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A novel spatiotemporal graph convolutional network framework for functional connectivity biomarkers identification of Alzheimer’s disease Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-14 Ying Zhang, Le Xue, Shuoyan Zhang, Jiacheng Yang, Qi Zhang, Min Wang, Luyao Wang, Mingkai Zhang, Jiehui Jiang, Yunxia Li
Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer’s disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to
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Differences in the treatment needs of patients with dementia with Lewy bodies and their caregivers and differences in their physicians’ awareness of those treatment needs according to the clinical department visited by the patients: a subanalysis of an observational survey study Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-14 Manabu Ikeda, Shunji Toya, Yuta Manabe, Hajime Yamakage, Mamoru Hashimoto
We investigated whether the treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers, along with their attending physicians’ perception of those treatment needs, differ according to the clinical department visited by the patients. This was a subanalysis of a multicenter, cross-sectional, observational survey study. Data from the main study were classified according to the
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Sex matters in the association between cardiovascular health and incident dementia: evidence from real world data Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-14 Anna Ponjoan, Jordi Blanch, Ester Fages-Masmiquel, Ruth Martí-Lluch, Lia Alves-Cabratosa, María del Mar Garcia-Gil, Gina Domínguez-Armengol, Francesc Ribas-Aulinas, Lluís Zacarías-Pons, Rafel Ramos
Cardiovascular health has been associated with dementia onset, but little is known about the variation of such association by sex and age considering dementia subtypes. We assessed the role of sex and age in the association between cardiovascular risk and the onset of all-cause dementia, Alzheimer’s disease, and vascular dementia in people aged 50–74 years. This is a retrospective cohort study covering
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The associations of herpes simplex virus and varicella zoster virus infection with dementia: a nationwide retrospective cohort study Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-12 Eunhae Shin, Sang Ah Chi, Tae-Young Chung, Hee Jin Kim, Kyunga Kim, Dong Hui Lim
In this study, the risk of dementia in patients with a history of herpes simplex virus (HSV) or varicella zoster virus (VZV) infection was evaluated. This nationwide cohort study used data from the Korean National Health Insurance Service collected between 2006 and 2017. A total of 752,205 subjects ≥ 45 years of age not diagnosed with dementia until 2006 were included. A multivariate Cox regression
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Amyloid β oligomer induces cerebral vasculopathy via pericyte-mediated endothelial dysfunction Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-12 Siqi Chen, Daji Guo, Yuanyuan Zhu, Songhua Xiao, Jiatian Xie, Zhan Zhang, Yu Hu, Jialin Huang, Xueying Ma, Zhiyuan Ning, Lin Cao, Jinping Cheng, Yamei Tang
Although abnormal accumulation of amyloid beta (Aβ) protein is thought to be the main cause of Alzheimer’s disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid β induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aβ deposition and vascular
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Plasma oligomer beta-amyloid is associated with disease severity and cerebral amyloid deposition in Alzheimer’s disease spectrum Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-11 Sheng-Min Wang, Dong Woo Kang, Yoo Hyun Um, Sunghwan Kim, Chang Uk Lee, Philip Scheltens, Hyun Kook Lim
Multimer detection system-oligomeric amyloid-β (MDS-OAβ) is a measure of plasma OAβ, which is associated with Alzheimer’s disease (AD) pathology. However, the relationship between MDS-OAβ and disease severity of AD is not clear. We aimed to investigate MDS-OAβ levels in different stages of AD and analyze the association between MDS-OAβ and cerebral Aβ deposition, cognitive function, and cortical thickness
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Prediction of conversion from mild cognitive impairment to Alzheimer’s disease and simultaneous feature selection and grouping using Medicaid claim data Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-09 Qi Zhang, Ron Coury, Wenlong Tang
Due to the heterogeneity among patients with Mild Cognitive Impairment (MCI), it is critical to predict their risk of converting to Alzheimer’s disease (AD) early using routinely collected real-world data such as the electronic health record data or administrative claim data. The study used MarketScan Multi-State Medicaid data to construct a cohort of MCI patients. Logistic regression with tree-guided
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Deciphering the effect of phytosterols on Alzheimer’s disease and Parkinson’s disease: the mediating role of lipid profiles Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-09 Xingzhi Guo, Jing Yu, Rui Wang, Ning Peng, Rui Li
Studies have suggested that blood circulating phytosterols, plant-derived sterols analogous to cholesterol, were associated with blood lipid levels and the risk of Alzheimer’s disease (AD) and Parkinson’s disease (PD). This Mendelian randomization (MR) study is performed to determine the causal effect of circulating phytosterols on AD and PD and evaluate the mediation effect of blood lipids. Leveraging
