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2. Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial

Author

Mummery, Catherine J., Börjesson-Hanson, Anne, Blackburn, Daniel J., Vijverberg, Everard G. B., De Deyn, Peter Paul, Ducharme, Simon, Jonsson, Michael, Schneider, Anja, Rinne, Juha O., Ludolph, Albert C., Bodenschatz, Ralf, Kordasiewicz, Holly, Swayze, Eric E., Fitzsimmons, Bethany, Mignon, Laurence, Moore, Katrina M., Yun, Chris, Baumann, Tiffany, Li, Dan, Norris, Daniel A., Crean, Rebecca, Graham, Danielle L., Huang, Ellen, Ratti, Elena, Bennett, C. Frank, Junge, Candice, and Lane, Roger M.

Published
2023
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3. A phase 1b randomized clinical trial of CT1812 to measure Aβ oligomer displacement in Alzheimer’s disease using an indwelling CSF catheter

Author

LaBarbera, Kelsie M., Sheline, Yvette I., Izzo, Nicholas J., Yuede, Carla M., Waybright, Lora, Yurko, Raymond, Edwards, Hannah M., Gardiner, Woodrow D., Blennow, Kaj, Zetterberg, Henrik, Börjesson-Hanson, Anne, Morgan, Roger, Davis, Charles S., Guttendorf, Robert J., Schneider, Lon S., DeKosky, Steven, LeVine, III, Harry, Grundman, Michael, Caggiano, Anthony O., Cirrito, John R., Catalano, Susan M., and Hamby, Mary E.

Published
2023
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4. Author Correction: Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial

Author

Mummery, Catherine J., Börjesson-Hanson, Anne, Blackburn, Daniel J., Vijverberg, Everard G. B., De Deyn, Peter Paul, Ducharme, Simon, Jonsson, Michael, Schneider, Anja, Rinne, Juha O., Ludolph, Albert C., Bodenschatz, Ralf, Kordasiewicz, Holly, Swayze, Eric E., Fitzsimmons, Bethany, Mignon, Laurence, Moore, Katrina M., Yun, Chris, Baumann, Tiffany, Li, Dan, Norris, Daniel A., Crean, Rebecca, Graham, Danielle L., Huang, Ellen, Ratti, Elena, Bennett, C. Frank, Junge, Candice, and Lane, Roger M.

Published
2024
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5. Disease Severity Staging System for NOTCH3-Associated Small Vessel Disease, Including CADASIL

Author

Gravesteijn, Gido, Rutten, Julie W., Cerfontaine, Minne N., Hack, Remco J., Liao, Yi-Chu, Jolly, Amy A., Guey, Stéphanie, Hsu, Shao-Lun, Park, Jae-young, Yuan, Yun, Kopczak, Anna, Rifino, Nicola, Neilson, Sam J., Poggesi, Anna, Shourav, Md Manjurul Islam, Saito, Satoshi, Ishiyama, Hiroyuki, Domínguez Mayoral, Ana, Nogueira, Renata, Muiño, Elena, Andersen, Pia, De Stefano, Nicola, Santo, Gustavo, Sukhonpanich, Nontapat, Mele, Francesco, Park, Ashley, Lee, Jung Seok, Rodríguez-Girondo, Mar, Vonk, Sebastiaan J. J., Brodtmann, Amy, Börjesson-Hanson, Anne, Pantoni, Leonardo, Fernández-Cadenas, Israel, Silva, Ana Rita, Montanaro, Vinícus V. A., Kalaria, Rajesh N., Lopergolo, Diego, Ihara, Masafumi, Meschia, James F., Muir, Keith W., Bersano, Anna, Pescini, Francesca, Duering, Marco, Choi, Jay Chol, Ling, Chen, Kim, Hyunjin, Markus, Hugh S., Chabriat, Hugues, Lee, Yi-Chung, and Lesnik Oberstein, Saskia A. J.

