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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
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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
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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
INTRODUCTIONMetabotropic 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).METHODSTen cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18F]SynVesT‐1 and [18F]PSS232 positron emission
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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
BACKGROUNDAlzheimer'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.METHODSGenome‐wide association studies identified 86 single nucleotide polymorphisms (SNPs) associated with AD risk. We estimated SNP frequency in 2281 AD cases, 3165 age‐matched
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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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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
INTRODUCTIONIn 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).METHODSUnivariate logistic regression models were used to
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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
INTRODUCTIONAge‐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.METHODSBrain samples from 51 oldest old Oregon Alzheimer's Disease Research Center participants
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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
INTRODUCTIONCerebral 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.METHODSMINERVA was a single‐center
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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
INTRODUCTIONAlzheimer'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.METHODSAn elevated plus maze was used to assess anxiety‐like
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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
INTRODUCTIONOzone (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.METHODSThe O3‐induced astrocyte phenotype was characterized in 5xFAD mice by spatial transcriptomics and proteomics. Hmgb1fl/fl LysM‐Cre+
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Progressive reduction of nuclear receptor Nr4a1 mediates age‐dependent cognitive decline Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-12 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
INTRODUCTIONCognitive 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.METHODSNr4a1 expressions were evaluated by quantitative PCR and immunochemical approaches. The cognition of mice was examined by multiple behavioral tests. Patch‐clamp experiments were conducted
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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
INTRODUCTIONWe investigated the association between sleep duration and neuropathologic changes 19 to 40 years later in oldest‐old (age 90+) participants of The 90+ Study.METHODSParticipants self‐reported sleep duration and underwent neuropathologic evaluation. We categorized sleep duration as < 7, 7 to 8 = reference, > 8 hours and dichotomized neuropathologic changes as present/absent. We estimated
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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
INTRODUCTIONRecent evidence suggests that exposure to the stress of racism may increase the risk of dementia for Black Americans.METHODSThe present study used 17 years of data from a sample of 255 Black Americans to investigate the extent to which exposure to racial discrimination predicts subsequent changes in serum Alzheimer's Disease Research Center (ADRC) biomarkers: serum phosphorylated tau181(p‐tau181)
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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, A.N., Wu, X., Astraea, N., Elenberger, T., Buennagel, D.P., Sin, C., Spezzaferri, M., Rising, S., Nolty, A., Chui, H.C., Minazad, Y., Kloner, R.A. and Arakaki, X. (2023), Amyloid ratios in plasma and CSF are biomarkers of pre-symptomatic Alzheimer's disease. Alzheimer's Dement., 19: e079861. https://doi.org/10.1002/alz.079861 In the above article, the third author's last name was misspelled
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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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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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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
INTRODUCTIONApolipoprotein E4 (APOE4) carriers’ tendency toward hypercholesterolemia may contribute to Alzheimer's disease (AD) risk through oxysterols, which traverse the blood‐brain barrier.METHODSRelationships between baseline plasma oxysterols, APOE status, serum lipids, and cognitive impairment risk were examined in 328 postmenopausal women from the Women's Health Initiative Memory Study. Women
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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
INTRODUCTIONData‐driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods.METHODSCluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the “normal
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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
INTRODUCTIONFundamental 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.METHODSCRISPR/Cas9 was used to generate
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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
INTRODUCTIONScreening 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).METHODSWe trained automatic classifiers with 99 speech features
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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
INTRODUCTIONAducanumab selectively targets aggregated forms of amyloid beta (Aβ), a neuropathological hallmark of Alzheimer's disease (AD).METHODSPRIME was a Phase 1b, double‐blind, randomized clinical trial of aducanumab. During the 12‐month placebo‐controlled period, participants with prodromal AD or mild AD dementia were randomized to receive aducanumab or placebo. At week 56, participants could
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Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-01 Ilse vom Hofe, Bruno H. Stricker, Meike W. Vernooij, M. Kamran Ikram, M. Arfan Ikram, Frank J. Wolters
We aimed to assess the effect of antidepressant use on dementia risk, cognitive decline, and brain atrophy.
