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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
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Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-13 J. Matthijs Biesbroek, Mirthe Coenen, Charles DeCarli, Evan M. Fletcher, Pauline M. Maillard, , Frederik Barkhof, Josephine Barnes, Thomas Benke, Christopher P. L. H. Chen, Peter Dal-Bianco, Anna Dewenter, Marco Duering, Christian Enzinger, Michael Ewers, Lieza G. Exalto, Nicolai Franzmeier, Saima Hilal, Edith Hofer, Huiberdina L. Koek, Andrea B. Maier, Cheryl R. McCreary, Janne M. Papma, Ross W. Paterson
White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-β1-42 (Aβ42)-positive status.
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Dementia, dementia's risk factors and premorbid brain structure are concentrated in disadvantaged areas: National register and birth‐cohort geographic analyses Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-14 Aaron Reuben, Leah S. Richmond‐Rakerd, Barry Milne, Devesh Shah, Amber Pearson, Sean Hogan, David Ireland, Ross Keenan, Annchen R. Knodt, Tracy Melzer, Richie Poulton, Sandhya Ramrakha, Ethan T. Whitman, Ahmad R. Hariri, Terrie E. Moffitt, Avshalom Caspi
INTRODUCTIONDementia risk may be elevated in socioeconomically disadvantaged neighborhoods. Reasons for this remain unclear, and this elevation has yet to be shown at a national population level.METHODSWe tested whether dementia was more prevalent in disadvantaged neighborhoods across the New Zealand population (N = 1.41 million analytic sample) over a 20‐year observation. We then tested whether premorbid
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Correction to Association of Gut Microbiome with Diabetes Mellitus and Alzheimer's Disease in a Puerto Rican Adult Population: A Preliminary Report Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-14
Cecilia Michelle Soler-Llompart, Filipa Godoy-Vitorino, Ana Cecilia Sala-Morales, Michel Santiago-Berríos, Javier A. Ruiz-Adames, Gerianne Olivieri-Henry, Carlos Herrero-Rivera, Fabián J. Pérez-Luzunaris, Vanessa Sepulveda Association of Gut Microbiome with Diabetes Mellitus and Alzheimer's Disease in a Puerto Rican Adult Population: A Preliminary Report Alzheimer's Dement. 2023;19(Suppl. 24):e083053
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Adapting prescribing criteria for amyloid‐targeted antibodies for adults with Down syndrome Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-14 Hampus Hillerstrom, Richard Fisher, Matthew P. Janicki, Brian Chicoine, Bradley T. Christian, Anna Esbensen, Lucille Esralew, Juan Fortea, Sigan Hartley, Jason Hassenstab, Seth M. Keller, Sharon Krinsky‐McHale, Florence Lai, Johannes Levin, Mary McCarron, Eric McDade, Anne Sophie Rebillat, Herminia Diana Rosas, Wayne Silverman, Andre Strydom, Shahid H. Zaman, Henrik Zetterberg
Prior authorization criteria for Federal Drug Administration (FDA) approved immunotherapeutics, among the class of anti‐amyloid monoclonal antibodies (mAbs), established by state drug formulary committees, are tailored for adults with late‐onset Alzheimer's disease. This overlooks adults with Down syndrome (DS), who often experience dementia at a younger age and with different diagnostic assessment
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Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-12 Ryota Sakurai, Frederico Pieruccini-Faria, Benjamin Cornish, Julia Fraser, Malcolm A. Binns, Derek Beaton, Allison Ann Dilliott, Donna Kwan, Joel Ramirez, Brian Tan, Christopher J. M. Scott, Kelly M. Sunderland, Carmela Tartaglia, Elizabeth Finger, Lorne Zinman, Morris Freedman, Paula M. McLaughlin, Richard H. Swartz, Sean Symons, Anthony E. Lang, Robert Bartha, Sandra E. Black, Mario Masellis, Robert
Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases.
