Journal of Alzheimer's disease : JAD最新文献

{"title":"Interplay Between Hippocampal Glutathione Depletion and pH Increment in Alzheimer's Disease.","authors":"P. Mandal, D. Dwivedi, D. Shukla, Avantika Samkaria, Rimil Guha Roy, Yashika Arora, Komal Jindal","doi":"10.3233/JAD-215729","DOIUrl":"https://doi.org/10.3233/JAD-215729","url":null,"abstract":"Oxidative stress (OS) is a critical factor in the pathogenesis of Alzheimer's disease (AD). Elevated OS in AD lowers the level of glutathione (GSH), a brain antioxidant. Currently, GSH is under examination in the clinical population for understanding its association with oxidative load in AD research. Significant depletion in hippocampal GSH, as observed using in vivo magnetic resonance spectroscopy (MRS), reportedly correlates with cognitive impairment in AD. Alterations in cellular-energy metabolism and increased hippocampal pH have also been reported in AD. Hence, this combined molecular interplay between hippocampal GSH and pH must be studied longitudinally for advancing AD research. Herein, we propose a schematic model depicting the molecular events in AD pathogenesis and provide a possible link between OS, GSH depletion, and pH alterations in the hippocampus. The model would further potentiate the need for in vivo longitudinal studies to confirm the interlinked mechanism between OS, hippocampal GSH depletion, and pH increment in an AD patient brain.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133467276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clustering Analysis of the Care Problems of People with Dementia Based on the Minimum Spanning Tree Algorithm: A Cross-Sectional Study.","authors":"M. Leng, Y. Sun, Hui-Te Chang, Zhiwen Wang","doi":"10.3233/JAD-215682","DOIUrl":"https://doi.org/10.3233/JAD-215682","url":null,"abstract":"BACKGROUND\u0000Recognizing the correlations between care problems of people with dementia could help clinicians choose treatment methods because related symptom groups might respond to the same treatment intervention.\u0000\u0000\u0000OBJECTIVE\u0000This study aimed to evaluate the prevalence of various care problems in people with dementia and to explore the core care problems and correlations between care problems of people with dementia.\u0000\u0000\u0000METHODS\u0000This cross-sectional study recruited family caregivers of people with dementia through memory clinics and WeChat groups. Care problems of people with dementia were measured using a care problems evaluation sheet, which involved three aspects: daily living care problems, behavioral and psychological symptoms, and safety risks. Clustering analysis of the care problems based on Kruskal's minimum spanning tree (MST) algorithm was performed in the Jupyter Notebook software to explore the core care problems and their correlations.\u0000\u0000\u0000RESULTS\u0000A total of 687 carer-patient pairs were included in the analysis. In general, the prevalence of having difficulty in language performance, agitated behavior, and incidence of falls was relatively higher than other care problems in people with dementia, which distressed their family caregivers. Through clustering analysis, the 63 care problems were clustered into 7 clusters and 7 core care problems were identified.\u0000\u0000\u0000CONCLUSION\u0000The prevalence of various care problems of people living with dementia in China was relatively high. The information regarding correlations in clusters among care problems will help practitioners and policymakers to identify the core care problems and optimize more rational treatments for people with dementia.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"2015 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121330957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychobiological Monitoring of a Home-Based Dyadic Intervention for People Living with Dementia and Their Caregivers: Added Value to Evaluate Treatment Success and Understand Underlying Mechanisms.","authors":"A. Wuttke-Linnemann, Clara Henrici, N. Skoluda, U. Nater, K. Endres, A. Fellgiebel","doi":"10.3233/JAD-210618","DOIUrl":"https://doi.org/10.3233/JAD-210618","url":null,"abstract":"BACKGROUND\u0000Research concerning people living with dementia (PwD) and their informal caregivers (ICs) has recently begun to focus on dyadic aspects of psychosocial interventions.\u0000\u0000\u0000OBJECTIVE\u0000We adapted a dyadic psychosocial intervention and examined its effects on psychobiological stress in daily life.\u0000\u0000\u0000METHODS\u0000Twenty-four PwD-caregiver dyads were visited seven times at home by specialized nursing staff. Momentary subjective stress, salivary cortisol (sCort), and salivary alpha-amylase (sAA) were measured in PwD and ICs before and after each home visit as well as six times per day at two days each at the beginning and end of the intervention as part of an ambulatory assessment. Hair cortisol concentrations (HCC) were measured twice.