Authors: Boada, Mercè | Santos-Santos, Miguel A. | Rodríguez-Gómez, Octavio | Alegret, Montserrat | Cañabate, Pilar | Lafuente, Asunción | Abdelnour, Carla | Buendía, Mar | de Dios, Maria José | Morera, América | Sanabria, Ángela | Campo, Laura | Ruiz, Agustín | Tárraga, Lluís
Article Type: Review Article
Abstract: Alzheimer’s disease (AD) research is at a critical time. The global society is increasingly aware of the frightening rate of growth of the human and financial burden caused by this condition and of the urgent need to halt its progression. Consequently, the scientific community holds great responsibility to quickly put in place and optimize the machinery necessary for testing new treatments or interventions. In this context demand for participants for AD research is at an all-time high. In this review, we will focus on a methodological factor that is increasingly recognized as a key factor that shapes trial populations and …affects validity of results in clinical trials: patient engagement, recruitment, and retention. We outline specific problems relevant to patient engagement in AD including recruiting enough participants, difficulties in participant retention, ensuring the recruited sample is representative of the general AD population, the burden of screening failures, and new challenges related to recruiting in preclinical disease. To address the urgent need for more research studying the applicability and cost-effectiveness of different recruitment strategies across different settings and nationalities, we describe the Models of Patient Engagement for Alzheimer’s Disease (MOPEAD) project, a public-private partnership promoted by the Innovative Medicine Initiative (IMI), which will provide a large multinational quantitative analysis comparing different innovative recruitment models. We also discuss strategies that address each problem and draw on the experience of Fundació ACE to argue that focusing resources on comprehensive AD centers that offer coordinated clinical and social care and participate in basic and clinical research, is an effective and efficient way of implementing many of the discussed strategies. Show more
Keywords: Alzheimer’s disease, clinical trials, community outreach, Fundació ACE, MOPEAD, patient engagement, recruitment, retention
DOI: 10.3233/JAD-170866
Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 1079-1090, 2018
Authors: Abdelnour, Carla | Esteban de Antonio, Ester | Pérez-Cordón, Alba | Lafuente, Asunción | Buendía, Mar | Pancho, Ana | Jofresa, Sara | Aguilera, Nuria | Ibarria, Marta | Cuevas, Rosario | Cañada, Laia | Calvet, Anna | Diego, Susana | González-Pérez, Antonio | Orellana, Adela | Montrreal, Laura | de Jorge, Laura | Marquié, Marta | Benaque, Alba | Gurruchaga, Miren | Tárraga, Lluís | Ruiz, Agustín | Boada, Mercè | For the Research Center and Memory Clinic, Fundació ACE
Collaborators: Isabel, Hernández | Montserrat, Alegret | Pilar, Cañabate | Isabel, Rodríguez | Maitee, Rosende-Roca | Juan Pablo, Tartari | Rogelio, López | Silvia, Gil | Liliana, Vargas | Ana, Mauleón | Ana, Espinosa | Gemma, Ortega | Angela, Sanabria | Emilio, Alarcón | Mariola, Moreno | Silvia, Preckler | Natalia, Roberto | Sergi, Valero | Itziar, de Rojas | Sonia, Moreno-Grau | Elvira, Martín
Article Type: Research Article
Abstract: Background: The COVID-19 pandemic has brought great disruption to health systems worldwide. This affected ongoing clinical research, particularly among those most vulnerable to the pandemic, like dementia patients. Fundació ACE is a research center and memory clinic based in Barcelona, Spain, one of the hardest-hit countries. Objective: To describe the ad-hoc strategic plan developed to cope with this crisis and to share its outcomes. Methods: We describe participants’ clinical and demographic features. Additionally, we explain our strategic plan aimed at minimizing the impact on clinical trial research activities, which included SARS-CoV-2 RT-PCR and IgG serological tests to all participants and …personnel. The outcomes of the plan are described in terms of observed safety events and drop-outs during the study period. Results: A total of 130 patients were participating in 16 active clinical trials in Fundació ACE when the lockdown was established. During the confinement, we performed 1018 calls to the participants, which led to identify adverse events in 26 and COVID-19 symptoms in 6. A total of 83 patients (64%) could restart on-site visits as early as May 11, 2020. All SARS-CoV-2 RT-PCR diagnostic tests performed before on-site visits were negative and only three IgG serological tests were positive. Throughout the study period, we only observed one drop-out, due to an adverse event unrelated to COVID-19. Discussion: The plan implemented by Fundació ACE was able to preserve safety and integrity of ongoing clinical trials. We must use the lessons learned from the pandemic and design crisis-proof protocols for clinical trials. Show more
