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Epidemiology and prevalence of dementia and Alzheimer's disease in American Indians: Data from the Strong Heart Study Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-15 Astrid M. Suchy-Dicey, Kimiko Domoto-Reilly, Lonnie Nelson, Suman Jayadev, Dedra S. Buchwald, Thomas J. Grabowski, Kristoffer Rhoads
Accurate epidemiologic estimates for dementia are lacking for American Indians, despite substantive social and health disparities.
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Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities in a community-dwelling cohort Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-15 Marc D. Rudolph, Courtney L. Sutphen, Thomas C. Register, Christopher T. Whitlow, Kiran K. Solingapuram Sai, Timothy M. Hughes, James R. Bateman, Jeffrey L. Dage, Kristen A. Russ, Michelle M. Mielke, Suzanne Craft, Samuel N. Lockhart
We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities.
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Medial temporal lobe gray matter microstructure in preclinical Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-15 Christopher Brown, Sandhitsu Das, Long Xie, Ilya Nasrallah, John Detre, Alice Chen-Plotkin, Leslie Shaw, Corey McMillan, Paul Yushkevich, David Wolk
Typical MRI measures of neurodegeneration have limited sensitivity in early disease stages. Diffusion MRI (dMRI) microstructural measures may allow for detection in preclinical stages.
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Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-15 William Robert Kwapong, Fei Tang, Peng Liu, Ziyi Zhang, Le Cao, Zijuan Feng, Shiyun Yang, Yang Shu, Heng Xu, Ying Lu, Xinjun Zhao, Baochen Chong, Bo Wu, Ming Liu, Peng Lei, Shuting Zhang
This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers.
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Characterizing molecular and synaptic signatures in mouse models of late‐onset Alzheimer's disease independent of amyloid and tau pathology Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-12 Kevin P. Kotredes, Ravi S. Pandey, Scott Persohn, Kierra Elderidge, Charles P Burton, Ethan W. Miner, Kathryn A. Haynes, Diogo Francisco S. Santos, Sean‐Paul Williams, Nicholas Heaton, Cynthia M. Ingraham, Christopher Lloyd, Dylan Garceau, Rita O'Rourke, Sarah Herrick, Claudia Rangel‐Barajas, Surendra Maharjan, Nian Wang, Michael Sasner, Bruce T. Lamb, Paul R. Territo, Stacey J. Sukoff Rizzo, Gregory
INTRODUCTIONMODEL‐AD (Model Organism Development and Evaluation for Late‐Onset Alzheimer's Disease) is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory and progression of late‐onset Alzheimer's disease (LOAD) more accurately.METHODSWe created the LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, and humanized
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Antidepressant exposure and long‐term dementia risk in a nationwide retrospective study on US veterans with midlife major depressive disorder Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-08 Jaime Ramos‐Cejudo, June K. Corrigan, Chunlei Zheng, Kaitlin N. Swinnerton, Sean R. Jacobson, Jennifer La, Rebecca A. Betensky, Ricardo S. Osorio, Sharon Madanes, Nunzio Pomara, Dan Iosifescu, Mary Brophy, Nhan V. Do, Nathanael R. Fillmore
INTRODUCTIONThe use of antidepressants in major depressive disorder (MDD) has been reported to influence long‐term risk of Alzheimer's disease (AD) and AD‐related dementias (AD/ADRD), but studies are conflicting.METHODSWe used inverse probability weighted (IPW) Cox models with time‐varying covariates in a retrospective cohort study among midlife veterans with MDD within the US Veterans Affairs healthcare
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Blood biomarkers of Alzheimer's disease in the community: Variation by chronic diseases and inflammatory status Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-08 Martina Valletta, Davide Liborio Vetrano, Debora Rizzuto, Bengt Winblad, Marco Canevelli, Sarah Andersson, Matilda Dale, Claudia Fredolini, Laura Fratiglioni, Giulia Grande
INTRODUCTIONWe explored the variations of blood biomarkers of Alzheimer's disease (AD) by chronic diseases and systemic inflammation.METHODSWe explored the association of AD blood biomarkers with chronic diseases and systemic inflammation (interleukin‐6 [IL‐6]), in 2366 dementia‐free participants of the Swedish National Study on Aging and Care‐in Kungsholmen, using quantile regression models.RESULTSA
