Neuropsychiatric diseases, including ADHD, schizophrenia, and bipolar disorder, are increasingly prevalent but poorly understood at the molecular level. The complexities of diagnosing and treating these disorders emph...Neuropsychiatric diseases, including ADHD, schizophrenia, and bipolar disorder, are increasingly prevalent but poorly understood at the molecular level. The complexities of diagnosing and treating these disorders emphasize the need for objective, quantitative data to improve diagnostic accuracy and treatment efficacy. This study aims to explore the genetic underpinnings of neuropsychiatric diseases, contrasting them with well-characterized diseases like breast cancer, and discuss the role of specific genetic mutations and their implications for personalized treatment. The paper delves into the genetic and molecular insights of neuropsychiatric diseases, examining the role of specific genetic mutations and the potential for gene editing technologies like CRISPR. It contrasts the genetic underpinnings of neuropsychiatric diseases with well-characterized diseases like breast cancer, highlighting the potential for a shift towards molecular and genetic-based diagnostics and treatments. The study argues that a shift towards molecular and genetic-based diagnostics and treatments could revolutionize our approach to neuropsychiatric diseases, much like how biomarker tests have transformed breast cancer treatment. It concludes by advocating for a more personalized approach to healthcare, tailored to an individual’s unique genetic makeup, as the future of neuropsychiatric disease diagnosis and treatment.展开更多
Although primarily affecting the respiratory system,growing attention is being paid to the neuropsychiatric consequences of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections.Acute and sub-acute neu...Although primarily affecting the respiratory system,growing attention is being paid to the neuropsychiatric consequences of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections.Acute and sub-acute neuropsychiatric manifestations of coronavirus disease 2019(COVID-19)disease and their mechanisms are better studied and understood currently than they had been when the pandemic began;however,many months or years will be necessary to fully comprehend how significant the consequences of such complications will be.In this editorial,we discuss the possible long-term sequelae of the COVID-19 pandemic,deriving our considerations on experiences drawn from past coronaviruses’outbreaks,such as the SARS and the middle east respiratory syndrome,and from the knowledge of the mechanisms of neurotropism and invasiveness of SARS-CoV-2.Acknowledging the global spread of COVID-19 and the vast number of people affected,to date amounting to many millions,the matter of this pandemic’s neuropsychiatric legacy appears concerning.Public health monitoring strategies and early interventions seem to be necessary to manage the possible emergence of a severe wave of neuropsychiatric distress among the survivors.展开更多
Although little is known about the current situation regarding autism spectrum disorder(ASD)in main land China,psychiatric disorders are common among Chinese mothers of preschool children with ASD.Previous studies sho...Although little is known about the current situation regarding autism spectrum disorder(ASD)in main land China,psychiatric disorders are common among Chinese mothers of preschool children with ASD.Previous studies showed ASD child's behavioral symptoms,maternal anxiety,and maternal depressive symptoms were associated with overall parenting stress in northern China.In the present study,we retrospectively analyzed medical records at the hospital related to neuropsychiatric symptoms,parenting stress and social support in mothers of children with ASD from southern China.A total of 80 mothers of children with ASD were screened.Among them,34 mothers were in low-functioning ASD group(L-ASD group)and 46 mothers were in highfunctioning ASD group(H-ASD group).Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory.Neuropsychiatric symptoms,parenting stress and social support were measured by neuropsychiatric inventory(NPI),parenting stress index short form(PSISF),and multi-dimensional scale of perceived social support(MSPSS).Total mean score of the NPI in the L-ASD group was significantly higher than that in the H-ASD group(P<0.01).The subscale scores of NPI,including depression,anxiety,apathy,irritability,agitation,night time behavior disturbances and change in appetite were significantly higher in the L-ASD group than those in the H-ASD group(P<0.01 or P<0.05).Meanwhile,the total PSI-SF scores and the scores of parental distress(PD),parental-child dysfunctional interaction(PCDI)and difficult child(DC)in the L-ASD group were significantly higher than those in the H-ASD group(P<0.01 or P<0.05).The total score of MSPSS was also higher in the L-ASD group than in the H-ASD group(P<0.01).This study goes further to show the neuropsychiatric symptoms and parenting stress are significantly higher in mothers of children with ASD,and more social supports are needed for mothers of children with ASD from southern China,especially for mothers of children with low-functioning ASD.展开更多
Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly prod...Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS)in the brain.Inhibiting nNOS benefits a variety of neurological and neuropsychiatric disorders,including stroke,depression and anxiety disorders,posttraumatic stress disorder,Parkinson’s disease,Alzheimer’s disease,chronic pain,and drug addiction.Due to critical roles of nNOS in learning and memory and synaptic plasticity,direct inhibition of nNOS may cause severe side effects.Importantly,interactions of several proteins,including post-synaptic density 95(PSD-95),carboxyterminal PDZ ligand of nNOS(CAPON)and serotonin transporter(SERT),with the PSD/Disc-large/ZO-1 homologous(PDZ)domain of nNOS have been demonstrated to influence the subcellular distribution and activity of the enzyme in the brain.Therefore,it will be a preferable means to interfere with nNOS-mediated proteinprotein interactions(PPIs),which do not lead to undesirable effects.Herein,we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders,and the discovery of drugs targeting the PPIs,which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.展开更多
