Contribution of Metabolic Imaging in the Exploration of Cognitive Disorders Related to COVID-19

On March 11, 2019, the WHO declared COVID-19 a pandemic disease. It is a respiratory tropism SARS COV 2 infection. In the emergency of the pandemic, in medical imaging, only computed tomography (CT) of the lungs was favored to assess lung lesions. In addition, many cases of post-COVID-19 cognitive disorders have been reported. As the curve dips and services restart correctly, other imaging techniques have been used to better explore the disease. The objective of this presentation is to illustrate the contribution of metabolic imaging in the exploration of post COVID-19 cognitive disorders and to discuss the pathophysiological mechanisms. Hypometabolism brain lesions are objective signs of functional impairment whose pathophysiological mechanism is not yet fully understood. Metabolic imaging with PET-SCAN is a suitable tool for exploring these disorders, both for the severity and extent of the lesions and for the topography of the brain damage.

Cognitive Disorders, Depression and Anxiety in Temporal Lobe Epilepsy: An Overview

Partial epilepsies, originating in a specific brain region, affect about 60% of adults with epilepsy. Temporal lobe epilepsy (TLE) is the most prevalent subtype within this category, often necessitating surgical intervention due to its refractoriness to antiepileptic drugs (AEDs). Hippocampal sclerosis, a common underlying pathology, often exacerbates the severity by introducing cognitive and emotional challenges. This review delves deeper into the cognitive profile of TLE, along with the risk factors for cognitive disorders, depression, and anxiety in this population.

Description of Post-Stroke Cognitive Disorders at Abidjan University Hospitals, Côte d’Ivoire

Stroke patients often experience motor deficits and cognitive problems after a stroke. Objective: To improve our understanding of the cognitive consequences of stroke. Method: a descriptive and analytical cross-sectional study was conducted over 12-month period in the neurology departments of the Cocody and Treichville Hospitals in Côte d’Ivoire. Results: Out of 724 patients admitted to the neurology department, 415 (57.32%) were stroke patients, of which 145 (34.94%) were screened. The frequency of global cognitive functioning impairment was 86.21%, significantly higher than the frequency of patients without impairment, which was 13.79%. The study focused on detailing the cognitive status of stroke patients in neurology departments, assessing several cognitive functions during the subacute phase of stroke. These functions included global cognitive functioning, executive functions, language and memory. The frequency of post-stroke cognitive impairment is high among stroke patients in Abidjan. This frequency is comparable to figures found in Subsaharian stroke populations. Demographic and clinical characteristics studied included age, gender, education level, employment status, vascular diseases and cerebral affected area. Among these characteristics, only the education level and the cerebral affected area have been found significant. Conclusion: The incidence of cognitive impairment after a stroke is significantly high among stroke patients in Abidjan.

Research progresses of resting-state functional MRI in mild cognitive impairment and Alzheimer's disease

Alzheimer's disease(AD)is a prevalent neurodegenerative disease characterized by cognitive decline in the early stage.Mild cognitive impairment(MCI)is considered as an intermediate stage between normal aging and AD.In recent years,studies related to resting-state functional MRI(rs-fMRI)indicated that the occurrence and development process of MCI and AD might be closely linked to spontaneous brain activity and alterations in functional connectivity among brain regions,and rs-fMRI could provide important reference for specific diagnosis and early treatment of MCI and AD.The research progresses of rs-fMRI for MCI and AD were reviewed in this article.

Latest assessment methods for mitochondrial homeostasis in cognitive diseases

Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).