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Racial and ethnic differences in the association between depressive symptoms and cognitive outcomes in older adults: Findings from KHANDLE and STAR Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-13 Marcia P. Jimenez, Emma L. Gause, Kendra D. Sims, Eleanor Hayes‐Larson, Emily P. Morris, Evan Fletcher, Jennifer Manly, Paola Gilsanz, Yenee Soh, Maria Corrada, Rachel A. Whitmer, Medellena Maria Glymour
INTRODUCTIONDepressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear.METHODSAsian, Black, Latino, or White participants (n = 2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel
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APOE ε4 is associated with decreased synaptic density in cognitively impaired participants Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-13 Kun He, Binyin Li, Jie Wang, Ying Wang, Zhiwen You, Xing Chen, Haijuan Chen, Junpeng Li, Qi Huang, Qihao Guo, Yiyun Henry Huang, Yihui Guan, Kewei Chen, Jun Zhao, Yulei Deng, Fang Xie
INTRODUCTIONWe aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants.METHODSOne hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18F‐florbetapir and synaptic density PET with 18F‐SynVesT‐1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype
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Cognitive resilience/reserve: Myth or reality? A review of definitions and measurement methods Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-13 Chiara Pappalettera, Claudia Carrarini, Francesca Miraglia, Fabrizio Vecchio, Paolo M. Rossini
INTRODUCTIONThis review examines the concept of cognitive reserve (CR) in relation to brain aging, particularly in the context of dementia and its early stages. CR refers to an individual's ability to maintain or regain cognitive function despite brain aging, damage, or disease. Various factors, including education, occupation complexity, leisure activities, and genetics are believed to influence CR
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Adapted problem adaptation therapy for depression in mild to moderate Alzheimer's disease dementia: A randomized controlled trial Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-13 Robert Howard, Elizabeth Cort, Charlotte Rawlinson, Martin Wiegand, Anne Downey, Vanessa Lawrence, Sube Banerjee, Peter Bentham, Chris Fox, Rowan Harwood, Rachel Hunter, Gill Livingston, Esme Moniz‐Cook, Monica Panca, Malgorzata Raczek, Chineze Ivenso, Gregor Russell, Alan Thomas, Philip Wilkinson, Nicholas Freemantle, Rebecca Gould
INTRODUCTIONTrials of effectiveness of treatment options for depression in dementia are an important priority.METHODSRandomized controlled trial to assess adapted Problem Adaptation Therapy (PATH) for depression in mild/moderate dementia caused by Alzheimer's disease.RESULTSThree hundred thirty‐six participants with mild or moderate dementia, >7 on Cornell Scale for Depression in Dementia (CSDD), randomized
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Genetic associations with dementia-related proteinopathy: Application of item response theory Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-09 Yuriko Katsumata, David W. Fardo, Lincoln M. P. Shade, Xian Wu, Shama D. Karanth, Timothy J. Hohman, Julie A. Schneider, David A. Bennett, Jose M. Farfel, Kathryn Gauthreaux, Charles Mock, Walter A. Kukull, Erin L. Abner, Peter T. Nelson,
Although dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.
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Person‐specific differences in ubiquitin‐proteasome mediated proteostasis in human neurons Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-12 Yi‐Chen Hsieh, Zachary M. Augur, Mason Arbery, Nancy Ashour, Katharine Barrett, Richard V. Pearse, Earvin S. Tio, Duc M. Duong, Daniel Felsky, Philip L. De Jager, David A. Bennett, Nicholas T. Seyfried, Tracy L. Young‐Pearse
BACKGROUNDImpairment of the ubiquitin‐proteasome system (UPS) has been implicated in abnormal protein accumulation in Alzheimer's disease. It remains unclear if genetic variation affects the intrinsic properties of neurons that render some individuals more vulnerable to UPS impairment.METHODSInduced pluripotent stem cell (iPSC)‐derived neurons were generated from over 50 genetically variant and highly
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Rural‐urban disparities in the diagnosis and treatment of hypertension and diabetes among aging Indians Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-09 Pooja Rai, Pravin Sahadevan, Abhishek L. Mensegere, Thomas G. Issac, Graciela Muniz‐Terrera, Jonas S. Sundarakumar
INTRODUCTIONHypertension and diabetes are modifiable risk factors for dementia. We aimed to assess rural‐urban disparities in the diagnosis and treatment of these conditions among aging Indians.METHODSParticipants (n = 6316) were from two parallel, prospective aging cohorts in rural and urban India. Using self‐report and clinical/biochemical assessments, we subdivided participants with diabetes and
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BIN1K358R suppresses glial response to plaques in mouse model of Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-09 Laura Fernandez Garcia‐Agudo, Zechuan Shi, Ian F. Smith, Enikö A. Kramár, Katelynn Tran, Shimako Kawauchi, Shuling Wang, Sherilyn Collins, Amber Walker, Kai‐Xuan Shi, Jonathan Neumann, Heidi Yahan Liang, Celia Da Cunha, Giedre Milinkeviciute, Samuel Morabito, Emily Miyoshi, Narges Rezaie, Angela Gomez‐Arboledas, Adrian Mendoza Arvilla, Daryan Iman Ghaemi, Andrea J. Tenner, Frank M. LaFerla, Marcelo