Nenropsychiatric symptoms are common in patients with Parkinson's disease(PD)and they are likely to outweigh the motor symptoms and become a major factor affecting the quality of life of PD patients.However,the st...Nenropsychiatric symptoms are common in patients with Parkinson's disease(PD)and they are likely to outweigh the motor symptoms and become a major factor affecting the quality of life of PD patients.However,the studies focusing on the non-motor symptoms in Chinese PD patients from different ethnicity are scarce.The aim of this retrospective study was to investigate neuropsychiatric symptoms and cognitive impairment in Chinese PD patients from Han and Hui populations from central China.Seventy-two Han Chinese PD patients(Han PD group)and 71 age-and sex-matched Hui Chinese PD patients(Hui PD group)were enrolled from Zhongnan Hospital of Wuhan University between Sept.2011 and Aug.2014 in the study.The neuropsychiatric symptoms and cognitive impairment were assessed using Neuropsychiatric Inventory(NPI)and Mini Mental State Examination(MMSE).We found that the proportion of depression,anxiety,apathy,irritability,euphoria and night time behavior disturbances were higher in the Han PD group than in the Hui PD group(P<0.05 or P<0.01).But the proportion of delusion,hallucination,agitation,disinhibition,aberrant motor behavior and change in appetite were not significantly different between the Han PD group and the Hui PD group(P>0.05).The total mean scores of the MMSE from patients in the Han PD group were similar to those in the Hui PD group(P>0.05).However,the subscale scores of recall domain and language domain in the Han PD group were significantly different from those in the Hui PD group(P<0.05).No significant difference was noted in the orientation,memory and calculation domains between the two PD groups(P>0.05).This study first showed the recall domain and language domain were different between the Han PD patients and the Hui PD patients.Depression,anxiety,apathy,irritability,euphoria and night time behavior disturbances were less presented in the Hui PD patients.All these differences may be related to the different ethnicity,which would be helpful for clinical physicians to recognize the different non-motor symptoms in Chinese PD patients with different ethnicity.展开更多
A spectrum of neuropsychiatric disorders is a common complication from stroke.Neuropsychiatric disorders after stroke have negative effects on functional recovery,increasing the rate of mortality and disability of str...A spectrum of neuropsychiatric disorders is a common complication from stroke.Neuropsychiatric disorders after stroke have negative effects on functional recovery,increasing the rate of mortality and disability of stroke survivors.Given the vital significance of maintaining physical and mental health in stroke patients,neuropsychiatric issues after stroke have raised concerns by clinicians and researchers.This mini-review focuses on the most common non-cognitive functional neuropsychiatric disorders seen after stroke,including depressive disorders,anxiety disorders,post-traumatic stress disorder,psychosis,and psychotic disorders.For each condition,the clinical performance,epidemiology,identification of the therapeutic implication,and strategies are reviewed and discussed;the main opinions and perspectives presented here are based on the latest controlled studies,meta-analysis,or updated systematic reviews.In the absence of data from controlled studies,consensus recommendations were provided accordingly.展开更多
Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019(COVID-19)from early disease onset.The most frequent symptoms and signs are fatigue,d...Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019(COVID-19)from early disease onset.The most frequent symptoms and signs are fatigue,dizziness,impaired consciousness,ageusia,anosmia,radicular pain,and headache,as well as others.Based on the high number of series of cases reported,there is evidence for the implication of the immune system in the pathological mechanism of COVID-19.Although the exact role of the immunological mechanism is not elucidated,two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and neuroinflammation.In the context of neurological manifestations associated with COVID-19,neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression,anxiety,mood alterations,psychosis,post-traumatic stress disorder,delirium,and cognitive impairment,which appear to be common in COVID-19 survivors.A worsened score on psychopathological measures is seen in those with a history of psychiatric comorbidities.We review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19.展开更多
We have read with interest the Letter to the Editor by Drs.Zhuang and Zhong,who presented the clinical data of 68 patients with Wilson’s disease(WD)who were admitted to the hospital before and during the coronavirus ...We have read with interest the Letter to the Editor by Drs.Zhuang and Zhong,who presented the clinical data of 68 patients with Wilson’s disease(WD)who were admitted to the hospital before and during the coronavirus disease 2019(COVID-19)pandemic,and appreciated their findings on hepatic and some extrahepatic manifestations.Nevertheless,given the strong impact of the pandemic on patients with neurological and psychiatric disorders,we would have expected a worsening of the psychiatric and/or neurological impairments in these patients.In contrast,according to the authors,these manifestations remained,somewhat unexpectedly,unchanged.This finding is in contrast with most of the current literature that highlights not only an increased incidence of mental health disorders in the general population but also an exacerbation of neurological and psychiatric symptoms in patients with chronic diseases,especially in those with pre-existing neuropsychiatric disorders,such as WD.Although the study was mainly focused on the hepatic features of WD patients taking anti-copper treatment,a generic and cumulative definition of neurological and psychiatric manifestations,as in this study,does not allow for further considerations.Future studies during and after the pandemic are necessary to clarify the real impact,either direct or indirect,of the COVID-19 pandemic on the neurological and psychiatric symptoms of WD patients.展开更多
