Current Alzheimer research最新文献

{"title":"Transforming Alzheimer's Digital Caregiving through Large Language Models.","authors":"Sujin Kim, Dong Y Han, Jihye Bae","doi":"10.2174/0115672050301740241118044604","DOIUrl":"10.2174/0115672050301740241118044604","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Alzheimer's Disease and Related Dementias (AD/ADRD) present significant caregiving challenges, with increasing burdens on informal caregivers. This study examines the potential of AI-driven Large Language Models (LLMs) in developing digital caregiving strategies for AD/ADRD. The objectives include analyzing existing caregiving education materials (CEMs) and mobile application descriptions (MADs) and aligning key caregiving tasks with digital functions across different stages of disease progression.</p><p><strong>Methods: </strong>We analyzed 38 CEMs from the National Library of Medicine's MedlinePlus, along with associated hyperlinked web resources, and 57 MADs focused on AD digital caregiving. Using ChatGPT 3.5, essential caregiving tasks were extracted and matched with digital functionalities suitable for each stage of AD progression, while also highlighting digital literacy requirements for caregivers.</p><p><strong>Results: </strong>The analysis categorizes AD caregiving into 4 stages-Pre-Clinical, Mild, Moderate, and Severe-identifying key tasks, such as behavior monitoring, daily assistance, direct supervision, and ensuring a safe environment. These tasks were supported by digital aids, including memory- enhancing apps, Global Positioning System (GPS) tracking, voice-controlled devices, and advanced GPS tracking for comprehensive care. Additionally, 6 essential digital literacy skills for AD/ADRD caregiving were identified: basic digital skills, communication, information management, safety and privacy, healthcare knowledge, and caregiver coordination, highlighting the need for tailored training.</p><p><strong>Conclusion: </strong>The findings advocate for an LLM-driven strategy in designing digital caregiving interventions, particularly emphasizing a novel paradigm in AD/ADRD support, offering adaptive assistance that evolves with caregivers' needs, thereby enhancing their shared decision-making and patient care capabilities.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"503-516"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735471","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":"Effects of Cycloastragenol on Alzheimer's Disease in Rats by Reducing Oxidative Stress, Inflammation, and Apoptosis.","authors":"Kadi M Alharbi, Shahad A Alshehri, Wasayf A Almarwani, Khulud K Aljohani, Ajwan Z Albalawi, Areej S Alatawi, Shekha M Al-Atwi, Lama S Alhwyty, Hanan M Hassan, Mohammed M H Al-Gayyar","doi":"10.2174/0115672050315334240508162754","DOIUrl":"10.2174/0115672050315334240508162754","url":null,"abstract":"<p><strong>Background: </strong>As individuals age, they may develop Alzheimer's disease (AD), which is characterized by difficulties in speech, memory loss, and other issues related to neural function. Cycloastragenol is an active ingredient of Astragalus trojanus and has been used to treat inflammation, aging, heart disease, and cancer.</p><p><strong>Objectives: </strong>This study aimed to explore the potential therapeutic benefits of cycloastragenol in rats with experimentally induced AD. Moreover, the underlying molecular mechanisms were also evaluated by measuring Nrf2 and HO-1, which are involved in oxidative stress, NFκB and TNF-α, which are involved in inflammation, and BCL2, BAX, and caspase-3, which are involved in apoptosis.</p><p><strong>Methods: </strong>Sprague-Dawley rats were given 70 mg/kg of aluminum chloride intraperitoneally daily for six weeks to induce AD. Following AD induction, the rats were given 25 mg/kg of cycloastragenol daily by oral gavage for three weeks. Hippocampal sections were stained with hematoxylin/ eosin and with anti-caspase-3 antibodies. The Nrf2, HO-1, NFκB, TNF-α, BCL2, BAX, and caspase-3 gene expressions and protein levels in the samples were analyzed.</p><p><strong>Results: </strong>Cycloastragenol significantly improved rats' behavioral test performance. It also strengthened the organization of the hippocampus. Cycloastragenol significantly improved behavioral performance and improved hippocampal structure in rats. It caused a marked decrease in the expression of NFκB, TNF-α, BAX, and caspase-3, which was associated with an increase in the expression of BCL2, Nrf2, and HO-1.