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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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Early‐onset dementia and risk of hip fracture and major osteoporotic fractures Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-02 Shoya Matsumoto, Tatsuya Hosoi, Mitsutaka Yakabe, Kenji Fujimori, Junko Tamaki, Shinichi Nakatoh, Shigeyuki Ishii, Nobukazu Okimoto, Masahiro Akishita, Masayuki Iki, Sumito Ogawa
INTRODUCTIONThere is limited knowledge about early‐onset dementia (EOD) on fracture risk.METHODSIndividuals ages 50 to 64 were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (2012 to 2019). The association between EOD and fractures and the association between cholinesterase inhibitors for EOD and fractures were evaluated using logistic regression
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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
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The six brain‐specific TAU isoforms and their role in Alzheimer's disease and related neurodegenerative dementia syndromes Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-01 Sarah Buchholz, Hans Zempel
INTRODUCTIONAlternative splicing of the human MAPT gene generates six brain‐specific TAU isoforms. Imbalances in the TAU isoform ratio can lead to neurodegenerative diseases, underscoring the need for precise control over TAU isoform balance. Tauopathies, characterized by intracellular aggregates of hyperphosphorylated TAU, exhibit extensive neurodegeneration and can be classified by the TAU isoforms
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The ABC's of Alzheimer risk gene ABCA7 Alzheimers Dement. (IF 14.0) Pub Date : 2024-04-01 Lena Duchateau, Nicole Wawrzyniak, Kristel Sleegers
Alzheimer's disease (AD) is a growing problem worldwide. Since ABCA7’s identification as a risk gene, it has been extensively researched for its role in the disease. We review its recently characterized structure and what the mechanistic insights teach us about its function. We furthermore provide an overview of identified ABCA7 mutations, their presence in different ancestries and protein domains
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Correction to the role of Apolipoprotein E4 allele in the gut microbiome of Puerto Ricans with Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-30
Gerianne Olivieri-Henry, Vanessa Sepulveda, Cecilia Michelle Soler-Llompart, Ana Cecilia Sala-Morales, Michel Santiago-Berríos, Javier A. Ruiz-Adames, Fabián J. Pérez-Luzunaris, Carlos Herrero-Rivera, Filipa Godoy-Vitorino. The role of apolipoprotein E4 allele in the gut microbiome of Puerto Ricans with Alzheimer's disease. Alzheimer Dement. 2023;19(Suppl. 24):e083054. doi/ 10.1002/alz.083054 Vanessa
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Histories of neighborhood socioeconomic status contribute to race differences in later‐life cognition Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-29 Ketlyne Sol, Emily P. Morris, Ji Hyun Lee, Afsara B. Zaheed, Jordan D. Palms, Kiana Scambray, Philippa Clarke, Laura B. Zahodne
INTRODUCTIONNeighborhood characteristics are increasingly implicated in cognitive health disparities, but no research has investigated how the historical context of neighborhoods shapes these disparities.METHODSFour hundred sixty‐four Black (55%) and White older adults (Mage = 63.6) were drawn from the Michigan Cognitive Aging Project, a community‐based, prospective study of older adults. Participants’
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Clinicopathological correlation of cerebrospinal fluid alpha‐synuclein seed amplification assay in a behavioral neurology autopsy cohort Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-28 Niyatee Samudra, D. Luke Fischer, Steven Lenio, Argentina Lario Lago, Peter A. Ljubenkov, Julio C. Rojas, William W. Seeley, Salvatore Spina, Adam M. Staffaroni, Jonathan Tablante, Fattin Wekselman, Jennifer Lamoureux, Luis Concha‐Marambio, Lea T. Grinberg, Adam L. Boxer, Lawren VandeVrede
INTRODUCTIONLewy body disease (LBD) is a common primary or co‐pathology in neurodegenerative syndromes. An alpha‐synuclein seed amplification assay (αSyn‐SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala‐predominant cases, is not well understood.METHODSAntemortem CSF from neuropathology‐confirmed LBD cases was tested with αSyn‐SAA (N = 56). Diagnostic
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Longitudinal normative standards for cognitive tests and composites using harmonized data from two Wisconsin AD‐risk‐enriched cohorts Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-28 Erin M. Jonaitis, Bruce P. Hermann, Kimberly D. Mueller, Lindsay R. Clark, Lianlian Du, Tobey J. Betthauser, Karly Cody, Carey E. Gleason, Bradley T. Christian, Sanjay Asthana, Richard J. Chappell, Nathaniel A. Chin, Sterling C. Johnson, Rebecca E. Langhough
INTRODUCTIONPublished norms are typically cross‐sectional and often are not sensitive to preclinical cognitive changes due to dementia. We developed and validated demographically adjusted cross‐sectional and longitudinal normative standards using harmonized outcomes from two Alzheimer's disease (AD) risk‐enriched cohorts.METHODSData from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin
