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4. Conclusion

Author

Dröes, Rose-Marie, primary, Orrell, Martin, additional, and Verhey, Frans R. J., additional

Published
2022
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6. The unique training programme of INDUCT

Author

Dassen, Fania C.M., primary, Bartels, Sara Laureen, additional, Christie, Hannah, additional, Van den Block, Lieve, additional, de Vugt, Marjolein, additional, and Verhey, Frans R. J., additional

Published
2022
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8. Correction: Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease

Author

Visser, Pieter Jelle, Reus, Lianne M., Gobom, Johan, Jansen, Iris, Dicks, Ellen, van der Lee, Sven J., Tsolaki, Magda, Verhey, Frans R. J., Popp, Julius, Martinez-Lage, Pablo, Vandenberghe, Rik, Lleó, Alberto, Molinuevo, José Luís, Engelborghs, Sebastiaan, Freund-Levi, Yvonne, Froelich, Lutz, Sleegers, Kristel, Dobricic, Valerija, Lovestone, Simon, Streffer, Johannes, Vos, Stephanie J. B., Bos, Isabelle, Smit, August B., Blennow, Kaj, Scheltens, Philip, Teunissen, Charlotte E., Bertram, Lars, Zetterberg, Henrik, and Tijms, Betty M.

Published
2022
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9. Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease

Author

Visser, Pieter Jelle, Reus, Lianne M., Gobom, Johan, Jansen, Iris, Dicks, Ellen, van der Lee, Sven J., Tsolaki, Magda, Verhey, Frans R. J., Popp, Julius, Martinez-Lage, Pablo, Vandenberghe, Rik, Lleó, Alberto, Molinuevo, José Luís, Engelborghs, Sebastiaan, Freund-Levi, Yvonne, Froelich, Lutz, Sleegers, Kristel, Dobricic, Valerija, Lovestone, Simon, Streffer, Johannes, Vos, Stephanie J. B., Bos, Isabelle, Smit, August B., Blennow, Kaj, Scheltens, Philip, Teunissen, Charlotte E., Bertram, Lars, Zetterberg, Henrik, and Tijms, Betty M.

Published
2022
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10. Associations between plasma kynurenines and cognitive function in individuals with normal glucose metabolism, prediabetes and type 2 diabetes: the Maastricht Study

Author

Bakker, Lieke, Ramakers, Inez H. G. B., van Boxtel, Martin P. J., Schram, Miranda T., Stehouwer, Coen D. A., van der Kallen, Carla J. H., Dagnelie, Pieter C., van Greevenbroek, Marleen M. J., Wesselius, Anke, Midttun, Øivind, Ueland, Per M., Verhey, Frans R. J., Eussen, Simone J. P. M., and Köhler, Sebastian

Published
2021
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11. Strategic infarct locations for post-stroke cognitive impairment: a pooled analysis of individual patient data from 12 acute ischaemic stroke cohorts

Author

Weaver, Nick A, Kuijf, Hugo J, Aben, Hugo P, Abrigo, Jill, Bae, Hee-Joon, Barbay, Mélanie, Best, Jonathan G, Bordet, Régis, Chappell, Francesca M, Chen, Christopher P L H, Dondaine, Thibaut, van der Giessen, Ruben S, Godefroy, Olivier, Gyanwali, Bibek, Hamilton, Olivia K L, Hilal, Saima, Huenges Wajer, Irene M C, Kang, Yeonwook, Kappelle, L Jaap, Kim, Beom Joon, Köhler, Sebastian, de Kort, Paul L M, Koudstaal, Peter J, Kuchcinski, Gregory, Lam, Bonnie Y K, Lee, Byung-Chul, Lee, Keon-Joo, Lim, Jae-Sung, Lopes, Renaud, Makin, Stephen D J, Mendyk, Anne-Marie, Mok, Vincent C T, Oh, Mi Sun, van Oostenbrugge, Robert J, Roussel, Martine, Shi, Lin, Staals, Julie, del C Valdés-Hernández, Maria, Venketasubramanian, Narayanaswamy, Verhey, Frans R J, Wardlaw, Joanna M, Werring, David J, Xin, Xu, Yu, Kyung-Ho, van Zandvoort, Martine J E, Zhao, Lei, Biesbroek, J Matthijs, and Biessels, Geert Jan

Published
2021
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16. Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions

Author

Reus, Lianne M., Jansen, Iris E., Mol, Merel O., van Ruissen, Fred, van Rooij, Jeroen, van Schoor, Natasja M., Tesi, Niccolò, Reinders, Marcel J. T., Huisman, Martijn A., Holstege, Henne, Visser, Pieter Jelle, de Boer, Sterre C. M., Hulsman, Marc, Ahmad, Shahzad, Amin, Najaf, Uitterlinden, Andre G., Ikram, Arfan, van Duijn, Cornelia M., Seelaar, Harro, Ramakers, Inez H. G. B., Verhey, Frans R. J., van der Lugt, Aad, Claassen, Jurgen A. H. R., Jan Biessels, Geert, De Deyn, Peter Paul, Scheltens, Philip, van der Flier, Wiesje M., van Swieten, John C., Pijnenburg, Yolande A. L., and van der Lee, Sven J.

