NPJ dementia最新文献

Non-coding variation in dementias: mechanisms, insights, and challenges. 痴呆的非编码变异：机制、见解和挑战。

NPJ dementia Pub Date : 2025-01-01 Epub Date: 2025-06-03 DOI: 10.1038/s44400-025-00012-4

Brianne B Rogers, J Nicholas Cochran

引用次数: 0

Augmenting radiological assessment of imaging evident dementias with radiomic analysis. 放射组学分析增强影像学明显痴呆的放射学评估。

NPJ dementia Pub Date : 2025-01-01 Epub Date: 2025-10-01 DOI: 10.1038/s44400-025-00031-1

Shreyas Puducheri, Olivia T Zhou, Krish Kapadia, Michael F Romano, Siddarth Yalamanchili, Armaan Agrawal, V Carlota Andreu-Arasa, Chad W Farris, Asim Z Mian, Aaron B Paul, Saurabh Rohatgi, Bindu N Setty, Juan E Small, Vijaya B Kolachalama

{"title":"Augmenting radiological assessment of imaging evident dementias with radiomic analysis.","authors":"Shreyas Puducheri, Olivia T Zhou, Krish Kapadia, Michael F Romano, Siddarth Yalamanchili, Armaan Agrawal, V Carlota Andreu-Arasa, Chad W Farris, Asim Z Mian, Aaron B Paul, Saurabh Rohatgi, Bindu N Setty, Juan E Small, Vijaya B Kolachalama","doi":"10.1038/s44400-025-00031-1","DOIUrl":"10.1038/s44400-025-00031-1","url":null,"abstract":"Accurate differential diagnosis of dementia is essential for guiding timely treatment, particularly as anti-amyloid therapies become more widely available and require precise patient characterization. Here, we developed a radiomics-based machine learning (ML) approach to enhance neuroimaging assessments in distinguishing Alzheimer's disease (AD) from other imaging-evident dementias (OIED). We retrospectively analyzed 1041 individuals from the National Alzheimer's Coordinating Center with confirmed dementia diagnoses and at least one T1 or T2/FLAIR MRI scan. Using FastSurfer and a Lesion Prediction Algorithm, we extracted volumetric and lesion features, which were then used to train ML models. Model performance was compared to the independent evaluations of seven fellowship-trained neuroradiologists. The classifier achieved an AUROC of 0.79 ± 0.01 for AD and 0.66 ± 0.03 for OIED, performing comparably to expert assessments. Interpretation using SHAP values showed strong alignment with imaging features known to align with AD or OIED, respectively. These findings highlight the potential of radiomics to augment neuroimaging workflows.","PeriodicalId":520469,"journal":{"name":"NPJ dementia","volume":"1 1","pages":"27"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating causal networks of dementia using causal discovery and natural language processing models. 使用因果发现和自然语言处理模型调查痴呆的因果网络。

NPJ dementia Pub Date : 2025-01-01 Epub Date: 2025-05-09 DOI: 10.1038/s44400-025-00006-2

Xinzhu Yu, Artitaya Lophatananon, Vivien Holmes, Kenneth R Muir, Hui Guo

{"title":"Investigating causal networks of dementia using causal discovery and natural language processing models.","authors":"Xinzhu Yu, Artitaya Lophatananon, Vivien Holmes, Kenneth R Muir, Hui Guo","doi":"10.1038/s44400-025-00006-2","DOIUrl":"https://doi.org/10.1038/s44400-025-00006-2","url":null,"abstract":"Comprehensively studying modifiable risk factors to understand their contributions to dementia mechanisms is imperative. This study used natural language processing (NLP) models to pre-select candidate risk factors for dementia from 5505 baseline variables in the UK Biobank. We then applied causal discovery approaches to examine the relationships among the selected variables and their links to dementia in later life, presenting these connections in a causal network. We identified eight risk factors that directly or indirectly influence dementia, with mental disorders due to brain dysfunction (ICD-10 F06) acting as direct causes and mediators in pathways from other neurological disorders to dementia. Although evidence for the direct link between biological age and dementia was less pronounced, its potential value in dementia management remains non-negligible. This study advances our understanding of dementia mechanisms and highlights the potential of NLP and machine learning for the causal discovery of complex diseases from high-dimensional data.","PeriodicalId":520469,"journal":{"name":"NPJ dementia","volume":"1 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiplex digital spatial profiling identifies subregion dependent targeted proteome changes across variants of dementia. 多重数字空间分析确定了痴呆症变体中依赖于亚区域的靶向蛋白质组变化。