BACKGROUND Neuropsychiatric symptoms(NPS)have been insufficiently examined in persons with aphasia(PWA)because most previous studies exclude participants with language and communication disorders.AIM To report a two-p...BACKGROUND Neuropsychiatric symptoms(NPS)have been insufficiently examined in persons with aphasia(PWA)because most previous studies exclude participants with language and communication disorders.AIM To report a two-part study consisting of a literature review and an observational study on NPS in post-stroke aphasia.METHODS Study 1 reviewed articles obtained from PubMed,PsycINFO,Google Scholar and Cochrane databases after cross-referencing key words of post-stroke aphasia to NPS and disorders.Study 2 examined language deficits and activities of daily living in 20 PWA(median age:58,range:28-65 years;13 men)with the Western Aphasia Battery-Revised and the Barthel Index,respectively.Informants of these 20 PWA were proxy-evaluated with the Neuropsychiatric Inventory and domain-specific scales,including the Stroke Aphasia Depression Questionnaire-10 item version and the Starkstein Apathy Scale.In addition,an adapted version of the Hospital Anxiety and Depression Scale was directly administered to the PWA themselves.This observational study is based on the baseline assessment of an intervention clinical trial(EudraCT:2017-002858-36;ClinicalTrials.gov identifier:NCT04134416).RESULTS The literature review revealed a broad spectrum of NPS in PWA,including depression,anxiety,apathy,agitation/aggression,eating and sleep disorders,psychosis,and hypomania/mania.These findings alert to the need for improving assessment and treatment approaches of NPS taking into consideration their frequent occurrence in PWA.Study 2 showed that the 20 participants had mild-to-moderate aphasia severity and were functionally independent.A wide range of comorbid NPS was found in the post-stroke aphasic population(median number of NPS:5,range:1-8).The majority of PWA(75%)had depressive symptoms,followed by agitation/aggression(70%),irritability(70%),anxiety(65%)and appetite/eating symptoms(65%).Half of them also presented symptoms of apathy,whereas euphoria and psychotic symptoms were rare(5%).Domain-specific scales revealed that 45%of participants had apathy and 30%were diagnosed with depression and anxiety.CONCLUSION Concurrent NPS are frequent in the chronic period of post-stroke aphasia.Therefore,further research on reliable and valid assessment tools and treatment for this aphasic population is strongly warranted.展开更多
Observational studies based on electronic health records (EHR) report anincreased risk of neurological/neuropsychiatric sequelae for patients who havehad coronavirus disease 2019 (COVID-19). However, these studies may...Observational studies based on electronic health records (EHR) report anincreased risk of neurological/neuropsychiatric sequelae for patients who havehad coronavirus disease 2019 (COVID-19). However, these studies may sufferfrom biases such as unmeasured confounding, residual reverse causality, or lackof precision in EHR-based diagnoses. To rule out these biases, we tested causallinks between COVID-19 and different potential neurological/neuropsychiatricsequelae through a two-sample Mendelian randomization analysis of summarystatistics from large Genome-Wide Association Scans of susceptibility to COVID-19 and different neurological and neuropsychiatric disorders, including majordepression, anxiety, schizophrenia, stroke, Parkinson’s and Alzheimer’s diseases.We found robust evidence suggesting that COVID-19 – notably the hospitalizedand most severe forms – carries an increased risk of neuropsychiatric sequelae,particularly Alzheimer’s disease, and to a lesser extent anxiety disorder. In linewith a large longitudinal EHR-based study, this evidence was stronger for moresevere COVID-19 forms. These results call for a targeted screening strategy totackle the post-COVID neuropsychiatric pandemic.展开更多
The pathogenesis of neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE) is multifactorial and can involve various inflammatory cytokines, autoantibodies such as anti-neuronal antibodies, anti-ribosomal ...The pathogenesis of neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE) is multifactorial and can involve various inflammatory cytokines, autoantibodies such as anti-neuronal antibodies, anti-ribosomal P antibodies, anti-NR2 glutamate receptor binding antibodies, anti-Sm antibodies, anti-U1-RNP antibodies and anti-phospholipid antibodies, and immune complexes (IC). Disruption of the blood-brain barrier (BBB) is integral to the neuropathology of SLE. Recently the possibility has been reported that aforementioned autoantibodies in the circulation may be strongly associated with disruption of the BBB. Each of these mechanisms might contribute to the pathogenesis of focal NPSLE (for example, cerebrovascular disease, movement disorders, myelopathy, seizures and cranial neuropathy) or diffuse NPSLE (for example, acute confusional state, psychosis and cognitive dysfunction) to varying degrees. In this review we focus on how the aforementioned autoantibodies, the BBB, IC and cytokines as well as chemokines are associated with the appearance of NPSLE.展开更多
The purpose of this review is to evaluate the role of chronic anemia on neuropsychiatric symptoms and conditions among the elderly. Anemia is defined as hemoglobin levels below 120 and 130 g/L for women and men, respe...The purpose of this review is to evaluate the role of chronic anemia on neuropsychiatric symptoms and conditions among the elderly. Anemia is defined as hemoglobin levels below 120 and 130 g/L for women and men, respectively. Anemia is not a consequence of the aging process. It is common in the elderly and easily overlooked. Nevertheless, chronic anemia is a risk factor associated with increased mortality, several geriatric syndromes including functional and cognitive impairments. Investigations have shown that anemic elderly and those with hemoglobin borderline levels may present higher proportion of neuropsychiatric impairment, such as Executive Function Disorder and Alzheimer disease. The association between anemia and depression is well established, but its causal pathway is not known: anemia can be regarded as cause or consequence of depression. There is evidence that dementia due to anemia can be prevented;renal chronic anemic patients who received erythropoietin (EPO) replacement therapy showed a lower risk for dementia, compared to those who did not receive it. Anemia may be associated with chronic psychiatric diseases such as bipolar disorders and cause their symptoms to become more severe.展开更多
