Neuropsychiatric Symptoms in AD: Clinical Trials Targeting Mild Behavioral Impairment: A Report from the International CTAD Task Force - 21/11/24

Doi : 10.14283/jpad.2023.125 
Maria Soto 1, 2, , P. Rosenberg 3, 8, C. Ballard 4, B. Vellas 1, 2, D. Miller 5, S. Gauthier 6, M.C. Carrillo 7, C. Lyketsos 3, 8, Z. Ismail 4, 9, Susan Abushakra 10, Mohammad Afshar 11, Sam Agus 12, Paul Aiden 13, John Alam 14, Alicia Algeciras-Schimnich 15, Sandrine Andrieu 16, Amos Baruch 17, Randall Bateman 18, Richard Batrla 19, Monika Baudler 20, Joanne Bell 19, Tobias Bittner 20, Sasha Bozeat 20, Joel Braunstein 18, Dawn Brooks 21, Tricia Brooks 19, Szofia Bullain 20, Jan Burmeister 22, Maria Carrillo 23, Min Cho 19, Emily Collins 21, Gavin Cook 19, Chris Dague 24, Susan De Santi 19, Rachelle Doody 20, Billy Dunn 25, Michael Egan 26, Sven Eriksson 27, Rianne Esquivel 24, Tom Fagan 19, Phyllis Ferrell 21, Howard Fillit 28, Michela Gallagher 29, Anna-Kaija Grönblad 27, Avis Hains 17, Harald Hampel 19, Oskar Hansson 30, Nanco Hefting 31, Suzanne Hendrix 32, Carole Ho 33, Helen Hu 19, Daryl Jones 19, Gene Kinney 17, Paul Kinnon 12, Ricky Kurzman 19, Lars Lannfelt 34, John Lawson 24, Nathalie LeBastard 24, Valérie Legrand 35, Nicole Lewandowski 19, Carine Lim 36, Donna Masterman 17, Colin Masters 37, Ming Lu 21, Mark Mintun 21, José Luis Molinuevo 31, Cecilia Monteiro 33, Bradford Navia 38, Tomas Odergren 27, Gunilla Osswald 27, Lewis Penny 39, Michael Pontecorvo 21, Anton Porsteinsson 15, Christine Rabe 33, Rema Raman 13, Gesine Respondek 20, Larisa Reyderman 19, Sharon Rogers 22, Paul Rosenberg 29, Sharon Rosenzweig-Lipson 29, Mark Roskey 40, Rubel Carrie 38, Ziad Saad 41, Stephen Salloway 42, Rachel Schindler 43, Dennis Selkoe 14, Melanie Shulman 38, John Sims 21, Kaycee Sink 33, Lisa Sipe 13, Daniel Skovronsky 21, Elizabeth Somers 19, Johannes Streffer 44, Pedro Such 31, Joyce Suhy 45, Masoud Toloue 46, Jacques Touchon 47, Manu Vandijck 24, Michael Weiner 17, Anne White 21, David Wilson 40, Wagner Zago 17, Jin Zhou 19

International CTAD Task Force members

EU/US CTAD Task force

1 AGING team, axe MAINTAIN CERPOP, UMR 1295, Toulouse, France 
2 Research and Clinical Alzheimer’s Disease Center, CMRR Gérontopôle, CHU Toulouse, HealthAge IHU, Toulouse, France 
3 Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, USA 
4 School of Medicine and Health, University of Exeter, Exeter, UK 
5 Signant Health, Blue Bell, PA, USA 
6 McGill University, Montreal, Canada 
7 Alzheimer’s Association, Chicago, USA 
8 Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Baltimore, USA 
9 Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences, Hotchkiss Brain Institute and O’Brien Institute for Public Health, University of Calgary, Calgary, Canada 
10 Framingham, USA 
11 Paris, France 
12 Solana Beach, USA 
13 San Diego, USA 
14 Boston, USA 
15 Rochester, USA 
16 Toulouse, France 
17 San Francisco, USA 
18 Saint Louis, USA 
19 Nutley, USA 
20 Basel, Switzerland 
21 Indianapolis, USA 
22 Los Angeles, USA 
23 Chicago, USA 
24 Malvern, USA 
25 Beltsville, USA 
26 North Wales, USA 
27 Stockholm, Sweden 
28 New york, USA 
29 Baltimore, USA 
30 Malmö, Sweden 
31 Valby, Denmark 
32 Salt Lake City, USA 
33 South San Francisco, USA 
34 Uppsala, Sweden 
35 Nanterre, France 
36 Singapore, Singapore 
37 Parkville, Australia 
38 Cambridge, England 
39 Aberdeen, Scotland 
40 Burlington, USA 
41 Titusville, USA 
42 Providence, USA 
43 New York, USA 
44 Lausane, Switzerland 
45 San Mateo, USA 
46 Billerica, USA 
47 Montpellier, France 

a soto-martin.me@chu-toulouse.fr soto-martin.me@chu-toulouse.fr

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Abstract

The International CTAD Task Force (TF) addressed challenges related to designing clinical trials for agitation in dementia, presenting accomplishments from the two previous TFs on neuropsychiatric symptoms (NPS). In addition, this TF proposed a paradigm shift in NPS assessment and management, presenting Mild Behavioral Impairment (MBI) as a clinical syndrome. MBI is marked by later-life emergent and persistent NPS in dementia-free older persons (ranging from cognitively unimpaired to subjective cognitive decline to mild cognitive impairment), which facilitates earlier detection and better prognostication of Alzheimer’s disease (AD). The TF has made the following recommendations for incorporation of NPS into AD preventative trials: (1) clinical trials targeting improvement in MBI symptoms should be undertaken; (2) treatment trials for MBI should be disease specific and confirm the diagnosis of participants using biomarkers; trials should include measures sensitive to cognitive changes in preclinical AD, which can serve as outcome measures, in addition to changes in biomarker levels; (3) as a first step, pharmacotherapeutic trials should address the full MBI complex as well as the specific symptoms/domains that constitute MBI; (4) clinical trials using problemadaptation psychotherapy to target affective MBI should be considered; and (5) MBI should be considered in AD trials of disease modifying therapies. The well-validated and widely-used MBI Checklist (MBI-C) is an appropriate symptom rating scale for these studies, as it was developed specifically to identify and measure MBI in dementia-free persons. Other scales such as the Neuropsychiatric Inventory (NPI) may be used, although administration at two timepoints may be necessary to operationalize the MBI criterion of symptom persistence.

Il testo completo di questo articolo è disponibile in PDF.

Key words : Neuropsychiatric symptoms, agitation, dementia, Alzheimer’s disease, clinical trials, mild behavioral impairment


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