NPJ dementia Pub Date : 2025-01-01 Epub Date: 2025-06-03 DOI: 10.1038/s44400-025-00010-6

MacKenzie L Bolen, Kelly B Menees, Marla Gearing, Jingjing Gong, Yuqi Ren, Andrea R Merchak, Melissa E Murray, Zachary T McEachin, Malú Gámez Tansey

{"title":"Multiplex digital spatial profiling identifies subregion dependent targeted proteome changes across variants of dementia.","authors":"MacKenzie L Bolen, Kelly B Menees, Marla Gearing, Jingjing Gong, Yuqi Ren, Andrea R Merchak, Melissa E Murray, Zachary T McEachin, Malú Gámez Tansey","doi":"10.1038/s44400-025-00010-6","DOIUrl":"10.1038/s44400-025-00010-6","url":null,"abstract":"Frontotemporal lobar degeneration (FTLD) is the leading cause of dementia in patients under the age of 65. Even in a single anatomical region, there is variance within pathological protein deposition within the FTLD spectrum, which drives difficulty in post-mortem clinicopathological diagnoses. We spatially multiplexed the proteome geography at two levels of the cortex and the subcortical white matter in patients with various types of dementia (Alzheimer's disease, C9orf72, MAPT also referred to as FTLD-tau, FTLD-TDP, FTLD-GRN; n = 6 per syndrome) and neurologically healthy controls (NHC). Layers II-V of the cortex from diseased individuals displayed the greatest protein dysregulation as compared to NHC. Traditional biomarkers of dementia, like phosphorylated tau proteins and Aβ42 displayed dysregulation, however, our data suggest spatial enrichment distinct to cortical sublayers. In conclusion, the specific localization of these protein deposits could be used to elucidate region-specific pathologic biomarkers unique to individual variants of dementia.","PeriodicalId":520469,"journal":{"name":"NPJ dementia","volume":"1 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Risk factors and predictors for Lewy body dementia: a systematic review. 路易体痴呆的危险因素和预测因素：一项系统综述。

NPJ dementia Pub Date : 2025-01-01 Epub Date: 2025-08-04 DOI: 10.1038/s44400-025-00022-2

Ahalya Ratnavel, Francesca R Dino, Celina Jiang, Sarah Azmy, Kathryn A Wyman-Chick, Ece Bayram

{"title":"Risk factors and predictors for Lewy body dementia: a systematic review.","authors":"Ahalya Ratnavel, Francesca R Dino, Celina Jiang, Sarah Azmy, Kathryn A Wyman-Chick, Ece Bayram","doi":"10.1038/s44400-025-00022-2","DOIUrl":"10.1038/s44400-025-00022-2","url":null,"abstract":"Lewy body dementia (LBD), including Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), is a common and burdensome dementia. Determining risk factors and predictors can provide insights into pathogenesis and guide treatment efforts. In this systematic review, we searched PubMed, Embase, and Web of Science for longitudinal studies assessing risk/prodromal factors; including participants without dementia at baseline; with LBD as the outcome; with good/high quality based on the Newcastle-Ottawa Quality Assessment Scale. Across 167 included studies, more consistently reported factors were older age, male sex, APOEe4, GBA, changes in cognition, mood, behavior, sleep, gait/posture, speech, parkinsonism, smell loss, autonomic dysfunction, white matter disease on MRI, lower CSF amyloid β42 and higher CSF/blood neurofilament light chain. The majority focused on clinical factors preceding PDD with cohorts from North America and Europe, limiting generalizability. Further efforts with more representative cohorts are needed to better identify people at risk for LBD.","PeriodicalId":520469,"journal":{"name":"NPJ dementia","volume":"1 1","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Case of early onset Alzheimer's disease associated with a novel PSEN1 variant identified in Colombia. 哥伦比亚发现一种新型PSEN1变异相关的早发性阿尔茨海默病病例

NPJ dementia Pub Date : 2025-01-01 Epub Date: 2025-10-10 DOI: 10.1038/s44400-025-00036-w

Lina M Zapata-Restrepo, Bruce L Miller, Juan Rivas, Katherine Possin, Victor Valcour, Stefanie D Piña-Escudero, Agustin Ibañez, Kenneth S Kosik