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Characterization of preclinical Alzheimer’s disease model: spontaneous type 2 diabetic cynomolgus monkeys with systemic pro-inflammation, positive biomarkers and developing AD-like pathology Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-08 Xinxin Huang, Shanshan Huang, Fangyan Fu, Junzhen Song, Yuling Zhang, Feng Yue
The key to the prevention and treatment of Alzheimer’s disease (AD) is to be able to predict and diagnose AD at the preclinical or early stage, but the lack of a preclinical model of AD is the critical factor that causes this problem to remain unresolved. We assessed 18 monkeys in vivo evaluation of pro-inflammatory cytokines and AD pathological biomarkers (n = 9 / type 2 diabetic mellitus (T2DM) group
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Exploring the potential of fully automated LUMIPULSE G plasma assays for detecting Alzheimer’s disease pathology Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-07 Anuschka Silva-Spínola, Maria João Leitão, Alicia Nadal, Nathalie Le Bastard, Isabel Santana, Inês Baldeiras
LUMIPULSE G-automated immunoassays represent a widely used method for the quantification of Alzheimer’s disease (AD) biomarkers in the cerebrospinal fluid (CSF). Less invasive blood-based markers confer a promising tool for AD diagnosis at prodromal stages (mild cognitive impairment (MCI)). Highly sensitive assays for the quantification of amyloid-beta (Aβ) and phosphorylated Tau-181 (p-Tau181) in
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Association between brain amyloid deposition and longitudinal changes of white matter hyperintensities Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-07 Woo-Jin Cha, Dahyun Yi, Hyejin Ahn, Min Soo Byun, Yoon Young Chang, Jung-Min Choi, Kyungtae Kim, Hyeji Choi, Gijung Jung, Koung Mi Kang, Chul-Ho Sohn, Yun-Sang Lee, Yu Kyeong Kim, Dong Young Lee
Growing evidence suggests that not only cerebrovascular disease but also Alzheimer’s disease (AD) pathological process itself cause cerebral white matter degeneration, resulting in white matter hyperintensities (WMHs). Some preclinical evidence also indicates that white matter degeneration may precede or affect the development of AD pathology. This study aimed to clarify the direction of influence
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Heterogeneity and overlap in the continuum of linguistic profile of logopenic and semantic variants of primary progressive aphasia: a Profile Analysis based on Multidimensional Scaling study Alz. Res. Therapy (IF 8.823) Pub Date : 2024-03-07 Gaia Chiara Santi, Francesca Conca, Valentina Esposito, Cristina Polito, Silvia Paola Caminiti, Cecilia Boccalini, Carmen Morinelli, Valentina Berti, Salvatore Mazzeo, Valentina Bessi, Alessandra Marcone, Sandro Iannaccone, Se-Kang Kim, Sandro Sorbi, Daniela Perani, Stefano F. Cappa, Eleonora Catricalà
Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce. Lexical, semantic, phonological, and
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Progression analysis versus traditional methods to quantify slowing of disease progression in Alzheimer’s disease Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-29 Linus Jönsson, Milana Ivkovic, Alireza Atri, Ron Handels, Anders Gustavsson, Julie Hviid Hahn-Pedersen, Teresa León, Mathias Lilja, Jens Gundgaard, Lars Lau Raket
The clinical meaningfulness of the effects of recently approved disease-modifying treatments (DMT) in Alzheimer’s disease is under debate. Available evidence is limited to short-term effects on clinical rating scales which may be difficult to interpret and have limited intrinsic meaning to patients. The main value of DMTs accrues over the long term as they are expected to cause a delay or slowing of
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Correction: Reduction of NgR in perforant path decreases amyloid-β peptide production and ameliorates synaptic and cognitive deficits in APP/PS1 mice Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-27 Rong Jiang, Xue-Fei Wu, Bin Wang, Rong-Xiao Guan, Lang-Man Lv, Ai-Ping Li, Lei Lei, Ye Ma, Na Li, Qi-Fa Li, Quan-Hong Ma, Jie Zhao, Shao Li
Correction: Alz Res Therapy 12, 47 (2020) https://doi.org/10.1186/s13195-020-00616-3 Following publication of the original article [1], the authors identified an error in Fig. 6C (a). The corrected Fig. 6C(a) with the correct band and original data is given hereafter. The incorrect Fig. 6: Fig. 6 NgR reduction promotes APP trafficking to lysosomes by Rho/ROCK2 pathway. A (a, b) Representative bands
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Machine learning prediction of future amyloid beta positivity in amyloid-negative individuals Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-27 Elaheh Moradi, Mithilesh Prakash, Anette Hall, Alina Solomon, Bryan Strange, Jussi Tohka
The pathophysiology of Alzheimer’s disease (AD) involves $$\beta$$ -amyloid (A $$\beta$$ ) accumulation. Early identification of individuals with abnormal $$\beta$$ -amyloid levels is crucial, but A $$\beta$$ quantification with positron emission tomography (PET) and cerebrospinal fluid (CSF) is invasive and expensive. We propose a machine learning framework using standard non-invasive (MRI, demographics
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Polygenic effects on the risk of Alzheimer’s disease in the Japanese population Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-27 Masataka Kikuchi, Akinori Miyashita, Norikazu Hara, Kensaku Kasuga, Yuko Saito, Shigeo Murayama, Akiyoshi Kakita, Hiroyasu Akatsu, Kouichi Ozaki, Shumpei Niida, Ryozo Kuwano, Takeshi Iwatsubo, Akihiro Nakaya, Takeshi Ikeuchi