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Altered fornix integrity is associated with sleep apnea‐related hypoxemia in mild cognitive impairment Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-08 Nicola Andrea Marchi, Véronique Daneault, Claire André, Marie‐Ève Martineau‐Dussault, Andrée‐Ann Baril, Cynthia Thompson, Jacques Yves Montplaisir, Danielle Gilbert, Dominique Lorrain, Arnaud Boré, Maxime Descoteaux, Julie Carrier, Nadia Gosselin
INTRODUCTIONThe limbic system is critical for memory function and degenerates early in the Alzheimer's disease continuum. Whether obstructive sleep apnea (OSA) is associated with alterations in the limbic white matter tracts remains understudied.METHODSPolysomnography, neurocognitive assessment, and brain magnetic resonance imaging (MRI) were performed in 126 individuals aged 55–86 years, including
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Long‐term exposure to air pollution and road traffic noise and incidence of dementia in the Danish Nurse Cohort Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-08 Stéphane Tuffier, Jiawei Zhang, Marie Bergmann, Rina So, George Maria Napolitano, Thomas Cole‐Hunter, Matija Maric, Sonja Antic, Jørgen Brandt, Matthias Ketzel, Steffen Loft, Youn‐Hee Lim, Zorana Jovanovic Andersen
INTRODUCTIONWe examined the association of long‐term exposure to air pollution and road traffic noise with dementia incidence in the Danish Nurse Cohort.METHODSFemale nurses were followed for dementia incidence (hospital contact or medication prescription) from 1993/1999 to 2020. Air pollution and road traffic noise levels were estimated at nurses’ residences, and their associations with dementia were
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Proteomic changes in the human cerebrovasculature in Alzheimer's disease and related tauopathies linked to peripheral biomarkers in plasma and cerebrospinal fluid Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-07 Aleksandra M. Wojtas, Eric B. Dammer, Qi Guo, Lingyan Ping, Ananth Shantaraman, Duc M. Duong, Luming Yin, Edward J. Fox, Fatemeh Seifar, Edward B. Lee, Erik C. B. Johnson, James J. Lah, Allan I. Levey, Yona Levites, Srikant Rangaraju, Todd E. Golde, Nicholas T. Seyfried
INTRODUCTIONCerebrovascular dysfunction is a pathological hallmark of Alzheimer's disease (AD). Nevertheless, detecting cerebrovascular changes within bulk tissues has limited our ability to characterize proteomic alterations from less abundant cell types.METHODSWe conducted quantitative proteomics on bulk brain tissues and isolated cerebrovasculature from the same individuals, encompassing control
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The impact of maternal smoking during pregnancy and the age of smoking initiation on incident dementia: A prospective cohort study Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-07 Jiyong Liu, Yi Xiao, Xiaoting Zheng, Yangfan Cheng, Sirui Zhang, Yuanzheng Ma, Qirui Jiang, Shichan Wang, Chunyu Li, Huifang Shang
INTRODUCTIONThe impact of early‐life tobacco exposure on dementia has remained unknown.METHODSUsing the UK Biobank, the associations of maternal smoking during pregnancy (MSDP) and age of smoking initiation (ASI) with the onset time of all‐cause dementia were estimated with accelerated failure time models. The effects of MSDP and ASI on brain structure and their genetic correlation to Alzheimer's disease
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Correlation analysis of peripheral platelet markers and disease phenotypes in Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-07 Jiajia Fu, Xiaohui Lai, Chongwei Zhang, Qianqian Wei, Xueping Chen, Huifang Shang
INTRODUCTIONPlatelets serve as the primary peripheral reservoir of amyloid beta (Aβ). However, there is limited research on platelet markers in routine blood examinations, particularly with regard to the large platelet ratio (P‐LCR) in Alzheimer's disease (AD).METHODSThis study included 512 AD patients and 205 healthy controls (HCs). Platelet markers and apolipoprotein E (APOE) 4 status were assessed
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Assessment of neurovascular uncoupling: APOE status is a key driver of early metabolic and vascular dysfunction Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-07 Kristen D. Onos, Peter B. Lin, Ravi S. Pandey, Scott A. Persohn, Charles P. Burton, Ethan W. Miner, Kierra Eldridge, Jonathan Nyandu Kanyinda, Kate E. Foley, Gregory W. Carter, Gareth R. Howell, Paul R. Territo
BACKGROUNDAlzheimer's disease (AD) is the most common cause of dementia worldwide, with apolipoprotein Eε4 (APOEε4) being the strongest genetic risk factor. Current clinical diagnostic imaging focuses on amyloid and tau; however, new methods are needed for earlier detection.METHODSPET imaging was used to assess metabolism‐perfusion in both sexes of aging C57BL/6J, and hAPOE mice, and were verified