</p><p><strong>Conclusion: </strong>Cycloastragenol improved the structure of the hippocampus in rats with AD. It enhanced the outcomes of behavioral tests, decreased the concentration of AChE in the brain, and exerted antioxidant and anti-inflammatory effects. Antiapoptotic effects were also noted, leading to significant improvements in cognitive function, memory, and behavior in treated rats.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"141-154"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066503","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":"Handwriting Markers for the Onset of Alzheimer's Disease.","authors":"Yury Chernov","doi":"10.2174/0115672050299338240222051023","DOIUrl":"10.2174/0115672050299338240222051023","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease has an impact on handwriting (AD). Numerous researchers reported that fact. Therefore, examining handwriting characteristics could be a useful way to screen for AD. The aim of the article is to present the reliability and effectiveness of the AD-HS tool.</p><p><strong>Methods: </strong>Most of the existing studies examine either linguistic manifestations of writing or certain motor functions. However, handwriting is a complex of cognitive and motor activities. Since the influence of AD on handwriting is individual, it is important to analyze the complete set of handwriting features. The AD-HS instrument is based on this principle. Validation of the AD-HS instrument for revealing cognitive impairment in AD-diagnosed persons in comparison to the control group. The study is based on the evaluation of free handwritten texts. AD-HS includes 40 handwriting and 2 linguistic features of handwritten texts. It is based on the standard protocol for handwriting analysis. The cumulative evaluation of all features builds a quantitative AD-Indicator (ADI) as a marker of possible AD conditions. The analyzed experiment includes 53 AD-diagnosed persons and a control group of 192 handwriting specimens from the existing database.</p><p><strong>Results: </strong>AD-HS shows a distinct difference in evaluated ADI for the participants (the mean value equals 0.49) and the control group (the mean value equals 0.28).</p><p><strong>Conclusion: </strong>The handwriting marker of AD could be an effective supplement instrument for earlier screening. It is also useful when traditional biomarkers and neurological tests could not be applied. AD-HS can accompany therapy as an indication of its effect on a person.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"791-801"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998797","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":"Disruptions of Gut Microbiota are Associated with Cognitive Deficit of Preclinical Alzheimer's Disease: A Cross-Sectional Study.","authors":"Binbin Yu, Guomeng Wan, Shupeng Cheng, Pengcheng Wen, Xi Yang, Jiahuan Li, Huifang Tian, Yaxin Gao, Qian Zhong, Jin Liu, Jianan Li, Yi Zhu","doi":"10.2174/0115672050303878240319054149","DOIUrl":"10.2174/0115672050303878240319054149","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's Disease (AD) is the most prevalent type of dementia. The early change of gut microbiota is a potential biomarker for preclinical AD patients.</p><p><strong>Objective: </strong>The study aimed to explore changes in gut microbiota characteristics in preclinical AD patients, including those with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI), and detect the correlation between gut microbiota characteristics and cognitive performances.</p><p><strong>Methods: </strong>This study included 117 participants [33 MCI, 54 SCD, and 30 Healthy Controls (HC)]. We collected fresh fecal samples and blood samples from all participants and evaluated their cognitive performance. We analyzed the diversity and structure of gut microbiota in all participants through qPCR, screened characteristic microbial species through machine learning models, and explored the correlations between these species and cognitive performances and serum indicators.</p><p><strong>Results: </strong>Compared to the healthy controls, the structure of gut microbiota in MCI and SCD patients was significantly different. The three characteristic microorganisms, including <i>Bacteroides ovatus, Bifidobacterium adolescentis</i>, and <i>Roseburia inulinivorans</i>, were screened based on the best classification model (HC and MCI) having intergroup differences. <i>Bifidobacterium adolescentis</i> is associated with better performance in multiple cognitive scores and several serum indicators. <i>Roseburia inulinivorans</i> showed negative correlations with the scores of the Functional Activities Questionnaire (FAQ).