Polygenic effects have been proposed to account for some disease phenotypes; these effects are calculated as a polygenic risk score (PRS). This score is correlated with Alzheimer’s disease (AD)-related phenotypes, such as biomarker abnormalities and brain atrophy, and is associated with conversion from mild cognitive impairment (MCI) to AD. However, the AD PRS has been examined mainly in Europeans
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GOIZ ZAINDU study: a FINGER-like multidomain lifestyle intervention feasibility randomized trial to prevent dementia in Southern Europe Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-27 Mikel Tainta, Mirian Ecay-Torres, Maria de Arriba, Myriam Barandiaran, Ane Otaegui-Arrazola, Ane Iriondo, Maite Garcia-Sebastian, Ainara Estanga, Jon Saldias, Montserrat Clerigue, Alazne Gabilondo, Naia Ros, Justo Mugica, Aitziber Barandiaran, Francesca Mangialasche, Miia Kivipelto, Arantzazu Arrospide, Javier Mar, Pablo Martinez-Lage
GOIZ ZAINDU (“caring early” in Basque) is a pilot study to adapt the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) methodology to the Basque population and evaluate the feasibility and adherence to a FINGER-like multidomain intervention program. Additional aims included the assessment of efficacy on cognition and data collection to design a large efficacy
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The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer’s disease continuum participants Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-20 Hui Hong, Luwei Hong, Xiao Luo, Qingze Zeng, Kaicheng Li, Shuyue Wang, Yeerfan Jiaerken, Ruiting Zhang, Xinfeng Yu, Yao Zhang, Cui Lei, Zhirong Liu, Yanxing Chen, Peiyu Huang, Minming Zhang
Glymphatic dysfunction is a crucial pathway for dementia. Alzheimer’s disease (AD) pathologies co-existing with cerebral small vessel disease (CSVD) is the most common pathogenesis for dementia. We hypothesize that AD pathologies and CSVD could be associated with glymphatic dysfunction, contributing to cognitive impairment. Participants completed with amyloid PET, diffusion tensor imaging (DTI), and
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Macular vessel density in the superficial plexus is not a proxy of cerebrovascular damage in non-demented individuals: data from the NORFACE cohort Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-20 Ainhoa García-Sánchez, Oscar Sotolongo-Grau, Juan Pablo Tartari, Ángela Sanabria, Ester Esteban - De Antonio, Alba Pérez-Cordón, Montserrat Alegret, Vanesa Pytel, Joan Martínez, Núria Aguilera, Itziar de Rojas, Amanda Cano, Pablo García-González, Raquel Puerta, Clàudia Olivé, Maria Capdevila, Fernando García-Gutiérrez, Assumpta Vivas, Marta Gómez-Chiari, Juan Giménez, Miguel Ángel Tejero, Miguel Castilla-Martí
Optical coherence tomography angiography (OCT-A) is a novel tool that allows the detection of retinal vascular changes. We investigated the association of macular vessel density (VD) in the superficial plexus assessed by OCT-A with measures of cerebrovascular pathology and atrophy quantified by brain magnetic resonance imaging (MRI) in non-demented individuals. Clinical, demographical, OCT-A, and brain
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Profiles of subgingival microbiomes and gingival crevicular metabolic signatures in patients with amnestic mild cognitive impairment and Alzheimer’s disease Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-19 Che Qiu, Wei Zhou, Hui Shen, Jintao Wang, Ran Tang, Tao Wang, Xinyi Xie, Bo Hong, Rujing Ren, Gang Wang, Zhongchen Song
The relationship between periodontitis and Alzheimer’s disease (AD) has attracted more attention recently, whereas profiles of subgingival microbiomes and gingival crevicular fluid (GCF) metabolic signatures in AD patients have rarely been characterized; thus, little evidence exists to support the oral-brain axis hypothesis. Therefore, our study aimed to characterize both the microbial community of
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The role of perfusion, grey matter volume and behavioural phenotypes in the data-driven classification of cognitive syndromes Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-17 Ashwati Vipin, Bernett Teck Kwong Lee, Dilip Kumar, See Ann Soo, Yi Jin Leow, Smriti Ghildiyal, Faith Phemie Hui En Lee, Saima Hilal, Nagaendran Kandiah
The use of structural and perfusion brain imaging in combination with behavioural information in the prediction of cognitive syndromes using a data-driven approach remains to be explored. Here, we thus examined the contribution of brain structural and perfusion imaging and behavioural features to the existing classification of cognitive syndromes using a data-driven approach. Study participants belonged
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Correction: Short leukocyte telomeres predict 25-year Alzheimer’s disease incidence in non-APOE ε4-carriers Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-16 Fernanda Schäfer Hackenhaar, Maria Josefsson, Annelie Nordin Adolfsson, Mattias Landfors, Karolina Kauppi, Magnus Hultdin, Rolf Adolfsson, Sofie Degerman, Sara Pudas
Correction: Alz Res Therapy 13, 130 (2021) https://doi.org/10.1186/s13195-021-00871-y Following the publication of the original article [1], the authors discovered that in contrast to what is stated in the article, the variable residualized leukocyte telomere length (rLTL) was not residualized for age, only gender. However, as the article describes, the effect of age and quadratic age were still accounted