Published
2021
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17. The association of hyperglycaemia and insulin resistance with incident depressive symptoms over 4 years of follow-up: The Maastricht Study

Author

Geraets, Anouk F. J., Köhler, Sebastian, Muzambi, Rutendo, Schalkwijk, Casper G., Oenema, Anke, Eussen, Simone J. P. M., Dagnelie, Pieter C., Stehouwer, Coen D. A., Schaper, Nicolaas C., Henry, Ronald M. A., van der Kallen, Carla J. H., Wesselius, Anke, Koster, Annemarie, Verhey, Frans R. J., and Schram, Miranda T.

Published
2020
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23. Smartphone-Based Experience Sampling in People With Mild Cognitive Impairment: Feasibility and Usability Study

Author

Bartels, Sara Laureen, van Knippenberg, Rosalia J M, Malinowsky, Camilla, Verhey, Frans R J, and de Vugt, Marjolein E

Subjects
Geriatrics, RC952-954.6
Abstract

BackgroundDaily functioning of people with cognitive disorders such as mild cognitive impairment (MCI) is usually depicted by retrospective questionnaires, which can be memory-biased and neglect fluctuations over time or contexts. ObjectiveThis study examines the feasibility and usability of applying the experience sampling method (ESM) in people with MCI to provide a detailed and dynamic picture of behavioral, emotional, and cognitive patterns in everyday life. MethodsFor 6 consecutive days, 21 people with MCI used an ESM app on their smartphones. At 8 semi-random timepoints per day, participants filled in momentary questionnaires on mood, activities, social context, and subjective cognitive complaints. Feasibility was determined through self-reports and observable human-technology interactions. Usability was demonstrated on an individual and group level. ResultsOf the 21 participants, 3 dropped out due to forgetting to carry their smartphones or forgetting the study instructions. In the remaining 18 individuals, the compliance rate was high, at 78.7%. Participants reported that momentary questions reflected their daily experiences well. Of the 18 participants, 13 (72%) experienced the increase in awareness of their own memory functions as pleasant or neutral. ConclusionsSupport was found for the general feasibility of smartphone-based experience sampling in people with MCI. However, many older adults with MCI are currently not in possession of smartphones, and study adherence seems challenging for a minority of individuals. Momentary data can increase the insights into daily patterns and may guide the person-tailored development of self-management strategies in clinical settings.

Published
2020
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26. Contributions of modifiable risk factors to increased dementia risk in depression.

Author

Geraets, Anouk F. J., Leist, Anja K., Deckers, Kay, Verhey, Frans R. J., Schram, Miranda T., and Köhler, Sebastian

Subjects
DEMENTIA risk factors, DEMENTIA prevention, STRUCTURAL equation modeling, CONFIDENCE intervals, AGE distribution, RISK assessment, SEX distribution, INCOME, MENTAL depression, CENTER for Epidemiologic Studies Depression Scale, DESCRIPTIVE statistics, RESEARCH funding, LONGITUDINAL method, EDUCATIONAL attainment, MIDDLE age
Abstract

Background: Individuals with depression have an increased dementia risk, which might be due to modifiable risk factors for dementia. This study investigated the extent to which the increased risk for dementia in depression is explained by modifiable dementia risk factors. Methods: We used data from the English Longitudinal Study of Ageing (2008–2009 to 2018–2019), a prospective cohort study. A total of 7460 individuals were included [mean(standard deviation) age, 65.7 ± 9.4 years; 3915(54.7%) were women]. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale-8 (score ≥3) or self-reported doctor's diagnosis. Ten modifiable risk factors for dementia were combined in the 'LIfestyle for BRAin health' (LIBRA) score. Dementia was determined by physician diagnosis, self-reported Alzheimer's disease or the shortened version of the Informant Questionnaire on Cognitive Decline in the Elderly (average score ≥3.38). Structural equation modelling was used to test mediation of LIBRA score. Results: During 61 311 person-years, 306 individuals (4.1%) developed dementia. Participants aged 50–70 years with depressive symptoms had higher LIBRA scores [difference(s.e.) = 1.15(0.10)] and a 3.59 times increased dementia risk [HR(95% CI) = 3.59(2.20–5.84)], adjusted for age, sex, education, wealth and clustering at the household level. In total, 10.4% of the dementia risk was mediated by differences in LIBRA score [indirect effect: HR = 1.14(1.03–1.26)], while 89.6% was attributed to a direct effect of depressive symptoms on dementia risk [direct effect: HR = 3.14(2.20–5.84)]. Conclusions: Modifiable dementia risk factors can be important targets for the prevention of dementia in individuals with depressive symptoms during midlife. Yet, effect sizes are small and other aetiological pathways likely exist. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Determinants of quality of life in family caregivers in MCI:a comparison with mild dementia

Author

Tan, Eva Y. L., Janssen, Niels, Handels, Ron, Ramakers, Inez H. G. B., Verhey, Frans R. J., van der Flier, Wiesje M., Melis, René J. F., Olde Rikkert, Marcel G. M., Schols, Jos M. G. A., and de Vugt, Marjolein E.