</p><p><strong>Conclusion: </strong>The gut microbiota in patients with preclinical AD has significantly changed in terms of composition and richness. Correlations have been discovered between changes in characteristic species and cognitive performances. Gut microbiota alterations have shown promise in affecting AD pathology and cognitive deficit.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"875-889"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290126","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 Relationship between Alzheimer's Disease and Ferroptosis: A Bibliometric Study Based on Citespace.","authors":"Fengwen Lin, Xiaolu Yang, Linqin Li, Jie Chen, Xuxiang Zheng, Lihua Qiu, Shaorui Shi, Bin Nie","doi":"10.2174/0115672050348799241211072746","DOIUrl":"10.2174/0115672050348799241211072746","url":null,"abstract":"<p><strong>Background: </strong>The potential relationship between Alzheimer's Disease (AD) and ferroptosis has received considerable attention, yet there is no comprehensive visualization analysis in this field. This study aimed to explore the research frontiers and hotspots through bibliometric analysis.</p><p><strong>Methods: </strong>Literature related to AD and ferroptosis was collected from the Web of Science Core Collection. Data, including countries, authors, institutions, journals, and keywords, were analyzed by Tableau Public Desktop and Citespace software.</p><p><strong>Results: </strong>A total of 305 articles published between January 1st, 2013, and December 31st, 2023, were included, and the number of articles on the relationship between AD and ferroptosis has increased annually, with the largest number reported from China (162 articles). The articles from Professor SJ Dixon were cited most frequently. Among the top ten most cited articles, four were published in top journals. The University of Melbourne emerged as the institution with the highest number of publications (27 articles). Among the journals, most of the articles were published in Frontiers in Aging Neuroscience (13 articles, accounting for 4.26%). The co-occurrence analysis of keywords revealed that major hotspots in this field contained oxidative stress, cell death, and lipid peroxidation. Keyword burst analysis indicated that antioxidant was the term with the longest duration of high interest, while clustering analysis showed that this research area primarily focused on amyloid precursor protein, drug development, and diagnostic models.</p><p><strong>Conclusion: </strong>Bibliometric analyses were conducted to comprehensively present the research progress and trends on the relationship between AD and ferroptosis, providing valuable evidence for future research in related fields.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"566-577"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884024","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":"Molecular Signatures and Clinical Significance of Notch Signaling Pathway in Peripheral Blood of Patients with Alzheimer's Disease.","authors":"Dongdong Jia, Ting He, Lu Sun, Qunsong Wang, Haitao Yu","doi":"10.2174/0115672050339307241108101528","DOIUrl":"10.2174/0115672050339307241108101528","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's Disease (AD) is the most common neurodegenerative disease, and timely and effective diagnosis is essential for the prevention and treatment of AD. Peripheral blood is readily available, inexpensive, and non-invasive, making it an ideal substrate for screening diagnostic biomarkers.</p><p><strong>Method: </strong>The Notch signaling pathway is closely related to AD, so genes related to the Notch signaling pathway may be candidate diagnostic biomarkers for AD. Here, we have performed an integrated analysis of peripheral blood cells transcriptomics from two AD cohorts (GSE63060: Ctrl = 104, MCI = 80, AD = 145; GSE63061: Ctrl = 134, MCI = 109, AD = 139) to reveal the expression levels of 16 Notch signals involving 100 genes.</p><p><strong>Result: </strong>The results have shown the changes in Notch signaling-related genes to be highly consistent in both AD cohorts. Bioinformatics analysis has found Differentially Expressed Genes (DEGs) related to Notch signaling to mainly play important roles in Alzheimer's disease, the Notch signaling pathway, and the C-type lectin receptor signaling pathway. Multiple machine learning analyses have revealed IKBKB, HDAC2, and PIK3R1 to exhibit good diagnostic value in both AD cohorts and that they may be ideal biomarkers for early diagnosis of AD.</p><p><strong>Conclusion: </strong>This study has provided a comprehensive description of the molecular signatures of the Notch signaling pathway in AD peripheral blood and a potential diagnostic model for AD clinical screening.