Mismatch negativity,social cognition,and functional outcomes in patients after traumatic brain injury

Mismatch negativity is generated automatically, and is an early monitoring indicator of neuronal integrity impairment and functional abnormality in patients with brain injury, leading to decline of cognitive function. Antipsychotic medication cannot affect mismatch negativity. The present study aimed to explore the relationships of mismatch negativity with neurocognition, daily life and social functional outcomes in patients after brain injury. Twelve patients with traumatic brain injury and 12 healthy controls were recruited in this study. We examined neurocogni-tion with the Wechsler Adult Intelligence Scale-Revised China, and daily and social functional outcomes with the Activity of Daily Living Scale and Social Disability Screening Schedule, re-spectively. Mismatch negativity was analyzed from electroencephalogram recording. The results showed that mismatch negativity amplitudes decreased in patients with traumatic brain injury compared with healthy controls. Mismatch negativity amplitude was negatively correlated with measurements of neurocognition and positively correlated with functional outcomes in patients after traumatic brain injury. Further, the most signiifcant positive correlations were found be-tween mismatch negativity in the fronto-central region and measures of functional outcomes. The most signiifcant positive correlations were also found between mismatch negativity at the FCz electrode and daily living function. Mismatch negativity amplitudes were extremely positive-ly associated with Social Disability Screening Schedule scores at the Fz electrode in brain injury patients. These experimental ifndings suggest that mismatch negativity might efifciently relfect functional outcomes in patients after traumatic brain injury.

Use of cognitive event-related potentials in the management of psychiatric disorders:Towards an individual follow-up and multicomponent clinical approach

Relapse prevention remains a major challenge in psychiatry,thus indicating that the established treatment methods combining psychotherapy with neuropharmacological interventions are not entirely effective.In recent years,several intervention strategies have been devised that are aimed at improving psychiatric treatment by providing a complementary set of add-on tools that can be used by clinicians to improve current patient assessment.Among these,cognitive eventrelated potentials(ERPs)have been indexed as valuable biomarkers of the pathophysiological mechanisms of various mental illnesses.However,despite decades of research,their clinical utility is still controversial and a matter of debate.In this opinion review,I present the main arguments supporting the use of cognitive ERPs in the management of psychiatric disorders,stressing why it is currently still not the case despite the vast number of ERP studies to date.I also propose a clinically-oriented suitable way in which this technique could—in my opinion—be effectively incorporated into individual patient care by promotion of the use of individual ERP test-retest sessions and the use of a multi-component approach.

Verbal Communication in HIV-1 Patients： A New Perspective on the Study of Cognitive Disorders

The aims were： （1） to study verbal communication skills presenting with verbal communication deficits by applying the MEC in HIV-1 patients, and （2） to analyze the proportion of patients Protocol. The authors evaluated 20 patients over 18 years of age HIV-1 positive; native speakers of Spanish; without alterations in language acquisition, reading, writing or history of neurological or psychiatric disease; patients undergoing antiretroviral treatment （not efavirenz） with viral load 〉 50 copies/mL, and patients not undergoing treatment. Their verbal communication abilities were evaluated with Protocol MEC. The results demonstrate that some of the skills evaluated are more vulnerable in HIV-1 patients. The tasks that showed the most frequent and systematic deficits among patients were discourse-level tasks and those that evaluate lexical semantic processing. The authors compared patients＇ performances with the ＂cut-off＇. The scores were turned into score Z. A hierarchic cluster analysis was carried out to identify subgroups with different profiles according to the areas that were affected. The detection of communication deficit profiles in HIV-1 patients would be the starting point for the identification of disorders and the admission of the patients to health care system. This research constitutes an initial approach towards the identification of clinical profiles among HIV-1 patients.

