-
Multimerization of TREM2 is impaired by Alzheimer's disease–associated variants Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-20 Hunter B. Dean, Rory A. Greer, Shan‐Zhong Yang, Daniel S. Elston, Thomas J. Brett, Erik D. Roberson, Yuhua Song
INTRODUCTIONThe immune receptor triggering receptor expressed on myeloid cells 2 (TREM2) is among the strongest genetic risk factors for Alzheimer's disease (AD) and is a therapeutic target. TREM2 multimers have been identified in crystallography and implicated in the efficacy of antibody therapeutics; however, the molecular basis for TREM2 multimerization remains poorly understood.METHODSWe used molecular
-
Optimizing cutpoints for clinical interpretation of brain amyloid status using plasma p‐tau217 immunoassays Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-19 Daniel J. Figdore, Michael Griswold, Joshua A. Bornhorst, Jonathan Graff‐Radford, Vijay K. Ramanan, Prashanthi Vemuri, Val J. Lowe, David S. Knopman, Clifford R. Jack, Ronald C. Petersen, Alicia Algeciras‐Schimnich
INTRODUCTIONWe aimed to evaluate clinical interpretation cutpoints for two plasma phosphorylated tau (p‐tau)217 assays (ALZpath and Lumipulse) as predictors of amyloid status for implementation in clinical practice.METHODSClinical performance of plasma p‐tau217 against amyloid positron emission tomography status was evaluated in participants with mild cognitive impairment or mild dementia (n = 427)
-
Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-19 Courtney M. Kloske, Michael E. Belloy, Elizabeth E. Blue, Gregory R. Bowman, Maria C. Carrillo, Xiaoying Chen, Ornit Chiba‐Falek, Albert A. Davis, Gilbert Di Paolo, Francesca Garretti, David Gate, Lesley R. Golden, Jay W. Heinecke, Joachim Herz, Yadong Huang, Costantino Iadecola, Lance A. Johnson, Takahisa Kanekiyo, Celeste M. Karch, Anastasia Khvorova, Sascha J. Koppes‐den Hertog, Bruce T. Lamb, Paige
INTRODUCTIONThe apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid‐beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex‐dependent disease manifestations. Furthermore, ancestral background may
-
Empowering a person‐centered long‐term care workforce Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-18 Doug Pace, Shadoworee Betts, Lillian Reda, Merle Griff, Lauren Stratton, Emily Shubeck, Lakelyn Eichenberger, Nikki Holles, Lisa Holloway, Rachel Little, Sharon McGuire, Joyce Mahoney, Cole Smith, Sam Fazio
Currently there is a crisis in the long‐term care workforce, as many workers experience poor pay, a lack of training, burnout, low quality working conditions, and physical strain, which is leading to a workforce shortage. To address this, the Alzheimer's Association Dementia Care Provider Roundtable (AADCPR) convened a panel of direct care workers to discuss and provide direction on their view of the
-
Genome‐wide meta‐analysis identifies ancestry‐specific loci for Alzheimer's disease Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-18 Yi‐Jun Ge, Shi‐Dong Chen, Bang‐Sheng Wu, Ya‐Ru Zhang, Jun Wang, Xiao‐Yu He, Wei‐Shi Liu, Yi‐Lin Chen, Ya‐Nan Ou, Xue‐Ning Shen, Yu‐Yuan Huang, Yi‐Han Gan, Liu Yang, Ling‐Zhi Ma, Ya‐Hui Ma, Ke‐Liang Chen, Shu‐Fen Chen, Mei Cui, Lan Tan, Qiang Dong, Qian‐Hua Zhao, Yan‐Jiang Wang, Jian‐Ping Jia, Jin‐Tai Yu
INTRODUCTIONAlzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late‐onset type AD in populations of European ancestry.METHODSWe performed a two‐stage genome‐wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals.RESULTSIn addition to the apolipoprotein E (APOE) locus, our
-
How many future dementia cases would be missed by a high‐risk screening program? A retrospective cohort study in a population‐based cohort Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-18 Sebastian Walsh, Lindsay Wallace, Richard Merrick, Shabina Hayat, Robert Luben, Oliver Mytton, Louise Lafortune, Carol Brayne
INTRODUCTIONRisk prediction models aim to identify those at high risk to receive targeted interventions. We aimed to identify the proportion of future dementia cases that would be missed by a high‐risk screening program.METHODSWe identified validated dementia risk prediction models from systematic reviews. We applied these to European Prospective Investigation of Cancer Norfolk, a large population‐based
-
Suppressing UBE2N ameliorates Alzheimer's disease pathology through the clearance of amyloid beta Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-17 Chen Zhang, Qingqing Jia, Longhong Zhu, Junqi Hou, Xiang Wang, Dandan Li, Jiawei Zhang, Yiran Zhang, Su Yang, Zhuchi Tu, Xiao‐Xin Yan, Weili Yang, Shihua Li, Xiao‐Jiang Li, Peng Yin
INTRODUCTIONAging is one of the risk factors for the early onset of Alzheimer's disease (AD). We previously discovered that the age‐dependent increase in Ubiquitin Conjugating Enzyme E2 N (UBE2N) plays a role in the accumulation of misfolded proteins through K63 ubiquitination, which has been linked to AD pathogenesis. However, the impact of UBE2N on amyloid pathology and clearance has remained unknown
-
Care partner‐informed meaningful change thresholds for the Clinical Dementia Rating‐Sum of Boxes for trials of early Alzheimer's disease Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-17 Claire J. Lansdall, Edmond Teng, Jerome Chague, Rohan Palanganda, Paul Delmar, Janice Smith, Jeffrey L. Cummings, Fiona McDougall
INTRODUCTIONConsensus definitions of meaningful within‐patient change (MWPC) on the Clinical Dementia Rating‐Sum of Boxes (CDR‐SB) are needed. Existing estimates use clinician‐rated anchors in clinically diagnosed Alzheimer's disease (AD) populations. Incorporating the care partner perspective offers important insights, and evaluating biomarker‐confirmed cohorts aligns estimates with ongoing trials
-
Sustained frailty remission and dementia risk in older adults: A longitudinal study Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-17 Shuomin Wang, Qianyuan Li, Shanshan Wang, Chongmei Huang, Qian‐Li Xue, Sarah L. Szanton, Minhui Liu