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"479-490"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775966","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 Potential Role of Enrichment Environment on Plasticity in Alzheimer's Disease Models: Insights About Therapeutic Approaches.","authors":"Rodrigo C Neves, Raquel C Figueiredo, Adriana C Faria-Melibeu","doi":"10.2174/0115672050348227241128095209","DOIUrl":"10.2174/0115672050348227241128095209","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is characterized by synapse loss and neurodegeneration, which leads to cognitive and psychiatric symptoms. Researchers worldwide have been studying therapeutic approaches aiming to induce plasticity and neuroprotection once AD has no cure and the existing treatments are limited. Environmental Enrichment (EE) is a change in housing conditions that promotes increased cognitive stimulus. Studies have demonstrated that EE acts as a plasticity modulator in several conditions and experimental models. In this review, we analyze and discuss the potential role of EE on plasticity modulation in different animal models but primarily on AD models. The data were extracted from the PubMed and ScienceDirect databases. The EE was shown to induce plasticity. LTP and behavior were enhanced in animals under different conditions, such as the AD model. The mechanisms were related to the glutamatergic system and excitatory/ inhibitory balance. Moreover, many studies have evidenced that EE promotes the upregulation of BDNF and the synaptic proteins SYN and PSD95. These data also suggest a neuroprotective function performed by EE in different contexts, such as aging and AD. Therefore, an enriched environment can be a target of new therapeutic approaches that aim to induce neuroplasticity and neuroprotection against AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"457-469"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775987","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":"A Cross-Sectional Study on the Association between Physical Activity and Cognitive Function Among Community-Dwelling Older Adults in Tianjin.","authors":"Tianyu Wang, Keran Duan, Xian Cai, Qi Chen, Liping Zu, Lingyan Liu, Xiaomin Wu, Chenyu Li, Fei Ma","doi":"10.2174/0115672050347596241111112811","DOIUrl":"10.2174/0115672050347596241111112811","url":null,"abstract":"<p><strong>Background: </strong>The association between physical activity (PA) and cognitive function remains controversial, and the impact of gender on this association remains underexplored. Therefore, this study aimed to investigate the association between PA and cognitive function and to explore whether this association was modified by gender among older adults.</p><p><strong>Methods: </strong>In 2016, a cluster sampling method was used to select community-dwelling older adults aged 65 and above. PA was assessed using the International Physical Activity Questionnaire-Short Form and classified as low, middle, and high. Cognitive function was assessed using the revised Chinese version of the Wechsler Adult Intelligence Scale. The multiple linear regression model was used to explore the association between PA and cognitive function and to assess whether this association differs by gender.</p><p><strong>Results: </strong>A total of 676 participants with a mean age of 73.63 ± 6.39 were included. The multiple linear regression analysis showed that higher PA was significantly statistically associated with higher Full Intelligence Quotient (FIQ), Performance Intelligence Quotient (PIQ), and verbal Intelligence Quotient (VIQ) scores (P<0.05). Among the WAIS-RC subtests, higher PA was significantly statistically associated with higher scores of the similarity subtest, picture completion subtest, and picture arrangement subtest (P<0.05). In the gender subgroup analysis, higher PA was significantly statistically associated with higher FIQ and PIQ scores (P<0.05), but no significant association was found with VIQ scores (P>0.05) in the male group, while in the female group, there was no significant statistical association between higher PA and FIQ, PIQ, or VIQ scores (P>0.05).</p><p><strong>Conclusion: </strong>Higher PA was significantly statistically associated with better cognitive function (P<0.05). In the male group, PA was significantly statistically associated with cognitive function, whereas no comparable association was found in the female group.