INTRODUCTIONThe BIN1 coding variant rs138047593 (K358R) is linked to Late‐Onset Alzheimer's Disease (LOAD) via targeted exome sequencing.METHODSTo elucidate the functional consequences of this rare coding variant on brain amyloidosis and neuroinflammation, we generated BIN1K358R knock‐in mice using CRISPR/Cas9 technology. These mice were subsequently bred with 5xFAD transgenic mice, which serve as
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Promoting diverse perspectives: Addressing health disparities related to Alzheimer's and all dementias Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-09 Gladys Maestre, Carl Hill, Percy Griffin, Stephen Hall, William Hu, Jason Flatt, Ganesh Babulal, Roland Thorpe, J. Neil Henderson, Dedra Buchwald, Spero Manson, Ethan Cicero, Andrea Gilmore‐Bykovskyi, Alyssa Gamaldo, Crystal Glover, Lisa Barnes, Amy Kind, Bryan James, Adina Zeki Al Hazzouri, Whitney Wharton, Paulo Caramelli, Sarah Szanton, Rachel Whitmer, Jada Benn Torres, Kacie Deters, Ozioma Okonkwo
Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well‐resourced, non‐Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's‐related risk factors in
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Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-07 Marinus Fislage, Stefan Winzeck, Rebecca Woodrow, Florian Lammers-Lietz, Emmanuel A. Stamatakis, Marta M. Correia, Jacobus Preller, Insa Feinkohl, Jeroen Hendrikse, Tobias Pischon, Claudia D. Spies, Arjen J. C. Slooter, Georg Winterer, David K. Menon, Norman Zacharias
Structural disconnectivity was found to precede dementia. Global white matter abnormalities might also be associated with postoperative delirium (POD).
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Data stewardship in FTLD research: Investigator and research participant views Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-08 Jalayne J. Arias, Ana M. Tyler, Laura M. Beskow, Maria C. Carillo, Susan Dickinson, Jill Goldman, Mary A. Majumder, Michelle M. Mello, Heather M. Snyder, Jennifer S. Yokoyama
INTRODUCTIONFederal policies and guidelines have expanded the return of individual results to participants and expectations for data sharing between investigators and through repositories. Here, we report investigators’ and study participants’ views and experiences with data stewardship practices within frontotemporal lobal degeneration (FTLD) research, which reveal unique ethical challenges.METHODSSemi‐structured
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Genetic modifiers of cognitive decline in PSEN1 E280A Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-07 Diego Sepulveda‐Falla, Jorge I. Vélez, Natalia Acosta‐Baena, Ana Baena, Sonia Moreno, Susanne Krasemann, Francisco Lopera, Claudio A. Mastronardi, Mauricio Arcos‐Burgos
INTRODUCTIONRate of cognitive decline (RCD) in Alzheimer's disease (AD) determines the degree of impairment for patients and of burden for caretakers. We studied the association of RCD with genetic variants in AD.METHODSRCD was evaluated in 62 familial AD (FAD) and 53 sporadic AD (SAD) cases, and analyzed by whole‐exome sequencing for association with common exonic functional variants. Findings were
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Association receives $25 million grant to enhance respite care for dementia caregivers Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-07
The Administration for Community Living, a division of the U.S. Department of Health and Human Services, has awarded the Alzheimer's Association a $25 million grant to enhance respite services for people living with dementia and their caregivers nationwide. It is the largest grant ever made to the Association. The 5-year grant will establish a new Center for Dementia Respite Innovation (CDRI) led by
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Blood tests for Alzheimer's disease: The impact of disease prevalence on test performance Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-06 Mari L. DeMarco, Alicia Algeciras‐Schimnich, Melissa M. Budelier
Regulatory agencies, including the US Food and Drug Administration, have recently approved Alzheimer's disease (AD) therapies targeting amyloid-beta (Aβ) pathology. This has placed a spotlight on the need for accurate and accessible diagnostic tools for AD pathology. Currently, AD cerebrospinal fluid (CSF) biomarkers and amyloid imaging have regulatory approval in many countries and are routinely used
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Nanoscale imaging of pT217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early‐stage neurodegeneration Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-06 Dibyadeep Datta, Isabella Perone, Denethi Wijegunawardana, Feng Liang, Yury M. Morozov, Jon Arellano, Alvaro Duque, Zhongcong Xie, Christopher H. van Dyck, Mary Kate P. Joyce, Amy F. T. Arnsten