INTRODUCTIONPhysical frailty is reversible, but little is known about the sustainability of frailty remission and its impact on dementia.METHODSData were derived from the National Health and Aging Trends Study (NHATS) (2011 to 2021). Physical frailty was assessed using the Fried frailty phenotype, and frailty transition patterns across three waves were defined. The relationship of sustained frailty
-
Prospects and challenges in using neuronal extracellular vesicles in biomarker research Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-16 Debora A. S. Rocha, Luis E. Santos, Pedro B. Da Fonseca, Fernanda G. De Felice
Extracellular vesicles (EVs) hold promise as a source of disease biomarkers. The diverse molecular cargo of EVs can potentially indicate the status of their tissue of origin, even against the complex background of whole plasma. The main tools currently available for assessing biomarkers of brain health include brain imaging and analysis of the cerebrospinal fluid of patients. Given the costs and difficulties
-
-
Neurochemical organization of cortical proteinopathy and neurophysiology along the Alzheimer's disease continuum Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-12 Alex I. Wiesman, Jonathan Gallego-Rudolf, Sylvia Villeneuve, Sylvain Baillet, Tony W. Wilson
Despite parallel research indicating amyloid-β accumulation, alterations in cortical neurophysiological signaling, and multi-system neurotransmitter disruptions in Alzheimer's disease (AD), the relationships between these phenomena remains unclear.
-
Assessing cognitive impairment and disability in older adults through the lens of whole brain white matter patterns Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-13 Hyun Woong Roh, Nishant Chauhan, Sang Won Seo, Seong Hye Choi, Eun‐Joo Kim, Soo Hyun Cho, Byeong C. Kim, Jin Wook Choi, Young‐Sil An, Bumhee Park, Sun Min Lee, So Young Moon, You Jin Nam, Sunhwa Hong, Sang Joon Son, Chang Hyung Hong, Dongha Lee
INTRODUCTIONThis study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults.METHODSWe conducted an in‐depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter‐subject
-
Inequalities in accelerated cognitive decline: Resolving observational window bias using nested non‐linear regression Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-13 Sean A. P. Clouston, Douglas W. Hanes, Dylan M. Smith, Lauren L. Richmond, Marcus Richards, Bruce Link
INTRODUCTIONLimited observational windows lead to conflicting results in studies examining educational differences in Alzheimer's disease and related dementias (ADRD) risk, due to observational window bias relative to onset of accelerated cognitive decline. This study tested a novel model to address observational window bias and tested for the presence and sources of disparities in accelerated cognitive
-
Tau‐mediated synaptic dysfunction is coupled with HCN channelopathy Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-12 Despoina Goniotaki, Francesco Tamagnini, Luca Biasetti, Svenja‐Lotta Rumpf, Claire Troakes, Saskia J. Pollack, Shalom Ukwesa, Haoyue Sun, Igor Kraev, Louise C. Serpell, Wendy Noble, Kevin Staras, Diane P. Hanger
INTRODUCTIONIn tauopathies, altered tau processing correlates with impairments in synaptic density and function. Changes in hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels contribute to disease‐associated abnormalities in multiple neurodegenerative diseases.METHODSTo investigate the link between tau and HCN channels, we performed histological, biochemical, ultrastructural, and functional
-
Cerebral arteriolosclerosis, lacunar infarcts, and cognition in older Black adults Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-11 Debra A. Fleischman, Konstantinos Arfanakis, Sue E. Leurgans, Zoe Arvanitakis, Melissa Lamar, S. Duke Han, Victoria N. Poole, David A. Bennett, Lisa L. Barnes
INTRODUCTIONOlder Black adults are at risk of cerebral small vessel disease (CSVD), which contributes to dementia risk. Two subtypes of CSVD, arteriolosclerosis and ischemic lacunar infarcts, have been independently linked to lower cognition and higher dementia risk, but their combined effects on cognition in older Black adults are unclear.METHODSMixed models were used to examine the associations of
-
The Anne and Henry Zarrow Foundation makes second $5 million grant to Alzheimer's Association for research Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-11
The Anne and Henry Zarrow Foundation has made its second $5 million grant to the Alzheimer's Association to support the Zenith Fellows Awards. The contribution brings the Tulsa, Oklahoma–based foundation's funding of the influential research program to $10 million. “Thanks to the generous support of philanthropic partners like The Anne and Henry Zarrow Foundation and other members of the Alzheimer's
-
Spatial extent as a sensitive amyloid‐PET metric in preclinical Alzheimer's disease Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-11 Michelle E. Farrell, Emma G. Thibault, J. Alex Becker, Julie C. Price, Brian C. Healy, Bernard J. Hanseeuw, Rachel F. Buckley, Heidi I. L. Jacobs, Aaron P. Schultz, Charles D. Chen, Reisa A. Sperling, Keith A. Johnson
INTRODUCTIONSpatial extent‐based measures of how far amyloid beta (Aβ) has spread throughout the neocortex may be more sensitive than traditional Aβ‐positron emission tomography (PET) measures of Aβ level for detecting early Aβ deposits in preclinical Alzheimer's disease (AD) and improve understanding of Aβ’s association with tau proliferation and cognitive decline.METHODSPittsburgh Compound‐B (PIB)‐PET
-
Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-10 Hulya Ulugut, Maxime Bertoux, Kyan Younes, Maxime Montembeault, Giorgio G. Fumagalli, Bedia Samanci, Ignacio Illán-Gala, Gregory Kuchcinski, Melanie Leroy, Jennifer C. Thompson, Christopher Kobylecki, Alexander F Santillo, Elisabet Englund, Maria Landqvist Waldö, Lina Riedl, Jan Van den Stock, Mathieu Vandenbulcke, Rik Vandenberghe, Robert Laforce Jr, Simon Ducharme, Peter S. Pressman, Paulo Caramelli
Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype.