Neuropsychiatric systemic lupus erythematosus (NP-SLE) is one of the major cause of morbidity in systemic lupus erythematosus patients and its treatment depends on identification of pathogenic mechanisms. We describe ...Neuropsychiatric systemic lupus erythematosus (NP-SLE) is one of the major cause of morbidity in systemic lupus erythematosus patients and its treatment depends on identification of pathogenic mechanisms. We describe the rare case of neuropsychiatric systemic lupus erythematosus (NP-SLE) complicated by pericardial effusion combined to low C4 level persisting and hyperprolactinaemia. A cyclophosphamide therapy showed a good response in a 21-year old woman with disturbances in thought processes and an acute confusional state with sierositis. This paper confirms that a cyclophosphamide therapy contributes to control a disease activity by a mechanism of prolactin level reduction. Other studies occur to evaluate this hypothesis.展开更多
Dementia is increasing dramatically with an increasing elderly population.Pharmacological interventions are proven to have limited efficacy to treat many of the features of dementia.In such a situation,non-pharmacolog...Dementia is increasing dramatically with an increasing elderly population.Pharmacological interventions are proven to have limited efficacy to treat many of the features of dementia.In such a situation,non-pharmacological means become important to help people with dementia,especially music therapy.The efficacy of music intervention on cognition has been barely explored in the literature,and the few studies that are available present inconsistent results.The aim of this systematic review is to have a meta-analysis on the effect of music therapy for improvements in cognitive functions as well as neuropsychiatric symptoms in the elderly with dementia.展开更多
1 Introduction Neuropsychiatric systemic lupus erythematosus(NPSLE)is a serious complication of systemic lupus erythematosus(SLE),with an incidence of about 30%to 40%[1].No matter early or late SLE patients are prone ...1 Introduction Neuropsychiatric systemic lupus erythematosus(NPSLE)is a serious complication of systemic lupus erythematosus(SLE),with an incidence of about 30%to 40%[1].No matter early or late SLE patients are prone to concurrent,so early diagnosis and treatment of NPSLE is extremely important.展开更多
In the central nervous system,nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS).In the past 20 years,the studies i...In the central nervous system,nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS).In the past 20 years,the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders.In particular,the interactions between the PDZ domain of nNOS and its adaptor proteins,including post-synaptic density 95,the carboxy-terminal PDZ ligand of nNOS,and the serotonin transporter,significantly influence the subcellular localization and functions of nNOS in the brain.The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders.Here,we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders.展开更多
Introduction:Agents that can be used for the treatment of neuropsychiatric lupus(NPSLE)are lacking in the therapeutic armamentarium.Belimumab is a monoclonal antibody targeting the B-cell activating factor(BAFF)and is...Introduction:Agents that can be used for the treatment of neuropsychiatric lupus(NPSLE)are lacking in the therapeutic armamentarium.Belimumab is a monoclonal antibody targeting the B-cell activating factor(BAFF)and is approved by the US Food and Drug Administration as an additional treatment for systemic lupus erythematosus patients with persistent disease activity and lupus nephritis(LN);however,severe active central nervous system manifestations were excluded.Case Report:We report on a treatment-naïve LN patient with refractory NPSLE complicated with progressive posterior reversible encephalopathy syndrome(PRES)who was successfully treated via the combination of mycophenolate and belimumab,resulting in reversal of persistent headache and neuroradiologic manifestations.Conclusion:Research on this topic could be relevant for identifying a possible correlation between BAFF and psychiatric NPSLE manifestations.展开更多
The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully unders...The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological process and its prognosis.Also,the effects of anti-amyloid-beta drugs,recently approved for the treatment of Alzheimer's disease,could be influenced by the APOE genotype.展开更多
Neuropsychiatric disorders are complex disorders characterized by heterogeneous genetic variations,variable symptoms,and widespread changes in anatomical pathology.In the context of neuropsychiatric disorders,limited ...Neuropsychiatric disorders are complex disorders characterized by heterogeneous genetic variations,variable symptoms,and widespread changes in anatomical pathology.In the context of neuropsychiatric disorders,limited access to relevant tissue types presents challenges for understanding disease etiology and developing effective treatments.Induced pluripotent stem cells(iPSCs)reprogrammed from patient somatic cells offer an opportunity to recapitulate disease development in relevant cell types,and they provide novel approaches for understanding disease mechanisms and for development of effective treatments.Here we review recent progress and challenges in differentiation paradigms for generating disease-relevant cells and recent studies of neuropsychiatric disorders using human pluripotent stem cell(hPSC)models where cellular phenotypes linked to disease have been reported.The use of iPSC-based disease models holds great promise for understanding disease mechanisms and supporting discovery of effective treatments.展开更多
The development of in vivo biomarkers of Alzheimer's disease(AD)has advanced the diagnosis of AD from a clinical syndrome to a biological construct.The preclinical stage of AD continuum is defined by the identific...The development of in vivo biomarkers of Alzheimer's disease(AD)has advanced the diagnosis of AD from a clinical syndrome to a biological construct.The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals.While neuropsychiatric symptoms(NPS)are non-cognitive symptoms that are increasingly recognized as early manifestations of AD,the associations of NPS with AD pathophysiology in preclinical AD remain unclear.Here,we review the associations between NPS and AD biomarkers amyloid-(3(Aβ),tau and neurodegeneration in preclinical AD and cognitivelyunimpaired individuals in 19 eligible English-language publications(8 cross-sectional studies,10 longitudinal,1 both cross-sectional and longitudinal).The cross-sectional studies have consistently shown that NPS,particularly depressive and anxiety symptoms,are associated with higher Aβ.The longitudinal studies have suggested that greater NPS are associated with higher Aβ and cognitive decline in cognitively unimpaired subjects over time.However,most of the studies have either cross-sectionally or longitudinally shown no association between NPS and tau pathology.For the association of NPS and neurodegeneration,two studies have shown that the cerebrospinal fluid total-tau is linked to longitudinal increase in NPS and that the NPS may predict longitudinal metabolic decline in preclinical AD,respectively.However,evidence for the association between atrophy and NPS in preclinical AD is less consistent.Therefore,future longitudinal studies with well-designed methodologies and NPS measurements are required not only to determine the relationship among AT(N)biomarkers,NPS and cognitive decline,but also to elucidate the contribution of comorbid pathology to preclinical AD.展开更多