Keywords: Alzheimer’s disease, clinical trials, coronavirus, pandemics, telemedicine
DOI: 10.3233/JAD-200750
Citation: Journal of Alzheimer's Disease, vol. 77, no. 4, pp. 1805-1813, 2020
Authors: Boada, Mercè | Anaya, Fernando | Ortiz, Pilar | Olazarán, Javier | Shua-Haim, Joshua R. | Obisesan, Thomas O. | Hernández, Isabel | Muñoz, Joan | Buendia, Mar | Alegret, Montserrat | Lafuente, Asunción | Tárraga, Lluís | Núñez, Laura | Torres, Mireia | Grifols, Joan Ramon | Ferrer, Isidre | Lopez, Oscar L. | Páez, Antonio
Article Type: Research Article
Abstract: Background: Studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid-β (Aβ) peptide between cerebrospinal fluid (CSF) and plasma compartments. Objective: To determine whether plasma exchange (PE) with albumin replacement was able to modify Aβ concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimer’s disease (AD). Methods: In a multicenter, randomized, patient- and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1 : 1) to PE treatment or control (sham) groups. Treated patients received a maximum of 18 PE with 5% albumin (Albutein® , Grifols) with …three different schedules: two PE/weekly (three weeks), one PE/weekly (six weeks), and one PE/bi- weekly (12 weeks), plus a six-month follow-up period. Plasma and CSF Aβ1–40 and Aβ1–42 levels, as well as cognitive, functional, and behavioral measures were determined. Results: CSF Aβ1–42 levels after the last PE compared to baseline were marginally higher in PE-treated group versus controls (adjusted means of variation: 75.3 versus –45.5 pg/mL; 95% CI: –19.8, 170.5 versus 135.1, 44.2; p = 0.072). Plasma Aβ1–42 levels were lower in the PE-treated group after each treatment period (p < 0.05). Plasma Aβ1–40 levels showed a saw-tooth pattern variation associated with PE. PE-treated patients scored better in the Boston Naming Test and Semantic Verbal Fluency (p < 0.05) throughout the study. Neuropsychiatric Inventory scores were higher in controls during the PE phase (p < 0.05). Conclusion: PE with human albumin modified CSF and plasma Aβ1–42 levels. Patients treated with PE showed improvement in memory and language functions, which persisted after PE was discontinued. Show more
Keywords: Albumin, Alzheimer’s disease, CSF Aβ, plasma Aβ, plasma exchange
DOI: 10.3233/JAD-160565
Citation: Journal of Alzheimer's Disease, vol. 56, no. 1, pp. 129-143, 2017
Authors: Espinosa, Ana | Alegret, Montserrat | Pesini, Pedro | Valero, Sergi | Lafuente, Asunción | Buendía, Mar | San José, Itziar | Ibarria, Marta | Tejero, Miguel A. | Giménez, Joan | Ruiz, Susana | Hernández, Isabel | Pujadas, Francesc | Martínez-Lage, Pablo | Munuera, Josep | Arbizu, Javier | Tárraga, Lluis | Hendrix, Suzanne B. | Ruiz, Agustín | Becker, James T. | Landau, Susan M. | Sotolongo-Grau, Oscar | Sarasa, Manuel | Boada, Mercè | for the AB255 Study Group | for the Alzheimer’s Disease Neuroimaging Initiative
Article Type: Research Article
Abstract: The probable-amnestic (Pr-a) mild cognitive impairment (MCI)-storage subtype is a phenotype with 8.5 times more risk of conversion to dementia, mainly Alzheimer’s disease (AD), than the possible non-amnestic (Pss-na) MCI. The aim of this study was to find the optimized cognitive composites (CCs) domain scores most related to neuroimaging biomarkers within Pr-aMCI-storage subtype patients. The Fundació ACE (ACE) study with 20 Pr-aMCI-storage subtype subjects (MCI) were analyzed. All subjects underwent a neuropsychological assessment, a structural MRI, FDG-PET, and PIB-PET. The adjusted hippocampal volume (aHV) on MRI, the standard uptake value ratio (SUVR) on FDG-PET and PIB-PET SUVR measures were analyzed. …The construction of the CCs domain scores, and the aHV on MRI and FDG-PET SUVR measures, were replicated in the parental AB255 study database (n = 133 MCI). Partial correlations adjusted by age, gender, and education were calculated with the associated p -value among every CC domain score and the neuroimaging biomarkers. The results were replicated in the “MCI due to AD” with memory storage impairments from ADNI. Delayed Recall CC domain score was significantly correlated with PIB-PET SUVR (β= –0.61, p = 0.003) in the ACE study and also with aHV on MRI (β= 0.27, p = 0.01) and FDG-PET SUVR (β= 0.27, p = 0.01) in the AB255 study. After a median survival time of 20.6 months, 85% from the ACE MCI converted to AD. The replication of our results in the ADNI dataset also confirmed our findings. Delayed Recall is the CC domain score best correlated with neuroimaging biomarkers associated with prodromal AD diagnosis. Show more
Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, amyloid, cognition, hippocampus, magnetic resonance imaging, memory, positron emission tomography
DOI: 10.3233/JAD-161223
Citation: Journal of Alzheimer's Disease, vol. 57, no. 2, pp. 447-459, 2017