-
Correlations between plasma markers and brain Aβ deposition across the AD continuum: Evidence from SILCODE Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-10 Xianfeng Yu, Rong Shi, Xia Zhou, Mingkai Zhang, Yue Cai, Jiehui Jiang, Ying Han
BACKGROUNDPrevious studies have found that Alzheimer's disease (AD)‐related plasma markers are associated with amyloid beta (Aβ) deposition, but the change of this association in different Aβ pathological stages remains unclear.METHODSData were obtained from the SILCODE. According to the standardized uptake value ratio (SUVR) and Aβ stage classification, correlation analysis was performed among plasma
-
Racial and ethnic differences in the risk of dementia diagnosis under hypothetical blood pressure–lowering interventions: The Multi‐Ethnic Study of Atherosclerosis Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-10 L. Paloma Rojas‐Saunero, Timothy M. Hughes, Elizabeth Rose Mayeda, Marcia Pescador Jimenez
INTRODUCTIONSubstantial racial and ethnic disparities in hypertension and dementia exist in the United States. We evaluated the effect of maintaining systolic blood pressure (SBP) below clinical thresholds on dementia incidence.METHODSWe included 6806 Multi‐Ethnic Study of Atherosclerosis participants (44 to 84 years old). We implemented the parametric g‐formula to simulate the hypothetical interventions
-
Association of neuroticism with incident dementia, neuroimaging outcomes, and cognitive function Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-10 Yaqing Gao, Najaf Amin, Cornelia van Duijn, Thomas J Littlejohns
INTRODUCTIONHigher neuroticism might be associated with dementia risk. Here we investigated modification by genetic predisposition to dementia, mediation by mental health and vascular conditions, neuroimaging outcomes, and cognitive function.METHODSCox proportional‐hazards models were used to assess the association between neuroticism score and incident dementia over up to 15 years in 1,74,164 participants
-
Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND‐China study Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-10 Cuicui Liu, Rui Liu, Na Tian, Wenxin Fa, Keke Liu, Nan Wang, Min Zhu, Xiaoyan Liang, Yixun Ma, Yifei Ren, Yongxiang Wang, Lin Cong, Shi Tang, Davide Liborio Vetrano, Tiia Ngandu, Miia Kivipelto, Tingting Hou, Yifeng Du, Chengxuan Qiu
INTRODUCTIONEvidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood.METHODSThis population‐based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid‐β (Aβ), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following
-
Caregiver coping mediates the relationship between caregivers’ understanding of dementia as terminal and their distress Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-06 Ishwarya Balasubramanian, Louisa Camille Poco, Ellie Bostwick Andres, Isha Chaudhry, Truls Østbye, Chetna Malhotra
We assessed which coping strategies (problem-focused, emotion-focused, dysfunctional) mediate the association between caregivers’ understanding of dementia as terminal and their distress. A total of 215 caregivers of community-dwelling persons with severe dementia were surveyed every 4 months over 3 years. A generalized structural equation model was used to test mediation. Caregivers who correctly
-
Interplay between orthopedic interventions and dementia: Dementia risk after total knee replacement Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-09 Hui‐Chin Chang, Ru‐Yin Tsai, Chen‐Pi Li, Wen‐Chieh Liao, Chih‐Lung Wu, Shiu‐Jau Chen, Shuo‐Yan Gau
The interplay between orthopedic events and dementia is complicated. A recent Japanese study by Matsumoto et al. revealed that individuals with early-onset dementia faced an increased likelihood of experiencing osteoporotic fractures compared to those without cognitive impairments.1 As for the reverse direction of orthopedic events–dementia association, integrated evidence showed that osteoarthritis
-
Early blood immune molecular alterations in cynomolgus monkeys with a PSEN1 mutation causing familial Alzheimer's disease Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-08 Mengqi Li, Mingfeng Guan, Jianbang Lin, Kaichuan Zhu, Jiayi Zhu, Ming Guo, Yinhu Li, Yefei Chen, Yijing Chen, Ying Zou, Daiqiang Wu, Junxin Xu, Wanying Yi, Yingying Fan, Shuangshuang Ma, Yuewen Chen, Jun Xu, Lixin Yang, Ji Dai, Tao Ye, Zhonghua Lu, Yu Chen