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A systematic review/meta‐analysis of prevalence and incidence rates illustrates systemic underrepresentation of individuals racialized as Asian and/or Asian‐American in ADRD research Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-06 Yiqi Zhu, Soobin Park, Ramana Kolady, Wenqing Zha, Ying Ma, Amanda Dias, Katherine McGuire, Angela Hardi, Sunny Lin, Zahinoor Ismail, Paris B. Adkins‐Jackson, Jean‐Francois Trani, Ganesh M. Babulal
We investigate Alzheimer's disease and related dementia (ADRD) prevalence, incidence rate, and risk factors in individuals racialized as Asian and/or Asian‐American and assess sample representation. Prevalence, incidence rate, risk factors, and heterogeneity of samples were assessed. Random‐effects meta‐analysis was conducted, generating pooled estimates. Of 920 records across 14 databases, 45 studies
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Generating real‐world evidence in Alzheimer's disease: Considerations for establishing a core dataset Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-06 James E. Galvin, Jeffrey L. Cummings, Mihaela Levitchi Benea, Carl de Moor, Ricardo F. Allegri, Alireza Atri, Howard Chertkow, Claire Paquet, Verna R. Porter, Craig W. Ritchie, Sietske A. M. Sikkes, Michael R. Smith, Christina Marsica Grassi, Ivana Rubino
Ongoing assessment of patients with Alzheimer's disease (AD) in postapproval studies is important for mapping disease progression and evaluating real‐world treatment effectiveness and safety. However, interpreting outcomes in the real world is challenging owing to variation in data collected across centers and specialties and greater heterogeneity of patients compared with trial participants. Here
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Diffuse optical tomography for mapping cerebral hemodynamics and functional connectivity in delirium Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-03 Shixie Jiang, Jingyu Huang, Hao Yang, Richard Czuma, Lauren Farley, Alexis Cohen‐Oram, Kimberly Hartney, Kristina Chechotka, F. Andrew Kozel, Huabei Jiang
INTRODUCTIONDelirium is associated with mortality and new onset dementia, yet the underlying pathophysiology remains poorly understood. Development of imaging biomarkers has been difficult given the challenging nature of imaging delirious patients. Diffuse optical tomography (DOT) offers a promising approach for investigating delirium given its portability and three‐dimensional capabilities.METHODSTwenty‐five
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The 2022 symposium on dementia and brain aging in low‐ and middle‐income countries: Highlights on research, diagnosis, care, and impact Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-02 Raj Kalaria, Gladys Maestre, Simin Mahinrad, Daisy M. Acosta, Rufus Olusola Akinyemi, Suvarna Alladi, Ricardo F. Allegri, Faheem Arshad, David Oluwasayo Babalola, Olusegun Baiyewu, Thomas H. Bak, Tarek Bellaj, David K. Brodie‐Mends, Maria C. Carrillo, Kaputu‐Kalala‐Malu Celestin, Albertino Damasceno, Ranil Karunamuni de Silva, Rohan de Silva, Mamuka Djibuti, Anna Jane Dreyer, Ratnavalli Ellajosyula
Two of every three persons living with dementia reside in low‐ and middle‐income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high‐income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC‐focused research to ensure
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Sleep–wake behavior, perceived fatigability, and cognitive reserve in older adults Alzheimers Dement. (IF 14.0) Pub Date : 2024-05-01 Nancy Kerner, Terry E. Goldberg, Hannah R. Cohen, Julia G. Phillips, Daniel E. Cohen, Howard Andrews, Gregory Pelton, Davangere P. Devanand
INTRODUCTIONThe effects of sleep–wake behavior on perceived fatigability and cognitive abilities when performing daily activities have not been investigated across levels of cognitive reserve (CR).METHODSCR Index Questionnaire (CRIq) data were collected and subjected to moderated mediation analysis.RESULTSIn amnestic mild cognitive impairment (aMCI; n = 41), CR moderated sleep‐related impairments (SRIs)
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Data-driven decomposition and staging of flortaucipir uptake in Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-29 Tom Earnest, Abdalla Bani, Sung Min Ha, Diana A. Hobbs, Deydeep Kothapalli, Braden Yang, John J. Lee, Tammie L. S. Benzinger, Brian A. Gordon, Aristeidis Sotiras
Previous approaches pursuing in vivo staging of tau pathology in Alzheimer's disease (AD) have typically relied on neuropathologically defined criteria. In using predefined systems, these studies may miss spatial deposition patterns which are informative of disease progression.