Abstract

IMPORTANCE: Typical cysteine-altering NOTCH3 (NOTCH3cys) variants are highly prevalent (approximately 1 in 300 individuals) and are associated with a broad spectrum of small vessel disease (SVD), ranging from early-onset stroke and dementia (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]) to nonpenetrance. A staging system that captures the full NOTCH3-SVD severity spectrum is needed and currently lacking. OBJECTIVE: To design a simple disease severity staging system that captures the broad clinicoradiological NOTCH3-SVD severity spectrum. DESIGN, SETTING, AND PARTICIPANTS: A cohort study was performed in which the NOTCH3-SVD severity staging system was developed using a discovery cohort (2019-2020) and validated in independent international CADASIL cohorts (1999-2023) and the UK Biobank. Clinical and imaging data were collected from participants originating from 23 international CADASIL cohorts and from the UK Biobank. Eligibility criteria were presence of a NOTCH3cys variant, availability of brain magnetic resonance imaging, and modified Rankin Scale score. The discovery cohort consisted of 195 NOTCH3cys-positive cases from families with CADASIL; the validation set included 1713 NOTCH3cys-positive cases from 15 countries. The UK Biobank cohort consisted of 101 NOTCH3cys-positive individuals. Data from 2-year (2019-2023) and 18-year (1999-2017) follow-up studies were also analyzed. Data analysis was performed from July 2023 to August 2024. MAIN OUTCOMES AND MEASURES: Percentage of cases following the sequence of events of the NOTCH3-SVD stages, and the association between the stages and ischemic stroke, intracerebral hemorrhage, global cognition, processing speed, brain volume, brain microstructural damage, and serum neurofilament light chain (NfL) level. RESULTS: The NOTCH3-SVD staging system encompasses 9 disease stages or substages, ranging from stage 0 (premanifest stage) to stage 4B (end stage). Of all 1908 cases, which included 195 in the discovery cohort (mean [SD] age, 52.4 [12.2] years) and 1713 in the validation cohorts (mean [SD] age, 53.1 [13.0] years), 1789 (94%) followed the sequence of events defined by the NOTCH3-SVD staging system. The NOTCH3-SVD stages were associated with neuroimaging outcomes in the NOTCH3cys-positive cases in the CADASIL cohorts and in the UK Biobank and with cognitive outcomes and serum NfL level in cases from the CADASIL cohorts. The NOTCH3-SVD staging system captured disease progression and was associated with 18-year survival. CONCLUSIONS AND RELEVANCE: The NOTCH3-SVD staging system captures the full disease spectrum, from asymptomatic individuals with a NOTCH3cys variant to patients with end-stage disease. The NOTCH3-SVD staging system is a simple but effective tool for uniform disease staging in the clinic and in research.

Published
2025
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6. Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD

Author

Lawlor, Brian, Segurado, Ricardo, Kennelly, Sean, Olde Rikkert, Marcel G.M., Howard, Robert, Pasquier, Florence, Börjesson-Hanson, Anne, Tsolaki, Magda, Lucca, Ugo, Molloy, D. William, Coen, Robert, Riepe, Matthias W., Kálmán, János, Kenny, Rose Anne, Cregg, Fiona, O'Dwyer, Sarah, Walsh, Cathal, Adams, Jessica, Banzi, Rita, Breuilh, Laetitia, Daly, Leslie, Hendrix, Suzanne, Aisen, Paul, Gaynor, Siobhan, Sheikhi, Ali, Taekema, Diana G., Verhey, Frans R., Nemni, Raffaello, Nobili, Flavio, Franceschi, Massimo, Frisoni, Giovanni, Zanetti, Orazio, Konsta, Anastasia, Anastasios, Orologas, Nenopoulou, Styliani, Tsolaki-Tagaraki, Fani, Pakaski, Magdolna, Dereeper, Olivier, Sayette, Vincent de la, Sénéchal, Olivier, Lavenu, Isabelle, Devendeville, Agnès, Calais, Gauthier, Crawford, Fiona, Mullan, Michael, Aalten, Pauline, Berglund, Maria A., Claassen, Jurgen A., De Heus, Rianne A., De Jong, Daan L.K., Godefroy, Olivier, Hutchinson, Siobhan, Ioannou, Aikaterini, Jonsson, Michael, Kent, Annette, Kern, Jürgen, Nemtsas, Petros, Panidou, Minoa-Kalliopi, Abdullah, Laila, Paris, Daniel, Santoso, Angelina M., van Spijker, Gerrita J., Spiliotou, Martha, Thomoglou, Georgia, Wallin, Anders, Dyer, Adam H., Murphy, Claire, and Kennelly, Sean P.