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Gene networks and systems biology in Alzheimer's disease: Insights from multi‐omics approaches Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-27 Negin Rahimzadeh, Shushrruth Sai Srinivasan, Jing Zhang, Vivek Swarup
Despite numerous studies in the field of dementia and Alzheimer's disease (AD), a comprehensive understanding of this devastating disease remains elusive. Bulk transcriptomics have provided insights into the underlying genetic factors at a high level. Subsequent technological advancements have focused on single‐cell omics, encompassing techniques such as single‐cell RNA sequencing and epigenomics,
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The shift in the fatty acid composition of the circulating lipidome in Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-27 Farida Dakterzada, Mariona Jové, José Luís Cantero, Natàlia Mota‐Martorell, Reinald Pamplona, Gerard Piñoll‐Ripoll
INTRODUCTIONFatty acids (FAs) are the building blocks of complex lipids and signaling compounds; the role of the lipidome fatty acid profile (LFA) in AD progression remains unclear.METHODSThe LFA of plasma and cerebrospinal fluid (CSF) samples from 289 participants (103 AD patients, 92 MCI patients, and 94 controls) was determined by GC‐FID. The MCI subjects were followed up for 58 ± 12.5 months.RESULTSIn
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Correction to “Feasibility of a remote dance intervention for institutionalized older people with cognitive impairment” Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-27
Drumond, GO, Menezes, ACN, Lamha, ACF, et al. Feasibility of a remote dance intervention for institutionalized older people with cognitive impairment. Alzheimer's Dement. 2023;19:e064160. https://doi.org/10.1002/alz.064160 In the above article, the name of the fourth author “Fernanda Mara do Nascimento Almada” was mistakenly separated to appear as two separate authors “Fernanda Mara” and “Nascimento
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Plasma glial fibrillary acidic protein in the visual and language variants of Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-26 Irene Sintini, Neha Atulkumar Singh, Danni Li, Michelle M. Mielke, Mary M. Machulda, Christopher G. Schwarz, Matthew L. Senjem, Clifford R. Jack, Val J. Lowe, Jonathan Graff‐Radford, Keith A. Josephs, Jennifer L. Whitwell
INTRODUCTIONGlial fibrillary acidic protein (GFAP) in plasma is a proxy for astrocytic activity and is elevated in amyloid‐β (Aβ)‐positive individuals, making GFAP a potential blood‐based biomarker for Alzheimer's disease (AD).METHODSWe assessed plasma GFAP in 72 Aβ‐positive participants diagnosed with the visual or language variant of AD who underwent Aβ‐ and tau‐PET. Fifty‐nine participants had follow‐up
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Ethical considerations for the use of anti‐amyloid immunotherapy in patients with early Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-26 Susanne J. van Veluw, Michael J. Young
Dear Editor, Recently, the US Food and Drug Administration (FDA) approved two anti-amyloid antibodies for the treatment of patients with early Alzheimer's disease (AD), with a third expected to be approved soon.1 These drugs are designed to remove amyloid-β peptides from the brains of patients in the early stages of AD to slow down cognitive decline. The use of anti-amyloid immunotherapy has raised
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Key variants via the Alzheimer's Disease Sequencing Project whole genome sequence data Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-21 Yanbing Wang, Chloé Sarnowski, Honghuang Lin, Achilleas N. Pitsillides, Nancy L. Heard-Costa, Seung Hoan Choi, Dongyu Wang, Joshua C. Bis, Elizabeth E. Blue, , Eric Boerwinkle, Philip L. De Jager, Myriam Fornage, Ellen M. Wijsman, Sudha Seshadri, Josée Dupuis, Gina M. Peloso, Anita L. DeStefano
Genome-wide association studies (GWAS) have identified loci associated with Alzheimer's disease (AD) but did not identify specific causal genes or variants within those loci. Analysis of whole genome sequence (WGS) data, which interrogates the entire genome and captures rare variations, may identify causal variants within GWAS loci.
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Novel ultrasensitive immunoassay for the selective quantification of tau oligomers and related soluble aggregates Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-23 Tohidul Islam, Hlin Kvartsberg, Anuradha Sehrawat, Przemysław R. Kac, Bruno Becker, Maria Olsson, Eric E. Abrahamson, Henrik Zetterberg, Milos D. Ikonomovic, Kaj Blennow, Thomas K. Karikari
INTRODUCTIONTau aggregation into paired helical filaments and neurofibrillary tangles is characteristic of Alzheimer's disease (AD) and related disorders. However, biochemical assays for the quantification of soluble, earlier‐stage tau aggregates are lacking. We describe an immunoassay that is selective for tau oligomers and related soluble aggregates over monomers.METHODSA homogeneous (single‐antibody)
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Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-19 Shu-Yi Huang, Ya-Ru Zhang, Yu Guo, Jing Du, Peng Ren, Bang-Sheng Wu, Jian-Feng Feng, , Wei Cheng, Jin-Tai Yu
Although glymphatic function is involved in Alzheimer's disease (AD), its potential for predicting the pathological and clinical progression of AD and its sequential association with core AD biomarkers is poorly understood.