INTRODUCTIONMore robust non‐human primate models of Alzheimer's disease (AD) will provide new opportunities to better understand the pathogenesis and progression of AD.METHODSWe designed a CRISPR/Cas9 system to achieve precise genomic deletion of exon 9 in cynomolgus monkeys using two guide RNAs targeting the 3′ and 5′ intron sequences of PSEN1 exon 9. We performed biochemical, transcriptome, proteome
-
Traumatic brain injury and cognitive change over 30 years among community‐dwelling older adults Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-06 Andrea L. C. Schneider, James R. Pike, Holly Elser, Josef Coresh, Thomas H. Mosley, Ramon Diaz‐Arrastia, Rebecca F. Gottesman
INTRODUCTIONThere is limited evidence regarding the rate of long‐term cognitive decline after traumatic brain injury (TBI) among older adults.METHODSIn this prospective cohort study, time‐varying TBI was defined by self‐report and International Classification of Disease diagnostic codes. Cognitive testing was performed at five visits over 30 years and scores were combined into a global cognition factor
-
CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-06 Aurore Delvenne, Johan Gobom, Suzanne E. Schindler, Mara ten Kate, Lianne M. Reus, Valerija Dobricic, Betty M. Tijms, Tammie L. S. Benzinger, Carlos Cruchaga, Charlotte E. Teunissen, Inez Ramakers, Pablo Martinez‐Lage, Mikel Tainta, Rik Vandenberghe, Jolien Schaeverbeke, Sebastiaan Engelborghs, Ellen De Roeck, Julius Popp, Gwendoline Peyratout, Magda Tsolaki, Yvonne Freund‐Levi, Simon Lovestone, Johannes
INTRODUCTIONWe aimed to unravel the underlying pathophysiology of the neurodegeneration (N) markers neurogranin (Ng), neurofilament light (NfL), and hippocampal volume (HCV), in Alzheimer's disease (AD) using cerebrospinal fluid (CSF) proteomics.METHODSIndividuals without dementia were classified as A+ (CSF amyloid beta [Aβ]42), T+ (CSF phosphorylated tau181), and N+ or N− based on Ng, NfL, or HCV
-
Lung function in relation to brain aging and cognitive transitions in older adults: A population‐based cohort study Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-06 Giulia Grande, Yuanjing Li, Caterina Trevisan, Debora Rizzuto, Grégoria Kalpouzos, Mozhu Ding, Erika J Laukka, Tom Bellander, Laura Fratiglioni, Chengxuan Qiu
BACKGROUNDWe investigated the association of peak expiratory flow (PEF) with dementia; cognitive impairment, no dementia (CIND); and transition from CIND to dementia, and possible underlying neuropathological mechanisms.METHODSA population‐based cohort of adults aged 60+ was followed over 15 years to detect dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria), CIND
-
Sex and gender differences in cognitive resilience to aging and Alzheimer's disease Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-05 Eider M. Arenaza-Urquijo, Rory Boyle, Kaitlin Casaletto, Kaarin J. Anstey, Clara Vila-Castelar, Aaron Colverson, Eleni Palpatzis, Jaclyn M. Eissman, Ted Kheng Siang Ng, Sheelakumari Raghavan, Muge Akinci, Jet M. J. Vonk, Luiza S. Machado, Preeti P. Zanwar, Hom L. Shrestha, Maude Wagner, Stefano Tamburin, Hamid R. Sohrabi, Samantha Loi, David Bartrés-Faz, Dena B. Dubal, Vemuri Prashanthi, Ozioma Okonkwo
Sex and gender—biological and social constructs—significantly impact the prevalence of protective and risk factors, influencing the burden of Alzheimer's disease (AD; amyloid beta and tau) and other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding the interplay of these factors is central to understanding resilience and resistance mechanisms explaining
-
Stress testing the Centiloid: Precision and variability of PET quantification of amyloid pathology Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-04 Mahnaz Shekari, David Vállez García, Lyduine E. Collij, Daniele Altomare, Fiona Heeman, Hugh Pemberton, Núria Roé Vellvé, Santiago Bullich, Christopher Buckley, Andrew Stephens, Gill Farrar, Giovanni Frisoni, William E. Klunk, Frederik Barkhof, Juan Domingo Gispert
Assessing the potential sources of bias and variability of the Centiloid (CL) scale is fundamental for its appropriate clinical application.
-
Longitudinal plasma phosphorylated-tau217 and other related biomarkers in a non-demented Alzheimer's risk-enhanced sample Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-05 Lianlian Du, Rebecca E. Langhough, Rachael E. Wilson, Ramiro Eduardo Rea Reyes, Bruce P. Hermann, Erin M. Jonaitis, Tobey J. Betthauser, Nathaniel A. Chin, Bradley Christian, Lauren Chaby, Andreas Jeromin, Guglielmo Di Molfetta, Wagner S. Brum, Burak Arslan, Nicholas Ashton, Kaj Blennow, Henrik Zetterberg, Sterling C. Johnson
Understanding longitudinal change in key plasma biomarkers will aid in detecting presymptomatic Alzheimer's disease (AD).