\u0000\u0000\u0000RESULTS\u0000After each home visit session, ICs reported lower subjective stress. sCort was lower in both ICs and PwD, whereas sAA did not change. In daily life, area under the curve (AUCg) concerning sCort secretion indicated that PwD had lower sCort daily output at the end of the intervention, and AUCg concerning subjective stress indicated that both PwD and ICs reported lower subjective stress than at the beginning of the intervention. AUCg concerning sAA did not change over time in either group. HCC did not vary over time but increased with disease severity.\u0000\u0000\u0000CONCLUSION\u0000The psychosocial intervention reduced psychobiological stress but affected psychobiological stress measures differently in PwD and ICs. In particular, the discrepancy between subjective and physiological markers of stress in PwD emphasizes the added value to evaluate treatment success and understand underlying mechanisms as a complement to self-reports.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128385243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small RNA Sequencing in the Tg4-42 Mouse Model Suggests the Involvement of snoRNAs in the Etiology of Alzheimer's Disease.","authors":"C. T. Lio, T. Kacprowski, Maik Klaedtke, L. Jensen, Y. Bouter, T. Bayer, A. Kuss","doi":"10.3233/JAD-220110","DOIUrl":"https://doi.org/10.3233/JAD-220110","url":null,"abstract":"BACKGROUND\u0000The Tg4-42 mouse model for sporadic Alzheimer's disease (AD) has unique features, as the neuronal expression of wild type N-truncated Aβ4-42 induces an AD-typical neurological phenotype in the absence of plaques. It is one of the few models developing neuron death in the CA1 region of the hippocampus. As such, it could serve as a powerful tool for preclinical drug testing and identification of the underlying molecular pathways that drive the pathology of AD.\u0000\u0000\u0000OBJECTIVE\u0000The aim of this study was to use a differential co-expression analysis approach for analyzing a small RNA sequencing dataset from a well-established murine model in order to identify potentially new players in the etiology of AD.\u0000\u0000\u0000METHODS\u0000To investigate small nucleolar RNAs in the hippocampus of Tg4-42 mice, we used RNA-Seq data from this particular tissue and, instead of analyzing the data at single gene level, employed differential co-expression analysis, which takes the comparison to gene pair level and thus affords a new angle to the interpretation of these data.\u0000\u0000\u0000RESULTS\u0000We identified two clusters of differentially correlated small RNAs, including Snord55, Snord57, Snord49a, Snord12, Snord38a, Snord99, Snord87, Mir1981, Mir106b, Mir30d, Mir598, and Mir99b. Interestingly, some of them have been reported to be functionally relevant in AD pathogenesis, as AD biomarkers, regulating tau phosphorylation, TGF-β receptor function or Aβ metabolism.\u0000\u0000\u0000CONCLUSION\u0000The majority of snoRNAs for which our results suggest a potential role in the etiology of AD were so far not conspicuously implicated in the context of AD pathogenesis and could thus point towards interesting new avenues of research in this field.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"91 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123598117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal Fluid Biomarkers for Cerebral Amyloid Angiopathy Diagnosis.","authors":"A. Charidimou","doi":"10.3233/JAD-220133","DOIUrl":"https://doi.org/10.3233/JAD-220133","url":null,"abstract":"An accurate diagnosis of sporadic cerebral amyloid angiopathy (CAA) is critical for patient management and research (including clinical trials) for this common small vessel pathology of the brain. While the \"big bang\" of the CAA field has been the device and wide adoption of the clinico-radiological Boston criteria which allowed for CAA diagnosis during life, these criteria are not without major shortcoming. As it is now becoming evident that CAA is probably not a single disease, but rather represents divergent pathophysiological phenotypes and clinical trajectories, new biomarker-driven diagnostic approaches should be sought. One such complimentary approach for CAA diagnosis is the use of cerebrospinal fluid biomarkers (CSF), which could provide dynamic measures of the underlying disease process and is discussed in this commentary given exciting new advances. A hint on how the practicing clinician could apply the current CSF data for CAA diagnosis is also provided.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121727142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Amyloid, Tau, and APOE Genotype on the Relationship Between Informant-Reported Sleep Disturbance and Alzheimer's Disease Risks.","authors":"Hyun Kim, Alina Levine, Daniel Cohen, P. Gehrman, Xi Zhu, D. Devanand, Seonjoo Lee, T. Goldberg","doi":"10.3233/jad-215417","DOIUrl":"https://doi.org/10.3233/jad-215417","url":null,"abstract":"BACKGROUND\u0000The association between sleep and Alzheimer's disease (AD) biomarkers are well-established, but little is known about how they interact to change the course of AD.\u0000\u0000\u0000OBJECTIVE\u0000To determine the potential interaction between sleep disturbance and Aβ, tau, and APOE4 on brain atrophy and cognitive decline.