INTRODUCTIONTau phosphorylated at threonine‐217 (pT217‐tau) is a novel fluid‐based biomarker that predicts onset of Alzheimer's disease (AD) symptoms, but little is known about how pT217‐tau arises in the brain, as soluble pT217‐tau is dephosphorylated post mortem in humans.METHODSWe used multilabel immunofluorescence and immunoelectron microscopy to examine the subcellular localization of early‐stage
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Diffusion MRI relates to plasma Aβ42/40 in PET negative participants without dementia Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-05 Jesse C. DeSimone, Wei‐en Wang, David A. Loewenstein, Ranjan Duara, Glenn E. Smith, Karen N. McFarland, Melissa J. Armstrong, Darren M. Weber, Warren Barker, Stephen A. Coombes, David E. Vaillancourt
INTRODUCTIONMagnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid‐β (Aβ42/40) positivity in Aβ positron emission tomography (PET) negative individuals.METHODSDiffusion free‐water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aβ plasma‐/PET‐ (NC = 22, MCI
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Entorhinal-based path integration selectively predicts midlife risk of Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-29 Coco Newton, Marianna Pope, Catarina Rua, Richard Henson, Zilong Ji, Neil Burgess, Christopher T. Rodgers, Matthias Stangl, Maria-Eleni Dounavi, Andrea Castegnaro, Ivan Koychev, Paresh Malhotra, Thomas Wolbers, Karen Ritchie, Craig W. Ritchie, John O'Brien, Li Su, Dennis Chan
Entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration (PI)–based spatial behaviors, we predicted that PI impairment would represent the first behavioral change in adults at risk of AD.
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Genetic diversity promotes resilience in a mouse model of Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-01 Neelakshi Soni, Lindsay A. Hohsfield, Kristine M. Tran, Shimako Kawauchi, Amber Walker, Dominic Javonillo, Jimmy Phan, Dina Matheos, Celia Da Cunha, Asli Uyar, Giedre Milinkeviciute, Angela Gomez‐Arboledas, Katelynn Tran, Catherine C. Kaczorowski, Marcelo A. Wood, Andrea J. Tenner, Frank M. LaFerla, Gregory W. Carter, Ali Mortazavi, Vivek Swarup, Grant R. MacGregor, Kim N. Green
INTRODUCTIONAlzheimer's disease (AD) is a neurodegenerative disorder with multifactorial etiology, including genetic factors that play a significant role in disease risk and resilience. However, the role of genetic diversity in preclinical AD studies has received limited attention.METHODSWe crossed five Collaborative Cross strains with 5xFAD C57BL/6J female mice to generate F1 mice with and without
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Analysis of agreement between measures of subjective cognitive impairment and probable dementia in the National Health and Aging Trends Study Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-01 Linda C. Chyr, Jennifer L. Wolff, Julie M. Zissimopoulos, Emmanuel F. Drabo
BACKGROUNDSubjective cognitive impairment (SCI) measures in population‐based surveys offer potential for dementia surveillance, yet their validation against established dementia measures is lacking.METHODSWe assessed agreement between SCI and a validated probable dementia algorithm in a random one‐third sample (n = 1936) of participants in the 2012 National Health and Aging Trends Study (NHATS).RESULTSSCI
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Early detection of diseases causing dementia using digital navigation and gait measures: A systematic review of evidence Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-01 Giedrė Čepukaitytė, Coco Newton, Dennis Chan
Wearable digital technologies capable of measuring everyday behaviors could improve the early detection of dementia‐causing diseases. We conducted two systematic reviews following Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines to establish the evidence base for measuring navigation and gait, two everyday behaviors affected early in AD and non‐AD disorders and
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Investigating the impact of hypertension with and without diabetes on Alzheimer's disease risk: A clinico‐pathological study Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-01 Myuri Ruthirakuhan, Walter Swardfager, Lisa Xiong, Bradley J. MacIntosh, Jennifer S. Rabin, Krista L. Lanctôt, Julie Ottoy, Joel Ramirez, Julia Keith, Sandra E. Black
INTRODUCTIONHypertension and diabetes are common cardiovascular risk factors that increase Alzheimer's disease (AD) risk. However, it is unclear whether AD risk differs in hypertensive individuals with and without diabetes.METHODSCognitively normal individuals (N = 11,074) from the National Alzheimer's Coordinating Center (NACC) were categorized as having (1) hypertension with diabetes (HTN+/DM+),
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The Bio-Hermes Study: Biomarker database developed to investigate blood-based and digital biomarkers in community-based, diverse populations clinically screened for Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-28 Richard C. Mohs, Douglas Beauregard, John Dwyer, Jennifer Gaudioso, Jason Bork, Tamiko MaGee-Rodgers, Mickeal N. Key, Diana R. Kerwin, Lynn Hughes, Cyndy B. Cordell
Alzheimer's disease (AD) trial participants are often screened for eligibility by brain amyloid positron emission tomography/cerebrospinal fluid (PET/CSF), which is inefficient as many are not amyloid positive. Use of blood-based biomarkers may reduce screen failures.