-
Effects of a multidomain intervention against cognitive decline on dementia risk profiles — Results from the AgeWell.de trial Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-05 Andrea E. Zülke, Alexander Pabst, Melanie Luppa, Anke Oey, Solveig Weise, Thomas Fankhänel, Robert P. Kosilek, Hannah Schillok, Christian Brettschneider, David Czock, Birgitt Wiese, Jochen René Thyrian, Wolfgang Hoffmann, Thomas Frese, Jochen Gensichen, Hans‐Helmut König, Hanna Kaduszkiewicz, Steffi G. Riedel‐Heller
INTRODUCTIONDementia risk scores constitute promising surrogate outcomes for lifestyle interventions targeting cognitive function. We investigated whether dementia risk, assessed using the LIfestyle for BRAin health (LIBRA) index, was reduced by the AgeWell.de intervention.METHODSSecondary analyses of the AgeWell trial, testing a multicomponent intervention (including optimization of nutrition, medication
-
Exploring microtubule dynamics in Alzheimer's disease: Longitudinal assessment using [11C]MPC‐6827 PET imaging in rodent models of Alzheimer's‐related pathology Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-05 Naresh Damuka, Riley E. Irmen, Ivan Krizan, Mack Miller, Krishna K. Gollapelli, Bhuvanachandra Bhoopal, Ojasvi Deep, Avinash Bansode, Samuel N. Lockhart, Miranda E. Orr, Pooja Jadiya, Nagaraju Bashetti, J. V. Shanmukha Kumar, Akiva Mintz, Christopher T. Whitlow, Suzanne Craft, Shannon L. Macauley, Kiran K. Solingapuram Sai
INTRODUCTIONMicrotubule (MT) stability is crucial for proper neuronal function. Understanding MT dysregulation is critical for connecting amyloid beta (Aβ) and tau‐based degenerative events and early changes in presymptomatic Alzheimer's disease (AD). Herein we present positron emission tomography (PET) imaging properties of our MT‐PET radiotracer, [11C]MPC‐6827, in multiple established AD mouse models
-
Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-04 Daniela Andriuta, Julie Ottoy, Myuri Ruthirakuhan, Ginelle Feliciano, Allison A. Dilliott, Robert A. Hegele, Fuqiang Gao, Paula M. McLaughlin, Jennifer S. Rabin, Madeline Wood Alexander, Christopher J. M. Scott, Vanessa Yhap, Courtney Berezuk, Miracle Ozzoude, Walter Swardfager, Julia Zebarth, M. Carmela Tartaglia, Ekaterina Rogaeva, David F. Tang-Wai, Leanne Casaubon, Sanjeev Kumar, Dar Dowlatshahi
We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases.
-
Effect of gamification with a support partner to increase physical activity in older adults at risk for Alzheimer's disease: The STEP 4Life randomized clinical trial Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-04 S. Ryan Greysen, Ai Leen Oon, Kristin Harkins, Charles Rareshide, Angira Mondal, Mitesh S. Patel, Joshua D. Grill, Jason Karlawish
INTRODUCTIONPhysical activity is associated with reduced risk of cognitive and functional decline but scalable, sustainable interventions for populations at risk for Alzheimer's disease (AD) and AD and related dementias (ADRD) are lacking.METHODSA 12‐week randomized‐controlled trial was conducted with a 3‐week follow‐up using a national AD prevention registry (GeneMatch). The control group (n = 50)
-
Florbetaben amyloid PET acquisition time: Influence on Centiloids and interpretation Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-04 Emily Johns, Hillary A. Vossler, Christina B. Young, Mackenzie L. Carlson, Joseph R. Winer, Kyan Younes, Jennifer Park, Julia Rathmann‐Bloch, Viktorija Smith, Theresa M. Harrison, Susan Landau, Victor Henderson, Anthony Wagner, Sharon J. Sha, Michael Zeineh, Greg Zaharchuk, Kathleen L. Poston, Guido A. Davidzon, Elizabeth C. Mormino
INTRODUCTIONAmyloid positron emission tomography (PET) acquisition timing impacts quantification.METHODSIn florbetaben (FBB) PET scans of 245 adults with and without cognitive impairment, we investigated the impact of post‐injection acquisition time on Centiloids (CLs) across five reference regions. CL equations for FBB were derived using standard methods, using FBB data collected between 90 and 110
-
Novel measures of cognition and function for the AD spectrum in the Novel Measures for Alzheimer's Disease Prevention Trials (NoMAD) project: Psychometric properties, convergent validation, and contrasts with established measures Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-04 Hyun Kim, Seonjoo Lee, Alina Levine, Benjamin Huber, Howard Andrews, Nancy A. Kerner, Daniel Cohen, Scott Carlson, Sophie A. Bell, Andres M. Rivera, Marc L. Gordon, Sabrina Simoes, Davangere. P. Devanand, Adam M. Brickman, Lon S. Schneider, Philip D. Harvey, Terry E. Goldberg
INTRODUCTIONThis study derived composite scores for two novel cognitive measures, the No Practice Effect (NPE) battery and the Miami Computerized Functional Skills Assessment and Training system for use in early‐stage Alzheimer's disease (AD) clinical trials. Their psychometric properties and associations with AD risk markers were compared to those of well‐established measures.METHODSFor 291 older
-
Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-03 Nicholas R. Ray, Brian W. Kunkle, Kara Hamilton-Nelson, Jiji T. Kurup, Farid Rajabli, Min Qiao, Badri N. Vardarajan, Mehmet I. Cosacak, Caghan Kizil, Melissa Jean-Francois, Michael Cuccaro, Dolly Reyes-Dumeyer, Laura Cantwell, Amanda Kuzma, Jeffery M. Vance, Sujuan Gao, Hugh C. Hendrie, Olusegun Baiyewu, Adesola Ogunniyi, Rufus O. Akinyemi, , Wan-Ping Lee, Eden R. Martin, Li-San Wang, Gary W. Beecham
Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts.