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2024 Alzheimer's disease facts and figures Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-30
This article describes the public health impact of Alzheimer's disease (AD), including prevalence and incidence, mortality and morbidity, use and costs of care and the ramifications of AD for family caregivers, the dementia workforce and society. The Special Report discusses the larger health care system for older adults with cognitive issues, focusing on the role of caregivers and non-physician health
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In vivo validation of late‐onset Alzheimer's disease genetic risk factors Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-30 Michael Sasner, Christoph Preuss, Ravi S. Pandey, Asli Uyar, Dylan Garceau, Kevin P. Kotredes, Harriet Williams, Adrian L. Oblak, Peter Bor‐Chian Lin, Bridget Perkins, Disha Soni, Cindy Ingraham, Audrey Lee‐Gosselin, Bruce T. Lamb, Gareth R. Howell, Gregory W. Carter
INTRODUCTIONGenome‐wide association studies have identified over 70 genetic loci associated with late‐onset Alzheimer's disease (LOAD), but few candidate polymorphisms have been functionally assessed for disease relevance and mechanism of action.METHODSCandidate genetic risk variants were informatically prioritized and individually engineered into a LOAD‐sensitized mouse model that carries the AD risk
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Experimental laboratory models as tools for understanding modifiable dementia risk Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-30 Duncan Sinclair, Alison J. Canty, Jenna M. Ziebell, Adele Woodhouse, Jessica M. Collins, Sharn Perry, Eddy Roccati, Maneesh Kuruvilla, Jacqueline Leung, Rachel Atkinson, James C. Vickers, Anthony L. Cook, Anna E. King
Experimental laboratory research has an important role to play in dementia prevention. Mechanisms underlying modifiable risk factors for dementia are promising targets for dementia prevention but are difficult to investigate in human populations due to technological constraints and confounds. Therefore, controlled laboratory experiments in models such as transgenic rodents, invertebrates and in vitro
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Lifestyle and incident dementia: A COSMIC individual participant data meta-analysis Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-27 Stephanie Van Asbroeck, Sebastian Köhler, Martin P. J. van Boxtel, Darren M. Lipnicki, John D. Crawford, Erico Castro-Costa, Maria Fernanda Lima-Costa, Sergio Luis Blay, Xiao Shifu, Tao Wang, Ling Yue, Richard B. Lipton, Mindy J. Katz, Carol A. Derby, Maëlenn Guerchet, Pierre-Marie Preux, Pascal Mbelesso, Joanna Norton, Karen Ritchie, Ingmar Skoog, Jenna Najar, Therese Rydberg Sterner, Nikolaos Scarmeas
The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics.
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α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-26 Johannes Levin, Simone Baiardi, Corinne Quadalti, Marcello Rossi, Angela Mammana, Jonathan Vöglein, Alexander Bernhardt, Richard J. Perrin, Mathias Jucker, Oliver Preische, Anna Hofmann, Günter U. Höglinger, Nigel J. Cairns, Erin E. Franklin, Patricio Chrem, Carlos Cruchaga, Sarah B. Berman, Jasmeer P. Chhatwal, Alisha Daniels, Gregory S. Day, Natalie S. Ryan, Alison M. Goate, Brian A. Gordon, Edward
Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains.
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Metabolomics profiling reveals distinct, sex‐specific signatures in serum and brain metabolomes in mouse models of Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-27 Ravi S. Pandey, Mattias Arnold, Richa Batra, Jan Krumsiek, Kevin P. Kotredes, Dylan Garceau, Harriet Williams, Michael Sasner, Gareth R. Howell, Rima Kaddurah‐Daouk, Gregory W. Carter
INTRODUCTIONIncreasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation.METHODSWe investigated differences in serum and brain metabolites between the early‐onset 5XFAD and late‐onset LOAD1 (APOE4.Trem2*R47H) mouse models of AD to C57BL/6J controls
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Atrophy links lower novelty‐related locus coeruleus connectivity to cognitive decline in preclinical AD Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-27 Christoph Schneider, Prokopis C. Prokopiou, Kathryn V. Papp, Nina Engels‐Domínguez, Stephanie Hsieh, Truley A. Juneau, Aaron P. Schultz, Dorene M. Rentz, Reisa A. Sperling, Keith A. Johnson, Heidi I. L. Jacobs
INTRODUCTIONAnimal research has shown that tau pathology in the locus coeruleus (LC) is associated with reduced norepinephrine signaling, lower projection density to the medial temporal lobe (MTL), atrophy, and cognitive impairment. We investigated the contribution of LC‐MTL functional connectivity (FCLC‐MTL) on cortical atrophy across Braak stage regions and its impact on cognition.METHODSWe analyzed
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Echocardiographic measures of the left heart and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact adults: The CABLE study Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-27 He‐Ying Hu, Hao Hu, Jing Jiang, Yan‐Lin Bi, Yan Sun, Ya‐Nan Ou, Lan Tan, Jin‐Tai Yu
INTRODUCTIONThis study delineated the interrelationships between subclinical alterations in the left heart, cerebrospinal fluid (CSF), Alzheimer's disease (AD) biomarkers, and cognition.METHODSMultiple linear regressions were conducted in 1244 cognitively normal participants (mean age = 65.5; 43% female) who underwent echocardiography (left atrial [LA] and left ventricular [LV] morphologic or functional
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Failure of the glymphatic system as possible link between lumbar spinal stenosis and dementia Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-27 Pasquale Gallina, Francesco Lolli, Berardino Porfirio
Lumbar spinal stenosis (LSS) is a disease of aging.1 It involves reduction of the spinal canal with compression of the nerve roots and vascular elements. This mainly degenerative condition results in posture-related low back and lower extremity pain. Symptoms are relieved by sitting or forward flexion. The cardinal sign of LSS is neurogenic claudication, that is, onset of weakness, tiredness/heaviness
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Japan-Multimodal Intervention Trial for the Prevention of Dementia: A randomized controlled trial Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-22 Takashi Sakurai, Taiki Sugimoto, Hiroyasu Akatsu, Takehiko Doi, Yoshinori Fujiwara, Akihiro Hirakawa, Fumie Kinoshita, Masafumi Kuzuya, Sangyoon Lee, Nanae Matsumoto, Koichiro Matsuo, Makoto Michikawa, Akinori Nakamura, Susumu Ogawa, Rei Otsuka, Kenji Sato, Hiroyuki Shimada, Hiroko Suzuki, Hiroyuki Suzuki, Hajime Takechi, Shinya Takeda, Kazuaki Uchida, Hiroyuki Umegaki, Satomu Wakayama, Hidenori Arai
We examined the efficacy of a multidomain intervention in preventing cognitive decline among Japanese older adults with mild cognitive impairment (MCI).