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Subsequent correlated changes in complement component 3 and amyloid beta oligomers in the blood of patients with Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-27 Kyu Hwan Shim, Danyeong Kim, Min Ju Kang, Jung-Min Pyun, Young Ho Park, Young Chul Youn, Kyung Won Park, Kyoungho Suk, Ho-Won Lee, Bárbara Fernandes Gomes, Henrik Zetterberg, Seong Soo A. An, SangYun Kim
Alzheimer's disease (AD) involves the complement cascade, with complement component 3 (C3) playing a key role. However, the relationship between C3 and amyloid beta (Aβ) in blood is limited.
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U.S. dementia care spending by state: 2010–2019 Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-27 Amy Lastuka, Michael R. Breshock, Theresa A. McHugh, William T. Sogge, Vivianne Swart, Joseph L. Dieleman
INTRODUCTIONDementia is the fourth largest cause of death for individuals 70 years of age and older in the United States, and it is tremendously costly. Existing estimates of the indirect costs of dementia are dated and do not report on differences across the United States.METHODSWe used data from multiple surveys to create cost estimates and projections for informal dementia caregiving at the U.S
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Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-23 Guoqiao Wang, Yan Li, Chengjie Xiong, Tammie L. S. Benzinger, Brian A. Gordon, Jason Hassenstab, Andrew J. Aschenbrenner, Eric McDade, David B. Clifford, Jorge J. Libre-Guerra, Xinyu Shi, Catherine J. Mummery, Christopher H. van Dyck, James J. Lah, Lawrence S. Honig, Gregg Day, John M. Ringman, William S. Brooks, Nick C. Fox, Kazushi Suzuki, Johannes Levin, Mathias Jucker, Paul Delmar, Tobias Bittner
Increasing evidence suggests that amyloid reduction could serve as a plausible surrogate endpoint for clinical and cognitive efficacy. The double-blind phase 3 DIAN-TU-001 trial tested clinical and cognitive declines with increasing doses of solanezumab or gantenerumab.
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Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-21 Nelly Joseph-Mathurin, Rebecca L. Feldman, Ruijin Lu, Zahra Shirzadi, Carmen Toomer, Junie R. Saint Clair, Yinjiao Ma, Nicole S. McKay, Jeremy F. Strain, Collin Kilgore, Karl A. Friedrichsen, Charles D. Chen, Brian A. Gordon, Gengsheng Chen, Russ C. Hornbeck, Parinaz Massoumzadeh, Austin A. McCullough, Qing Wang, Yan Li, Guoqiao Wang, Sarah J. Keefe, Stephanie A. Schultz, Carlos Cruchaga, Gregory M
Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages.
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Whole genome-wide sequence analysis of long-lived families (Long-Life Family Study) identifies MTUS2 gene associated with late-onset Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-21 Laura Xicota, Stephanie Cosentino, Badri Vardarajan, Richard Mayeux, Thomas T. Perls, Stacy L. Andersen, Joseph M. Zmuda, Bharat Thyagarajan, Anatoli Yashin, Mary K. Wojczynski, Sharon Krinsky-McHale, Benjamin L. Handen, Bradley T. Christian, Elizabeth Head, Mark E. Mapstone, Nicole Schupf, Joseph H. Lee, Sandra Barral,
Late-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics.