Published
2020
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8. Author Correction: Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial

Author

Mummery, Catherine J., primary, Börjesson-Hanson, Anne, additional, Blackburn, Daniel J., additional, Vijverberg, Everard G. B., additional, De Deyn, Peter Paul, additional, Ducharme, Simon, additional, Jonsson, Michael, additional, Schneider, Anja, additional, Rinne, Juha O., additional, Ludolph, Albert C., additional, Bodenschatz, Ralf, additional, Kordasiewicz, Holly, additional, Swayze, Eric E., additional, Fitzsimmons, Bethany, additional, Mignon, Laurence, additional, Moore, Katrina M., additional, Yun, Chris, additional, Baumann, Tiffany, additional, Li, Dan, additional, Norris, Daniel A., additional, Crean, Rebecca, additional, Graham, Danielle L., additional, Huang, Ellen, additional, Ratti, Elena, additional, Bennett, C. Frank, additional, Junge, Candice, additional, and Lane, Roger M., additional

Published
2023
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12. Additional file 1 of A phase 1b randomized clinical trial of CT1812 to measure Aβ oligomer displacement in Alzheimer’s disease using an indwelling CSF catheter

Author

LaBarbera, Kelsie M., Sheline, Yvette I., Izzo, Nicholas J., Yuede, Carla M., Waybright, Lora, Yurko, Raymond, Edwards, Hannah M., Gardiner, Woodrow D., Blennow, Kaj, Zetterberg, Henrik, Börjesson-Hanson, Anne, Morgan, Roger, Davis, Charles S., Guttendorf, Robert J., Schneider, Lon S., DeKosky, Steven, LeVine, Harry, Grundman, Michael, Caggiano, Anthony O., Cirrito, John R., Catalano, Susan M., and Hamby, Mary E.

Abstract

Additional file 1. Methods. Table S1: CT1812 pharmacokinetic parameters in plasma and CSF of two AD patients after a single 560-mg oral dose.

Published
2023
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13. Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer’s disease: randomized, double-blind, placebo-controlled study

Author

Timmers, Maarten, Streffer, Johannes Rolf, Russu, Alberto, Tominaga, Yushin, Shimizu, Hiroko, Shiraishi, Ayako, Tatikola, Kanaka, Smekens, Pascale, Börjesson-Hanson, Anne, Andreasen, Niels, Matias-Guiu, Jorge, Baquero, Miquel, Boada, Mercè, Tesseur, Ina, Tritsmans, Luc, Van Nueten, Luc, and Engelborghs, Sebastiaan

Published
2018
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17. Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial

Author

Lawlor, Brian, Segurado, Ricardo, Kennelly, Sean, Olde Rikkert, Marcel G. M., Howard, Robert, Pasquier, Florence, Börjesson-Hanson, Anne, Tsolaki, Magda, Lucca, Ugo, Molloy, D. William, Coen, Robert, Riepe, Matthias W., Kálmán, János, Kenny, Rose Anne, Cregg, Fiona, O'Dwyer, Sarah, Walsh, Cathal, Adams, Jessica, Banzi, Rita, Breuilh, Laetitia, Daly, Leslie, Hendrix, Suzanne, Aisen, Paul, Gaynor, Siobhan, Sheikhi, Ali, Taekema, Diana G., Verhey, Frans R., Nemni, Raffaello, Nobili, Flavio, Franceschi, Massimo, Frisoni, Giovanni, Zanetti, Orazio, Konsta, Anastasia, Anastasios, Orologas, Nenopoulou, Styliani, Tsolaki-Tagaraki, Fani, Pakaski, Magdolna, Dereeper, Olivier, de la Sayette, Vincent, Sénéchal, Olivier, Lavenu, Isabelle, Devendeville, Agnès, Calais, Gauthier, Crawford, Fiona, and Mullan, Michael

Subjects
Care and treatment, Analysis, Research, Clinical trials -- Analysis, Anti-inflammatory agents -- Research, Hypertension -- Care and treatment, Treatment outcome -- Analysis, Alzheimer's disease -- Care and treatment
Abstract

Author(s): Brian Lawlor 1,2,*, Ricardo Segurado 3,4, Sean Kennelly 5,6, Marcel G. M. Olde Rikkert 7, Robert Howard 8, Florence Pasquier 9, Anne Börjesson-Hanson 10, Magda Tsolaki 11, Ugo Lucca [...], Background This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. Methods and findings NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged >50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of [greater than or equal to]12 and Conclusions The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease. Trial registration Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27.