Relationship of cerebral arterial stenosis to cognitive and memory disorders

BACKGROUND: Cerebral arterial stenosis can cause cerebral hypoperfusion, and than result in the decline of cognitive function, whereas the cognitive dysfunction induced by different cerebral arterial stenosis have different manifestations and types. OBJECTIVE: To observe the differences of cognitive and memory dysfunctions in patients with cerebral arterial stenosis of different types. DESIGN: A comparative observation. SETTING: Affiliated Hospital of Jining Medical College. PARTICIPANTS: Forty-two outpatients or inpatients with cerebral arterial stenosis were selected from the Department of Neurology, Affiliated Hospital of Jining Medical College from February 2005 to January 2006, including 25 males and 17 females. There were 18 cases of internal carotid arterial stenosis, 14 cases of vertebrobasilar arterial stenosis and 10 cases of whole cerebral arterial stenosis. The diagnostic standards for cerebral arterial stenosis were identified according to North American Symptomatic Carotid Endarterectomy Trial (NASCET). Meanwhile, 18 healthy physical examinees were enrolled as the control group, including 10 males and 8 females, aged 58-80 years old. All the enrolled subjects were informed and agreed with the detection and evaluation. METHODS: ① The memory function was evaluated using revised Wechsler memory scale for adults, including long-term memory (experience, orientation and counting), short-term memory (visual recognition, picture memory, visual regeneration, association and thigmesthesia) and sensory memory (forward and backward recitation of numbers). The scale scores were turned to memory quotients. The higher the scores, the better the memory function. ② The cognitive function was evaluated using revised Wechsler adult intelligence scale: It consisted of eleven subtests, including six language scales (information, digit span, vocabulary, arithmetics, apprehension, similarity) and five operation scales (picture completion, picture arrangement, block design, geometric design, digit-symbol test). The intelligence quotients were obtained. The higher the scores, the better the cognitive function. MAIN OUTCOME MEASURES: Results of memory and cognitive function test in patients with cerebral arterial stenosis of different types. RESULTS: All the 42 patients with cerebral artery stenosis and 11 healthy subjects were involved in the final analysis of results. ① Results of memory function test: The memory function was worse in the arterial stensis groups than in the control group (P < 0.05-0.01). There were very significant differences in the scores of orientation, association and picture memory between the internal carotid arterial stenosis group and control group (P < 0.01). There were also very significant differences in the scores of counting, logic memory, forward and backward recitation of numbers, visual regeneration, visual recognition and thigmesthesia between the vertebrobasilar arterial stenosis group and control group (P < 0.01). Except experience and visual regeneration, there were significant very differences in the scores of the other tests between the whole cerebral arterial stenosis group and control group (P < 0.01). The memory quotient was obviously lower in the vertebrobasilar arterial stenosis group than in the internal carotid arterial stenosis group [(72.31±26.46), (87.38±21.86) points, P < 0.05], and it was the lowest in the whole cerebral arterial stenosis group [(63.74±25.25) points]. ② Results of cognitive function test: The cognitive function was worse in the arterial stensis groups than in the control group (P < 0.05-0.01). There were very significant differences in the scores of apprehension, arithmetics, similarity, digit-symbol test, picture completion and block design between the internal carotid arterial stenosis group and control group (P < 0.01). There were also very significant differences in the scores of backward recitation of numbers, vocabulary and geometric design between the vertebrobasilar arterial stenosis group and control group (P < 0.01). Except information, there were significant very differences in the scores of the other tests between the whole cerebral arterial stenosis group and control group (P < 0.01). The intelligence quotient was obviously lower in the internal carotid arterial stenosis group than in the vertebrobasilar arterial stenosis group [(72.65±23.39), (81.34±25.46) points, P < 0.05], and it was the lowest in the whole cerebral arterial stenosis group [(65.98±27.34) points]. CONCLUSION: Different cerebral arterial stenosis can induce different cognitive dysfunctions. The main manifestation of the patients with internal carotid arterial stenosis was the declined cognitive function, and that in patients with vertebrobasilar arterial stenosis was the declined memory, and the decrease of total intelligence was more obvious in the formers than in the latters, whereas the decrease of total memory quotient was more obvious in the patients with vertebrobasilar arterial stenosis; The cognitive and memory dysfunction were the most serious in patients with whole cerebral arterial stenosis.