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Genome-wide association study and polygenic risk scores of retinal thickness across the cognitive continuum: data from the NORFACE cohort Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-16 María Eugenia Sáez, Ainhoa García-Sánchez, Itziar de Rojas, Emilio Alarcón-Martín, Joan Martínez, Amanda Cano, Pablo García-González, Raquel Puerta, Clàudia Olivé, Maria Capdevila, Fernando García-Gutiérrez, Miguel Castilla-Martí, Luis Castilla-Martí, Ana Espinosa, Montserrat Alegret, Mario Ricciardi, Vanesa Pytel, Sergi Valero, Lluís Tárraga, Mercè Boada, Agustín Ruiz, Marta Marquié
Several studies have reported a relationship between retinal thickness and dementia. Therefore, optical coherence tomography (OCT) has been proposed as an early diagnosis method for Alzheimer’s disease (AD). In this study, we performed a genome-wide association study (GWAS) aimed at identifying genes associated with retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness
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The search for clarity regarding “clinically meaningful outcomes” in Alzheimer disease clinical trials: CLARITY-AD and Beyond Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-16 Rawan Tarawneh, Vernon S. Pankratz
CLARITY-AD is an 18-month, double-blinded, placebo-controlled, phase 3 trial which examined the safety and efficacy of the anti-amyloid agent, lecanemab, in mild cognitive impairment and mild dementia due to Alzheimer disease (AD). Lecanemab effectively reduced mean brain amyloid burden and was associated with statistically significant favorable effects, reflected by moderately less decline in the
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Relationships of change in Clinical Dementia Rating (CDR) on patient outcomes and probability of progression: observational analysis Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-15 Pierre N. Tariot, Mercè Boada, Krista L. Lanctôt, Julie Hahn-Pedersen, Firas Dabbous, Sariya Udayachalerm, Lars Lau Raket, Yuliya Halchenko, Wojciech Michalak, Wendy Weidner, Jeffrey Cummings
Understanding the relationship among changes in Clinical Dementia Rating (CDR), patient outcomes, and probability of progression is crucial for evaluating the long-term benefits of disease-modifying treatments. We examined associations among changes in Alzheimer’s disease (AD) stages and outcomes that are important to patients and their care partners including activities of daily living (ADLs), geriatric
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Impaired 24-h activity patterns are associated with an increased risk of Alzheimer’s disease, Parkinson’s disease, and cognitive decline Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-14 Joseph R. Winer, Renske Lok, Lara Weed, Zihuai He, Kathleen L. Poston, Elizabeth C. Mormino, Jamie M. Zeitzer
Sleep-wake regulating circuits are affected during prodromal stages in the pathological progression of both Alzheimer’s disease (AD) and Parkinson’s disease (PD), and this disturbance can be measured passively using wearable devices. Our objective was to determine whether accelerometer-based measures of 24-h activity are associated with subsequent development of AD, PD, and cognitive decline. This
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The use of synaptic biomarkers in cerebrospinal fluid to differentiate behavioral variant of frontotemporal dementia from primary psychiatric disorders and Alzheimer’s disease Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-14 Shreyasee Das, Marie-Paule E. van Engelen, Julie Goossens, Dirk Jacobs, Bram Bongers, Jay L. P. Fieldhouse, Yolande A. L. Pijnenburg, Charlotte E. Teunissen, Eugeen Vanmechelen, Inge M. W. Verberk
Lack of early molecular biomarkers in sporadic behavioral variants of frontotemporal dementia (bvFTD) and its clinical overlap with primary psychiatric disorders (PPD) hampers its diagnostic distinction. Synaptic dysfunction is an early feature in bvFTD and identification of specific biomarkers might improve its diagnostic accuracy. Our goal was to understand the differential diagnostic potential of
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Correction: Is later‑life depression a risk factor for Alzheimer’s disease or a prodromal symptom: a study using post‑mortem human brain tissue? Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-13 Lindsey I. Sinclair, Asher Mohr, Mizuki Morisaki, Martin Edmondson, Selina Chan, A. Bone‑Connaughton, Gustavo Turecki, Seth Love
Correction: Alz Res Therapy 15, 153 (2023) https://doi.org/10.1186/s13195-023-01299-2 Following the publication of the original article [1], the authors added the funder grant number (204813/Z/16/Z) of the Elizabeth-Blackwell institute for Health Research University of Bristol and the Wellcome Trust Institutional Strategic Support in Competing interests section. The original article [1] has been updated
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The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-12 Jie Wu, Zhenxu Xiao, Mengjing Wang, Wanqing Wu, Xiaoxi Ma, Xiaoniu Liang, Li Zheng, Saineng Ding, Jianfeng Luo, Yang Cao, Zhen Hong, Jing Chen, Qianhua Zhao, Ding Ding
The blood-based biomarkers are approaching the clinical practice of Alzheimer’s disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers. Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants
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Effects of certain pre-analytical factors on the performance of plasma phospho-tau217 Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-08 Divya Bali, Oskar Hansson, Shorena Janelidze
Pre-analytical factors can cause substantial variability in the measurements of cerebrospinal fluid (CSF) and plasma biomarkers of Alzheimer’s disease (AD). However, their effects on the performance of one of the most promising plasma AD biomarkers, phosphorylated tau (p-tau)217, are not known. We included 50 amyloid-β positive (Aβ+) and 50 Aβ− participants from the Swedish BioFINDER-1 study. Plasma