Abstract

Objectives: The aim of the current study was to investigate the health-related quality of life (HRQol) of the family caregiver in MCI, explore possible determinants and study possible differences with mild dementia. Methods: This secondary data analysis included 145 persons with MCI and 154 persons with dementia and their family caregivers from two Dutch cohort studies. HRQoL was measured with the VAS of the EuroQol-5D-3L version. Regressions analyses were conducted to examine potential demographic and clinical determinants of the caregiver’s HRQoL. Results: The mean EQ5D-VAS in family caregivers of persons with MCI was 81.1 (SD 15.7), and did not significantly differ from family caregivers in mild dementia (81.9 (SD 13.0)). In MCI, patient measurements were not significantly associated with caregiver mean EQ5D-VAS. Concerning caregiver characteristics, being a spouse and a lower educational level were associated with a lower mean EQ5D-VAS (in a multiple linear regression model: unstandardized B −8.075, p = 0.013 and unstandardized B −6.162, p = 0.037 resp.). In mild dementia, the NPI item irritability showed an association with caregiver EQ5D-VAS in bivariate linear regression analyses. Conclusion: Results indicate that especially family caregiver characteristics seem to influence family caregiver HRQoL in MCI. Future research should include other potential determinants such as burden, coping strategies and relationship quality.

Published
2023

29. MRI predictors of amyloid pathology: results from the EMIF-AD Multimodal Biomarker Discovery study

Author

ten Kate, Mara, Redolfi, Alberto, Peira, Enrico, Bos, Isabelle, Vos, Stephanie J., Vandenberghe, Rik, Gabel, Silvy, Schaeverbeke, Jolien, Scheltens, Philip, Blin, Olivier, Richardson, Jill C., Bordet, Regis, Wallin, Anders, Eckerstrom, Carl, Molinuevo, José Luis, Engelborghs, Sebastiaan, Van Broeckhoven, Christine, Martinez-Lage, Pablo, Popp, Julius, Tsolaki, Magdalini, Verhey, Frans R. J., Baird, Alison L., Legido-Quigley, Cristina, Bertram, Lars, Dobricic, Valerija, Zetterberg, Henrik, Lovestone, Simon, Streffer, Johannes, Bianchetti, Silvia, Novak, Gerald P., Revillard, Jerome, Gordon, Mark F., Xie, Zhiyong, Wottschel, Viktor, Frisoni, Giovanni, Visser, Pieter Jelle, and Barkhof, Frederik

Published
2018
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32. Distinct Patterns Link the BDNF Val66Met Polymorphism to Alzheimer's Disease Pathology

Author

Riphagen, Joost M, van Hooren, Roy W E, Kenis, Gunter, Verhey, Frans R J, Jacobs, Heidi I L, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, Psychology 1, Psychology 4, MUMC+: MA Niet Med Staf Psychiatrie (9), RS: MHeNs - R3 - Neuroscience, Basic Neuroscience 1, and MUMC+: MA Med Staf Spec Psychiatrie (9)

Subjects
INTERLEUKIN-6, BETA, interleukin 6, tau Proteins, brain-derived neurotropic growth factor, phosphorylated tau, APOLIPOPROTEIN-E, MECHANISMS, NEUROINFLAMMATION, Apolipoproteins E, Alzheimer Disease, Humans, Cognitive Dysfunction, Inflammation, Amyloid beta-Peptides, General Neuroscience, Brain-Derived Neurotrophic Factor, CYTOKINES, ASSOCIATION, General Medicine, Alzheimer's disease, IMPAIRMENT, amyloid-beta, Peptide Fragments, Psychiatry and Mental health, Clinical Psychology, COGNITIVE DECLINE, Geriatrics and Gerontology, Biomarkers, NEUROTROPHIC FACTOR
Abstract

The brain-derived neurotropic growth factor (BDNF) gene has been linked to dementia, inflammation, and Apolipoprotein E (APOE) ɛ4 status. We used cerebrospinal fluid (CSF) amyloid-β (Aβ)42 and phosphorylated tau (p-tau) to investigate associations with BDNF polymorphisms and modifications by APOE ɛ4 or inflammation in a memory clinic population (n = 114; subjective cognitive decline, mild cognitive impairment, Alzheimer’s disease). We found distinct pathways to Alzheimer’s disease pathology: Val-Met displayed lower CSF-Aβ42 in APOE ɛ4+ carriers, independent of p-tau, while Val-Val displayed greater p-tau at higher IL-6 and sub-threshold Aβ42. This may contribute to resolving some inconsistencies in the BDNF literature and provide possible inroads to specific Aβ and tau interventions depending on BDNF polymorphism.