文摘Neuropsychiatric diseases, including ADHD, schizophrenia, and bipolar disorder, are increasingly prevalent but poorly understood at the molecular level. The complexities of diagnosing and treating these disorders emphasize the need for objective, quantitative data to improve diagnostic accuracy and treatment efficacy. This study aims to explore the genetic underpinnings of neuropsychiatric diseases, contrasting them with well-characterized diseases like breast cancer, and discuss the role of specific genetic mutations and their implications for personalized treatment. The paper delves into the genetic and molecular insights of neuropsychiatric diseases, examining the role of specific genetic mutations and the potential for gene editing technologies like CRISPR. It contrasts the genetic underpinnings of neuropsychiatric diseases with well-characterized diseases like breast cancer, highlighting the potential for a shift towards molecular and genetic-based diagnostics and treatments. The study argues that a shift towards molecular and genetic-based diagnostics and treatments could revolutionize our approach to neuropsychiatric diseases, much like how biomarker tests have transformed breast cancer treatment. It concludes by advocating for a more personalized approach to healthcare, tailored to an individual’s unique genetic makeup, as the future of neuropsychiatric disease diagnosis and treatment.
文摘Although primarily affecting the respiratory system,growing attention is being paid to the neuropsychiatric consequences of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections.Acute and sub-acute neuropsychiatric manifestations of coronavirus disease 2019(COVID-19)disease and their mechanisms are better studied and understood currently than they had been when the pandemic began;however,many months or years will be necessary to fully comprehend how significant the consequences of such complications will be.In this editorial,we discuss the possible long-term sequelae of the COVID-19 pandemic,deriving our considerations on experiences drawn from past coronaviruses’outbreaks,such as the SARS and the middle east respiratory syndrome,and from the knowledge of the mechanisms of neurotropism and invasiveness of SARS-CoV-2.Acknowledging the global spread of COVID-19 and the vast number of people affected,to date amounting to many millions,the matter of this pandemic’s neuropsychiatric legacy appears concerning.Public health monitoring strategies and early interventions seem to be necessary to manage the possible emergence of a severe wave of neuropsychiatric distress among the survivors.
文摘Although little is known about the current situation regarding autism spectrum disorder(ASD)in main land China,psychiatric disorders are common among Chinese mothers of preschool children with ASD.Previous studies showed ASD child's behavioral symptoms,maternal anxiety,and maternal depressive symptoms were associated with overall parenting stress in northern China.In the present study,we retrospectively analyzed medical records at the hospital related to neuropsychiatric symptoms,parenting stress and social support in mothers of children with ASD from southern China.A total of 80 mothers of children with ASD were screened.Among them,34 mothers were in low-functioning ASD group(L-ASD group)and 46 mothers were in highfunctioning ASD group(H-ASD group).Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory.Neuropsychiatric symptoms,parenting stress and social support were measured by neuropsychiatric inventory(NPI),parenting stress index short form(PSISF),and multi-dimensional scale of perceived social support(MSPSS).Total mean score of the NPI in the L-ASD group was significantly higher than that in the H-ASD group(P<0.01).The subscale scores of NPI,including depression,anxiety,apathy,irritability,agitation,night time behavior disturbances and change in appetite were significantly higher in the L-ASD group than those in the H-ASD group(P<0.01 or P<0.05).Meanwhile,the total PSI-SF scores and the scores of parental distress(PD),parental-child dysfunctional interaction(PCDI)and difficult child(DC)in the L-ASD group were significantly higher than those in the H-ASD group(P<0.01 or P<0.05).The total score of MSPSS was also higher in the L-ASD group than in the H-ASD group(P<0.01).This study goes further to show the neuropsychiatric symptoms and parenting stress are significantly higher in mothers of children with ASD,and more social supports are needed for mothers of children with ASD from southern China,especially for mothers of children with low-functioning ASD.
基金supported by grants from National Natural Science Foundation of China (82090042, 31530091,81870912)National Key Research and Development Program of China (2016YFC1306703)。
文摘Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS)in the brain.Inhibiting nNOS benefits a variety of neurological and neuropsychiatric disorders,including stroke,depression and anxiety disorders,posttraumatic stress disorder,Parkinson’s disease,Alzheimer’s disease,chronic pain,and drug addiction.Due to critical roles of nNOS in learning and memory and synaptic plasticity,direct inhibition of nNOS may cause severe side effects.Importantly,interactions of several proteins,including post-synaptic density 95(PSD-95),carboxyterminal PDZ ligand of nNOS(CAPON)and serotonin transporter(SERT),with the PSD/Disc-large/ZO-1 homologous(PDZ)domain of nNOS have been demonstrated to influence the subcellular distribution and activity of the enzyme in the brain.Therefore,it will be a preferable means to interfere with nNOS-mediated proteinprotein interactions(PPIs),which do not lead to undesirable effects.Herein,we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders,and the discovery of drugs targeting the PPIs,which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.
