{"title":"Morphometric Analysis of Corpus Callosum in Individuals with Alzheimer's Disease: Magnetic Resonance Imaging (MRI) Study.","authors":"Musa Acar, Sultan Uğur","doi":"10.2174/0115672050335744240820065952","DOIUrl":"10.2174/0115672050335744240820065952","url":null,"abstract":"<p><strong>Introduction: </strong>The Corpus Callosum (CC) is the largest commissural tract in the nervous system. Few studies have examined the extent of CC in Alzheimer's disease (AD) patients, and these studies have reported conflicting findings.</p><p><strong>Materials and methods: </strong>The study was performed using 176 brain MRI images of 88 Alzheimer's patients (55 women-32 men) and 88 healthy individuals (44 women-44 men).</p><p><strong>Results: </strong>In our study, 7 different parameters of the CC were measured, and their average values were determined. We measured each parameter separately in AD patients and healthy individuals and compared them with each other.</p><p><strong>Conclusion: </strong>CC has an important place not only in Patients with AD but also in other neurodegenerative diseases. We consider that our study will be useful in the evaluation of Patients with AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"289-294"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038160","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":"Drive My CAR-AD Research here, there and Everywhere.","authors":"Juan Manuel Górriz Sáez","doi":"10.2174/156720502101240524145811","DOIUrl":"https://doi.org/10.2174/156720502101240524145811","url":null,"abstract":"","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":"21 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636394","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}
Hatice Yuksel, Elif Bademci Eren, Baris Maldar, Ayse Pinar Titiz
{"title":"The Importance of Long-term Partner Observation in Cognitive Evaluation: A Very Early Creutzfeldt-Jakob Disease in a Patient with Mild Cognitive Impairment.","authors":"Hatice Yuksel, Elif Bademci Eren, Baris Maldar, Ayse Pinar Titiz","doi":"10.2174/0115672050309694240708052535","DOIUrl":"10.2174/0115672050309694240708052535","url":null,"abstract":"<p><strong>Background: </strong>Creutzfeldt-Jakob disease (CJD) is a fatal degenerative brain disease characterized by rapidly progressive dementia. Sporadic CJD (sCJD) is the best-known and most common subtype. Because the disease is uncommon and has highly diverse presenting symptoms, early diagnosis is challenging. We herein report a case of probable sCJD diagnosed at a very early stage.</p><p><strong>Case presentation: </strong>A 61-year-old female patient had mild attention and memory problems for a few months that were noticed by her husband but did not bother her and did not affect her daily life activities. The first brain magnetic resonance imaging (MRI) at another hospital was normal, lacking diffusion-weighted imaging (DWI). Although the newly taken brain MRI without DWI was normal, the patient's husband brought his patient to our outpatient clinic because he continued to think that there was a difference in his wife's attention and memory. A neurological examination of the patient revealed almost normal findings. The neuropsychiatric evaluation of the patient was consistent with mild cognitive impairment. The patient's electroencephalography taken upon admission had no characteristic findings for CJD but showed generalized epileptiform activity. Therefore, the patient was hospitalized, and a second brain MRI, including DWI sequences, was performed. DWI displayed bilateral asymmetrical typical patterns of restricted diffusion. Cerebrospinal fluid 14-3-3 was positive, and total-tau was highly elevated. She had a diagnosis of probable sCJD at an early stage. Later, the patient developed progressive dementia, ataxia, seizures, and extrapyramidal symptoms, followed by mutism, and died.</p><p><strong>Conclusion: </strong>Although there is no cure for CJD today, early diagnosis is essential, mainly because of its potential infectivity and for future planning. Diagnosing sCJD in its early stages is difficult. However, taking into account the observations of not only the patient's history but also their longterm partners in cognitive evaluations will be helpful in making an early and accurate diagnosis.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"214-218"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750155","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}
Mohamed T Almeaqli, Yazeed Alaidaa, Faisal M Alnajjar, Abdullah S Al Shararh, Danah S Alharbi, Yazeed I Almslmani, Yousef A Alotibi, Hani S Alrashidi, Wael A Alshehri, Hanan M Hassan, Mohammed M H Al-Gayyar
{"title":"Therapeutic Effects of Arctiin on Alzheimer's Disease-like Model in Rats by Reducing Oxidative Stress, Inflammasomes and Fibrosis.","authors":"Mohamed T Almeaqli, Yazeed Alaidaa, Faisal M Alnajjar, Abdullah S Al Shararh, Danah S Alharbi, Yazeed I Almslmani, Yousef A Alotibi, Hani S Alrashidi, Wael A Alshehri, Hanan M Hassan, Mohammed M H Al-Gayyar","doi":"10.2174/0115672050333388240801043509","DOIUrl":"10.2174/0115672050333388240801043509","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic.</p><p><strong>Objectives: </strong>We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.</p><p><strong>Methods: </strong>AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.</p><p><strong>Results: </strong>In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.</p><p><strong>Conclusion: </strong>Arctiin can enhance rats' behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-β. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"276-288"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972521","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":"Plasma Biomarkers in Neurodegenerative Dementias: Unrevealing the Potential of Serum Oxytocin, BDNF, NPTX1, TREM2, TNF-alpha, IL-1 and Prolactin.","authors":"Yeşim Olğun, Cana Aksoy Poyraz, Melda Bozluolçay, Dildar Konukoğlu, Burç Çağrı Poyraz","doi":"10.2174/0115672050313419240520051751","DOIUrl":"10.2174/0115672050313419240520051751","url":null,"abstract":"<p><strong>Background: </strong>Dementia encompasses a range of neurodegenerative disorders characterized by cognitive decline and functional impairment. The identification of reliable biomarkers is essential for accurate diagnosis and gaining insights into the mechanisms underlying diseases.</p><p><strong>Objective: </strong>This study aimed to investigate the plasma biomarker profiles associated with Brain- Derived Neurotrophic Factor (BDNF), Oxytocin, Neuronal Pentraxin-1 (NPTX1), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin- 1 (IL-1) and Prolactin in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD) and healthy controls.</p><p><strong>Methods: </strong>Serum levels of the aforementioned biomarkers were analyzed in 23 AD, 28 DLB, 15 FTD patients recruited from outpatient units and 22 healthy controls. Diagnostic evaluations followed established criteria and standardized clinical tests were conducted. Blood samples were collected and analyzed using ELISA and electrochemiluminescence immunoassay methods.</p><p><strong>Results: </strong>Serum BDNF and oxytocin levels did not significantly differ across groups. NPTX1, TREM2, TNF-alpha and IL-1 levels also did not show significant differences among dementia groups. However, prolactin levels exhibited distinct patterns, with lower levels in male DLB patients and higher levels in female AD patients compared to controls.</p><p><strong>Conclusion: </strong>The study findings suggest potential shared mechanisms in dementia pathophysiology and highlight the importance of exploring neuroendocrine responses, particularly in AD and DLB. However, further research is warranted to elucidate the role of these biomarkers in dementia diagnosis and disease progression.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"109-119"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158674","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}
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
{"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}
Binbin Yu, Guomeng Wan, Shupeng Cheng, Pengcheng Wen, Xi Yang, Jiahuan Li, Huifang Tian, Yaxin Gao, Qian Zhong, Jin Liu, Jianan Li, Yi Zhu
{"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}
Ming-Zhan Zhang, Yan Sun, Yan-Ming Chen, Fan Guo, Pei-Yang Gao, Lan Tan, Meng-Shan Tan
{"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-β<sub>42</sub> (Aβ<sub>42</sub>), 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 Aβ<sub>42</sub> (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}