{"title":"Case of early onset Alzheimer's disease associated with a novel PSEN1 variant identified in Colombia.","authors":"Lina M Zapata-Restrepo, Bruce L Miller, Juan Rivas, Katherine Possin, Victor Valcour, Stefanie D Piña-Escudero, Agustin Ibañez, Kenneth S Kosik","doi":"10.1038/s44400-025-00036-w","DOIUrl":"10.1038/s44400-025-00036-w","url":null,"abstract":"Early-onset Alzheimer's disease (EOAD) is a rare form of dementia that often progresses more quickly than late-onset cases, and is more commonly associated with autosomal dominant mutations. A 47-year-old male presented with progressive cognitive and behavioral decline, a family history of EOAD, and was later found to have a novel pathogenic PSEN1 variant (c.519 G > T, p.Leu173Phe). Initial evaluations, including neuroimaging and laboratory tests, were unremarkable. Neuropsychological testing later revealed memory impairment, executive dysfunction, and neuropsychiatric symptoms. These features, alongside the identified mutation, are consistent with phenotypic presentations of EOAD involving the third transmembrane domain of PSEN1. Pharmacological treatment with cholinesterase inhibitors and antipsychotics yielded limited benefit. Notably, the extended follow-up time, of more than 10 years from the early symptomatic stage, is a unique and valuable feature of this case study, providing rare longitudinal insight into the natural course of genetically confirmed EOAD.","PeriodicalId":520469,"journal":{"name":"NPJ dementia","volume":"1 1","pages":"31"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Phase IIa clinical trial to evaluate the effects of anti-retroviral therapy in Alzheimer's disease (ART-AD). 一项评估抗逆转录病毒治疗阿尔茨海默病（ART-AD）效果的IIa期临床试验。

NPJ dementia Pub Date : 2025-01-01 Epub Date: 2025-03-12 DOI: 10.1038/s44400-024-00001-z

A Campbell Sullivan, Gabrielle Zuniga, Paulino Ramirez, Roman Fernandez, Chen-Pin Wang, Ji Li, Lisa Davila, Kristine Pelton, Sandra Gomez, Claira Sohn, Elias Gonzalez, Marisa Lopez-Cruzan, David A Gonzalez, Alicia Parker, Eduardo Zilli, Gabriel A de Erausquin, Sudha Seshadri, Sara Espinoza, Nicolas Musi, Bess Frost

{"title":"A Phase IIa clinical trial to evaluate the effects of anti-retroviral therapy in Alzheimer's disease (ART-AD).","authors":"A Campbell Sullivan, Gabrielle Zuniga, Paulino Ramirez, Roman Fernandez, Chen-Pin Wang, Ji Li, Lisa Davila, Kristine Pelton, Sandra Gomez, Claira Sohn, Elias Gonzalez, Marisa Lopez-Cruzan, David A Gonzalez, Alicia Parker, Eduardo Zilli, Gabriel A de Erausquin, Sudha Seshadri, Sara Espinoza, Nicolas Musi, Bess Frost","doi":"10.1038/s44400-024-00001-z","DOIUrl":"10.1038/s44400-024-00001-z","url":null,"abstract":"Retrotransposons constitute over 40% of the human genome. Studies in Drosophila, mice, cultured cells, and human brain show that retrotransposons are activated in tauopathies, including Alzheimer's disease, and causally drive neurodegeneration. The reverse transcriptase inhibitor 3TC (lamivudine) reduces retrotransposon activation and suppresses tau neurotoxicity among model systems. This phase 2a open-label trial (Pilot Study to Investigate the Safety and Feasibility of Anti-Retroviral Therapy for Alzheimer's Disease, NCT04552795, registered 09/10/2020) followed 12 participants with early Alzheimer's disease (MMSE > 24, CDR = 0.5) over 24 weeks to assess safety, tolerability, and feasibility of daily 300 mg 3TC treatment. The sample was well-educated (12-20 years) and culturally diverse (25% from underrepresented groups). In addition to a favorable safety profile and stable cognitive measures, notable significant changes in fluid-based biomarkers include reduction of glial fibrillary acidic protein (GFAP) (P = 0.03) in CSF, suggestive of reduced neuroinflammation, and elevation of Aβ42/40 (P = 0.009) in plasma, suggestive of reduced plaque load in the brain. These results warrant further exploration in a larger, placebo-controlled trial.","PeriodicalId":520469,"journal":{"name":"NPJ dementia","volume":"1 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High inter-rater reliability in consensus diagnoses and overall assessment in the Asian Cohort for Alzheimer's Disease Study. 阿尔茨海默病亚洲队列研究中共识诊断和总体评估的高可靠性