文摘Nenropsychiatric symptoms are common in patients with Parkinson's disease(PD)and they are likely to outweigh the motor symptoms and become a major factor affecting the quality of life of PD patients.However,the studies focusing on the non-motor symptoms in Chinese PD patients from different ethnicity are scarce.The aim of this retrospective study was to investigate neuropsychiatric symptoms and cognitive impairment in Chinese PD patients from Han and Hui populations from central China.Seventy-two Han Chinese PD patients(Han PD group)and 71 age-and sex-matched Hui Chinese PD patients(Hui PD group)were enrolled from Zhongnan Hospital of Wuhan University between Sept.2011 and Aug.2014 in the study.The neuropsychiatric symptoms and cognitive impairment were assessed using Neuropsychiatric Inventory(NPI)and Mini Mental State Examination(MMSE).We found that the proportion of depression,anxiety,apathy,irritability,euphoria and night time behavior disturbances were higher in the Han PD group than in the Hui PD group(P<0.05 or P<0.01).But the proportion of delusion,hallucination,agitation,disinhibition,aberrant motor behavior and change in appetite were not significantly different between the Han PD group and the Hui PD group(P>0.05).The total mean scores of the MMSE from patients in the Han PD group were similar to those in the Hui PD group(P>0.05).However,the subscale scores of recall domain and language domain in the Han PD group were significantly different from those in the Hui PD group(P<0.05).No significant difference was noted in the orientation,memory and calculation domains between the two PD groups(P>0.05).This study first showed the recall domain and language domain were different between the Han PD patients and the Hui PD patients.Depression,anxiety,apathy,irritability,euphoria and night time behavior disturbances were less presented in the Hui PD patients.All these differences may be related to the different ethnicity,which would be helpful for clinical physicians to recognize the different non-motor symptoms in Chinese PD patients with different ethnicity.
基金National Natural Science Foundation of China,No.81801712,No.81801710,No.81771271the Science and Technology Project Funds from Education Department of Liaoning Province of China,No.LK2016022.
文摘A spectrum of neuropsychiatric disorders is a common complication from stroke.Neuropsychiatric disorders after stroke have negative effects on functional recovery,increasing the rate of mortality and disability of stroke survivors.Given the vital significance of maintaining physical and mental health in stroke patients,neuropsychiatric issues after stroke have raised concerns by clinicians and researchers.This mini-review focuses on the most common non-cognitive functional neuropsychiatric disorders seen after stroke,including depressive disorders,anxiety disorders,post-traumatic stress disorder,psychosis,and psychotic disorders.For each condition,the clinical performance,epidemiology,identification of the therapeutic implication,and strategies are reviewed and discussed;the main opinions and perspectives presented here are based on the latest controlled studies,meta-analysis,or updated systematic reviews.In the absence of data from controlled studies,consensus recommendations were provided accordingly.
文摘Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019(COVID-19)from early disease onset.The most frequent symptoms and signs are fatigue,dizziness,impaired consciousness,ageusia,anosmia,radicular pain,and headache,as well as others.Based on the high number of series of cases reported,there is evidence for the implication of the immune system in the pathological mechanism of COVID-19.Although the exact role of the immunological mechanism is not elucidated,two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and neuroinflammation.In the context of neurological manifestations associated with COVID-19,neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression,anxiety,mood alterations,psychosis,post-traumatic stress disorder,delirium,and cognitive impairment,which appear to be common in COVID-19 survivors.A worsened score on psychopathological measures is seen in those with a history of psychiatric comorbidities.We review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19.
文摘We have read with interest the Letter to the Editor by Drs.Zhuang and Zhong,who presented the clinical data of 68 patients with Wilson’s disease(WD)who were admitted to the hospital before and during the coronavirus disease 2019(COVID-19)pandemic,and appreciated their findings on hepatic and some extrahepatic manifestations.Nevertheless,given the strong impact of the pandemic on patients with neurological and psychiatric disorders,we would have expected a worsening of the psychiatric and/or neurological impairments in these patients.In contrast,according to the authors,these manifestations remained,somewhat unexpectedly,unchanged.This finding is in contrast with most of the current literature that highlights not only an increased incidence of mental health disorders in the general population but also an exacerbation of neurological and psychiatric symptoms in patients with chronic diseases,especially in those with pre-existing neuropsychiatric disorders,such as WD.Although the study was mainly focused on the hepatic features of WD patients taking anti-copper treatment,a generic and cumulative definition of neurological and psychiatric manifestations,as in this study,does not allow for further considerations.Future studies during and after the pandemic are necessary to clarify the real impact,either direct or indirect,of the COVID-19 pandemic on the neurological and psychiatric symptoms of WD patients.
