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2. Challenges and recommendations for the translation of biomarkers of aging

Author

Herzog, Chiara M. S., Goeminne, Ludger J. E., Poganik, Jesse R., Barzilai, Nir, Belsky, Daniel W., Betts-LaCroix, Joe, Chen, Brian H., Chen, Michelle, Cohen, Alan A., Cummings, Steven R., Fedichev, Peter O., Ferrucci, Luigi, Fleming, Alexander, Fortney, Kristen, Furman, David, Gorbunova, Vera, Higgins-Chen, Albert, Hood, Lee, Horvath, Steve, Justice, Jamie N., Kiel, Douglas P., Kuchel, George A., Lasky-Su, Jessica, LeBrasseur, Nathan K., Maier, Andrea B., Schilling, Birgit, Sebastiano, Vittorio, Slagboom, P. Eline, Snyder, Michael P., Verdin, Eric, Widschwendter, Martin, Zhavoronkov, Alex, Moqri, Mahdi, and Gladyshev, Vadim N.

Published
2024
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5. Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients

Author

Biesbroek, J Matthijs, Coenen, Mirthe, DeCarli, Charles, Fletcher, Evan M, Maillard, Pauline M, Initiative, Alzheimer's Disease Neuroimaging, Barkhof, Frederik, Barnes, Josephine, Benke, Thomas, Chen, Christopher PLH, Dal‐Bianco, Peter, Dewenter, Anna, Duering, Marco, Enzinger, Christian, Ewers, Michael, Exalto, Lieza G, Franzmeier, Nicolai, Hilal, Saima, Hofer, Edith, Koek, Huiberdina L, Maier, Andrea B, McCreary, Cheryl R, Papma, Janne M, Paterson, Ross W, Pijnenburg, Yolande AL, Rubinski, Anna, Schmidt, Reinhold, Schott, Jonathan M, Slattery, Catherine F, Smith, Eric E, Sudre, Carole H, Steketee, Rebecca ME, Teunissen, Charlotte E, van den Berg, Esther, van der Flier, Wiesje M, Venketasubramanian, Narayanaswamy, Venkatraghavan, Vikram, Vernooij, Meike W, Wolters, Frank J, Xin, Xu, Kuijf, Hugo J, and Biessels, Geert Jan

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Vascular Cognitive Impairment/Dementia, Brain Disorders, Clinical Research, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease Related Dementias (ADRD), Aging, Dementia, Cerebrovascular, Alzheimer's Disease, Neurodegenerative, Neurological, Humans, Female, Middle Aged, Aged, Aged, 80 and over, Male, White Matter, Arteriolosclerosis, Amyloid beta-Peptides, Magnetic Resonance Imaging, amyloid pathology, arteriolosclerosis, dementia, lesion pattern, white matter hyperintensities, Alzheimer's Disease Neuroimaging Initiative, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionWhite 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.MethodsIndividual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume.ResultsVRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p

Published
2024

10. Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes

Author

Ravikrishnan, Aarthi, Wijaya, Indrik, Png, Eileen, Chng, Kern Rei, Ho, Eliza Xin Pei, Ng, Amanda Hui Qi, Mohamed Naim, Ahmad Nazri, Gounot, Jean-Sebastien, Guan, Shou Ping, Hanqing, Jasinda Lee, Guan, Lihuan, Li, Chenhao, Koh, Jia Yu, de Sessions, Paola Florez, Koh, Woon-Puay, Feng, Lei, Ng, Tze Pin, Larbi, Anis, Maier, Andrea B., Kennedy, Brian K., and Nagarajan, Niranjan

Published
2024
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11. Outcome measures for Alzheimer's disease: A global inter‐societal Delphi consensus

Author

Ellison, Tim S, Cappa, Stefano F, Garrett, Dawne, Georges, Jean, Iwatsubo, Takeshi, Kramer, Joel H, Lehmann, Maryna, Lyketsos, Constantine, Maier, Andrea B, Merrilees, Jennifer, Morris, John C, Naismith, Sharon L, Nobili, Flavio, Pahor, Marco, Pond, Dimity, Robinson, Louise, Soysal, Pinar, Vandenbulcke, Mathieu, Weber, Christopher J, Visser, Pieter Jelle, Weiner, Michael, and Frisoni, Giovanni B

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Psychology, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurodegenerative, Alzheimer's Disease, Aging, Brain Disorders, Behavioral and Social Science, Acquired Cognitive Impairment, Clinical Research, Health Services, Neurosciences, Neurological, Humans, Alzheimer Disease, Quality of Life, Consensus, Delphi Technique, Outcome Assessment, Health Care, Alzheimer's disease, consensus, Delphi, dementia, measures, outcomes, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionWe aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome.MethodsA consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria.ResultsConsensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains. A number of outcomes and measurement instruments were ranked for: Cognitive abilities; Functional abilities/dependency; Behavioural and neuropsychiatric symptoms; Patient quality of life (QoL); Caregiver QoL; Healthcare and treatment-related outcomes; Medical investigations; Disease-related life events; and Global outcomes.DiscussionThis work provides indications on the domains and ideal pertinent measurement instruments that clinicians may wish to use to follow patients with cognitive impairment. More work is needed to develop instruments that are more feasible in the context of the constraints of clinical routine.