Published
2018
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18. The Gothenburg MCI study: Design and distribution of Alzheimer’s disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up

Author

Wallin, Anders, Nordlund, Arto, Jonsson, Michael, Lind, Karin, Edman, Åke, Göthlin, Mattias, Stålhammar, Jacob, Eckerström, Marie, Kern, Silke, Börjesson-Hanson, Anne, Carlsson, Mårten, Olsson, Erik, Zetterberg, Henrik, Blennow, Kaj, Svensson, Johan, Öhrfelt, Annika, Bjerke, Maria, Rolstad, Sindre, and Eckerström, Carl

Published
2016
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24. Tau-targeting antisense oligonucleotide MAPTRxin mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial

Author

Mummery, Catherine J., Börjesson-Hanson, Anne, Blackburn, Daniel J., Vijverberg, Everard G. B., De Deyn, Peter Paul, Ducharme, Simon, Jonsson, Michael, Schneider, Anja, Rinne, Juha O., Ludolph, Albert C., Bodenschatz, Ralf, Kordasiewicz, Holly, Swayze, Eric E., Fitzsimmons, Bethany, Mignon, Laurence, Moore, Katrina M., Yun, Chris, Baumann, Tiffany, Li, Dan, Norris, Daniel A., Crean, Rebecca, Graham, Danielle L., Huang, Ellen, Ratti, Elena, Bennett, C. Frank, Junge, Candice, and Lane, Roger M.

Abstract

Tau plays a key role in Alzheimer’s disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPTexpression with a tau-targeting antisense oligonucleotide (MAPTRx) and reduce tau levels in patients with mild AD. A randomized, double-blind, placebo-controlled, multiple-ascending dose phase 1b trial evaluated the safety, pharmacokinetics and target engagement of MAPTRx. Four ascending dose cohorts were enrolled sequentially and randomized 3:1 to intrathecal bolus administrations of MAPTRxor placebo every 4 or 12 weeks during the 13-week treatment period, followed by a 23 week post-treatment period. The primary endpoint was safety. The secondary endpoint was MAPTRxpharmacokinetics in cerebrospinal fluid (CSF). The prespecified key exploratory outcome was CSF total-tau protein concentration. Forty-six patients enrolled in the trial, of whom 34 were randomized to MAPTRxand 12 to placebo. Adverse events were reported in 94% of MAPTRx-treated patients and 75% of placebo-treated patients; all were mild or moderate. No serious adverse events were reported in MAPTRx-treated patients. Dose-dependent reduction in the CSF total-tau concentration was observed with greater than 50% mean reduction from baseline at 24 weeks post-last dose in the 60 mg (four doses) and 115 mg (two doses) MAPTRxgroups. Clinicaltrials.gov registration number: NCT03186989.

Published
2023
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27. Potentially inappropriate medication use in older adults with mild-moderate Alzheimer's disease: Prevalence and associations with adverse events

Author

Murphy, Claire, Dyer, Adam H., Lawlor, Brian, Kennelly, Sean P., Olde Rikkert, Marcel G.M., Segurado, Ricardo, Howard, Robert, Tsolaki, Magda, Börjesson-Hanson, Anne, Pasquier, Florence, Lucc, Ugo, Kálmán, János, William Molloy, D., Riepe, Matthias W., Coen, Robert, Pakaski, Magdolna, Kenny, Rose Anne, Cregg, Fiona, O'Dwyer, Sarah, Walsh, Cathal, Sheikhi, Ali, Adams, Jessica, Breuilh, Laetitia, Daly, Leslie, Hendrix, Suzanne, Aisen, Paul, Gaynor, Siobhan, Taekema, Diana G., Verhey, Frans R., Nemni, Raffaello, Nobili, Flavio, Franceschi, Massimo, Frisoni, Giovanni, Zanetti, Orazio, Konsta, Anastasia, Anastasios, Orologas, Nenopoulou, Styliani, Tsolaki-Tagaraki, Fani, Dereeper, Olivier, De La Sayette, Vincent, Sénéchal, Olivier, Lavenu, Isabelle, Devendeville, Agnès, Calais, Gauthier, Crawford, Fiona, Mullan, Michael, Aalten, Pauline, Berglund, Maria A., NILVAD Study Group, Murphy, Claire, Dyer, Adam H., Lawlor, Brian, Kennelly, Sean P., Olde Rikkert, Marcel G.M., Segurado, Ricardo, Howard, Robert, Tsolaki, Magda, Börjesson-Hanson, Anne, Pasquier, Florence, Lucc, Ugo, Kálmán, János, William Molloy, D., Riepe, Matthias W., Coen, Robert, Pakaski, Magdolna, Kenny, Rose Anne, Cregg, Fiona, O'Dwyer, Sarah, Walsh, Cathal, Sheikhi, Ali, Adams, Jessica, Breuilh, Laetitia, Daly, Leslie, Hendrix, Suzanne, Aisen, Paul, Gaynor, Siobhan, Taekema, Diana G., Verhey, Frans R., Nemni, Raffaello, Nobili, Flavio, Franceschi, Massimo, Frisoni, Giovanni, Zanetti, Orazio, Konsta, Anastasia, Anastasios, Orologas, Nenopoulou, Styliani, Tsolaki-Tagaraki, Fani, Dereeper, Olivier, De La Sayette, Vincent, Sénéchal, Olivier, Lavenu, Isabelle, Devendeville, Agnès, Calais, Gauthier, Crawford, Fiona, Mullan, Michael, Aalten, Pauline, Berglund, Maria A., and NILVAD Study Group