Evolving Profile and Determinants of Post-Stroke Cognitive Impairment in the 3rd Month among Kinshasa’s Survivors (Democratic Republic of the Congo)

Background: Neurocognitive impairments are common among stroke survivors. Despite their negative impact on daily life, their evolving, and determinants are not fully known in our context. To determine evolving characteristics of post-stroke cognitive impairment in the 3rd month as well as determinants among Kinshasa’s adult survivors is the aim of this study. Methods: We sought to determine neurocognitive deficits in the 3rd month in a prospective single-group cohort study in 3 hospital centers in Kinshasa. Eighty-six adult stroke survivors with a neurological and neuroimaging computerized diagnosis of stroke were assessed using MOCA (Montreal Cognitive Assessment) in the first and the third months post-stroke. Results: Neurocognitive disorders ranged from 79.1% in the first month to 54.7% in the third month after stroke (with 4.7% with severe decline). Gender female [AOR = 86.3 (CI95%: 2.8 - 2643.7);p 0.01], Chronic hypertension ([AOR = 26.8 (CI95%: 2.55 - 282.55);p 0.01]), the pathological lipid profile [AOR = 8.7 (CI95%: 1.10 - 68.82);p = 0.04] and worse MOCA score at the first month ([AOR = 41.2 (CI95%: 8.13 - 2134.81);p = 0.021]) were identified as worse predictors of cognitive impairments at the third month post-stroke. Conclusion: Post-stroke cognitive impairment is common and decreases in the 3rd month post-stroke. Chronic hypertension, gender, lipid profile, and the first month MOCA score are predictors of worse cognitive performance in Kinshasa survivors. These findings suggested the role of early management in improving cognition and the control of stroke risk factors.

Diabetes mellitus and cognitive impairments

There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer&#x02019;s disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings.

The impact of synapsins on synaptic plasticity and cognitive behaviors

Synapsins are a family of phosphoproteins specifically associated with the cytoplasmic surface of the synaptic vesicle membrane, appearing to regulate neurotransmitter release, the formation and maintenance of synaptic contacts. They could induce the change of the synaptic plasticity to regulate various adaptation reactions, and change the cognitive behaviors. So we presume that if some cognitive behavior are damaged, synapsins would be changed as well. This gives us a new recognition of better diagnosis and therapy of cognitive disorder desease.

Shenqi Fuzheng Injection Ameliorates Radiation-induced Brain Injury

Shenqi Fuzheng injection(SFI)has been confirmed to be able to alleviate brain injury in mice.This study examined the brain-protective effect of SFI on patients after cranial radiation.Lung cancer patients with brain metastasis were randomly assigned to two groups.The SFI group received cranial radiation in combination with SFI.The control group received cranial radiation alone.The changes in cognitive function were evaluated pre- and post-radiation against the Mini-Mental State Exam(MMSE),Montreal Cognitive Assessement(MoCA),Zung Self-Rating Depression Scale(SDS)and Zung Self-Rating Anxiety Scale(SAS).The changes in inflammatory factors,such as TGF-β1,TNF-α and IL-10,were also detected before,during and after radiation(15Gy/5F).The results showed that 6 months after cranial radiation,the total scores on the MMSE and MoCA scales of the patients decreased,especially memory ability.The control group experienced a more evident decline,the memory ability being the greatest.TGF-β1 and TNF-α increased shortly after radiation and decreased one month later,and the change was more conspicuous in SFI group than in control group.IL-10 increased after radiation and stayed at a high level one month later in both groups,the level being higher in the SFI group than in the control group.Our study indicated that cognitive functions,especially memory ability,were impaired after cranial radiation.SFI could alleviate radiation-induced brain injury by regulating inflammatory factors.

APOE and APOC1 gene polymorphisms are associated with cognitive impairment progression in Chinese patients with late-onset Alzheimer's disease

Current evidence shows that apolipoprotein E （APOE）, apolipoprotein CI （APOC1） and low density lipoprotein receptor-related protein （LRP） variations are related to late-onset Alzheimer＇s disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer＇s disease patients. We performed a 30-month longitudi- nal cohort study to investigate the relationship between Alzheimer＇s disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer＇s disease were recruit- ed form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess pa- tients＇ cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE 4 carriers compared with non-carriers. In addition, the APOE 4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive im- pairment progression group. In conclusion, APOE e4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ~4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer＇s disease.