Published
2022

33. Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia

Author

Jansen, Willemijn J., Ossenkoppele, Rik, Tijms, Betty M., Fagan, Anne M., Hansson, Oskar, Klunk, William E., van der Flier, Wiesje M., Villemagne, Victor L., Frisoni, Giovanni B., Fleisher, Adam S., Lleó, Alberto, Mintun, Mark A., Wallin, Anders, Engelborghs, Sebastiaan, Na, Duk L., Chételat, Gäel, Molinuevo, José Luis, Landau, Susan M., Mattsson, Niklas, Kornhuber, Johannes, Sabri, Osama, Rowe, Christopher C., Parnetti, Lucilla, Popp, Julius, Fladby, Tormod, Jagust, William J., Aalten, Pauline, Lee, Dong Young, Vandenberghe, Rik, Resende de Oliveira, Catarina, Kapaki, Elisabeth, Froelich, Lutz, Ivanoiu, Adrian, Gabryelewicz, Tomasz, Verbeek, Marcel M., Sanchez-Juan, Páscual, Hildebrandt, Helmut, Camus, Vincent, Zboch, Marzena, Brooks, David J., Drzezga, Alexander, Rinne, Juha O., Newberg, Andrew, de Mendonça, Alexandre, Sarazin, Marie, Rabinovici, Gil D., Madsen, Karine, Kramberger, Milica G., Nordberg, Agneta, Mok, Vincent, Mroczko, Barbara, Wolk, David A., Meyer, Philipp T., Tsolaki, Magda, Scheltens, Philip, Verhey, Frans R. J., Visser, Pieter Jelle, Aarsland, Dag, Alcolea, Daniel, Alexander, Myriam, Almdahl, Ina S., Arnold, Steven E., Baldeiras, Inês, Barthel, Henryk, van Berckel, Bart N.M., Blennow, Kaj, van Buchem, Mark A., Cavedo, Enrica, Chen, Kewei, Chipi, Elena, Cohen, Ann D., Förster, Stefan, Fortea, Juan, Frederiksen, Kristian S., Freund-Levi, Yvonne, Gkatzima, Olymbia, Gordon, Mark Forrest, Grimmer, Timo, Hampel, Harald, Hausner, Lucrezia, Hellwig, Sabine, Herukka, Sanna-Kaisa, Johannsen, Peter, Klimkowicz-Mrowiec, Aleksandra, Köhler, Sebastian, Koglin, Norman, van Laere, Koen, de Leon, Mony, Lisetti, Viviana, Maier, Wolfgang, Marcusson, Jan, Meulenbroek, Olga, Møllergård, Hanne M., Morris, John C., Nordlund, Arto, Novak, Gerald P., Paraskevas, George P., Perera, Gayan, Peters, Oliver, Ramakers, Inez H. G. B., Rami, Lorena, Rodríguez-Rodríguez, Eloy, Roe, Catherine M., Rot, Uros, Rüther, Eckart, Santana, Isabel, Schröder, Johannes, Seo, Sang W., Soininen, Hilkka, Spiru, Luiza, Stomrud, Erik, Struyfs, Hanne, Teunissen, Charlotte E., Vos, Stephanie J. B., van Waalwijk van Doorn, Linda J. C., Waldemar, Gunhild, Wallin, Åsa K., Wiltfang, Jens, and Zetterberg, Henrik

Published
2018
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35. Towards age‐friendly municipalities: What are municipalities doing to support their ageing population with mental health problems?

Author

Schichel, Mignon C. P., Veenstra, Marja Y., Kempen, Gertrudis I. J. M., de Vugt, Marjolein E., and Verhey, Frans R. J.

Subjects
MENTAL illness, CITIES & towns, MENTAL age, POPULATION aging, COMMUNITIES
Abstract

Municipalities in Western Europe have increasingly gained a responsibility to support their populations' healthy ageing, but are they ready to do so? In this case study, we are looking into the awareness, attitudes, capacities and mandates of 33 neighboring Belgian, Dutch, and German municipalities to support ageing people, and especially people with dementia, people with late‐life depression and informal caregivers. As part of the Senior Friendly Communities Interreg project, we conducted semi‐structured interviews with municipal policymakers and relevant stakeholders from May 2017 to January 2018. The results show that dementia was a more salient theme in municipality policies than depression; that informal caregivers were considered important but difficult for municipalities to identify; that there was a difference between how embedded these health themes were in policies versus in practice; and lastly, that conducting this assessment turned out to act as an intervention itself. We discuss the similarities and differences between the regions, and the context that needs to be taken into account for municipalities when becoming more age‐friendly. These results do not only provide an insight into the status quo of the participating municipalities with regard to becoming more age‐friendly but can provide a starting point for further development of policies in this area. Key points: The Senior Friendly Communities project stimulates age‐friendly municipality policies for people with dementia, people with late‐life depression, and informal caregivers.This paper describes the results of interviews with officials from municipalities in the Meuse‐Rhine Euroregion who participated in the Senior Friendly Communities project.The results indicate that dementia is a more salient topic in municipality policies than depression.Informal caregivers are regarded as difficult to identify for municipalities.The support of healthy ageing differs between policies and practice.Conducting assessments of municipal health policies acted as an intervention itself. [ABSTRACT FROM AUTHOR]