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Prevalence and trend of central nervous system–active medication polypharmacy among US commercially insured adults with vs without early-onset dementia: a multi-year cross-sectional study Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-08 Yu-Jung Jenny Wei, Nistha Shrestha, ChienWei Chiang, Steven T. DeKosky
Limited data exist on the prevalence and trend of central nervous system (CNS)-active medication polypharmacy among adults with early-onset dementia (EOD) and whether these estimates differ for adults without EOD but with chronic pain, depression, or epilepsy, conditions managed by CNS-active medications. A multi-year, cross-sectional study using 2012–2021 MarketScan Commercial Claims data was conducted
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DNA hypomethylation promotes the expression of CASPASE-4 which exacerbates inflammation and amyloid-β deposition in Alzheimer’s disease Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-08 Kylene P. Daily, Asmaa Badr, Mostafa Eltobgy, Shady Estfanous, Owen Whitham, Michelle H. Tan, Cierra Carafice, Kathrin Krause, Andrew McNamara, Kaitlin Hamilton, Samuel Houle, Spandan Gupta, Gauruv A. Gupta, Shruthi Madhu, Julie Fitzgerald, Abbey A. Saadey, Brooke Laster, Pearlly Yan, Amy Webb, Xiaoli Zhang, Maciej Pietrzak, Olga N. Kokiko-Cochran, Hazem E. Ghoneim, Amal O. Amer
Alzheimer’s disease (AD) is the sixth leading cause of death in the USA. It is established that neuroinflammation contributes to the synaptic loss, neuronal death, and symptomatic decline of AD patients. Accumulating evidence suggests a critical role for microglia, innate immune phagocytes of the brain. For instance, microglia release pro-inflammatory products such as IL-1β which is highly implicated
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Associations between cardiometabolic multimorbidity and cerebrospinal fluid biomarkers of Alzheimer’s disease pathology in cognitively intact adults: the CABLE study Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-06 Qiong-Yao Li, He-Ying Hu, Gao-Wen Zhang, Hao Hu, Ya-Nan Ou, Liang-Yu Huang, An-Yi Wang, Pei-Yang Gao, Li-Yun Ma, Lan Tan, Jin-Tai Yu
Cardiometabolic multimorbidity is associated with an increased risk of dementia, but the pathogenic mechanisms linking them remain largely undefined. We aimed to assess the associations of cardiometabolic multimorbidity with cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology to enhance our understanding of the underlying mechanisms linking cardiometabolic multimorbidity and
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Anodal HD-tDCS on the dominant anterior temporal lobe and dorsolateral prefrontal cortex: clinical results in patients with mild cognitive impairment Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-03 Soheila Rezakhani, Mahmood Amiri, Atefe Hassani, Khadijeh Esmaeilpour, Vahid Sheibani
Mild cognitive impairment (MCI) is a neurocognitive disorder in which the cognitive and mental abilities of humans are declined. Transcranial direct-current stimulation (tDCS) is an emerging noninvasive brain stimulation technique aimed at neuromodulation. In this study, we investigate whether high-definition anodal tDCS stimulation (anodal HD-tDCS) in MCI patients in two different brain regions will
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Unveiling the sound of the cognitive status: Machine Learning-based speech analysis in the Alzheimer’s disease spectrum Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-02 Fernando García-Gutiérrez, Montserrat Alegret, Marta Marquié, Nathalia Muñoz, Gemma Ortega, Amanda Cano, Itziar De Rojas, Pablo García-González, Clàudia Olivé, Raquel Puerta, Ainhoa García-Sanchez, María Capdevila-Bayo, Laura Montrreal, Vanesa Pytel, Maitee Rosende-Roca, Carla Zaldua, Peru Gabirondo, Lluís Tárraga, Agustín Ruiz, Mercè Boada, Sergi Valero
Advancement in screening tools accessible to the general population for the early detection of Alzheimer’s disease (AD) and prediction of its progression is essential for achieving timely therapeutic interventions and conducting decentralized clinical trials. This study delves into the application of Machine Learning (ML) techniques by leveraging paralinguistic features extracted directly from a brief
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Small vessel cerebrovascular disease is associated with cognition in prospective Alzheimer’s clinical trial participants Alz. Res. Therapy (IF 8.823) Pub Date : 2024-02-02 Clarissa D. Morales, Dejania Cotton-Samuel, Patrick J. Lao, Julia F. Chang, Jeffrey D. Pyne, Mohamad J. Alshikho, Rafael V. Lippert, Kelsang Bista, Christiane Hale, Natalie C. Edwards, Kay C. Igwe, Kacie Deters, Molly E. Zimmerman, Adam M. Brickman
Secondary prevention clinical trials for Alzheimer’s disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal
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Differential effects of cholesterol levels on cognition according to body mass index in Parkinson’s disease Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-31 Seong Ho Jeong, Seok Jong Chung, Han Soo Yoo, Jin Ho Jung, Jong Sam Baik, Young H. Sohn, Phil Hyu Lee
Cholesterol is an essential component of the neuronal cell membrane and is crucial for neuronal function; however, the role of cholesterol levels in Parkinson’s disease (PD) is debatable. This study investigated the complex relationship between total cholesterol (TC) levels, body mass index (BMI), and cognition in patients with PD. This study included 321 drug-naïve patients with PD who underwent dopamine