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Pathologic and cognitive correlates of plasma biomarkers in neurodegenerative disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-22 Katheryn A. Q. Cousins, Jeffrey S. Phillips, Sandhitsu R. Das, Kyra O'Brien, Thomas F. Tropea, Alice Chen‐Plotkin, Leslie M. Shaw, Ilya M. Nasrallah, Dawn Mechanic‐Hamilton, Corey T. McMillan, David J. Irwin, Edward B. Lee, David A. Wolk
INTRODUCTIONWe investigate pathological correlates of plasma phosphorylated tau 181 (p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) across a clinically diverse spectrum of neurodegenerative disease, including normal cognition (NormCog) and impaired cognition (ImpCog).METHODSParticipants were NormCog (n = 132) and ImpCog (n = 461), with confirmed β‐amyloid (Aβ+/‐)
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Overrepresentation of APOE ε4 carriers in genome‐wide association studies of memory function and memory decline Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-22 Md Shafiqur Rahman
Archer et al. reported a cross-ancestry genome-wide association study (GWAS) on memory performance (n = 27,633) and cognitive decline (n = 22,365), using data from four aging cohorts.1 Associations were adjusted for age, sex, and the first five principal components. The study of this nature is rare and important for understanding cognitive performance and its relation to neurodegenerative diseases
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Linking white matter hyperintensities to regional cortical thinning, amyloid deposition, and synaptic density loss in Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-22 Junfang Zhang, Haijuan Chen, Jie Wang, Qi Huang, Xiaomeng Xu, Wenjing Wang, Wei Xu, Yihui Guan, Jun Liu, Joanna M Wardlaw, Yulei Deng, Fang Xie, Binyin Li
INTRODUCTIONWe investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid and tau deposition, and synaptic density in the WMH‐connected cortex using multimodal images.METHODSWe included 107 participants (59 with Alzheimer's disease [AD]; 27 with mild cognitive impairment; 21 cognitively normal controls) with amyloid beta (Aβ) positivity on amyloid
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Cortical microinfarcts in adults with Down syndrome assessed with 3T‐MRI Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-22 Mateus Rozalem Aranha, Victor Montal, Hilde van den Brink, Jordi Pegueroles, Maria Carmona‐Iragui, Laura Videla, Lucia Maure Blesa, Bessy Benejam, Javier Arranz, Sílvia Valldeneu, Isabel Barroeta, Susana Fernández, Laia Ribas, Daniel Alcolea, Sofía González‐Ortiz, Núria Bargalló, Geert Jan Biessels, Rafael Blesa, Alberto Lleó, Artur Martins Coutinho, Cláudia Costa Leite, Alexandre Bejanin, Juan Fortea
BACKGROUNDCortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS.METHODSWe included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in
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Alzheimer's disease genetic risk score and neuroimaging in the FINGER lifestyle trial Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-22 Gazi Saadmaan, Maria Carolina Dalmasso, Alfredo Ramirez, Mikko Hiltunen, Nina Kemppainen, Jenni Lehtisalo, Francesca Mangialasche, Tiia Ngandu, Juha Rinne, Hilkka Soininen, Ruth Stephen, Miia Kivipelto, Alina Solomon
INTRODUCTIONWe assessed a genetic risk score for Alzheimer's disease (AD‐GRS) and apolipoprotein E (APOE4) in an exploratory neuroimaging substudy of the FINGER trial.METHODS1260 at‐risk older individuals without dementia were randomized to multidomain lifestyle intervention or health advice. N = 126 participants underwent magnetic resonance imaging (MRI), and N = 47 positron emission tomography (PET)
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Critical Alzheimer's disease legislation advances in Congress Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-21
In March, the Health Subcommittee of the US House Committee on Energy & Commerce unanimously passed the bipartisan National Alzheimer's Project Act (NAPA) Reauthorization Act (H.R. 619/S. 133), the Alzheimer's Accountability and Investment Act (AAIA; H.R. 620/S. 134), the Building Our Largest Dementia (BOLD) Infrastructure for Alzheimer's Reauthorization Act (H.R. 7218/S. 3775), and the Lifespan Respite
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Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-18 Jie Wang, Qi Huang, Kun He, Junpeng Li, Tengfei Guo, Yang Yang, Zengping Lin, Songye Li, Greet Vanderlinden, Yiyun Huang, Koen Van Laere, Yihui Guan, Qihao Guo, Ruiqing Ni, Binying Li, 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 pathophysiological mechanism of Alzheimer's disease (AD).