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The Abca7V1613M variant reduces Aβ generation, plaque load, and neuronal damage Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-20 Claire A. Butler, Adrian Mendoza Arvilla, Giedre Milinkeviciute, Celia Da Cunha, Shimako Kawauchi, Narges Rezaie, Heidi Y. Liang, Dominic Javonillo, Annie Thach, Shuling Wang, Sherilyn Collins, Amber Walker, Kai‐Xuan Shi, Jonathan Neumann, Angela Gomez‐Arboledas, Caden M. Henningfield, Lindsay A. Hohsfield, Mark Mapstone, Andrea J. Tenner, Frank M. LaFerla, Ali Mortazavi, Grant R. MacGregor, Kim N
BACKGROUNDVariants in ABCA7, a member of the ABC transporter superfamily, have been associated with increased risk for developing late onset Alzheimer's disease (LOAD).METHODSCRISPR‐Cas9 was used to generate an Abca7V1613M variant in mice, modeling the homologous human ABCA7V1599M variant, and extensive characterization was performed.RESULTSAbca7V1613M microglia show differential gene expression profiles
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Age of Alzheimer's disease diagnosis in people with Down syndrome and associated factors: Results from the Horizon 21 European Down syndrome consortium Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-20 Frode Kibsgaard Larsen, R. Asaad Baksh, Eimear McGlinchey, Ellen Melbye Langballe, Bessy Benejam, Jessica Beresford‐Webb, Mary McCarron, Antonia Coppus, Segolene Falquero, Juan Fortea, Johannes Levin, Sandra V. Loosli, Ruth Mark, Anne‐Sophie Rebillat, Shahid Zaman, Andre Strydom
INTRODUCTIONPeople with Down syndrome (DS) have high risk of developing Alzheimer's disease (AD). This study examined mean ages of AD diagnosis and associations with co‐occurring conditions among adults with DS from five European countries.METHODSData from 1335 people with DS from the Horizon 21 European DS Consortium were used for the analysis.RESULTSMean ages of AD diagnosis ranged between 51.4 (SD
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Dementias Platform UK: Bringing genetics into life Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-20 Ganna Leonenko, Sarah Bauermeister, Dipanwita Ghanti, Joshua Stevenson‐Hoare, Emily Simmonds, Keeley Brookes, Kevin Morgan, Nishi Chaturvedi, Paul Elliott, Alan Thomas, Nicholas Wareham, John Gallacher, Valentina Escott‐Price
INTRODUCTIONThe Dementias Platform UK (DPUK) Data Portal is a data repository bringing together a wide range of cohorts. Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and an overlapping genetic component that is poorly understood. The DPUK collection of independent cohorts can facilitate research in neurodegeneration by combining their genetic and phenotypic
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Racial, ethnic, and rural disparities in distance to physicians among decedents with Alzheimer's disease and related dementias in Washington State Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-20 Solmaz Amiri, Jonae I. Keffeler, Dennis R. Crain, Justin T. Denney, Dedra Buchwald
INTRODUCTIONDistance to physicians may explain some of the disparities in Alzheimer's disease and related dementia (AD/ADRD) outcomes.METHODSWe generated round trip distance between residences of decedents with AD/ADRD and the nearest neurologist and primary care physician in Washington State.RESULTSThe overall mean distance to the nearest neurologist and primary care physician was 17 and 4 miles,
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Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole‐brain modeling Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-19 Carlos Coronel‐Oliveros, Raúl Gónzalez Gómez, Kamalini Ranasinghe, Agustín Sainz‐Ballesteros, Agustina Legaz, Sol Fittipaldi, Josephine Cruzat, Rubén Herzog, Gorsev Yener, Mario Parra, David Aguillon, Francisco Lopera, Hernando Santamaria‐Garcia, Sebastián Moguilner, Vicente Medel, Patricio Orio, Robert Whelan, Enzo Tagliazucchi, Pavel Prado, Agustín Ibañez
INTRODUCTIONAlzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost‐effective technique for studying dementia globally, but lacks mechanistic models and produces non‐replicable results.METHODSWe developed a generative whole‐brain model
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Dementia and mild cognitive impairment screening in an emergency homeless shelter Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-18 Heather M. Ross, Primrose Dzenga, Martha Myers, Alisa Squires, Stephanie Duncan, Jamilyn Caradine, Phillip Scharf, Diana M. Bowman