Published
2023
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40. Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum

Author

Jansen, Willemijn J, Janssen, Olin, von Arnim, Christine, Marquié, Marta, Martinez-Lage, Pablo, Maserejian, Nancy, Mattsson, Niklas, de Mendonça, Alexandre, Meyer, Philipp T, Miller, Bruce L, Minatani, Shinobu, Mintun, Mark A, Mok, Vincent C T, Baiardi, Simone, Molinuevo, Jose Luis, Morbelli, Silvia Daniela, Morris, John C, Mroczko, Barbara, Na, Duk L, Newberg, Andrew, Nobili, Flavio, Nordberg, Agneta, Olde Rikkert, Marcel G M, de Oliveira, Catarina Resende, Baldeiras, Ines, Olivieri, Pauline, Orellana, Adela, Paraskevas, George, Parchi, Piero, Pardini, Matteo, Parnetti, Lucilla, Peters, Oliver, Poirier, Judes, Popp, Julius, Prabhakar, Sudesh, Barthel, Henryk, Rabinovici, Gil D, Ramakers, Inez H, Rami, Lorena, Reiman, Eric M, Rinne, Juha O, Rodrigue, Karen M, Rodríguez-Rodriguez, Eloy, Roe, Catherine M, Rosa-Neto, Pedro, Rosen, Howard J, Bateman, Randall J, Rot, Uros, Rowe, Christopher C, Rüther, Eckart, Ruiz, Agustín, Sabri, Osama, Sakhardande, Jayant, Sánchez-Juan, Pascual, Sando, Sigrid Botne, Santana, Isabel, Sarazin, Marie, Van Berckel, Bart, Scheltens, Philip, Schröder, Johannes, Selnes, Per, Seo, Sang Won, Silva, Dina, Skoog, Ingmar, Snyder, Peter J, Soininen, Hilkka, Sollberger, Marc, Sperling, Reisa A, Binette, Alexa Pichet, Spiru, Luisa, Stern, Yaakov, Stomrud, Erik, Takeda, Akitoshi, Teichmann, Marc, Teunissen, Charlotte E, Thompson, Louisa I, Tomassen, Jori, Tsolaki, Magda, Vandenberghe, Rik, Blennow, Kaj, Verbeek, Marcel M, Verhey, Frans R J, Villemagne, Victor, Villeneuve, Sylvia, Vogelgsang, Jonathan, Waldemar, Gunhild, Wallin, Anders, Wallin, Åsa K, Wiltfang, Jens, Wolk, David A, Boada, Merce, Yen, Tzu-Chen, Zboch, Marzena, Zetterberg, Henrik, Boecker, Henning, Tijms, Betty M, Bottlaender, Michel, den Braber, Anouk, Brooks, David J, Van Buchem, Mark A, Camus, Vincent, Carill, Jose Manuel, Cerman, Jiri, Chen, Kewei, Chételat, Gaël, Chipi, Elena, Vos, Stephanie J B, Cohen, Ann D, Daniels, Alisha, Delarue, Marion, Didic, Mira, Drzezga, Alexander, Dubois, Bruno, Eckerström, Marie, Ekblad, Laura L, Engelborghs, Sebastiaan, Epelbaum, Stéphane, Ossenkoppele, Rik, Fagan, Anne M, Fan, Yong, Fladby, Tormod, Fleisher, Adam S, Van der Flier, Wiesje M, Förster, Stefan, Fortea, Juan, Frederiksen, Kristian Steen, Freund-Levi, Yvonne, Frings, Lars, Visser, Pieter Jelle, Frisoni, Giovanni B, Fröhlich, Lutz, Gabryelewicz, Tomasz, Gertz, Hermann-Josef, Gill, Kiran Dip, Gkatzima, Olymbia, Gómez-Tortosa, Estrella, Grimmer, Timo, Guedj, Eric, Habeck, Christian G, Group, Amyloid Biomarker Study, Hampel, Harald, Handels, Ron, Hansson, Oskar, Hausner, Lucrezia, Hellwig, Sabine, Heneka, Michael, Herukka, Sanna-Kaisa, Hildebrandt, Helmut, Hodges, John, Hort, Jakub, Aarsland, Dag, Huang, Chin-Chang, Iriondo, Ane Juaristi, Itoh, Yoshiaki, Ivanoiu, Adrian, Jagust, William J, Jessen, Frank, Johannsen, Peter, Johnson, Keith A, Kandimalla, Ramesh, Kapaki, Elisabeth N, Alcolea, Daniel, Kern, Silke, Kilander, Lena, Klimkowicz-Mrowiec, Aleksandra, Klunk, William E, Koglin, Norman, Kornhuber, Johannes, Kramberger, Milica G, Kuo, Hung-Chou, Van Laere, Koen, Landau, Susan M, Altomare, Daniele, Landeau, Brigitte, Lee, Dong Young, de Leon, Mony, Leyton, Cristian E, Lin, Kun-Ju, Lleó, Alberto, Löwenmark, Malin, Madsen, Karine, Maier, Wolfgang, Marcusson, Jan, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Laboratory Medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation, APH - Personalized Medicine, APH - Methodology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Psychiatrie & Neuropsychologie