Published
2023

12. Validation of biomarkers of aging

Author

Moqri, Mahdi, Herzog, Chiara, Poganik, Jesse R., Ying, Kejun, Justice, Jamie N., Belsky, Daniel W., Higgins-Chen, Albert T., Chen, Brian H., Cohen, Alan A., Fuellen, Georg, Hägg, Sara, Marioni, Riccardo E., Widschwendter, Martin, Fortney, Kristen, Fedichev, Peter O., Zhavoronkov, Alex, Barzilai, Nir, Lasky-Su, Jessica, Kiel, Douglas P., Kennedy, Brian K., Cummings, Steven, Slagboom, P. Eline, Verdin, Eric, Maier, Andrea B., Sebastiano, Vittorio, Snyder, Michael P., Gladyshev, Vadim N., Horvath, Steve, and Ferrucci, Luigi

Published
2024
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14. The Semmelweis Study: a longitudinal occupational cohort study within the framework of the Semmelweis Caring University Model Program for supporting healthy aging

Author

Ungvari, Zoltan, Tabák, Adam G., Adany, Roza, Purebl, György, Kaposvári, Csilla, Fazekas-Pongor, Vince, Csípő, Tamás, Szarvas, Zsófia, Horváth, Krisztián, Mukli, Peter, Balog, Piroska, Bodizs, Robert, Ujma, Peter, Stauder, Adrienne, Belsky, Daniel W., Kovács, Illés, Yabluchanskiy, Andriy, Maier, Andrea B., Moizs, Mariann, Östlin, Piroska, Yon, Yongjie, Varga, Péter, Vokó, Zoltán, Papp, Magor, Takács, István, Vásárhelyi, Barna, Torzsa, Péter, Ferdinandy, Péter, Csiszar, Anna, Benyó, Zoltán, Szabó, Attila J., Dörnyei, Gabriella, Kivimäki, Mika, Kellermayer, Miklos, and Merkely, Bela

Published
2024
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16. Spatial distributions of white matter hyperintensities on brain MRI: A pooled analysis of individual participant data from 11 memory clinic cohorts

Author

Coenen, Mirthe, Biessels, Geert Jan, DeCarli, Charles, Fletcher, Evan F, Maillard, Pauline M, Initiative, Alzheimer's Disease Neuroimaging, Barkhof, Frederik, Barnes, Josephine, Benke, Thomas, Boomsma, Jooske MF, Chen, Christopher PLH, Dal-Bianco, Peter, Dewenter, Anna, Duering, Marco, Enzinger, Christian, Ewers, Michael, Exalto, Lieza G, Franzmeier, Nicolai, Groeneveld, Onno, Hilal, Saima, Hofer, Edith, Koek, Huiberdina L, Maier, Andrea B, McCreary, Cheryl R, Papma, Janne M, Paterson, Ross W, Pijnenburg, Yolande AL, Rubinski, Anna, Schmidt, Reinhold, Schott, Jonathan M, Slattery, Catherine F, Smith, Eric E, Sudre, Carole H, Steketee, Rebecca ME, van den Berg, Esther, van der Flier, Wiesje M, Venketasubramanian, Narayanaswamy, Vernooij, Meike W, Wolters, Frank J, Xin, Xu, Biesbroek, J Matthijs, and Kuijf, Hugo J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Alzheimer's Disease Related Dementias (ADRD), Cerebrovascular, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Machine Learning and Artificial Intelligence, Clinical Research, Acquired Cognitive Impairment, Vascular Cognitive Impairment/Dementia, Aging, Neurodegenerative, Networking and Information Technology R&D (NITRD), Neurosciences, Brain Disorders, Dementia, Neurological, Humans, White Matter, Brain, Magnetic Resonance Imaging, Neuroimaging, Cognitive Dysfunction, Multicenter Studies as Topic, White matter hyperintensities, Brain MRI, Distribution frequencies, Lesion location, Alzheimer's Disease Neuroimaging Initiative, Biological psychology, Clinical and health psychology
Abstract