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A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-31 Mariagnese Barbera, Jenni Lehtisalo, Dinithi Perera, Malin Aspö, Mary Cross, Celeste A. De Jager Loots, Emanuela Falaschetti, Naomi Friel, José A. Luchsinger, Hanna Malmberg Gavelin, Markku Peltonen, Geraint Price, Anna Stigsdotter Neely, Charlotta Thunborg, Jaakko Tuomilehto, Francesca Mangialasche, Lefkos Middleton, Tiia Ngandu, Alina Solomon, Miia Kivipelto
Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer’s Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence)
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A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-27 Zhouquan Jiang, Jing Wang, Yongpeng Qin, Shanggong Liu, Bin Luo, Fan Bai, Huiyi Wei, Shaojuan Zhang, Junjie Wei, Guoyu Ding, Long Ma, Shu He, Rongjie Chen, Ying Sun, Yi Chen, Lu Wang, Hao Xu, Xiangyu Wang, Gong Chen, Wenliang Lei
Alzheimer’s disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pathogenesis of AD and potential therapies. However, the use of NHPs in AD research has been hindered by the paucity of AD
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Mild behavioral impairment in early Alzheimer’s disease and its association with APOE and BDNF risk genetic polymorphisms Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-26 Veronika Matuskova, Katerina Veverova, Dylan J. Jester, Vaclav Matoska, Zahinoor Ismail, Katerina Sheardova, Hana Horakova, Jiri Cerman, Jan Laczó, Ross Andel, Jakub Hort, Martin Vyhnalek
Mild behavioral impairment (MBI) has been commonly reported in early Alzheimer’s disease (AD) but rarely using biomarker-defined samples. It is also unclear whether genetic polymorphisms influence MBI in such individuals. We thus aimed to examine the association between the cognitive status of participants (amnestic mild cognitive impairment (aMCI-AD) vs cognitively normal (CN) older adults) and MBI
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A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-25 Christopher H. van Dyck, Adam P. Mecca, Ryan S. O’Dell, Hugh H. Bartlett, Nina G. Diepenbrock, Yiyun Huang, Mary E. Hamby, Michael Grundman, Susan M. Catalano, Anthony O. Caggiano, Richard E. Carson
Effective, disease-modifying therapeutics for the treatment of Alzheimer’s disease (AD) remain a large unmet need. Extensive evidence suggests that amyloid beta (Aβ) is central to AD pathophysiology, and Aβ oligomers are among the most toxic forms of Aβ. CT1812 is a novel brain penetrant sigma-2 receptor ligand that interferes with the binding of Aβ oligomers to neurons. Preclinical studies of CT1812
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Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-23 Amber Nous, Laura Seynaeve, Odile Feys, Vincent Wens, Xavier De Tiège, Pieter Van Mierlo, Amir G. Baroumand, Koenraad Nieboer, Gert-Jan Allemeersch, Shana Mangelschots, Veronique Michiels, Julie van der Zee, Christine Van Broeckhoven, Annemie Ribbens, Ruben Houbrechts, Sara De Witte, Mandy Melissa Jane Wittens, Maria Bjerke, Caroline Vanlersberghe, Sarah Ceyssens, Guy Nagels, Ilse Smolders, Sebastiaan
Epileptic seizures are an established comorbidity of Alzheimer’s disease (AD). Subclinical epileptiform activity (SEA) as detected by 24-h electroencephalography (EEG) or magneto-encephalography (MEG) has been reported in temporal regions of clinically diagnosed AD patients. Although epileptic activity in AD probably arises in the mesial temporal lobe, electrical activity within this region might not
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Correction: Neuron‑derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-23 Francheska Delgado‑Peraza, Carlos Nogueras‑Ortiz, Anja Hviid Simonsen, De’Larrian DeAnté Knight, Pamela J. Yao, Edward J. Goetzl, Camilla Steen Jensen, Peter Høgh, Hanne Gottrup, Karsten Vestergaard, Steen Gregers Hasselbalch, Dimitrios Kapogiannis
CorrectionAlz Res Therapy 15, 156 (2023) https://doi.org/10.1186/s13195-023-01303-9 Following the publication of the original article [1], the author reported that “Additional file 1” file in the published article is not the correct file. The original article [1] has been updated. Delgado-Peraza F, Nogueras-Ortiz C, Simonsen AH, et al. Neuron-derived extracellular vesicles in blood reveal effects of
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Diet patterns and cognitive performance in a UK Female Twin Registry (TwinsUK) Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-23 Claire T. McEvoy, Amy Jennings, Claire J. Steves, Alexander Macgregor, Tim Spector, Aedin Cassidy
Plant-based diets may provide protection against cognitive decline and Alzheimer’s disease, but observational data have not been consistent. Previous studies include early life confounding from socioeconomic conditions and genetics that are known to influence both cognitive performance and diet behaviour. This study investigated associations between Mediterranean (MED) diet and MIND diets and cognitive
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Plasma metabolic profiles predict future dementia and dementia subtypes: a prospective analysis of 274,160 participants Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-22 Yi-Xuan Qiang, Jia You, Xiao-Yu He, Yu Guo, Yue-Ting Deng, Pei-Yang Gao, Xin-Rui Wu, Jian-Feng Feng, Wei Cheng, Jin-Tai Yu
Blood-based biomarkers for dementia are gaining attention due to their non-invasive nature and feasibility in regular healthcare settings. Here, we explored the associations between 249 metabolites with all-cause dementia (ACD), Alzheimer’s disease (AD), and vascular dementia (VaD) and assessed their predictive potential. This study included 274,160 participants from the UK Biobank. Cox proportional