Subjects
Male, MILD COGNITIVE IMPAIRMENT, epidemiology [Cognitive Dysfunction], positron emission tomography, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], epidemiology [Alzheimer Disease], Neuroscience(all), diagnostic imaging [Cognitive Dysfunction], Amyloidogenic Proteins, tau Proteins, cerebrospinal fluid [Amyloid beta-Peptides], DIAGNOSIS, cerebrospinal fluid, Apolipoproteins E, Alzheimer Disease, Prevalence, Humans, Amyloid, Alzheimer, PET, Cognitive Dysfunction, ddc:610, cerebrospinal fluid [Peptide Fragments], Aged, Amyloid beta-Peptides, neurology, DEMENTIA, Correction, ASSOCIATION, Amyloidosis, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], health care planning, clinical trial design, Peptide Fragments, cerebrospinal fluid [Alzheimer Disease], PET, DRIFT, Cross-Sectional Studies, cerebrospinal fluid [Biomarkers], cerebrospinal fluid [tau Proteins], Radiology Nuclear Medicine and imaging, Positron-Emission Tomography, genetics [Apolipoproteins E], Female, Neurology (clinical), diagnostic imaging [Alzheimer Disease], cerebral amyloid aggregation, Biomarkers
Abstract

Importance: One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.Objective: To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.Design, Setting, and Participants: This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Exposures: Alzheimer disease biomarkers detected on PET or in CSF.Main Outcomes and Measures: Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Results: Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P = .18).Conclusions and Relevance: This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.

Published
2022

42. Additional file 2 of Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease

Author

Visser, Pieter Jelle, Reus, Lianne M., Gobom, Johan, Jansen, Iris, Dicks, Ellen, van der Lee, Sven J., Tsolaki, Magda, Verhey, Frans R. J., Popp, Julius, Martinez-Lage, Pablo, Vandenberghe, Rik, Lleó, Alberto, Molinuevo, José Luís, Engelborghs, Sebastiaan, Freund-Levi, Yvonne, Froelich, Lutz, Sleegers, Kristel, Dobricic, Valerija, Lovestone, Simon, Streffer, Johannes, Vos, Stephanie J. B., Bos, Isabelle, Smit, August B., Blennow, Kaj, Scheltens, Philip, Teunissen, Charlotte E., Bertram, Lars, Zetterberg, Henrik, and Tijms, Betty M.

Subjects
mental disorders, sense organs
Abstract

Additional file 2: Figure S1. Longitudinal change in CSF total tau. Figure S2. Enrichment of synaptic processes in individuals with AD according to t-tau status. Figure S3. Enriched GO biological processes and SUZ12 and REST transcription factors associated with proteins that differed between AD individuals with increased t-tau and normal t-tau and proteins that changed with disease severity.

Published
2022
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43. Characteristics of subjective cognitive decline associated with amyloid positivity

Author

Janssen, Olin, Jansen, Willemijn J, Epelbaum, Stéphane, Lleó, Alberto, Engelborghs, Sebastiaan, van der Flier, Wiesje M, Landau, Susan, Popp, Julius, Wallin, Anders, Scheltens, Philip, Rikkert, Marcel Olde, Snyder, Peter J, Vos, Stephanie J B, Rowe, Chris, Chételat, Gaël, Ruíz, Agustin, Marquié, Marta, Chipi, Elena, Wolfsgruber, Steffen, Heneka, Michael, Boecker, Henning, Peters, Oliver, Jarholm, Jonas, Boada, Merce, Rami, Lorena, Tort-Merino, Adrià, Binette, Alexa Pichet, Poirier, Judes, Rosa-Neto, Pedro, Cerman, Jiri, Dubois, Bruno, Teichmann, Marc, Alcolea, Daniel, Fortea, Juan, Parnetti, Lucilla, Sánchez-Saudinós, M Belén, Ebenau, Jarith, Pocnet, Cornelia, Eckerström, Marie, Thompson, Louisa, Villemagne, Victor, Buckley, Rachel, Burnham, Samantha, Delarue, Marion, Freund-Levi, Yvonne, Gabryelewicz, Tomasz, Wallin, Åsa K, Ramakers, Inez, Tsolaki, Magda, Soininen, Hilkka, Hampel, Harald, Spiru, Luiza, Initiative, Alzheimer's Disease Neuroimaging, group, FACEHBI study, group, PREVENT-AD research, Tijms, Betty, Fladby, Tormod, Ossenkoppele, Rik, Verhey, Frans R J, Jessen, Frank, Visser, Pieter Jelle, Molinuevo, José Luis, Villeneuve, Sylvia, Hort, Jakub, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, Neurology, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Brain Imaging, Alzheimers Dis Neuroimaging Initia, Facehbi Study Grp, PREVENT-AD Res Grp, Clinical sciences, and Neuroprotection & Neuromodulation