\u0000\u0000\u0000METHODS\u0000Sample included 351 participants (mean age 72.01 ± 6.67, 50.4%female) who were followed for approximately 5 years as part of the Alzheimer's Disease Neuroimaging Initiative. Informant-reported sleep disturbance (IRSD) was measured using the Neuropsychiatric Inventory (NPI). Changes in magnetic resonance imaging (MRI)-measured AD signature brain regions and cognitive performance and IRSD's interaction with cerebrospinal fluid amyloid-β (Aβ42) and p-Tau depositions and APOE4 status were examined using the linear mixed models.\u0000\u0000\u0000RESULTS\u0000Baseline IRSD was not significantly associated with the rate of atrophy after adjusting for covariates (age, sex, education, total NPI severity score, and sleep medications). However, there was a significant interaction between IRSD and AD biomarkers on faster atrophy rates in multiple brain regions, including the cortical and middle temporal volumes. Post-hoc analyses indicated that Aβ and p-Tau/Aβ predicted a faster decline in these regions/domains in IRSD, compared with biomarker-negative individuals with IRSD (ps≤0.001). There was a significant IRSD*APOE4 interaction for brain atrophy rate (ps≤0.02) but not for cognition.\u0000\u0000\u0000CONCLUSION\u0000IRSD may increase the future risk of AD by contributing to faster brain atrophy and cognitive decline when combined with the presence of AD biomarkers and APOE4. Early intervention for sleep disturbance could help reduce the risk of developing AD.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124944870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Among Inflammatory Diet, Glycohemoglobin, and Cognitive Function Impairment in the Elderly: Based on the NHANES 2011-2014.","authors":"M. Sun, Ling Wang, Yinpei Guo, Shoumeng Yan, Jing Li, Xuhan Wang, Xiaotong Li, Bo Li","doi":"10.3233/jad-215688","DOIUrl":"https://doi.org/10.3233/jad-215688","url":null,"abstract":"BACKGROUND\u0000Dietary inflammatory index (DII) was associated with Type 2 diabetes mellitus and cognitive function impairment (CFI).\u0000\u0000\u0000OBJECTIVE\u0000The aim of this study was to explore whether the associations among DII, glycohemoglobin (HbA1c), and CFI were similar in the participants with or without diabetes.\u0000\u0000\u0000METHODS\u0000A total of 1,198 participants aged 60 and over from the National Health and Nutrition Examination Survey (NHANES) in 2011-2014 were involved in this study, dividing into subgroups as diabetes and non-diabetes for further analysis.\u0000\u0000\u0000RESULTS\u0000We found that participants with pro-inflammatory diet had higher proportion of CFI patients (p <  0.05). Pro-inflammatory diet and HbA1c were positively associated with the risk of CFI; participants with pro-inflammatory diet was 1.479 times on occurrence of CFI compared with anti-inflammatory diet group. The interaction between inflammatory diet and HbA1c was positive on the risk of CFI and was negative on the CERAD-immediate and CERAD-delayed, respectively. Among the participants without diabetes, the associations of Energy-adjusted DII (E-DII) with Animal Fluency test and Digit Symbol Substitution Test (DSST) were partially mediated by HbA1c, and the mediated proportion was 5.8% and 6.6%, respectively. However, there was no such mediation effect in the diabetes patients.\u0000\u0000\u0000CONCLUSION\u0000In elderly participants without diabetes, there was an interaction between inflammatory diet and HbA1c on the association with CFI, especially for the dimension of CERAD-immediate and CERAD-delayed. Besides, the associations of E-DII with Animal Fluency test and DSST were partially mediated by HbA1c. For diabetic patients, HbA1c, rather than the inflammatory diet has a positive effect on the CFI risk.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"86 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116002324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal Fluid sTREM2 Has Paradoxical Association with Brain Structural Damage Rate in Early- and Late-Stage Alzheimer's Disease.","authors":"Fangda Leng, Zhenying Zhan, Yunchuang Sun, Fang Liu, P. Edison, Yongan Sun, Zhaoxia Wang","doi":"10.3233/jad-220102","DOIUrl":"https://doi.org/10.3233/jad-220102","url":null,"abstract":"BACKGROUND\u0000Recently it has been proposed that microglial response has a stage-dependent effect on the progression of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) sTREM2 has emerged as a promising microglial activation marker.\u0000\u0000\u0000OBJECTIVE\u0000To test the stage-dependent role of microglia by studying the association between baseline sTREM2 and dynamic brain structural changes in AD and mild cognitive impairment (MCI) patients.\u0000\u0000\u0000METHODS\u000022 amyloid-β-positive (A+) and tau-positive (T+) AD and 24 A+T+MCI patients were identified from the Alzheimer's Disease Neuroimaging Initiative. The patients had baseline CSF amyloid-β, phosphorylated-tau, and sTREM2, and were followed up for at least one year by T1-weighted and diffusion tensor imaging scans. Gray matter volumes and white matter microstructural integrity were evaluated. Linear mixed models were applied to analyze how baseline sTREM2 may influence the rate of brain structural changes while adjusting for the effects of age, APOE4 status, and the CSF core markers.