Abstract

Aim: Potentially inappropriate medication (PIM) use is prevalent in older adults and is associated with adverse events, hospitalisation and mortality. We assessed the patterns and associations of PIM use in older adults with mild-to-moderate Alzheimer's Disease (AD), who may represent a particularly vulnerable group. Design: Analysis of data from NILVad, an 18-month Randomised Control Trial of Nilvadapine in mild-to-moderate AD. The v2 STOPP criteria were applied in duplicate to identify PIM use. Associations between PIM use and adverse events/unscheduled healthcare visits in addition to the associations between PIM use and AD progression were evaluated. Setting and Participants: 448 older adults with mild-to-moderate AD from 23 centres in nine European countries. Results: Of 448 participants (mean age: 72.56 ± 8.19 years), over half (55.8%) were prescribed a PIM with 30.1% being prescribed 2+ PIMs. The most frequent PIMs were (i) long-term benzodiazepines (11.6% N = 52/448), (ii) selective serotonin reuptake inhibitors without appropriate indication (11.1% N = 50/448), and (iii) Proton-Pump Inhibitors (PPIs) without appropriate indication (10.7% N = 48/448). Increasing number of PIMs was associated with a greater risk of adverse events (IRR 1.17, 1.13-1.19, P < 0.001), serious adverse events (IRR 1.27; 1.17-1.37, P < 0.001), unscheduled hospitalisations (IRR 1.16, 1.03-1.30, P = 0.016) and GP visits (IRR 1.22, 1.15-1.28, P < 0.001). PIM use was not associated with dementia progression. Conclusions and Implications: PIM use is highly prevalent in mild-to-moderate AD and is associated with adverse events and unscheduled healthcare utilisation. Further attention to de-prescribing in this vulnerable group is warranted.

Published
2020

28. The Influence of Baseline Alzheimer's Disease Severity on Cognitive Decline and CSF Biomarkers in the NILVAD Trial

Author

Abdullah, Laila, primary, Crawford, Fiona, additional, Tsolaki, Magda, additional, Börjesson-Hanson, Anne, additional, Olde Rikkert, Marcel, additional, Pasquier, Florence, additional, Wallin, Anders, additional, Kennelly, Sean, additional, Ait-Ghezala, Ghania, additional, Paris, Daniel, additional, Hendrix, Suzanne, additional, Blennow, Kaj, additional, Lawlor, Brian, additional, and Mullan, Michael, additional

Published
2020
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29. Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD