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Histone deacetylase inhibitors VPA and WT161 ameliorate the pathological features and cognitive impairments of the APP/PS1 Alzheimer’s disease mouse model by regulating the expression of APP secretases Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-20 Miaomiao Zhang, Wanyao Wang, Qun Ye, Yun Fu, Xuemin Li, Ke Yang, Fan Gao, An Zhou, Yonghui Wei, Shuang Tian, Shen Li, Fengjiang Wei, Wentao Shi, Wei-Dong Li
Alzheimer’s disease (AD) is a degenerative neurological disorder. Recent studies have indicated that histone deacetylases (HDACs) are among the most prominent epigenetic therapy targets and that HDAC inhibitors have therapeutic effects on AD. Here, we identified sodium valproate (VPA), a pan-HDAC inhibitor, and WT161, a novel HDAC6 selective inhibitor, as potential therapeutic agents for AD. Underlying
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Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-20 Hao Mei, Jeannette Simino, Lianna Li, Fan Jiang, Joshua C. Bis, Gail Davies, W David Hill, Charley Xia, Vilmundur Gudnason, Qiong Yang, Jari Lahti, Jennifer A. Smith, Mirna Kirin, Philip De Jager, Nicola J. Armstrong, Mohsen Ghanbari, Ivana Kolcic, Christopher Moran, Alexander Teumer, Murali Sargurupremraj, Shamsed Mahmud, Myriam Fornage, Wei Zhao, Claudia L. Satizabal, Ozren Polasek, Katri Räikkönen
Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent
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Correction: Baseline structural MRI and plasma biomarkers predict longitudinal structural atrophy and cognitive decline in early Alzheimer’s disease Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-12 Long Xie, Sandhitsu R. Das, Laura E. M. Wisse, Ranjit Ittyerah, Robin de Flores, Leslie M. Shaw, Paul A. Yushkevich, David A. Wolk
Correction: Alz Res Therapy 15, 79 (2023) https://doi.org/10.1186/s13195-023-01210-z Following the publication of the original article [1], the author reported that “Additional file 1” file in the published article is not the correct file. The original article [1] has been updated. Xie L, Das SR, Wisse LEM, et al. Baseline structural MRI and plasma biomarkers predict longitudinal structural atrophy
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Diagnostic accuracy of research criteria for prodromal frontotemporal dementia Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-12 Alberto Benussi, Enrico Premi, Mario Grassi, Antonella Alberici, Valentina Cantoni, Stefano Gazzina, Silvana Archetti, Roberto Gasparotti, Giorgio G. Fumagalli, Arabella Bouzigues, Lucy L. Russell, Kiran Samra, David M. Cash, Martina Bocchetta, Emily G. Todd, Rhian S. Convery, Imogen Swift, Aitana Sogorb-Esteve, Carolin Heller, John C. van Swieten, Lize C. Jiskoot, Harro Seelaar, Raquel Sanchez-Valle
The Genetic Frontotemporal Initiative Staging Group has proposed clinical criteria for the diagnosis of prodromal frontotemporal dementia (FTD), termed mild cognitive and/or behavioral and/or motor impairment (MCBMI). The objective of the study was to validate the proposed research criteria for MCBMI-FTD in a cohort of genetically confirmed FTD cases against healthy controls. A total of 398 participants
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Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer’s disease: A [18F]PSS232 PET/MRI study Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-12 Jie Wang, Yingfang He, Xing Chen, Lin Huang, Junpeng Li, Zhiwen You, Qi Huang, Shuhua Ren, Kun He, Roger Schibli, Linjing Mu, Yihui Guan, Qihao Guo, Jun Zhao, Fang Xie
Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the initial pathophysiological mechanism of Alzheimer’s disease (AD). The study aims to investigate the association between mGluR5 availability and AD’s biomarkers and cognitive function. We examined 35
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Associations between genetically predicted plasma protein levels and Alzheimer’s disease risk: a study using genetic prediction models Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-11 Jingjing Zhu, Shuai Liu, Keenan A. Walker, Hua Zhong, Dalia H. Ghoneim, Zichen Zhang, Praveen Surendran, Sarah Fahle, Adam Butterworth, Md Ashad Alam, Hong-Wen Deng, Chong Wu, Lang Wu
Specific peripheral proteins have been implicated to play an important role in the development of Alzheimer’s disease (AD). However, the roles of additional novel protein biomarkers in AD etiology remains elusive. The availability of large-scale AD GWAS and plasma proteomic data provide the resources needed for the identification of causally relevant circulating proteins that may serve as risk factors
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Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-11 Emilie T. Reas, Curtis Triebswetter, Sarah J. Banks, Linda K. McEvoy
APOE4 is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD), whereas APOE2 confers protection. However, effects of APOE on neurodegeneration in cognitively intact individuals, and how these associations evolve with cognitive decline, are unclear. Furthermore, few studies have evaluated whether effects of APOE on neurodegenerative changes are modified by other AD key risk factors
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Cognitive training and brain stimulation in patients with cognitive impairment: a randomized controlled trial Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-11 Daria Antonenko, Anna Elisabeth Fromm, Friederike Thams, Anna Kuzmina, Malte Backhaus, Elena Knochenhauer, Shu-Chen Li, Ulrike Grittner, Agnes Flöel