Subjects
PRECLINICAL ALZHEIMERS-DISEASE, Amyloid, SYMPTOMS, positron emission tomography, Epidemiology, Neuroscience(all), Apolipoprotein E4, Amyloidogenic Proteins, cerebrospinal fluid, Cellular and Molecular Neuroscience, Developmental Neuroscience, mental disorders, Humans, Cognitive Dysfunction, ddc:610, DEPOSITION, OLDER-ADULTS, genetics [Apolipoprotein E4], POPULATION, RISK, neurology, Health Policy, DEMENTIA, genetics [Cognitive Dysfunction], Brain, amyloid, Amyloidosis, Alzheimer's disease, PREVALENCE, COMMUNITY, Psychiatry and Mental health, metabolism [Brain], Positron-Emission Tomography, Neurology (clinical), Human medicine, psychology [Cognitive Dysfunction], Geriatrics and Gerontology, subjective cognitive decline, MEMORY COMPLAINTS, Biomarkers
Abstract

Introduction The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) epsilon 4 carriership, and neuropsychiatric symptoms with amyloid positivity. Results Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE epsilon 4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. Discussion Next to age, setting, and APOE epsilon 4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.

Published
2022

48. Anxiety and cognitive functioning in the Maastricht study: A cross-sectional population study

Author

Gulpers, Bernice J. A., Verhey, Frans R. J., Eussen, Simone J. P. M., Schram, M.T., Galan, B.E. de, Boxtel, Martin P. J. van, Stehouwer, Coen D. A., Kohler, S., RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, RS: CAPHRI - R5 - Optimising Patient Care, Epidemiologie, MUMC+: HVC Pieken Maastricht Studie (9), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Interne Geneeskunde, Psychology 2, Section Neuropsychology, RS: FPN NPPP I, MUMC+: MA Interne Geneeskunde (3), and Psychology 5

Subjects
Psychiatry and Mental health, Clinical Psychology, All institutes and research themes of the Radboud University Medical Center, Cross-Sectional Studies, Cognition, Diabetes Mellitus, Type 2, Humans, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Anxiety, Anxiety Disorders, Aged
Abstract

BACKGROUND: Higher anxiety levels in older adults are associated with worse executive functioning and an increased risk for dementia. In this study individual anxiety disorders and clinically relevant generalized anxiety symptoms are studied in relation to multiple cognitive domains.METHOD: This cross-sectional study includes 7344 community-dwelling participants of The Maastricht Study aged 40-75 years and oversampling of type 2 diabetes. Panic disorder with and without agoraphobia, agoraphobia and lifetime panic disorder were measured with the Mini International Neuropsychiatric Interview. Generalized anxiety symptoms were measured with the Generalized Anxiety Disorder 7-item scale (GAD-7). Multiple cognitive domains (executive functioning, memory and processing speed) and cognitive impairment were assessed. Multivariable linear and logistic regression analyses were used with adjustment for potential confounders. Interaction analyses were performed to test the moderation of age, sex and type 2 diabetes (due to oversampling).RESULTS: Agoraphobia was associated with worse scores on all cognitive domains (range B = -0.12 to -0.10; range 95%CI = -0.20 to -0.04) and with higher odds of cognitive impairment (OR = 1.51, 95%CI = 1.18-1.93). High scores on the GAD-7 were associated with worse scores on processing speed (B = -0.11, 95%CI = -0.20 to -0.03) and higher odds of cognitive impairment (OR = 1.42, 95%CI = 1.02-1.97). Panic disorder was significantly associated with worse scores on memory tasks (B = -0.25, 95%CI = -0.48 to -0.02). Associations were stronger in the younger participants and for agoraphobia and GAD-7 scores also in those with type 2 diabetes.CONCLUSION: Multiple anxiety disorders and generalized anxiety symptoms were associated with worse cognitive functioning on several cognitive domains.

Published
2021

49. The relation of depression with structural brain abnormalities and cognitive functioning: the Maastricht study.

Author

Geraets, Anouk F. J., Schram, Miranda T., Jansen, Jacobus F. A., Koster, Annemarie, Dagnelie, Pieter C., van Greevenbroek, Marleen M. J., Stehouwer, Coen D. A., Verhey, Frans R. J., and Köhler, Sebastian

Subjects
BRAIN anatomy, BRAIN, COGNITION disorders, CEREBRAL small vessel diseases, CEREBRAL hemorrhage, CROSS-sectional method, MULTIPLE regression analysis, LACUNAR stroke, MAGNETIC resonance imaging, ATROPHY, MENTAL depression, DESCRIPTIVE statistics, LOGISTIC regression analysis, ODDS ratio
Abstract