\u0000\u0000\u0000RESULTS\u0000In A+T+AD patients, baseline CSF sTREM2 was associated with faster mean diffusivity increase in the bilateral posterior corona radiata and right superior longitudinal fasciculus. In A+T+MCI patients, baseline CSF sTREM2 was associated slower gray matter volumetric loss in parahippocampal gyrus, left fusiform cortex, left middle temporal gyrus, and left lateral occipital cortex. Baseline CSF sTREM2 also had a protective effect against mean diffusivity increase in right inferior fronto-occipital fasciculus, left superior longitudinal fasciculus, left forceps minor, and left uncinate fasciculus.\u0000\u0000\u0000CONCLUSION\u0000Microglial activation at early stage might have a protective effect against neurodegeneration, while at late stage it might facilitate AD. Future efforts on modulating microglial activation could be promising, given a carefully selected time window for intervention.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130542624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Photobiomodulation Improves Sleep Quality in Subjective Cognitive Decline: A Randomized, Sham-Controlled Study.","authors":"Xing Zhao, Wenying Du, Jiehui Jiang, Ying Han","doi":"10.3233/jad-215715","DOIUrl":"https://doi.org/10.3233/jad-215715","url":null,"abstract":"BACKGROUND\u0000Sleep appears to be a sensitive biomarker that facilitates early detection and effective intervention for Alzheimer's disease, while subjective cognitive decline (SCD) is a risk factor for Alzheimer's disease. Prefrontal cortex atrophy is associated with both sleep disruption and cognitive decline. Transcranial brain photobiomodulation (PBM) therapy can enhance frontal cortex oxygen consumption, increasing frontal cortex mediated memory function.\u0000\u0000\u0000OBJECTIVE\u0000This study aimed to test whether PBM therapy targeting the frontal cortex could improve sleep and cognitive function in SCD.\u0000\u0000\u0000METHODS\u0000Fifty-eight SCDs were divided into the PBM group (N = 32) in which real light therapy was administered and a sham light therapy group (N = 26). All the participants received either real light or sham light therapy for 6 days consecutively, while the sleep data were recorded. The n-back task was employed to measure each participant's working memory.\u0000\u0000\u0000RESULTS\u0000We found no differences in sleep efficiency change (F = 211, p = 0.279), REM stage percent change (F = 420, p = 0.91), and wake-up time (F = 212, p = 0.277) between the two groups. The sleep efficiency and REM were improved within the true light group on the fifth day. The true light group perform better than the control group in the n-back test, the accuracy was higher in the 2-back test (88.6% versus 79.6%, p = 0.001), and the reaction time in 1-back was shorter (544.80±202.00 versus 592.87±222.05, p = 0.003).\u0000\u0000\u0000CONCLUSION\u0000After five days of PBM therapy targeting the prefrontal cortex, sleep efficiency and N-back cognitive performance were improved on the fifth day.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"75 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121772018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination Therapy in Alzheimer's Disease: Is It Time?","authors":"A. Salehipour, Motahareh Bagheri, Mohammadmahdi Sabahi, M. Dolatshahi, D. Boche","doi":"10.3233/jad-215680","DOIUrl":"https://doi.org/10.3233/jad-215680","url":null,"abstract":"Alzheimer's disease (AD) is the most common cause of dementia globally. There is increasing evidence showing AD has no single pathogenic mechanism, and thus treatment approaches focusing only on one mechanism are unlikely to be meaningfully effective. With only one potentially disease modifying treatment approved, targeting amyloid-β (Aβ), AD is underserved regarding effective drug treatments. Combining multiple drugs or designing treatments that target multiple pathways could be an effective therapeutic approach. Considering the distinction between added and combination therapies, one can conclude that most trials fall under the category of added therapies. For combination therapy to have an actual impact on the course of AD, it is likely necessary to target multiple mechanisms including but not limited to Aβ and tau pathology. Several challenges have to be addressed regarding combination therapy, including choosing the correct agents, the best time and stage of AD to intervene, designing and providing proper protocols for clinical trials. This can be achieved by a cooperation between the pharmaceutical industry, academia, private research centers, philanthropic institutions, and the regulatory bodies. Based on all the available information, the success of combination therapy to tackle complicated disorders such as cancer, and the blueprint already laid out on how to implement combination therapy and overcome its challenges, an argument can be made that the field has to move cautiously but quickly toward designing new clinical trials, further exploring the pathological mechanisms of AD, and re-examining the previous studies with combination therapies so that effective treatments for AD may be finally found.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"82 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122619112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}