INTRODUCTIONOlder adults represent the fastest growing segment of the homeless community. Little is known about the prevalence of dementia and mild cognitive impairment (MCI) in this population.METHODSDementia and MCI screening using the Montreal Cognitive Assessment (MoCA) was incorporated into the standard senior evaluation for adult clients aged ≥ 55 in a large emergency homeless shelter.RESULTSIn
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Delineating cognitive resilience using fractal regulation: Cross‐sectional and longitudinal evidence from the Rush Memory and Aging Project Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-18 Peng Li, Chenlu Gao, Lei Yu, Lei Gao, Ruixue Cai, David A. Bennett, Julie A. Schneider, Aron S. Buchman, Kun Hu
INTRODUCTIONDegradation of fractal patterns in actigraphy independently predicts dementia risk. Such observations motivated the study to understand the role of fractal regulation in the context of neuropathologies.METHODSWe examined associations of fractal regulation with neuropathologies and longitudinal cognitive changes in 533 older participants who were followed annually with actigraphy and cognitive
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Wrist‐worn actigraphy in agitated late‐stage dementia patients: A feasibility study on digital inclusion Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-18 Ta‐Wei Guu, Anna‐Katharine Brem, Christopher P. Albertyn, Pooja Kandangwa, Dag Aarsland, Dominic ffytche
BACKGROUNDWrist‐worn actigraphy can be an objective tool to assess sleep and other behavioral and psychological symptoms in dementia (BPSD). We investigated the feasibility of using wearable actigraphy in agitated late‐stage dementia patients.METHODSAgitated, late‐stage Alzheimer's dementia care home residents in Greater London area (n = 29; 14 females, mean age ± SD: 80.8 ± 8.2; 93.1% White) were
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Deriving life‐course residential histories in brain bank cohorts: A feasibility study Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-18 Eleanna M. Melcher, Leigha Vilen, Aly Pfaff, Sarah Lim, Amanda DeWitt, W. Ryan Powell, Barbara B. Bendlin, Amy J. H. Kind
INTRODUCTIONThe exposome is theorized to interact with biological mechanisms to influence risk for Alzheimer's disease but is not well‐integrated into existing Alzheimer's Disease Research Center (ADRC) brain bank data collection.METHODSWe apply public data tracing, an iterative, dual abstraction and validation process rooted in rigorous historic archival methods, to develop life‐course residential
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Association between hippocampal microglia, AD and LATE‐NC, and cognitive decline in older adults Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-18 Alifiya Kapasi, Lei Yu, Sue E Leurgans, Sonal Agrawal, Patricia A Boyle, David A Bennett, Julie A Schneider
INTRODUCTIONThis study investigates the relationship between microglia inflammation in the hippocampus, brain pathologies, and cognitive decline.METHODSParticipants underwent annual clinical evaluations and agreed to brain donation. Neuropathologic evaluations quantified microglial burden in the hippocampus, amyloid beta (Aβ), tau tangles, and limbic age‐related transactive response DNA‐binding protein
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Clinical validation of the PrecivityAD2 blood test: A mass spectrometry‐based test with algorithm combining %p‐tau217 and Aβ42/40 ratio to identify presence of brain amyloid Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-16 Matthew R. Meyer, Kristopher M. Kirmess, Stephanie Eastwood, Traci L. Wente‐Roth, Faith Irvin, Mary S. Holubasch, Venky Venkatesh, Ilana Fogelman, Mark Monane, Lucy Hanna, Gil D. Rabinovici, Barry A. Siegel, Rachel A. Whitmer, Charles Apgar, Randall J. Bateman, David M. Holtzman, Michael Irizarry, David Verbel, Pallavi Sachdev, Satoshi Ito, John Contois, Kevin E. Yarasheski, Joel B. Braunstein, Philip
BACKGROUNDWith the availability of disease‐modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment.METHODSHigh‐throughput, mass spectrometry‐based assays were used to measure %p‐tau217 and amyloid beta (Aβ)42/40 ratio in blood samples from 583 individuals
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Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-16 Marie‐Emmanuelle Riviere, Jessica B. Langbaum, R. Scott Turner, Juha O. Rinne, Yihan Sui, Pilar Cazorla, Javier Ricart, Kathleen Meneses, Angelika Caputo, Pierre N. Tariot, Eric M. Reiman, Ana Graf
INTRODUCTIONAlzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (Aβ) active immunotherapy (vaccine) CAD106 and BACE‐1 inhibitor umibecestat in cognitively unimpaired 60‐ to 75‐year‐old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented.METHODSSixty‐five apolipoprotein E ε4