Author

Dyer, Adam H., primary, Murphy, Claire, additional, Lawlor, Brian, additional, Kennelly, Sean P., additional, Segurado, Ricardo, additional, Kennelly, Sean, additional, Olde Rikkert, Marcel G.M., additional, Howard, Robert, additional, Pasquier, Florence, additional, Börjesson-Hanson, Anne, additional, Tsolaki, Magda, additional, Lucca, Ugo, additional, Molloy, D. William, additional, Coen, Robert, additional, Riepe, Matthias W., additional, Kálmán, János, additional, Kenny, Rose Anne, additional, Cregg, Fiona, additional, O'Dwyer, Sarah, additional, Walsh, Cathal, additional, Adams, Jessica, additional, Banzi, Rita, additional, Breuilh, Laetitia, additional, Daly, Leslie, additional, Hendrix, Suzanne, additional, Aisen, Paul, additional, Gaynor, Siobhan, additional, Sheikhi, Ali, additional, Taekema, Diana G., additional, Verhey, Frans R., additional, Nemni, Raffaello, additional, Nobili, Flavio, additional, Franceschi, Massimo, additional, Frisoni, Giovanni, additional, Zanetti, Orazio, additional, Konsta, Anastasia, additional, Anastasios, Orologas, additional, Nenopoulou, Styliani, additional, Tsolaki-Tagaraki, Fani, additional, Pakaski, Magdolna, additional, Dereeper, Olivier, additional, Sayette, Vincent de la, additional, Sénéchal, Olivier, additional, Lavenu, Isabelle, additional, Devendeville, Agnès, additional, Calais, Gauthier, additional, Crawford, Fiona, additional, Mullan, Michael, additional, Aalten, Pauline, additional, Berglund, Maria A., additional, Claassen, Jurgen A., additional, De Heus, Rianne A., additional, De Jong, Daan L.K., additional, Godefroy, Olivier, additional, Hutchinson, Siobhan, additional, Ioannou, Aikaterini, additional, Jonsson, Michael, additional, Kent, Annette, additional, Kern, Jürgen, additional, Nemtsas, Petros, additional, Panidou, Minoa-Kalliopi, additional, Abdullah, Laila, additional, Paris, Daniel, additional, Santoso, Angelina M., additional, van Spijker, Gerrita J., additional, Spiliotou, Martha, additional, Thomoglou, Georgia, additional, and Wallin, Anders, additional

Published
2020
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30. Additional file 2: of Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer’s disease: randomized, double-blind, placebo-controlled study

Author

Timmers, Maarten, Streffer, Johannes, Russu, Alberto, Yushin Tominaga, Shimizu, Hiroko, Shiraishi, Ayako, Kanaka Tatikola, Smekens, Pascale, Börjesson-Hanson, Anne, Andreasen, Niels, Matias-Guiu, Jorge, Baquero, Miquel, Boada, Mercè, Tesseur, Ina, Tritsmans, Luc, Nueten, Luc Van, and Engelborghs, Sebastiaan

Abstract

Supplementary information on the methods. (DOCX 43 kb)

Published
2018
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31. Sedative Load in Community-Dwelling Older Adults with Mild–Moderate Alzheimer's Disease: Longitudinal Relationships with Adverse Events, Delirium and Falls.

Author

Dyer, Adam H., Murphy, Claire, Lawlor, Brian, Kennelly, Sean P., for the NILVAD StudyGroup, Segurado, Ricardo, Kennelly, Sean, Rikkert, Marcel G. M. Olde, Howard, Robert, Pasquier, Florence, Börjesson-Hanson, Anne, Tsolaki, Magda, Lucca, Ugo, Molloy, D. William, Coen, Robert, Riepe, Matthias W., Kálmán, János, Kenny, Rose Anne, Cregg, Fiona, and O'Dwyer, Sarah

Subjects
RISK of delirium, ALZHEIMER'S disease, ANTIDEPRESSANTS, ANTIPSYCHOTIC agents, CONFIDENCE intervals, DEMENTIA, DRUG utilization, DRUGS, ACCIDENTAL falls, LONGITUDINAL method, MEDICAL appointments, PHARMACEUTICAL arithmetic, POISSON distribution, SECONDARY analysis, INDEPENDENT living, DISEASE prevalence, DISEASE progression, DESCRIPTIVE statistics
Abstract