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Cognitively healthy centenarians are genetically protected against Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-18 Niccolo’ Tesi, Sven van der Lee, Marc Hulsman, Natasja M. van Schoor, Martijn Huisman, Yolande Pijnenburg, Wiesje M. van der Flier, Marcel Reinders, Henne Holstege
Alzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated with such resilience against AD.
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Racial and ethnic differences in plasma biomarker eligibility for a preclinical Alzheimer's disease trial Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-17 Doris Patricia Molina-Henry, Rema Raman, Andy Liu, Oliver Langford, Keith Johnson, Leona K. Shum, Crystal M. Glover, Shobha Dhadda, Michael Irizarry, Gustavo Jimenez-Maggiora, Joel B. Braunstein, Kevin Yarasheski, Venky Venkatesh, Tim West, Philip B. Verghese, Robert A. Rissman, Paul Aisen, Joshua D. Grill, Reisa A. Sperling
In trials of amyloid-lowering drugs for Alzheimer's disease (AD), differential eligibility may contribute to under-inclusion of racial and ethnic underrepresented groups. We examined plasma amyloid beta 42/40 and positron emission tomography (PET) amyloid eligibility for the ongoing AHEAD Study preclinical AD program (NCT04468659).
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White matter hyperintensities and the surrounding normal appearing white matter are associated with water channel disruption in the oldest old Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-17 Lisa C. Silbert, Natalie E. Roese, Victoria Krajbich, Justin Hurworth, David Lahna, Daniel L. Schwartz, Hiroko H. Dodge, Randall L. Woltjer
Age-related magnetic resonance imaging (MRI) T2 white matter hyperintensities (WMHs) are common and associated with neurological decline. We investigated the histopathological underpinnings of MRI WMH and surrounding normal appearing white matter (NAWM), with a focus on astroglial phenotypes.
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MINocyclinE to Reduce inflammation and blood-brain barrier leakage in small Vessel diseAse (MINERVA): A phase II, randomized, double-blind, placebo-controlled experimental medicine trial Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-17 Robin B. Brown, Daniel J. Tozer, Laurence Loubière, Eric L. Harshfield, Young T. Hong, Tim D. Fryer, Guy B. Williams, Martin J. Graves, Franklin I. Aigbirhio, John T. O'Brien, Hugh S. Markus
Cerebral small vessel disease (SVD) is a common cause of stroke/vascular dementia with few effective treatments. Neuroinflammation and increased blood-brain barrier (BBB) permeability may influence pathogenesis. In rodent models, minocycline reduced inflammation/BBB permeability. We determined whether minocycline had a similar effect in patients with SVD.
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Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-16 Maurice Pasternak, Saira S. Mirza, Nicholas Luciw, Henri J. M. M. Mutsaerts, Jan Petr, David Thomas, David Cash, Martina Bocchetta, Maria Carmela Tartaglia, Sara B. Mitchell, Sandra E. Black, Morris Freedman, David Tang-Wai, Ekaterina Rogaeva, Lucy L. Russell, Arabella Bouzigues, John C. van Swieten, Lize C. Jiskoot, Harro Seelaar, Robert Laforce, Pietro Tiraboschi, Barbara Borroni, Daniela Galimberti
Effective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers.
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Anxiety in Alzheimer's disease rats is independent of memory and impacted by genotype, age, sex, and exercise Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-16 Danielle C. Lopez, Zachary J. White, Stephanie E. Hall
Alzheimer's disease (AD) is characterized by cognitive impairments; however, heightened anxiety often accompanies and, in some cases, exacerbates cognitive its. The present study aims to understand the influence of multiple variables on anxiety-like behavior in TgF344-AD rats and determine whether anxiety impacts memory performance.
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Peripheral HMGB1 is linked to O3 pathology of disease-associated astrocytes and amyloid Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-16 Chandrama Ahmed, Hendrik J. Greve, Carla Garza-Lombo, Jamie A. Malley, James A. Johnson, Adrian L. Oblak, Michelle L. Block
Ozone (O3) is an air pollutant associated with Alzheimer's disease (AD) risk. The lung–brain axis is implicated in O3-associated glial and amyloid pathobiology; however, the role of disease-associated astrocytes (DAAs) in this process remains unknown.