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"517-525"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735468","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":"Associations of Multimorbidity with Cerebrospinal Fluid Biomarkers for Neurodegenerative Disorders in Early Parkinson's Disease: A Crosssectional and Longitudinal Study.","authors":"Ming-Zhan Zhang, Yan Sun, Yan-Ming Chen, Fan Guo, Pei-Yang Gao, Lan Tan, Meng-Shan Tan","doi":"10.2174/0115672050314397240708060314","DOIUrl":"10.2174/0115672050314397240708060314","url":null,"abstract":"<p><strong>Object: </strong>The study aims to determine whether multimorbidity status is associated with cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders.</p><p><strong>Methods: </strong>A total of 827 patients were enrolled from the Parkinson's Progression Markers Initiative (PPMI) database, including 638 patients with early-stage Parkinson's disease (PD) and 189 healthy controls (HCs). Multimorbidity status was evaluated based on the count of long-term conditions (LTCs) and the multimorbidity pattern. Using linear regression models, cross-sectional and longitudinal analyses were conducted to assess the associations of multimorbidity status with CSF biomarkers for neurodegenerative disorders, including α-synuclein (αSyn), amyloid-β₄₂ (Aβ₄₂), total tau (t-tau), phosphorylated tau (p-tau), glial fibrillary acidic protein (GFAP), and neurofilament light chain protein (NfL).</p><p><strong>Results: </strong>At baseline, the CSF t-tau (p = 0.010), p-tau (p = 0.034), and NfL (p = 0.049) levels showed significant differences across the three categories of LTC counts. In the longitudinal analysis, the presence of LTCs was associated with lower Aβ₄₂ (β < -0.001, p = 0.020), and higher t-tau (β = 0.007, p = 0.026), GFAP (β = 0.013, p = 0.022) and NfL (β = 0.020, p = 0.012); Participants with tumor/musculoskeletal/mental disorders showed higher CSF levels of t-tau (β = 0.016, p = 0.011) and p-tau (β = 0.032, p = 0.044) than those without multimorbidity.</p><p><strong>Conclusion: </strong>Multimorbidity, especially severe multimorbidity and the pattern of mental/musculoskeletal/ tumor disorders, was associated with CSF biomarkers for neurodegenerative disorders in early-stage PD patients, suggesting that multimorbidity might play a crucial role in aggravating neuronal damage in neurodegenerative diseases.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"201-213"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750154","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":"Estimating Dementia Onset: AT(N) Profiles and Predictive Modeling in Mild Cognitive Impairment Patients.","authors":"Carlos Platero, Jussi Tohka, Bryan Strange","doi":"10.2174/0115672050295317240223162312","DOIUrl":"10.2174/0115672050295317240223162312","url":null,"abstract":"<p><strong>Background: </strong>Mild Cognitive Impairment (MCI) usually precedes the symptomatic phase of dementia and constitutes a window of opportunities for preventive therapies.</p><p><strong>Objectives: </strong>The objective of this study was to predict the time an MCI patient has left to reach dementia and obtain the most likely natural history in the progression of MCI towards dementia.</p><p><strong>Methods: </strong>This study was conducted on 633 MCI patients and 145 subjects with dementia through 4726 visits over 15 years from Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. A combination of data from AT(N) profiles at baseline and longitudinal predictive modeling was applied. A data-driven approach was proposed for categorical diagnosis prediction and timeline estimation of cognitive decline progression, which combined supervised and unsupervised learning techniques.</p><p><strong>Results: </strong>A reduced vector of only neuropsychological measures was selected for training the models. At baseline, this approach had high performance in detecting subjects at high risk of converting from MCI to dementia in the coming years. Furthermore, a Disease Progression Model (DPM) was built and also verified using three metrics. As a result of the DPM focused on the studied population, it was inferred that amyloid pathology (A+) appears about 7 years before dementia, and tau pathology (T+) and neurodegeneration (N+) occur almost simultaneously, between 3 and 4 years before dementia. In addition, MCI-A+ subjects were shown to progress more rapidly to dementia compared to MCI-A- subjects.</p><p><strong>Conclusion: </strong>Based on proposed natural histories and cross-sectional and longitudinal analysis of AD markers, the results indicated that only a single cerebrospinal fluid sample is necessary during the prodromal phase of AD. Prediction from MCI into dementia and its timeline can be achieved exclusively through neuropsychological measures.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"778-790"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998795","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}