantalizing.Copyright © 2019 Elsevier Inc. All rights reserved.

Low-grade inflammation is a hallmark of old age and a central driver of ageing-associated impairment and disease1. Multiple factors can contribute to ageing-associated inflammation2; however, the molecular pathways that transduce aberrant inflammatory signalling and their impact in natural ageing remain unclear. Here we show that the cGAS–STING signalling pathway, which mediates immune sensing of DNA3, is a critical driver of chronic inflammation and functional decline during ageing. Blockade of STING suppresses the inflammatory phenotypes of senescent human cells and tissues, attenuates ageing-related inflammation in multiple peripheral organs and the brain in mice, and leads to an improvement in tissue function. Focusing on the ageing brain, we reveal that activation of STING triggers reactive microglial transcriptional states, neurodegeneration and cognitive decline. Cytosolic DNA released from perturbed mitochondria elicits cGAS activity in old microglia, defining a mechanism by which cGAS–STING signalling is engaged in the ageing brain. Single-nucleus RNA-sequencing analysis of microglia and hippocampi of a cGAS gain-of-function mouse model demonstrates that engagement of cGAS in microglia is sufficient to direct ageing-associated transcriptional microglial states leading to bystander cell inflammation, neurotoxicity and impaired memory capacity. Our findings establish the cGAS–STING pathway as a driver of ageing-related inflammation in peripheral organs and the brain, and reveal blockade of cGAS–STING signalling as a potential strategy to halt neurodegenerative processes during old age.

Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. The anti-inflammatory signal of vagus nerve is mediated by α7 nicotinic acetylcholine receptor (α7nAchR), and the hippocampus, the region with the most distribution of α7nAchR, regulates emotions. Here, we investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (−/−) gene knockout and α7nAchR antagonist (methyllycaconitine, MLA).