基金Supported by Ministerio de Economía,Industria y Competitividad,Instituto de Salud Carlos III,Madrid,Spain,No. PI16/01514
文摘BACKGROUND Neuropsychiatric symptoms(NPS)have been insufficiently examined in persons with aphasia(PWA)because most previous studies exclude participants with language and communication disorders.AIM To report a two-part study consisting of a literature review and an observational study on NPS in post-stroke aphasia.METHODS Study 1 reviewed articles obtained from PubMed,PsycINFO,Google Scholar and Cochrane databases after cross-referencing key words of post-stroke aphasia to NPS and disorders.Study 2 examined language deficits and activities of daily living in 20 PWA(median age:58,range:28-65 years;13 men)with the Western Aphasia Battery-Revised and the Barthel Index,respectively.Informants of these 20 PWA were proxy-evaluated with the Neuropsychiatric Inventory and domain-specific scales,including the Stroke Aphasia Depression Questionnaire-10 item version and the Starkstein Apathy Scale.In addition,an adapted version of the Hospital Anxiety and Depression Scale was directly administered to the PWA themselves.This observational study is based on the baseline assessment of an intervention clinical trial(EudraCT:2017-002858-36;ClinicalTrials.gov identifier:NCT04134416).RESULTS The literature review revealed a broad spectrum of NPS in PWA,including depression,anxiety,apathy,agitation/aggression,eating and sleep disorders,psychosis,and hypomania/mania.These findings alert to the need for improving assessment and treatment approaches of NPS taking into consideration their frequent occurrence in PWA.Study 2 showed that the 20 participants had mild-to-moderate aphasia severity and were functionally independent.A wide range of comorbid NPS was found in the post-stroke aphasic population(median number of NPS:5,range:1-8).The majority of PWA(75%)had depressive symptoms,followed by agitation/aggression(70%),irritability(70%),anxiety(65%)and appetite/eating symptoms(65%).Half of them also presented symptoms of apathy,whereas euphoria and psychotic symptoms were rare(5%).Domain-specific scales revealed that 45%of participants had apathy and 30%were diagnosed with depression and anxiety.CONCLUSION Concurrent NPS are frequent in the chronic period of post-stroke aphasia.Therefore,further research on reliable and valid assessment tools and treatment for this aphasic population is strongly warranted.
基金Supported by Fondazione Umberto Veronesi (to Gialluisi A)
文摘Observational studies based on electronic health records (EHR) report anincreased risk of neurological/neuropsychiatric sequelae for patients who havehad coronavirus disease 2019 (COVID-19). However, these studies may sufferfrom biases such as unmeasured confounding, residual reverse causality, or lackof precision in EHR-based diagnoses. To rule out these biases, we tested causallinks between COVID-19 and different potential neurological/neuropsychiatricsequelae through a two-sample Mendelian randomization analysis of summarystatistics from large Genome-Wide Association Scans of susceptibility to COVID-19 and different neurological and neuropsychiatric disorders, including majordepression, anxiety, schizophrenia, stroke, Parkinson’s and Alzheimer’s diseases.We found robust evidence suggesting that COVID-19 – notably the hospitalizedand most severe forms – carries an increased risk of neuropsychiatric sequelae,particularly Alzheimer’s disease, and to a lesser extent anxiety disorder. In linewith a large longitudinal EHR-based study, this evidence was stronger for moresevere COVID-19 forms. These results call for a targeted screening strategy totackle the post-COVID neuropsychiatric pandemic.
文摘The pathogenesis of neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE) is multifactorial and can involve various inflammatory cytokines, autoantibodies such as anti-neuronal antibodies, anti-ribosomal P antibodies, anti-NR2 glutamate receptor binding antibodies, anti-Sm antibodies, anti-U1-RNP antibodies and anti-phospholipid antibodies, and immune complexes (IC). Disruption of the blood-brain barrier (BBB) is integral to the neuropathology of SLE. Recently the possibility has been reported that aforementioned autoantibodies in the circulation may be strongly associated with disruption of the BBB. Each of these mechanisms might contribute to the pathogenesis of focal NPSLE (for example, cerebrovascular disease, movement disorders, myelopathy, seizures and cranial neuropathy) or diffuse NPSLE (for example, acute confusional state, psychosis and cognitive dysfunction) to varying degrees. In this review we focus on how the aforementioned autoantibodies, the BBB, IC and cytokines as well as chemokines are associated with the appearance of NPSLE.
文摘The purpose of this review is to evaluate the role of chronic anemia on neuropsychiatric symptoms and conditions among the elderly. Anemia is defined as hemoglobin levels below 120 and 130 g/L for women and men, respectively. Anemia is not a consequence of the aging process. It is common in the elderly and easily overlooked. Nevertheless, chronic anemia is a risk factor associated with increased mortality, several geriatric syndromes including functional and cognitive impairments. Investigations have shown that anemic elderly and those with hemoglobin borderline levels may present higher proportion of neuropsychiatric impairment, such as Executive Function Disorder and Alzheimer disease. The association between anemia and depression is well established, but its causal pathway is not known: anemia can be regarded as cause or consequence of depression. There is evidence that dementia due to anemia can be prevented;renal chronic anemic patients who received erythropoietin (EPO) replacement therapy showed a lower risk for dementia, compared to those who did not receive it. Anemia may be associated with chronic psychiatric diseases such as bipolar disorders and cause their symptoms to become more severe.
文摘Neuropsychiatric systemic lupus erythematosus (NP-SLE) is one of the major cause of morbidity in systemic lupus erythematosus patients and its treatment depends on identification of pathogenic mechanisms. We describe the rare case of neuropsychiatric systemic lupus erythematosus (NP-SLE) complicated by pericardial effusion combined to low C4 level persisting and hyperprolactinaemia. A cyclophosphamide therapy showed a good response in a 21-year old woman with disturbances in thought processes and an acute confusional state with sierositis. This paper confirms that a cyclophosphamide therapy contributes to control a disease activity by a mechanism of prolactin level reduction. Other studies occur to evaluate this hypothesis.