Background: Older adults are frequently prescribed medications with sedative effects, which are associated with numerous adverse consequences. However, the prevalence and longitudinal associations of sedative medication use in community-dwelling older adults with mild–moderate Alzheimer's disease (AD) has not been explored to date. Objectives: Our objective was to assess the prevalence of sedative medication use in community-dwelling older adults with mild–moderate AD and examine the longitudinal association between sedative medication use and adverse events (AEs). Methods: The association between baseline sedative load (SL) and AEs, unscheduled healthcare utilisation, delirium and falls was assessed in older adults with mild–moderate AD over 18 months using secondary analysis of NILVAD trial data (collected from 2014 to 2016). Baseline medication use was assessed, and the SL model was applied to each participant's medication individually. The SL model classifies medications into one of four categories: (1) primary sedatives, (2) medications with a sedating component or prominent side effect, (3) medications with sedation as a potential adverse reaction and (4) all other medications with no known sedative side effects. Medications in group 1 were assigned an SL score of 2, those in group 2 were assigned an SL score of 1, and those in categories 3 and 4 an SL score of 0. SL scores for each medication participants were taking were summed and the total SL calculated as an arithmetic sum of individual medications score. A total SL score ≥ 3 was classed as high. Statistical analysis was conducted using Poisson regression and mixed-effects linear regression, with adjustment for important clinical covariates. We also assessed the impact of SL on dementia progression and cognitive decline. Results: Over half (55.7% [284/510]) of those with mild–moderate AD (age 72.8 ± 8.3 years, 61.9% female) were prescribed a regular medication with sedation as a primary effect or prominent side effect, with 22.2% (113/510) having a high SL (≥ 3). The most common medications contributing to SL were antidepressants, antipsychotics, anxiolytics and hypnotics. Over 18 months, increasing baseline SL was associated with incident AEs (incidence rate ratio [IRR] 1.15; 95% confidence interval [CI] 1.11–1.19; p < 0.001), serious AEs (IRR 1.23; 95% CI 1.11–1.36; p < 0.001) and unscheduled general practitioner visits (IRR 1.23; 95% CI 1.13–1.34; p < 0.001). Further, increasing SL was associated with a greater likelihood of incident delirium (IRR 1.30; 95% CI 1.11–1.53; p < 0.001) and falls (IRR 1.20; 95% CI 1.03–1.42; p = 0.02). Associations persisted after robust covariate adjustment. SL was not associated with accelerated cognitive decline or AD progression. Conclusions: In the current study, over half of older adults with mild–moderate AD were prescribed at least one drug with a sedative effect, and a significant minority had a high SL. Increasing baseline SL was associated with a greater likelihood of incident AEs, delirium and falls, highlighting the need for optimal prescribing in this potentially vulnerable cohort. [ABSTRACT FROM AUTHOR]

Published
2020
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32. Prevalence of preclinical Alzheimer disease

Author

Kern, Silke, primary, Zetterberg, Henrik, additional, Kern, Jürgen, additional, Zettergren, Anna, additional, Waern, Margda, additional, Höglund, Kina, additional, Andreasson, Ulf, additional, Wetterberg, Hanna, additional, Börjesson-Hanson, Anne, additional, Blennow, Kaj, additional, and Skoog, Ingmar, additional

Published
2018
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35. Pharmacodynamics of the Oral BACE Inhibitor JNJ-54861911 in Early Alzheimer's Disease

Author

Streffer, J., Börjesson-Hanson, Anne, Van Broek, B., Smekens, P., Timmers, M., Tesseur, I., Tatikola, Kanaka, Russo, A., Sinha, Vivek, Salvadore, G., Aguilar, M., Frank, A., Matias-Guiu, Jorge, Boada, Merce, Baquero, M., Tristmans, L., Van Nueten, L., Andreassen, N., Engelborghs, Sebastiaan, Clinical sciences, and Neurology

Subjects
Medicine(all), Alzheimer Disease
Published
2016

39. Multi-infarct dementia of Swedish type is caused by a 3’UTR mutation of COL4A1

Author

Siitonen, Maija, primary, Börjesson-Hanson, Anne, additional, Pöyhönen, Minna, additional, Ora, Ari, additional, Pasanen, Petra, additional, Bras, Jose, additional, Kern, Silke, additional, Kern, Jürgen, additional, Andersen, Oluf, additional, Stanescu, Horia, additional, Kleta, Robert, additional, Baumann, Marc, additional, Kalaria, Rajesh, additional, Kalimo, Hannu, additional, Singleton, Andy, additional, Hardy, John, additional, Viitanen, Matti, additional, Myllykangas, Liisa, additional, and Guerreiro, Rita, additional

Published
2017
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42. O1-10-05: Pharmacodynamics of the Oral Bace Inhibitor JNJ-54861911 in Early Alzheimer's Disease

Author

Streffer, Johannes, primary, Börjesson-Hanson, Anne, additional, Van Broeck, Bianca, additional, Smekens, Pascale, additional, Timmers, Maarten, additional, Tesseur, Ina, additional, Tatikola, Kanaka, additional, Russu, Alberto, additional, Sinha, Vikash, additional, Salvadore, Giacomo, additional, Aguilar, Miguel, additional, Frank, Anna, additional, Matias-Guiu, Jorge, additional, Boada, Mercè, additional, Baquero, Miquel, additional, Tritsmans, Luc, additional, Van Nueten, Luc, additional, Andreassen, Niels, additional, and Engelborghs, Sebastiaan, additional