-
Neuropsychiatric symptom burden in early‐onset and late‐onset Alzheimer's disease as a function of age Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-03 Angelina J. Polsinelli, Sierah Johnson, Adele Crouch, Kathleen A. Lane, Alex Pena‐Garcia, Dustin B. Hammers, Sophia Wang, Sujuan Gao, Liana G. Apostolova
INTRODUCTIONWe examined the burden of neuropsychiatric symptoms (NPSs) in early‐onset (EO) and late‐onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals.METHODSCross‐sectional data from 2940 EOAD, 8665 LOAD, and 8775 age‐stratified CU individuals (early‐CU, n = 2433; late‐CU, n = 6342) from the National Alzheimer's Coordinating
-
Heterogeneous treatment effects of sodium‐glucose cotransporter 2 inhibitors on risk of dementia in people with type 2 diabetes: A population‐based cohort study Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-03 Huilin Tang, William T. Donahoo, Mikael Svensson, C. Elizabeth Shaaban, Glenn Smith, Michael S. Jaffee, Yu Huang, Xia Hu, Ying Lu, Ramzi G. Salloum, Steven T. DeKosky, Jiang Bian, Jingchuan Guo
INTRODUCTIONSodium‐glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain.METHODSIndividuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016–2022). A doubly robust learning was deployed to estimate risk difference
-
The role of the Alzheimer's Disease Neuroimaging Initiative in establishing the Dominantly Inherited Alzheimer Network Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-03 John C. Morris, Virginia D. Buckles
The Dominantly Inherited Alzheimer Network (DIAN) initially was funded by the National Institute on Aging (NIA) in 2008 and thus was able to adopt and incorporate the protocols developed by the Alzheimer's Disease Neuroimaging Initiative (ADNI) that had been established by the NIA in 2004. The use of ADNI protocols for DIAN neuroimaging studies and assays of biological fluids for Alzheimer disease
-
Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-03 Cameron D. Owens, Camila Bonin Pinto, Peter Mukli, Rafal Gulej, Faddi Saleh Velez, Sam Detwiler, Lauren Olay, Jordan R. Hoffmeister, Zsofia Szarvas, Mihaly Muranyi, Anna Peterfi, Ana Clara da C. Pinaffi‐Langley, Cheryl Adams, Jason Sharps, Zalan Kaposzta, Calin I. Prodan, Angelia C. Kirkpatrick, Stefano Tarantini, Anna Csiszar, Zoltan Ungvari, Ann L. Olson, Guangpu Li, Priya Balasubramanian, Veronica
INTRODUCTIONMild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention.METHODSPatients with MCI and age‐matched controls (CN) were administered cognitive tasks during functional near‐infrared spectroscopy (fNIRS) recording, and changes in plasma
-
Nanoscale flow cytometry‐based quantification of blood‐based extracellular vesicle biomarkers distinguishes MCI and Alzheimer's disease Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-03 Thamara Dayarathna, Austyn D. Roseborough, Janice Gomes, Reza Khazaee, Carolina R. A. Silveira, Kathy Borron, Soojung Yu, Kristy Coleman, Sarah Jesso, Elizabeth Finger, Penny MacDonald, Michael Borrie, Jennie Wells, Robert Bartha, Guangyong Zou, Shawn N. Whitehead, Hon S. Leong, Stephen H. Pasternak
INTRODUCTIONAccurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure.METHODSWe developed a nanoscale flow cytometry (nFC)‐based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls.RESULTSCirculating amyloid
-
HbA1c variability associated with dementia risk in people with type 2 diabetes Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-03 Chris Moran, Rachel A. Whitmer, Zoe Dove, Mary E. Lacy, Yenee Soh, Ai‐Lin Tsai, Charles P. Quesenberry, Andrew J. Karter, Alyce S. Adams, Paola Gilsanz
INTRODUCTIONAlthough poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A1c (HbA1c) levels, increases dementia risk.METHODSAmong 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long‐term HbA1c variability using five operationalizations, including standard deviation
-
Time‐encoded ASL reveals lower cerebral blood flow in the early AD continuum Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-03 Carles Falcon, Paula Montesinos, Lena Václavů, Michalis Kassinopoulos, Carolina Minguillon, Karine Fauria, Diego Cascales‐Lahoz, José Contador, Aida Fernández‐Lebrero, Irene Navalpotro, Albert Puig‐Pijoan, Oriol Grau‐Rivera, Gwendlyn Kollmorgen, Clara Quijano‐Rubio, José Luis Molinuevo, Henrik Zetterberg, Kaj Blennow, Marc Suárez‐Calvet, Matthias J. P. Van Osch, Javier Sanchez‐Gonzalez, Juan Domingo
INTRODUCTIONCerebral blood flow (CBF) is reduced in cognitively impaired (CI) Alzheimer's disease (AD) patients. We checked the sensitivity of time‐encoded arterial spin labeling (te‐ASL) in measuring CBF alterations in individuals with positive AD biomarkers and associations with relevant biomarkers in cognitively unimpaired (CU) individuals.METHODSWe compared te‐ASL with single‐postlabel delay (PLD)
-
Correlates of missed or late versus timely diagnosis of dementia in healthcare settings Alzheimers Dement. (IF 13.0) Pub Date : 2024-06-27 Yi Chen, Melinda C. Power, Francine Grodstein, Ana W. Capuano, Brittney S. Lange-Maia, Ali Moghtaderi, Emma K. Stapp, Joya Bhattacharyya, Raj C. Shah, Lisa L. Barnes, David X. Marquez, David A. Bennett, Bryan D. James
There is limited evidence about factors related to the timeliness of dementia diagnosis in healthcare settings.