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Meeting report of the fifth annual workshop on Principles and Techniques for Improving Preclinical to Clinical Translation in Alzheimer's Disease Research Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-24 Michael Sasner, Kristen D. Onos, Paul R. Territo, Stacey J. Sukoff Rizzo
The fifth annual workshop on Principles and Techniques for Improving Preclinical Translation of Alzheimer's Disease Research was held in May 2023 at The Jackson Laboratory in Bar Harbor, Maine, USA. The workshop was established in 2018 to address training gaps in preclinical translational studies for Alzheimer's disease (AD). In addition to providing fundamental knowledge and hands‐on skills essential
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Neighborhood disadvantage reduces cognitive reserve independent of neuropathologic change Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-24 Boram Kim, Isabel Yannatos, Kaitlin Blam, Douglas Wiebe, Sharon X. Xie, Corey T. McMillan, Dawn Mechanic‐Hamilton, David A. Wolk, Edward B. Lee
INTRODUCTIONIndividuals in socioeconomically disadvantaged neighborhoods exhibit increased risk for impaired cognitive function. Whether this association relates to the major dementia‐related neuropathologies is unknown.METHODSThis cross‐sectional study included 469 autopsy cases from 2011 to 2023. The relationships between neighborhood disadvantage measured by Area Deprivation Index (ADI) percentiles
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Patient‐ and proxy‐reported quality of life in advanced dementia with Lewy bodies Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-24 Melissa J. Armstrong, Brian LaBarre, Kaitlin Sovich, Susan M. Maixner, Henry L. Paulson, Carol Manning, Julie A. Fields, Angela Lunde, Leah Forsberg, Bradley F. Boeve, James E. Galvin, Angela S. Taylor, Zhigang Li
INTRODUCTIONLittle is known regarding quality of life (QoL) in dementia with Lewy bodies (DLB), particularly in advanced stages.METHODSDyads of individuals with moderate–advanced DLB and their primary caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease‐related measures, and measures of patient/caregiver experiences
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Potential impact of unblinding on observed treatment effects in Alzheimer's disease trials Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-21 Frank J. Wolters, Jeremy A. Labrecque
INTRODUCTIONAdverse effects of monoclonal antibodies against amyloid beta are common, and may affect validity of randomized controlled trials (RCTs) through unblinding of participants.METHODSWe used observations from published phase 3 RCTs in Alzheimer's disease to calculate the magnitude of unblinding effects on cognition that would be required to explain observed cognitive benefits in RCTs.RESULTSIn
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Alzheimer's Association and ASNR announce recipients of imaging grants Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-21
The Alzheimer's Association and The Foundation of the American Society of Neuroradiology (ASNR) have announced the recipients of a new funding program for imaging-related research. The goal of The Alzheimer's Association & The Foundation of the American Society of Neuroradiology Funding Opportunity: Imaging Research in Alzheimer's and Other Neurodegenerative Diseases is to support the development of
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Silencing Apoe with divalent‐siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-20 Chantal M. Ferguson, Samuel Hildebrand, Bruno M. D. C. Godinho, Julianna Buchwald, Dimas Echeverria, Andrew Coles, Anastasia Grigorenko, Lorenc Vangjeli, Jacquelyn Sousa, Nicholas McHugh, Matthew Hassler, Francesco Santarelli, Michael T. Heneka, Evgeny Rogaev, Anastasia Khvorova
INTRODUCTIONThe most significant genetic risk factor for late‐onset Alzheimer's disease (AD) is APOE4, with evidence for gain‐ and loss‐of‐function mechanisms. A clinical need remains for therapeutically relevant tools that potently modulate APOE expression.METHODSWe optimized small interfering RNAs (di‐siRNA, GalNAc) to potently silence brain or liver Apoe and evaluated the impact of each pool of
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Protective effect of bilingualism on aging, MCI, and dementia: A community‐based study Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-20 Aparna Venugopal, Avanthi Paplikar, Feba Anna Varghese, Nithin Thanissery, Divya Ballal, Rakshith Maneshwar Hoskeri, Revathi Shekar, Binukumar Bhaskarapillai, Faheem Arshad, Vandana Valiyaparambath Purushothaman, Aravind Banavaram Anniappan, Girish Nagaraja Rao, Suvarna Alladi
INTRODUCTIONLifelong bilingualism is associated with a delayed age at onset of dementia, but evidence from community‐based studies is limited. We investigated the relationship between bilingualism and the prevalence of cognitive impairment in a linguistically diverse community.METHODSA door‐to‐door community study was conducted from January to December 2021 in urban Bengaluru, India. 1234 individuals
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Sensory and motor deficits as contributors to early cognitive impairment Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-20 Zahra N. Sayyid, Hang Wang, Yurun Cai, Alden L. Gross, Bonnielin K. Swenor, Jennifer A. Deal, Frank R. Lin, Amal A. Wanigatunga, Ryan J. Dougherty, Qu Tian, Eleanor M. Simonsick, Luigi Ferrucci, Jennifer A. Schrack, Susan M. Resnick, Yuri Agrawal