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Progressive reduction of nuclear receptor Nr4a1 mediates age-dependent cognitive decline Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-11 Jiang Chen, Zhi Zhang, Ying Liu, Lili Huang, Yi Liu, Dan Yang, Xinyu Bao, Pinyi Liu, Yuhan Ge, Qingqing Li, Xin Shu, Lushan Xu, Yun Stone Shi, Xiaolei Zhu, Yun Xu
Cognitive decline progresses with age, and Nr4a1 has been shown to participate in memory functions. However, the relationship between age-related Nr4a1 reduction and cognitive decline is undefined.
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Neuropathologic changes at age 90+ related to sleep duration 19 to 40 years earlier: The 90+ Study Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-11 Zarui A. Melikyan, Claudia H. Kawas, Annlia Paganini-Hill, Luohua Jiang, Syed Bukhari, Thomas J. Montine, Bryce A. Mander, María M. Corrada
We investigated the association between sleep duration and neuropathologic changes 19 to 40 years later in oldest-old (age 90+) participants of The 90+ Study.
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Racial discrimination during middle age predicts higher serum phosphorylated tau and neurofilament light chain levels a decade later: A study of aging black Americans Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-10 Ronald L. Simons, Mei Ling Ong, Man-Kit Lei, Steven R. H. Beach, Yue Zhang, Robert Philibert, Michelle M. Mielke
Recent evidence suggests that exposure to the stress of racism may increase the risk of dementia for Black Americans.
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20‐year depressive symptoms, dementia, and structural neuropathology in older women Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-09 Andrew J. Petkus, Xinhui Wang, Diana Younan, Lauren E. Salminen, Susan M. Resnick, Stephen R. Rapp, Mark A. Espeland, Margaret Gatz, Keith F. Widaman, Ramon Casanova, Helena Chui, Ryan T. Barnard, Sarah A. Gaussoin, Joseph S. Goveas, Kathleen M. Hayden, Victor W. Henderson, Bonnie C. Sachs, Santiago Saldana, Aladdin H. Shadyab, Sally A. Shumaker, Jiu‐Chiuan Chen
INTRODUCTIONThe course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes.METHODSUtilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In
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Correction to “Amyloid ratios in plasma and CSF are biomarkers of pre-symptomatic Alzheimer's disease” Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-08
Fonteh AN., Wu X, Astraea N, et al. Amyloid ratios in plasma and CSF are biomarkers of pre-symptomatic Alzheimer's disease. Alzheimer's Dement., 2023;19:e079861. doi:10.1002/alz.079861 In the above article, the third author's last name was misspelled as Astaea. The correct spelling is Astraea. The original article has been corrected. We apologize for this error.
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Distinct spatial contributions of amyloid pathology and cerebral small vessel disease to hippocampal morphology Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-04 Kristiana Xhima, Julie Ottoy, Erin Gibson, Katherine Zukotynski, Christopher Scott, Ginelle J. Feliciano, Sabrina Adamo, Phillip H. Kuo, Michael J. Borrie, Howard Chertkow, Richard Frayne, Robert Laforce, Michael D. Noseworthy, Frank S. Prato, Demetrios J. Sahlas, Eric E. Smith, Vesna Sossi, Alexander Thiel, Jean-Paul Soucy, Jean-Claude Tardif, Maged Goubran, Sandra E. Black, Joel Ramirez
Cerebral small vessel disease (SVD) and amyloid beta (Aβ) pathology frequently co-exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood.
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Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-04 Ariane Bollack, Lyduine E. Collij, David Vállez García, Mahnaz Shekari, Daniele Altomare, Pierre Payoux, Bruno Dubois, Oriol Grau-Rivera, Mercè Boada, Marta Marquié, Agneta Nordberg, Zuzana Walker, Philip Scheltens, Michael Schöll, Robin Wolz, Jonathan M. Schott, Rossella Gismondi, Andrew Stephens, Christopher Buckley, Giovanni B. Frisoni, Bernard Hanseeuw, Pieter Jelle Visser, Rik Vandenberghe, Alexander
To support clinical trial designs focused on early interventions, our study determined reliable early amyloid-β (Aβ) accumulation based on Centiloids (CL) in pre-dementia populations.
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Plasma oxysterols are associated with serum lipids and dementia risk in older women Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-04 Michelle M. Dunk, Stephen R. Rapp, Kathleen M. Hayden, Mark A. Espeland, Ramon Casanova, JoAnn E. Manson, Aladdin H. Shadyab, Robert Wild, Ira Driscoll
Apolipoprotein E4 (APOE4) carriers’ tendency toward hypercholesterolemia may contribute to Alzheimer's disease (AD) risk through oxysterols, which traverse the blood-brain barrier.