-
Alzheimer's disease biomarker burden in primary motor cortices is associated with poorer dexterity performance Alzheimers Dement. (IF 13.0) Pub Date : 2024-06-27 Lily Gupta, Yue Ma, Akshay Kohli, Kao Lee Yang, Jennifer M. Oh, Tobey J. Betthauser, Nathaniel A. Chin, Ozioma C. Okonkwo, Mary-Elizabeth Pasquesi, Veena Nair, Vivek Prabhakaran, Shi-Jiang Li, Barbara Bendlin
Motor function has correlated with longevity and functionality; however, there is limited research on those with Alzheimer's disease (AD). We studied the association between motor functionality and AD pathology in primary motor and medial temporal cortices.
-
Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease–related cognitive decline: Multi‐site validation in the MarkVCID Consortium Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-02 Peiying Liu, Zixuan Lin, Kaisha Hazel, George Pottanat, Cuimei Xu, Dengrong Jiang, Jay J. Pillai, Emma Lucke, Christopher E. Bauer, Brian T. Gold, Steven M. Greenberg, Karl G. Helmer, Kay Jann, Gregory Jicha, Joel Kramer, Pauline Maillard, Rachel M. Mulavelil, Pavel Rodriguez, Claudia L. Satizabal, Kristin Schwab, Sudha Seshadri, Herpreet Singh, Ángel G. Velarde Dediós, Danny J. J. Wang, Rita R. Kalyani
INTRODUCTIONVascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi‐site study, using a predefined hypothesis.METHODSWe conducted the study in a total of three analysis
-
Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid Alzheimers Dement. (IF 13.0) Pub Date : 2024-06-28 Sophia Krasny, Cynthia Yan, Sigan L. Hartley, Ben L. Handen, Julie K. Wisch, Anna H. Boehrwinkle, Beau M. Ances, Michael S. Rafii
Trisomy 21, or Down syndrome (DS), predisposes individuals to early-onset Alzheimer's disease (AD). While monoclonal antibodies (mAbs) targeting amyloid are approved for older AD patients, their efficacy in DS remains unexplored. This study examines amyloid positron emission tomography (PET) positivity (A+), memory function, and clinical status across ages in DS to guide mAb trial designs.
-
Analysis of changes in social isolation, loneliness, or both, and subsequent cognitive function among older adults: Findings from a nationwide cohort study Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-01 Qing‐Mei Huang, Pei‐Dong Zhang, Dong Shen, Jian Gao, Zhi‐Hao Li, Yue‐Bin Lv, Xiao‐Ming Shi, Chen Mao
INTRODUCTIONThe study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function.METHODSData were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine‐category variable to represent the joint changes
-
The association between liver fibrosis score and incident dementia: A nationwide retrospective cohort study Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-01 Galit Weinstein, Yochai Schonmann, Hanny Yeshua, Shira Zelber‐Sagi
BACKGROUNDWe assessed the relationship of liver fibrosis score with incident dementia in a large, national sample.METHODSFor this retrospective cohort study, data of dementia‐free individuals aged 40‐69 years were derived from electronic records of the largest healthcare provider in Israel. The association between liver fibrosis score (FIB‐4), assessed from routine laboratory measurements, and incident
-
Reproductive hormones in relation to white matter hyperintensity volumes among midlife women Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-01 Rebecca C. Thurston, Yuefang Chang, Minjie Wu, Emma M. Harrison, Howard J. Aizenstein, Carol A. Derby, Emma Barinas‐Mitchell, Pauline M. Maki
INTRODUCTIONAlthough reproductive hormones are implicated in cerebral small vessel disease in women, few studies consider measured hormones in relation to white matter hyperintensity volume (WMHV), a key indicator of cerebral small vessel disease. Even fewer studies consider estrone (E1), the primary postmenopausal estrogen, or follicle‐stimulating hormone (FSH), an indicator of ovarian age. We tested
-
Admixture mapping of cognitive function in diverse Hispanic and Latino adults: Results from the Hispanic Community Health Study/Study of Latinos Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-01 Rui Xia, Xueqiu Jian, Amanda L. Rodrigue, Jan Bressler, Eric Boerwinkle, Biqi Cui, Martha L. Daviglus, Charles DeCarli, Linda C. Gallo, David C. Glahn, Emma E. M. Knowles, Jee‐Young Moon, Thomas H. Mosley, Claudia L. Satizabal, Tamar Sofer, Wassim Tarraf, Fernando Testai, John Blangero, Sudha Seshadri, Hector M. González, Myriam Fornage