INTRODUCTIONAge‐related sensory and motor impairment are associated with risk of dementia. No study has examined the joint associations of multiple sensory and motor measures on prevalence of early cognitive impairment (ECI).METHODSSix hundred fifty participants in the Baltimore Longitudinal Study of Aging completed sensory and motor function tests. The association between sensory and motor function
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General cognitive ability in high school, attained education, occupational complexity, and dementia risk Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-20 Jimi Huh, Thalida Em Arpawong, Tara L. Gruenewald, Gwenith G. Fisher, Carol A. Prescott, Jennifer J. Manly, Dominika Seblova, Ellen E. Walters, Margaret Gatz
INTRODUCTIONWe address the extent to which adolescent cognition predicts dementia risk in later life, mediated by educational attainment and occupational complexity.METHODSUsing data from Project Talent Aging Study (PTAS), we fitted two structural equation models to test whether adolescent cognition predicts cognitive impairment (CI) and Ascertain Dementia 8 (AD8) status simultaneously (NCognitive
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Three‐dimensional histology reveals dissociable human hippocampal long‐axis gradients of Alzheimer's pathology Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-19 Diana Ortega‐Cruz, Kimberly S. Bress, Harshvardhan Gazula, Alberto Rabano, Juan Eugenio Iglesias, Bryan A. Strange
INTRODUCTIONThree‐dimensional (3D) histology analyses are essential to overcome sampling variability and understand pathological differences beyond the dissection axis. We present Path2MR, the first pipeline allowing 3D reconstruction of sparse human histology without a magnetic resonance imaging (MRI) reference. We implemented Path2MR with post‐mortem hippocampal sections to explore pathology gradients
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Tracing synaptic loss in Alzheimer's brain with SV2A PET-tracer UCB-J Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-16 Amit Kumar, Miriam Scarpa, Agneta Nordberg
Synaptic loss is an early prominent feature of Alzheimer's disease (AD). The recently developed novel synaptic vesicle 2A protein (SV2A) PET-tracer UCB-J has shown great promise in tracking synaptic loss in AD. However, there have been discrepancies between the findings and a lack of mechanistic insight.
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The dementia care study (D-CARE): Recruitment strategies and demographic characteristics of participants in a pragmatic randomized trial of dementia care Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-15 Mia Yang, Rafael Samper-Ternent, Elena Volpi, Aval-Na'Ree Green, Maya Lichtenstein, Katy Araujo, Pamela Borek, Peter Charpentier, James Dziura, Thomas M. Gill, Rebecca Galloway, Erich J. Greene, Kristin Lenoir, Peter Peduzzi, Can Meng, Jordan Reese, Amy Shelton, Eleni A. Skokos, Jenny Summapund, Erin Unger, David B. Reuben, Jeff D. Williamson, Alan B. Stevens
Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare.
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Lewy body pathology modifies risk factors for cerebral amyloid angiopathy when comorbid with Alzheimer's disease pathology Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-14 Jagan A. Pillai, James Bena, Babak Tousi, Kasia Rothenberg, C. Dirk Keene, James B. Leverenz
Cerebral amyloid angiopathy (CAA) often accompanies dementia-associated pathologies and is important in the context of anti-amyloid monoclonal therapies and risk of hemorrhage.
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Speech patterns during memory recall relates to early tau burden across adulthood Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-13 Christina B. Young, Viktorija Smith, Cody Karjadi, Selah-Marie Grogan, Ting Fang Alvin Ang, Philip S. Insel, Victor W. Henderson, Meghan Sumner, Kathleen L. Poston, Rhoda Au, Elizabeth C. Mormino
Early cognitive decline may manifest in subtle differences in speech.
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INviting Veterans InTo Enrollment in Alzheimer's Disease Research Centers (INVITE-ADRC): An NIA and VA–sponsored initiative to increase veteran participation in aging and dementia research Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-13 Claudia B. Padula, Sherry Ball, Mary F. Wyman, Kirsten Evans, Harli Grant, Vyjeyanthi S. Periyakoil, Carolyn W. Zhu, Kristine Yaffe, Grant D. Huang
Older military veterans often present with unique and complex risk factors for Alzheimer's disease (AD) and related dementias. Increasing veteran participation in research studies offers one avenue to advance the field and improve health outcomes.
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Differential DNA methylation in the brain as potential mediator of the association between traffic-related PM2.5 and neuropathology markers of Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-12 Zhenjiang Li, Donghai Liang, Stefanie Ebelt, Marla Gearing, Michael S. Kobor, Chaini Konwar, Julie L. Maclsaac, Kristy Dever, Aliza P. Wingo, Allan I. Levey, James J. Lah, Thomas S. Wingo, Anke Hüls
Growing evidence indicates that fine particulate matter (PM2.5) is a risk factor for Alzheimer's disease (AD), but the underlying mechanisms have been insufficiently investigated. We hypothesized differential DNA methylation (DNAm) in brain tissue as a potential mediator of this association.