NPJ dementia Pub Date : 2025-01-01 Epub Date: 2025-07-30 DOI: 10.1038/s44400-025-00015-1

Yara Alkhodair, Ging-Yuek R Hsiung, Boon Lead Tee, Pei-Chuan Ho, Phoenix Au Yeung, Wai Haung Yu, Guerry Peavy, Victor W Henderson, Yun-Beom Choi, Clara Li, Dolly Reyes-Dumeyer, Haeok Lee, Walter A Kukull

引用次数: 0

Identifying obesity and dementia risk: body adiposity and neural connectivity in cognitively normal, mid-life adults. 识别肥胖和痴呆风险：认知正常的中年成年人的身体肥胖和神经连通性。

NPJ dementia Pub Date : 2025-01-01 Epub Date: 2025-09-16 DOI: 10.1038/s44400-025-00028-w

Won Jong Chwa, Farzaneh Rahmani, Mahsa Dolatshahi, Paul K Commean, Sara H Kassani, Lanya T Cai, Pratik Mukherjee, Cyrus A Raji

{"title":"Identifying obesity and dementia risk: body adiposity and neural connectivity in cognitively normal, mid-life adults.","authors":"Won Jong Chwa, Farzaneh Rahmani, Mahsa Dolatshahi, Paul K Commean, Sara H Kassani, Lanya T Cai, Pratik Mukherjee, Cyrus A Raji","doi":"10.1038/s44400-025-00028-w","DOIUrl":"10.1038/s44400-025-00028-w","url":null,"abstract":"Obesity is a risk factor for dementia, creating a chronic inflammatory state that results in white matter (WM) injury. Edge density imaging (EDI) is a novel technique that has demonstrated reliability in quantifying WM changes. Thirty obese and 20 non-obese cognitively normal adults underwent structural and diffusion-weighted magnetic resonance imaging. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were quantified via VOXel Analysis Suite by separating signal intensities of adipose and non-adipose tissue. Scans were processed by a pipeline (MaPPeRTrac) to generate EDI. Among obese participants, there was a negative association between the VAT/SAT ratio and EDI, which was not seen among non-obese participants. Additionally, males had decreased EDI compared to females. The results of this study suggest that obesity, through WM damage, may confer increased risk of dementia, with sex as a potential differential factor. EDI demonstrates promise in delineating the neuropathology of obesity and dementia.","PeriodicalId":520469,"journal":{"name":"NPJ dementia","volume":"1 1","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cysteine string protein α and a link between rare and common neurodegenerative dementias. 半胱氨酸弦蛋白α与罕见和常见的神经退行性痴呆之间的联系。

NPJ dementia Pub Date : 2025-01-01 Epub Date: 2025-07-03 DOI: 10.1038/s44400-025-00016-0

Matthew J Rosene, Bruno A Benitez

{"title":"Cysteine string protein α and a link between rare and common neurodegenerative dementias.","authors":"Matthew J Rosene, Bruno A Benitez","doi":"10.1038/s44400-025-00016-0","DOIUrl":"10.1038/s44400-025-00016-0","url":null,"abstract":"The maintenance of protein homeostasis and overall protein quality control dysfunction are associated with dementia. Cysteine string protein α (CSPα) is an endolysosomal cochaperone that facilitates the fusion of secretory and synaptic vesicles to the cell membrane. CSPα interacts with multiple proteins related to the proteostasis network and exocytic pathways and is often dysfunctional in synaptopathies. Since the initial discovery of CSPα 30 years ago, subsequent research has demonstrated a protective role of CSPα, especially in synaptic maintenance. However, the discovery of heterozygous CSPα mutations in 2011 causing adult-onset neuronal ceroid lipofuscinosis (ANCL) shifted the back-then prevalent dogma of unique synaptic function to include an endolysosomal role for CSPα. Recently, CSPα has been involved in the exocytosis of aggregate-prone proteins through either the misfolding-associated protein secretion (MAPS) or unconventional secretory pathways linking the molecular mechanism of rare and common neurodegenerative diseases. Here, we propose a novel molecular and pathophysiological model of CSPα-associated dementia, outline the increasing evidence of a broader role of CSPα in neurodegeneration, propose the role of CSPα in the synaptic secretion of neurodegenerative-associated proteins, and discuss the modulation of CSPα as a molecular target for common dementias.","PeriodicalId":520469,"journal":{"name":"NPJ dementia","volume":"1 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0