INTRODUCTIONWe conducted admixture mapping and fine‐mapping analyses to identify ancestry‐of‐origin loci influencing cognitive abilities.METHODSWe estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in
-
Plasma and CSF biomarkers of aging and cognitive decline in Caribbean vervets Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-01 Curran Varma, Eva Luo, Gustaf Bostrom, Praveen Bathini, Daniela Berdnik, Tony Wyss‐Coray, Tingting Zhao, Xianjun Dong, Frank R. Ervin, Amy Beierschmitt, Roberta M. Palmour, Cynthia A. Lemere
INTRODUCTIONVervets are non‐human primates that share high genetic homology with humans and develop amyloid beta (Aβ) pathology with aging. We expand current knowledge by examining Aβ pathology, aging, cognition, and biomarker proteomics.METHODSAmyloid immunoreactivity in the frontal cortex and temporal cortex/hippocampal regions from archived vervet brain samples ranging from young adulthood to old
-
Effect of early menopause on cognition and brain morphology in an Urban Indian Cohort Alzheimers Dement. (IF 13.0) Pub Date : 2024-07-01 Abhishek Mensegere, Sadhana Singh, Albert Stezin, Jonas S. Sundarakumar, Thomas Gregor Issac
BACKGROUNDEvidence for the effect of early menopause on cognition among older women is not consistent and is scant among the Indian population.METHODSWe aimed to examine the effect of early menopause (≤45 years) on cognitive performance and brain morphology among older dementia‐free females of the TLSA cohort using a multiple linear regression analysis.RESULTSIn a sample of 528 women, 144 (27%) had
-
The link between gut microbiome and Alzheimer's disease: From the perspective of new revised criteria for diagnosis and staging of Alzheimer's disease Alzheimers Dement. (IF 13.0) Pub Date : 2024-06-28 Yuan Liang, Congcong Liu, Manman Cheng, Lijie Geng, Jing Li, Wenying Du, Minfang Song, Nian Chen, Traore Aicha Noura Yeleen, Li Song, Xiaoni Wang, Ying Han, Can Sheng
Over the past decades, accumulating evidence suggests that the gut microbiome exerts a key role in Alzheimer's disease (AD). The Alzheimer's Association Workgroup is updating the diagnostic criteria for AD, which changed the profiles and categorization of biomarkers from “AT(N)” to “ATNIVS.” Previously, most of studies focus on the correlation between the gut microbiome and amyloid beta deposition
-
Prevalence and clinicopathological features of primary age‐related tauopathy (PART): A large forensic autopsy study Alzheimers Dement. (IF 13.0) Pub Date : 2024-06-28 Koji Yoshida, Yukiko Hata, Shojiro Ichimata, Ryo Tanaka, Naoki Nishida
INTRODUCTIONPrimary age‐related tauopathy (PART), often regarded as a minimally symptomatic pathology of old age, lacks comprehensive cohorts across various age groups.METHODSWe examined PART prevalence and clinicopathologic features in 1589 forensic autopsy cases (≥40 years old, mean age ± SD 70.2 ± 14.2 years).RESULTSPART cases meeting criteria for argyrophilic grain diseases (AGD) were AGD+PART
-
PKCδ serves as a potential biomarker and therapeutic target for microglia‐mediated neuroinflammation in Alzheimer's disease Alzheimers Dement. (IF 13.0) Pub Date : 2024-06-28 Ying Du, Tiantian Guo, Yunfeng Hao, Chuan Li, Linghui Tang, Xia Li, Xiaoxiao Zhang, Lin Li, Dan Yao, Xia Xu, Huaxing Si, Jinghan Zhang, Nana Zhao, Tong Yu, Yingjun Zhao, Wei Zhang, Huaxi Xu
INTRODUCTIONTo investigate the role of a novel type of protein kinase C delta (PKCδ) in the neuroinflammation of Alzheimer's disease (AD).METHODSWe analyzed PKCδ and inflammatory cytokines levels in cerebrospinal fluid (CSF) of AD and normal controls, as well as their correlations. The cellular expression pattern of PKCδ and the effects of PKCδ modulation on microglia‐mediated neuroinflammation were
-
Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease Alzheimers Dement. (IF 13.0) Pub Date : 2024-06-28 Viswanath Devanarayan, Thomas Doherty, Arnaud Charil, Pallavi Sachdev, Yuanqing Ye, Leema Krishna Murali, Daniel A. Llano, Jin Zhou, Larisa Reyderman, Harald Hampel, Lynn D. Kramer, Shobha Dhadda, Michael C. Irizarry
BACKGROUNDThis study investigated the potential of phosphorylated plasma Tau217 ratio (pTau217R) and plasma amyloid beta (Aβ) 42/Aβ40 in predicting brain amyloid levels measured by positron emission tomography (PET) Centiloid (CL) for Alzheimer's disease (AD) staging and screening.METHODSQuantification of plasma pTau217R and Aβ42/Aβ40 employed immunoprecipitation‐mass spectrometry. CL prediction models