Trillium tschonoskii maxim extract attenuates abnormal Tau phosphorylation

Large-scale epidemiological studies have found that hyperhomocysteinemia is a powerful, independent risk factor for Alzheimer＇s disease. Trillium tschonoskii maxim is a traditional Chinese medicine that is used to promote memory. However, scientific understanding of its mechanism of action is limited. This report studied the potential neuroprotective effects of Trillium tschonoskii maxim extract against homocysteine-induced cognitive deficits. Rats were intravenously injected with homocysteine（400 μg/kg） for 14 days to induce a model of Alzheimer＇s disease. These rats were then intragastrically treated with Trillium tschonoskii maxim extract（0.125 or 0.25 g/kg） for 7 consecutive days. Open field test and Morris water maze test were conducted to measure spontaneous activity and learning and memory abilities. Western blot assay was used to detect the levels of Tau protein and other factors involved in Tau phosphorylation in the hippocampus. Immunohistochemical staining was used to examine Tau protein in the hippocampus. Golgi staining was applied to measure hippocampal dendritic spines. Our results demonstrated that homocysteine produced learning and memory deficits and increased levels of Tau phosphorylation, and diminished the activity of catalytic protein phosphatase 2A. The total number of hippocampal dendritic spines was also decreased. Trillium tschonoskii maxim extract treatment reversed the homocysteine-induced changes. The above results suggest that Trillium tschonoskii maxim extract can lessen homocysteine-induced abnormal Tau phosphorylation and improve cognitive deterioration such as that present in Alzheimer＇s disease.

Microbiota shaping — the effects of probiotics, prebiotics, and fecal microbiota transplant on cognitive functions: A systematic review

BACKGROUND Dementia is a chronic progressive neurological disease affecting millions of people worldwide,and represents a relevant economic burden for healthcare systems.Although its pathogenesis is still unknown,recent findings have reported that a dysregulated gut-brain axis communication,a fundamental relationship mediated by several host and microbial molecules,is associated with cognitive disorders.In addition,gut microbiota manipulation reduces neuroinflammation,improving cognitive function by restoring the functional gut-brain axis.AIM To better define the effects of probiotics,prebiotics,synbiotics,and fecal microbiota transplant(FMT)on cognitive function.METHODS We performed a literature search of human randomized clinical trials to examine the effects of the administration of probiotics,prebiotics,synbiotics,or FMT on cognition outcomes in healthy or sick people of every age,sex,and nationality.We systematically searched Embase,Medline/PubMed,Cochrane Library,central and clinicaltrials.gov databases with a combination of comprehensive terms related to cognition and gut microbiota manipulation.Then we carefully reviewed and synthesized the data by type of study design and setting,characteristics of the studied population,kind of intervention(strain type or mixture type,dosage,and frequency of administration),control treatment,inclusion and exclusion criteria,follow-up duration,and cognitive or memory outcomes.RESULTS After examining the titles and abstracts,the initial literature screening identified 995 articles,but we added 23 papers in our systematic review.The analyses of these selected studies highlighted that both probiotic supplementation and FMT improved cognitive function regardless of the type and posology of administration and the adopted cognitive tests and questionnaires.We found that most of the studies conducted in healthy people showed a significant positive effect of the intervention on at least one of the performed cognitive tests.Regarding unhealthy subjects,while FMT and especially probiotic administration had multiple beneficial effects on different cognitive functions,supplementation with prebiotics did not provide any cognitive improvement.CONCLUSION Probiotic supplementation and FMT may represent a promising strategy to restore gut eubiosis and enhance the cognitive functions of healthy people and patients with neurological disorders.

Abnormal activation of the occipital lobes during emotion picture processing in major depressive disorder patients

A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for cognitive disorder in depressed patients.