Background: Individuals with depression often experience widespread and persistent cognitive deficits, which might be due to brain atrophy and cerebral small vessel disease (CSVD). We therefore studied the associations between depression, markers of brain atrophy and CSVD, and cognitive functioning. Methods: We used cross-sectional data from the population-based Maastricht study (n = 4734; mean age 59.1 ± 8.6 years, 50.2% women), which focuses on type 2 diabetes. A current episode of major depressive disorder (MDD, n = 151) was assessed by the Mini-International Neuropsychiatric Interview. Volumes of cerebral spinal fluid, white matter, gray matter and white matter hyperintensities, presence of lacunar infarcts and cerebral microbleeds, and total CSVD burden were assessed by 3 T magnetic resonance imaging. Multiple linear and logistic regression analyses tested the associations between MDD, brain markers and cognitive functioning in memory, information processing speed, and executive functioning & attention, and presence of cognitive impairment. Structural equation modeling was used to test mediation. Results: In fully adjusted models, MDD was associated with lower scores in information processing speed [mean difference = −0.18(−0.28;−0.08)], executive functioning & attention [mean difference = −0.13(−0.25;−0.02)], and with higher odds of cognitive impairment [odds ratio (OR) = 1.60(1.06;2.40)]. MDD was associated with CSVD in participants without type 2 diabetes [OR = 1.65(1.06;2.56)], but CSVD or other markers of brain atrophy or CSVD did not mediate the association with cognitive functioning. Conclusions: MDD is associated with more impaired information processing speed and executive functioning & attention, and overall cognitive impairment. Furthermore, MDD was associated with CSVD in participants without type 2 diabetes, but this association did not explain an impaired cognitive profile. [ABSTRACT FROM AUTHOR]

Published
2022
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50. Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia: A Meta-analysis

Author

Jansen, Willemijn J., Ossenkoppele, Rik, Knol, Dirk L., Tijms, Betty M., Scheltens, Philip, Verhey, Frans R. J., Visser, Pieter Jelle, Aalten, Pauline, Aarsland, Dag, Alcolea, Daniel, Alexander, Myriam, Almdahl, Ina S., Arnold, Steven E., Baldeiras, Inês, Barthel, Henryk, van Berckel, Bart N. M., Bibeau, Kristen, Blennow, Kaj, Brooks, David J., van Buchem, Mark A., Camus, Vincent, Cavedo, Enrica, Chen, Kewei, Chetelat, Gael, Cohen, Ann D., Drzezga, Alexander, Engelborghs, Sebastiaan, Fagan, Anne M., Fladby, Tormod, Fleisher, Adam S., van der Flier, Wiesje M., Ford, Lisa, Förster, Stefan, Fortea, Juan, Foskett, Nadia, Frederiksen, Kristian S., Freund-Levi, Yvonne, Frisoni, Giovanni B., Froelich, Lutz, Gabryelewicz, Tomasz, Gill, Kiran Dip, Gkatzima, Olymbia, Gómez-Tortosa, Estrella, Gordon, Mark Forrest, Grimmer, Timo, Hampel, Harald, Hausner, Lucrezia, Hellwig, Sabine, Herukka, Sanna-Kaisa, Hildebrandt, Helmut, Ishihara, Lianna, Ivanoiu, Adrian, Jagust, William J., Johannsen, Peter, Kandimalla, Ramesh, Kapaki, Elisabeth, Klimkowicz-Mrowiec, Aleksandra, Klunk, William E., Köhler, Sebastian, Koglin, Norman, Kornhuber, Johannes, Kramberger, Milica G., Van Laere, Koen, Landau, Susan M., Lee, Dong Young, de Leon, Mony, Lisetti, Viviana, Lleó, Alberto, Madsen, Karine, Maier, Wolfgang, Marcusson, Jan, Mattsson, Niklas, de Mendonça, Alexandre, Meulenbroek, Olga, Meyer, Philipp T., Mintun, Mark A., Mok, Vincent, Molinuevo, José Luis, Møllergård, Hanne M., Morris, John C., Mroczko, Barbara, Van der Mussele, Stefan, Na, Duk L., Newberg, Andrew, Nordberg, Agneta, Nordlund, Arto, Novak, Gerald P., Paraskevas, George P., Parnetti, Lucilla, Perera, Gayan, Peters, Oliver, Popp, Julius, Prabhakar, Sudesh, Rabinovici, Gil D., Ramakers, Inez H. G. B., Rami, Lorena, Resende de Oliveira, Catarina, Rinne, Juha O., Rodrigue, Karen M., Rodríguez-Rodríguez, Eloy, Roe, Catherine M., Rot, Uros, Rowe, Christopher C., Rüther, Eckart, Sabri, Osama, Sanchez-Juan, Páscual, Santana, Isabel, Sarazin, Marie, Schröder, Johannes, Schütte, Christin, Seo, Sang W., Soetewey, Femke, Soininen, Hilkka, Spiru, Luiza, Struyfs, Hanne, Teunissen, Charlotte E., Tsolaki, Magda, Vandenberghe, Rik, Verbeek, Marcel M., Villemagne, Victor L., Vos, Stephanie J. B., van Waalwijk van Doorn, Linda J. C., Waldemar, Gunhild, Wallin, Anders, Wallin, Åsa K., Wiltfang, Jens, Wolk, David A., Zboch, Marzena, and Zetterberg, Henrik

Published
2015
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