文摘Dementia is increasing dramatically with an increasing elderly population.Pharmacological interventions are proven to have limited efficacy to treat many of the features of dementia.In such a situation,non-pharmacological means become important to help people with dementia,especially music therapy.The efficacy of music intervention on cognition has been barely explored in the literature,and the few studies that are available present inconsistent results.The aim of this systematic review is to have a meta-analysis on the effect of music therapy for improvements in cognitive functions as well as neuropsychiatric symptoms in the elderly with dementia.
基金Guangdong Obers Blood Purification Academician Work station(2013B090400004)Construction of collaborative platform for clinical research and clinical research of blood purifica tion(201604020175)+2 种基金Guangzhou entrepreneurial leader talent/LCY201215Guangdong University blood purification technology and Engineering Re search Center(GCZX-A1104)Guangdong Provincial Center for clinical engineering of blood purification(507204531040)
文摘1 Introduction Neuropsychiatric systemic lupus erythematosus(NPSLE)is a serious complication of systemic lupus erythematosus(SLE),with an incidence of about 30%to 40%[1].No matter early or late SLE patients are prone to concurrent,so early diagnosis and treatment of NPSLE is extremely important.
基金This review was supported by grants from the National Natural Science Foundation of China(82090042).
文摘In the central nervous system,nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS).In the past 20 years,the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders.In particular,the interactions between the PDZ domain of nNOS and its adaptor proteins,including post-synaptic density 95,the carboxy-terminal PDZ ligand of nNOS,and the serotonin transporter,significantly influence the subcellular localization and functions of nNOS in the brain.The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders.Here,we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders.
基金Nature Science Foundation Project of Guangdong Province,Grant/Award Number:2019A1515011094。
文摘Introduction:Agents that can be used for the treatment of neuropsychiatric lupus(NPSLE)are lacking in the therapeutic armamentarium.Belimumab is a monoclonal antibody targeting the B-cell activating factor(BAFF)and is approved by the US Food and Drug Administration as an additional treatment for systemic lupus erythematosus patients with persistent disease activity and lupus nephritis(LN);however,severe active central nervous system manifestations were excluded.Case Report:We report on a treatment-naïve LN patient with refractory NPSLE complicated with progressive posterior reversible encephalopathy syndrome(PRES)who was successfully treated via the combination of mycophenolate and belimumab,resulting in reversal of persistent headache and neuroradiologic manifestations.Conclusion:Research on this topic could be relevant for identifying a possible correlation between BAFF and psychiatric NPSLE manifestations.
文摘The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological process and its prognosis.Also,the effects of anti-amyloid-beta drugs,recently approved for the treatment of Alzheimer's disease,could be influenced by the APOE genotype.
基金supported by the Paul G.Allen Family Foundation,the National Institutes of Health U01#MH106882the JPB Foundation,the Leona M.and Harry B.Helmsley Charitable Trust(#2017-PG-MED001)Annette Merle-Smith and the Lookout Foundation,and the G.Harold&Leila Y.Mathers Charitable Foundation to F.H.G.
文摘Neuropsychiatric disorders are complex disorders characterized by heterogeneous genetic variations,variable symptoms,and widespread changes in anatomical pathology.In the context of neuropsychiatric disorders,limited access to relevant tissue types presents challenges for understanding disease etiology and developing effective treatments.Induced pluripotent stem cells(iPSCs)reprogrammed from patient somatic cells offer an opportunity to recapitulate disease development in relevant cell types,and they provide novel approaches for understanding disease mechanisms and for development of effective treatments.Here we review recent progress and challenges in differentiation paradigms for generating disease-relevant cells and recent studies of neuropsychiatric disorders using human pluripotent stem cell(hPSC)models where cellular phenotypes linked to disease have been reported.The use of iPSC-based disease models holds great promise for understanding disease mechanisms and supporting discovery of effective treatments.
文摘The development of in vivo biomarkers of Alzheimer's disease(AD)has advanced the diagnosis of AD from a clinical syndrome to a biological construct.The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals.While neuropsychiatric symptoms(NPS)are non-cognitive symptoms that are increasingly recognized as early manifestations of AD,the associations of NPS with AD pathophysiology in preclinical AD remain unclear.Here,we review the associations between NPS and AD biomarkers amyloid-(3(Aβ),tau and neurodegeneration in preclinical AD and cognitivelyunimpaired individuals in 19 eligible English-language publications(8 cross-sectional studies,10 longitudinal,1 both cross-sectional and longitudinal).The cross-sectional studies have consistently shown that NPS,particularly depressive and anxiety symptoms,are associated with higher Aβ.The longitudinal studies have suggested that greater NPS are associated with higher Aβ and cognitive decline in cognitively unimpaired subjects over time.However,most of the studies have either cross-sectionally or longitudinally shown no association between NPS and tau pathology.For the association of NPS and neurodegeneration,two studies have shown that the cerebrospinal fluid total-tau is linked to longitudinal increase in NPS and that the NPS may predict longitudinal metabolic decline in preclinical AD,respectively.However,evidence for the association between atrophy and NPS in preclinical AD is less consistent.Therefore,future longitudinal studies with well-designed methodologies and NPS measurements are required not only to determine the relationship among AT(N)biomarkers,NPS and cognitive decline,but also to elucidate the contribution of comorbid pathology to preclinical AD.