Published
2016
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43. P4-159: Screening and Recruitment Experience When Using Biomarker-Based Population Definition in Alzheimer’s Disease Studies

Author

Smekens, Pascale, primary, Mesens, Sofie, additional, Engelborghs, Sebastiaan, additional, Börjesson-Hanson, Anne, additional, Christoph, Laske, additional, Prins, Niels D., additional, Hugon, Jacques, additional, Andreassen, Niels, additional, Cuevas Jiméne, Ana Isabel, additional, Timmers, Maarten, additional, Tesseur, Ina, additional, Van Nueten, Luc, additional, and Streffer, Johannes, additional

Published
2016
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45. Reported cognitive and depressive symptoms in relation to history of TIA/stroke in CADASIL- patients in Sweden

Author

Andersen, Pia, Viitanen, Matti, Karlström, Helena, Kivipelto, Miia, and Börjesson-Hanson, Anne

Abstract

CADASIL is the most common monogenic small vessel disease and the most common inherited cause of stroke. The disease is caused by mutations in the NOTCH3-gene, which lead to arteriopathy in small vessels and ischemic events, i.e., transient ischemic attacks and ischemic strokes in 60-85% of the patients. Cognitive impairment is the second most frequent clinical manifestation of CADASIL and often worsens with recurrent strokes. Clinical hallmarks of CADASIL even include migraine with aura and mood disturbances. The project explores the clinical phenotype, including potential biomarkers for disease progress, and course of CADASIL in Swedish patients.

Published
2024
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46. Author Correction: Tau-targeting antisense oligonucleotide MAPTRxin mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial

Author

Mummery, Catherine J., Börjesson-Hanson, Anne, Blackburn, Daniel J., Vijverberg, Everard G. B., De Deyn, Peter Paul, Ducharme, Simon, Jonsson, Michael, Schneider, Anja, Rinne, Juha O., Ludolph, Albert C., Bodenschatz, Ralf, Kordasiewicz, Holly, Swayze, Eric E., Fitzsimmons, Bethany, Mignon, Laurence, Moore, Katrina M., Yun, Chris, Baumann, Tiffany, Li, Dan, Norris, Daniel A., Crean, Rebecca, Graham, Danielle L., Huang, Ellen, Ratti, Elena, Bennett, C. Frank, Junge, Candice, and Lane, Roger M.

Published
2024
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48. The Gothenburg MCI study: Design and distribution of Alzheimer’s disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up

Author

Wallin, Anders, primary, Nordlund, Arto, additional, Jonsson, Michael, additional, Lind, Karin, additional, Edman, Åke, additional, Göthlin, Mattias, additional, Stålhammar, Jacob, additional, Eckerström, Marie, additional, Kern, Silke, additional, Börjesson-Hanson, Anne, additional, Carlsson, Mårten, additional, Olsson, Erik, additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, Svensson, Johan, additional, Öhrfelt, Annika, additional, Bjerke, Maria, additional, Rolstad, Sindre, additional, and Eckerström, Carl, additional

Published
2015
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49. Dementia and other mental disorders among 95-year olds

Author

Börjesson-Hanson, Anne

Subjects
nonagenarians, 95-year-olds, dementia, Alzheimer’s disease, vascular dementia, depression, anxiety, psychotic, paranoid ideation, cognitive function, mortality, population attributable risk, population study, prevalence, epidemiology, oldest old, very elderly
Abstract

The aims of this study were to estimate the prevalence of mental disorders and age related differences in the very elderly. In addition, five-year mortality after age 95 in relation to dementia and cognitive function in non-demented, was examined. A population sample of 338 95-year olds (response rate 65%) living in Gothenburg, Sweden, was compared with 85- (N=494) and 75-year olds (N=303) from the same birth cohort. All participants were examined by psychiatrists. The assessments included the Comprehensive Psychopathological Rating Scale, cognitive tests, the Mini Mental State Examination (MMSE), medical history, physical examination and a telephone interview with a key informant. Dementia, depression, anxiety and psychosis were classified according to DSM-III-R criteria, Alzheimer’s disease according to NINCDS-ADRDA criteria and vascular dementia (VaD) according to NINDS-AIREN criteria. Two-thirds (66%) of the 95-year olds fulfilled criteria for a mental disorder. Dementia was more common (52% vs. 30%; p

Published
2008

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