Repeated sessions of training and non-invasive brain stimulation have the potential to enhance cognition in patients with cognitive impairment. We hypothesized that combining cognitive training with anodal transcranial direct current stimulation (tDCS) will lead to performance improvement in the trained task and yield transfer to non-trained tasks. In our randomized, sham-controlled, double-blind study
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miR-129-5p as a biomarker for pathology and cognitive decline in Alzheimer’s disease Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-09 Sang-Won Han, Jung-Min Pyun, Paula J. Bice, David A. Bennett, Andrew J. Saykin, Sang Yun Kim, Young Ho Park, Kwangsik Nho
Alzheimer’s dementia (AD) pathogenesis involves complex mechanisms, including microRNA (miRNA) dysregulation. Integrative network and machine learning analysis of miRNA can provide insights into AD pathology and prognostic/diagnostic biomarkers. We performed co-expression network analysis to identify network modules associated with AD, its neuropathology markers, and cognition using brain tissue miRNA
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The fluorescent ligand bTVBT2 reveals increased p-tau uptake by retinal microglia in Alzheimer’s disease patients and AppNL−F/NL−F mice Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-02 Cristina Nuñez-Diaz, Emelie Andersson, Nina Schultz, Dovilė Pocevičiūtė, Oskar Hansson, K Peter R. Nilsson, Malin Wennström
Amyloid beta (Aβ) deposits and hyperphosphorylated tau (p-tau) accumulation have been identified in the retina of Alzheimer’s disease (AD) patients and transgenic AD mice. Previous studies have shown that retinal microglia engulf Aβ, but this property decreases in AD patients. Whether retinal microglia also take up p-tau and if this event is affected in AD is yet not described. In the current study
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Unraveling the intercellular communication disruption and key pathways in Alzheimer’s disease: an integrative study of single-nucleus transcriptomes and genetic association Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-02 Andi Liu, Brisa S. Fernandes, Citu Citu, Zhongming Zhao
Recently, single-nucleus RNA-seq (snRNA-seq) analyses have revealed important cellular and functional features of Alzheimer's disease (AD), a prevalent neurodegenerative disease. However, our knowledge regarding intercellular communication mediated by dysregulated ligand-receptor (LR) interactions remains very limited in AD brains. We systematically assessed the intercellular communication networks
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Digital Clock and Recall is superior to the Mini-Mental State Examination for the detection of mild cognitive impairment and mild dementia Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-02 Ali Jannati, Claudio Toro-Serey, Joyce Gomes-Osman, Russell Banks, Marissa Ciesla, John Showalter, David Bates, Sean Tobyne, Alvaro Pascual-Leone
Disease-modifying treatments for Alzheimer’s disease highlight the need for early detection of cognitive decline. However, at present, most primary care providers do not perform routine cognitive testing, in part due to a lack of access to practical cognitive assessments, as well as time and resources to administer and interpret the tests. Brief and sensitive digital cognitive assessments, such as
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Interest in genetic susceptibility testing and disclosure of AD dementia risk in cognitively normal adults: a survey study Alz. Res. Therapy (IF 8.823) Pub Date : 2024-01-02 Lisa Waterink, Larissa A. Masselink, Sven J. van der Lee, Leonie N. C. Visser, Solange Cleutjens, Jetske van der Schaar, Argonde C. van Harten, Philip Scheltens, Sietske A. M. Sikkes, Wiesje M. van der Flier, Marissa D. Zwan
Apolipoprotein-E (APOE) genetic testing for Alzheimer’s disease is becoming more important as clinical trials are increasingly targeting individuals carrying APOE-ε4 alleles. Little is known about the interest in finding out one’s genetic risk for Alzheimer’s disease in the general population. Our objective was to examine this in a sample of cognitively normal (CN) adults within a population-based
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Statins and cognitive decline in patients with Alzheimer’s and mixed dementia: a longitudinal registry-based cohort study Alz. Res. Therapy (IF 8.823) Pub Date : 2023-12-20 Bojana Petek, Henrike Häbel, Hong Xu, Marta Villa-Lopez, Irena Kalar, Minh Tuan Hoang, Silvia Maioli, Joana B. Pereira, Shayan Mostafaei, Bengt Winblad, Milica Gregoric Kramberger, Maria Eriksdotter, Sara Garcia-Ptacek
Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer’s disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms. To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with
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Multimodal lifestyle engagement patterns support cognitive stability beyond neuropathological burden Alz. Res. Therapy (IF 8.823) Pub Date : 2023-12-18 Emily W. Paolillo, Rowan Saloner, Anna VandeBunte, Shannon Lee, David A. Bennett, Kaitlin B. Casaletto
Modifiable lifestyle behaviors account for a large proportion of dementia risk. However, the combined contributions of multidomain lifestyle patterns to cognitive aging are poorly understood, as most studies have examined individual lifestyle behaviors in isolation and without neuropathological characterization. This study examined data-driven patterns of lifestyle behaviors across multiple domains