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Gene replacement-Alzheimer's disease (GR-AD): Modeling the genetics of human dementias in mice Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-11 Kellie Benzow, Kul Karanjeet, Adrian L. Oblak, Gregory W. Carter, Michael Sasner, Michael D. Koob
Genetic studies conducted over the past four decades have provided us with a detailed catalog of genes that play critical roles in the etiology of Alzheimer's disease (AD) and related dementias (ADRDs). Despite this progress, as a field we have had only limited success in incorporating this rich complexity of human AD/ADRD genetics findings into our animal models of these diseases. Our primary goal
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Tau accumulation and atrophy predict amyloid independent cognitive decline in aging Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-09 Corrina S. Fonseca, Suzanne L. Baker, Lindsey Dobyns, Mustafa Janabi, William J. Jagust, Theresa M. Harrison
Amyloid beta (Aβ) and tau pathology are cross-sectionally associated with atrophy and cognitive decline in aging and Alzheimer's disease (AD).
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Post-disclosure distress among racial and ethnic groups in a preclinical AD trial Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-08 Marina Ritchie, Christian R. Salazar, Daniel L. Gillen, Joshua D. Grill
Trialists need a thorough understanding of whether reactions to Alzheimer's disease (AD) biomarker information differ among racial and ethnic groups in preclinical AD trials.
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Brain artery diameters and risk of dementia and stroke Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-08 Jesus D. Melgarejo, Kursat Gurel, Cassidy Rose Compton, Minghua Liu, Vanessa Guzman, Stephanie Assuras, Bonnie E. Levin, Mitchell S. V. Elkind, M. Kamran Ikram, Maryam Kavousi, M. Arfan Ikram, Clinton Wright, Fabrice Crivello, Alexandre Laurent, Christophe Tzourio, Meike W. Vernooij, Tatjana Rundek, Zhen-Yu Zhang, Daniel Bos, Jose Gutierrez
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Analytical and clinical validation of Alzheimer's disease blood biomarkers with a focus on plasma p-tau217 Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-08 Fernando Gonzalez-Ortiz, Thomas K. Karikari, Kaj Blennow
Alzheimer's disease (AD) represents a growing global health challenge, necessitating accurate and reliable diagnostic methodologies for timely intervention and management. Immunoassays, specifically designed to detect biomarkers associated with AD pathology, have emerged as pivotal tools in diagnostic development. Understanding of the established protocols ensures assay sensitivity, specificity, and
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Incremental value of amyloid PET in a tertiary memory clinic setting in China Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-08 Ke-Liang Chen, Ming-Yu Wang, Jie Wu, Chuan-Tao Zuo, Yu-Yuan Huang, Wei-Yi Wang, Meng Zhao, Ya-Ru Zhang, Xue Zhang, Shu-Fen Chen, Wei-Shi Liu, Meng-Meng Li, Jing-Jie Ge, Xiao-Xi Ma, Jie Wang, Li Zheng, Yi-Hui Guan, Qiang Dong, Mei Cui, Fang Xie, Qian-Hua Zhao, Jin-Tai Yu
The objective of this study is to investigate the incremental value of amyloid positron emission tomography (Aβ-PET) in a tertiary memory clinic setting in China.
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Early detection of subjective cognitive decline and Alzheimer's disease: Analytical validation of a newly developed pT217-tau assay Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-08 Hash Brown Taha
I read with interest the insightful article by Gonzalez-Ortiz et al.1 regarding the development of a new assay for quantification of phosphorylated threonine 217 tau (pT217-tau) in the plasma of persons with subjective cognitive decline or early Alzheimer's disease (AD). This novel assay could potentially offer a more precise and earlier diagnosis of persons with AD. With regard to the analytical validation
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Plasma biomarkers of Alzheimer's disease in the continuum of dementia with Lewy bodies Alzheimers Dement. (IF 14.0) Pub Date : 2024-02-08 Patricia Diaz-Galvan, Scott A. Przybelski, Alicia Algeciras-Schimnich, Dan J. Figdore, Timothy G. Lesnick, Christopher G. Schwarz, Matthew L. Senjem, Jeffrey L. Gunter, Clifford R. Jack, Paul H Min, Manoj K. Jain, Toji Miyagawa, Leah K. Forsberg, Julie A. Fields, Rodolfo Savica, Jonathan Graff-Radford, Vijay K. Ramanan, David T. Jones, Hugo Botha, Erik K. St Louis, David S. Knopman, Neill R. Graff-Radford
Patients with dementia with Lewy bodies (DLB) may have Alzheimers disease (AD) pathology that can be detected by plasma biomarkers. Our objective was to evaluate plasma biomarkers of AD and their association with positron emission tomography (PET) biomarkers of amyloid and tau deposition in the continuum of DLB, starting from prodromal stages of the disease.