IntroductionThe spatial distribution of white matter hyperintensities (WMH) on MRI is often considered in the diagnostic evaluation of patients with cognitive problems. In some patients, clinicians may classify WMH patterns as "unusual", but this is largely based on expert opinion, because detailed quantitative information about WMH distribution frequencies in a memory clinic setting is lacking. Here we report voxel wise 3D WMH distribution frequencies in a large multicenter dataset and also aimed to identify individuals with unusual WMH patterns.MethodsIndividual participant data (N = 3525, including 777 participants with subjective cognitive decline, 1389 participants with mild cognitive impairment and 1359 patients with dementia) from eleven memory clinic cohorts, recruited through the Meta VCI Map Consortium, were used. WMH segmentations were provided by participating centers or performed in Utrecht and registered to the Montreal Neurological Institute (MNI)-152 brain template for spatial normalization. To determine WMH distribution frequencies, we calculated WMH probability maps at voxel level. To identify individuals with unusual WMH patterns, region-of-interest (ROI) based WMH probability maps, rule-based scores, and a machine learning method (Local Outlier Factor (LOF)), were implemented.ResultsWMH occurred in 82% of voxels from the white matter template with large variation between subjects. Only a small proportion of the white matter (1.7%), mainly in the periventricular areas, was affected by WMH in at least 20% of participants. A large portion of the total white matter was affected infrequently. Nevertheless, 93.8% of individual participants had lesions in voxels that were affected in less than 2% of the population, mainly located in subcortical areas. Only the machine learning method effectively identified individuals with unusual patterns, in particular subjects with asymmetric WMH distribution or with WMH at relatively rarely affected locations despite common locations not being affected.DiscussionAggregating data from several memory clinic cohorts, we provide a detailed 3D map of WMH lesion distribution frequencies, that informs on common as well as rare localizations. The use of data-driven analysis with LOF can be used to identify unusual patterns, which might serve as an alert that rare causes of WMH should be considered.

Published
2023

36. Meeting Report: Aging Research and Drug Discovery

Author

Meron, Esther, Thaysen, Maria, Angeli, Suzanne, Antebi, Adam, Barzilai, Nir, Baur, Joseph A, Bekker-Jensen, Simon, Birkisdottir, Maria, Bischof, Evelyne, Bruening, Jens, Brunet, Anne, Buchwalter, Abigail, Cabreiro, Filipe, Cai, Shiqing, Chen, Brian H, Ermolaeva, Maria, Ewald, Collin Y, Ferrucci, Luigi, Florian, Maria Carolina, Fortney, Kristen, Freund, Adam, Georgievskaya, Anastasia, Gladyshev, Vadim N, Glass, David, Golato, Tyler, Gorbunova, Vera, Hoejimakers, Jan, Houtkooper, Riekelt H, Jager, Sibylle, Jaksch, Frank, Janssens, Georges, Jensen, Martin Borch, Kaeberlein, Matt, Karsenty, Gerard, de Keizer, Peter, Kennedy, Brian, Kirkland, James L, Kjaer, Michael, Kroemer, Guido, Lee, Kai-Fu, Lemaitre, Jean-Marc, Liaskos, David, Longo, Valter D, Lu, Yu-Xuan, MacArthur, Michael R, Maier, Andrea B, Manakanatas, Christina, Mitchell, Sarah J, Moskalev, Alexey, Niedernhofer, Laura, Ozerov, Ivan, Partridge, Linda, Passegué, Emmanuelle, Petr, Michael A, Peyer, James, Radenkovic, Dina, Rando, Thomas A, Rattan, Suresh, Riedel, Christian G, Rudolph, Lenhard, Ai, Ruixue, Serrano, Manuel, Schumacher, Björn, Sinclair, David A, Smith, Ryan, Suh, Yousin, Taub, Pam, Trapp, Alexandre, Trendelenburg, Anne-Ulrike, Valenzano, Dario Riccardo, Verburgh, Kris, Verdin, Eric, Vijg, Jan, Westendorp, Rudi GJ, Zonari, Alessandra, Bakula, Daniela, Zhavoronkov, Alex, and Scheibye-Knudsen, Morten

Subjects
Aging, aging, drug discovery, conference, AI, longevity, Biochemistry and Cell Biology, Physiology, Oncology and Carcinogenesis, Developmental Biology
Abstract

Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery (ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community.

Published
2022

46. Biomarkers of aging for the identification and evaluation of longevity interventions

Author

Moqri, Mahdi, Herzog, Chiara, Poganik, Jesse R., Justice, Jamie, Belsky, Daniel W., Higgins-Chen, Albert, Moskalev, Alexey, Fuellen, Georg, Cohen, Alan A., Bautmans, Ivan, Widschwendter, Martin, Ding, Jingzhong, Fleming, Alexander, Mannick, Joan, Han, Jing-Dong Jackie, Zhavoronkov, Alex, Barzilai, Nir, Kaeberlein, Matt, Cummings, Steven, Kennedy, Brian K., Ferrucci, Luigi, Horvath, Steve, Verdin, Eric, Maier, Andrea B., Snyder, Michael P., Sebastiano, Vittorio, and Gladyshev, Vadim N.

Published
2023
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47. Patterns of Objectively Measured Sedentary Behavior and Physical Activity and Their Association with Changes in Physical and Functional Performance in Geriatric Rehabilitation Inpatients

Author

Rojer, Anna G.M., Ramsey, Keenan A., Trappenburg, Marijke C., Meskers, Carel G.M., Twisk, Jos W.R., Goonan, Rose, Marston, Celia, Kay, Jacqui, Lim, Wen Kwang, Turbić, Alisa, Island, Louis, Denehy, Linda, Parry, Selina M., Reijnierse, Esmee M., Pijnappels, Mirjam, and Maier, Andrea B.

Published
2023
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