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Sex‐specific associations between AD genotype and the microbiome of human amyloid beta knock‐in (hAβ‐KI) mice Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-04 Sage J. B. Dunham, Julio Avelar‐Barragan, Jason A. Rothman, Eric D. Adams, Gina Faraci, Stefania Forner, Shimako Kawauchi, Andrea J. Tenner, Kim N. Green, Frank M. LaFerla, Grant R. MacGregor, Mark Mapstone, Katrine L. Whiteson
INTRODUCTIONEmerging evidence links changes in the gut microbiome to late‐onset Alzheimer's disease (LOAD), necessitating examination of AD mouse models with consideration of the microbiome.METHODSWe used shotgun metagenomics and untargeted metabolomics to study the human amyloid beta knock‐in (hAβ‐KI) murine model for LOAD compared to both wild‐type (WT) mice and a model for early‐onset AD (3xTg‐AD)
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Data-driven classification of cognitively normal and mild cognitive impairment subtypes predicts progression in the NACC dataset Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-04 Emily C. Edmonds, Kelsey R. Thomas, Steven Z. Rapcsak, Shannon L. Lindemer, Lisa Delano-Wood, David P. Salmon, Mark W. Bondi
Data-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods.
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Early molecular events of autosomal-dominant Alzheimer's disease in marmosets with PSEN1 mutations Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-04 Gregg E. Homanics, Jung Eun Park, Lauren Bailey, David J. Schaeffer, Lauren Schaeffer, Jie He, Shuoran Li, Tingting Zhang, Annat Haber, Catrina Spruce, Anna Greenwood, Takeshi Murai, Laura Schultz, Lauren Mongeau, Seung-Kwon Ha, Julia Oluoch, Brianne Stein, Sang Ho Choi, Hasi Huhe, Amantha Thathiah, Peter L. Strick, Gregory W. Carter, Afonso C. Silva, Stacey J. Sukoff Rizzo
Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically engineered marmosets that carry knock-in (KI) point mutations in the presenilin 1 (PSEN1) gene that can be studied from birth throughout lifespan.
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Automatic classification of AD pathology in FTD phenotypes using natural speech Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-04 Sunghye Cho, Christopher A. Olm, Sharon Ash, Sanjana Shellikeri, Galit Agmon, Katheryn A. Q. Cousins, David J. Irwin, Murray Grossman, Mark Liberman, Naomi Nevler
Screening for Alzheimer's disease neuropathologic change (ADNC) in individuals with atypical presentations is challenging but essential for clinical management. We trained automatic speech-based classifiers to distinguish frontotemporal dementia (FTD) patients with ADNC from those with frontotemporal lobar degeneration (FTLD).
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Results from the long-term extension of PRIME: A randomized Phase 1b trial of aducanumab Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-03 Tianle Chen, John O'Gorman, Carmen Castrillo-Viguera, Rajasimhan Rajagovindan, Gioacchino G. Curiale, Ying Tian, Dakshaben Patel, Philipp von Rosenstiel, Christian von Hehn, Stephen Salloway, Christoph Hock, Roger M. Nitsch, Samantha Budd Haeberlein, Alfred Sandrock, Priya Singhal
Aducanumab selectively targets aggregated forms of amyloid beta (Aβ), a neuropathological hallmark of Alzheimer's disease (AD).
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Structural white matter properties and cognitive resilience to tau pathology Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-01 Ting Qiu, Zhen-Qi Liu, François Rheault, Jon Haitz Legarreta, Alex Valcourt Caron, Frédéric St-Onge, Cherie Strikwerda-Brown, Amelie Metz, Mahsa Dadar, Jean-Paul Soucy, Alexa Pichet Binette, R. Nathan Spreng, Maxime Descoteaux, Sylvia Villeneuve
We assessed whether macro- and/or micro-structural white matter properties are associated with cognitive resilience to Alzheimer's disease pathology years prior to clinical onset.
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On the effect heterogeneity of established disease susceptibility loci for Alzheimer's disease across different genetic ancestries Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-02 Sanghun Lee, Julian Hecker, Georg Hahn, Kristina Mullin, , Sharon M. Lutz, Rudolph E. Tanzi, Christoph Lange, Dmitry Prokopenko
Genome-wide association studies have identified numerous disease susceptibility loci (DSLs) for Alzheimer's disease (AD). However, only a limited number of studies have investigated the dependence of the genetic effect size of established DSLs on genetic ancestry.
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Minimal clinically important difference in Alzheimer's disease: Rapid review Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-02 Ryan T. Muir, Michael D. Hill, Sandra E. Black, Eric E. Smith
INTRODUCTIONWe conducted a rapid systematic review of minimal clinically important differences (MCIDs) for Alzheimer's disease (AD) trial endpoints.METHODSTwo reviewers searched EMBASE, MEDLINE, and PubMed from inception to June 4, 2023.RESULTSTen articles were retrieved. For mild cognitive impairment (MCI), a change of +2 to +3 points on the Alzheimer's Disease Assessment Scale–Cognitive Subscale