The synthetic thyroid hormone, levothyroxine, protects cholinergic neurons in the hippocampus of naturally aged mice

The thyroid hormones, triiodothyronine and thyroxine, play important roles in cognitive func- tion during the mammalian lifespan. However, thyroid hormones have not yet been used as a therapeutic agent for normal age-related cognitive deficits. In this study, CD-1 mice （aged 24 months） were intraperitoneally injected with levothyroxine （L-T4; 1.6 gg/kg per day） for 3 consecutive months. Our findings revealed a significant improvement in hippocampal cyto- skeletal rearrangement of actin and an increase in serum hormone levels of L-T4-treated aged mice. Furthermore, the survival rate of these mice was dramatically increased from 60% to 93.3%. The Morris water maze task indicated that L-T4 restored impaired spatial memory in aged mice. Furthermore, level of choline acetyltransferase, acetylcholine, and superoxide dismutase were in- creased in these mice, thus suggesting that a possible mechanism by which L-T4 reversed cognitive impairment was caused by increased activity of these markers. Overall, supplement of low-dosage L-T4 may be a potential therapeutic strategy for normal age-related cognitive deficits.

Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagonlike peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease

Alzheimer’s disease(AD)is the most common reason for progressive dementia in the elderly.It has been shown that disorders of the mammalian/mechanistic target of rapamycin(mTOR)signaling pathways are related to the AD.On the other hand,diabetes mellitus(DM)is a risk factor for the cognitive dysfunction.The pathogenesis of the neuronal impairment caused by diabetic hyperglycemia is intricate,which contains neuro-inflammation and/or neurodegeneration and dementia.Glucagon-like peptide-1(GLP1)is interesting as a possible link between metabolism and brain impairment.Modulation of GLP1 activity can influence amyloid-beta peptide aggregation via the phosphoinositide-3 kinase/AKT/mTOR signaling pathway in AD.The GLP1 receptor agonists have been shown to have favorable actions on the brain such as the improvement of neurological deficit.They might also exert a beneficial effect with refining learning and memory on the cognitive impairment induced by diabetes.Recent experimental and clinical evidence indicates that dipeptidyl-peptidase-4(DPP4)inhibitors,being currently used for DM therapy,may also be effective for AD treatment.The DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models.Although further studies for mTOR,GLP1,and DPP4 signaling pathways in humans would be intensively required,they seem to be a promising approach for innovative AD-treatments.We would like to review the characteristics of AD pathogenesis,the key roles of mTOR in AD and the preventive and/or therapeutic suggestions of directing the mTOR signaling pathway.

Age-related connectivity differences between attention deficit and hyperactivity disorder patients and typically developing subjects：a resting-state functional MRI study

Attention deficit and hyperactivity disorder（ADHD） is a disorder characterized by behavioral symptoms including hyperactivity/impulsivity among children,adolescents,and adults.These ADHD related symptoms are influenced by the complex interaction of brain networks which were under explored.We explored age-related brain network differences between ADHD patients and typically developing（TD） subjects using resting state f MRI（rs-f MRI） for three age groups of children,adolescents,and adults.We collected rs-f MRI data from 184 individuals（27 ADHD children and 31 TD children;32 ADHD adolescents and 32 TD adolescents;and 31 ADHD adults and 31 TD adults）.The Brainnetome Atlas was used to define nodes in the network analysis.We compared three age groups of ADHD and TD subjects to identify the distinct regions that could explain age-related brain network differences based on degree centrality,a well-known measure of nodal centrality.The left middle temporal gyrus showed significant interaction effects between disease status（i.e.,ADHD or TD） and age（i.e.,child,adolescent,or adult）（P 0.001）.Additional regions were identified at a relaxed threshold（P 0.05）.Many of the identified regions（the left inferior frontal gyrus,the left middle temporal gyrus,and the left insular gyrus） were related to cognitive function.The results of our study suggest that aberrant development in cognitive brain regions might be associated with age-related brain network changes in ADHD patients.These findings contribute to better understand how brain function influences the symptoms of ADHD.