03/2020 journal articles
NEXT-GENERATION ALZHEIMER’S THERAPEUTICS: LEVERAGING DEEP BIOLOGY
F.M. Longo, S.M. Massa
J Prev Alz Dis 2020;3(7):138-139Show summaryHide summary
F.M. Longo ; S.M. Massa (2020): Next-generation Alzheimer’s Therapeutics: Leveraging Deep Biology. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.30
A IS FOR AMYLOID
J Prev Alz Dis 2020;3(7):140-141Show summaryHide summary
D.J. Selkoe (2020): A Is for Amyloid. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.27
AN INDUSTRY PERSPECTIVE: FUTURE OF ANTI-AMYLOID TRIALS
J Prev Alz Dis 2020;3(7):142-143Show summaryHide summary
L.D. Kramer (2020): An Industry Perspective: Future of Anti-Amyloid Trials. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.26
SCREENING FOR MILD COGNITIVE IMPAIRMENT: THERE IS THE WILL BUT IS THERE A WAY?
J Prev Alz Dis 2020;3(7):144-145Show summaryHide summary
J.E. Galvin (2020): Screening for Mild Cognitive Impairment: There is the Will but Is There a Way?. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.16
CTAD Task Force
THE FUTURE OF ANTI-AMYLOID TRIALS
P.S. Aisen, J. Cummings, R. Doody, L. Kramer, S. Salloway, D.J. Selkoe, J. Sims, R.A. Sperling, B. Vellas, and the EU/US CTAD 2019 Task Force
J Prev Alz Dis 2020;3(7):146-151Show summaryHide summary
The termination of many clinical trials of amyloid-targeting therapies for the treatment of Alzheimer’s disease (AD) has had a major impact on the AD clinical research enterprise. However, positive signals in recent studies have reinvigorated support for the amyloid hypothesis and amyloid-targeting strategies. In December 2019, the EU-US Clinical Trials on Alzheimer’s Disease (CTAD) Task Force met to share learnings from these studies in order to inform future trials and promote the development of effective AD treatments. Critical factors that have emerged in studies of anti-amyloid monoclonal antibody therapies include developing a better understanding of the specific amyloid species targeted by different antibodies, advancing our insight into the mechanism by which those antibodies may reduce pathology, implementing more comprehensive repertoires of biomarkers into trials, and identifying appropriate doses. Studies suggest that Amyloid-Related Imaging Abnormalities – effusion type (ARIA-E) are a manageable safety concern and that caution should be exercised before terminating studies based on interim analyses. The Task Force concluded that opportunities for developing effective treatments include developing new biomarkers, intervening in early stages of disease, and use of combination therapies.
P.S. Aisen ; J. Cummings ; R. Doody ; L. Kramer ; S. Salloway ; D.J. Selkoe ; J. Sims ; R.A. Sperling ; B. Vellas ; and the EU/US CTAD 2019 Task Force (2020): The Future of Anti-Amyloid Trials. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.24
NON-AMYLOID APPROACHES TO DISEASE MODIFICATION FOR ALZHEIMER’S DISEASE: AN EU/US CTAD TASK FORCE REPORT
S. Gauthier, P.S. Aisen, J. Cummings, M.J. Detke, F.M. Longo, R. Raman, M. Sabbagh, L. Schneider, R. Tanzi, P. Tariot, M. Weiner, J. Touchon, B. Vellas, and the EU/US CTAD Task Force
J Prev Alz Dis 2020;3(7):152-157Show summaryHide summary
While amyloid-targeting therapies continue to predominate in the Alzheimer’s disease (AD) drug development pipeline, there is increasing recognition that to effectively treat the disease it may be necessary to target other mechanisms and pathways as well. In December 2019, The EU/US CTAD Task Force discussed these alternative approaches to disease modification in AD, focusing on tau-targeting therapies, neurotrophin receptor modulation, anti-microbial strategies, and the innate immune response; as well as vascular approaches, aging, and non-pharmacological approaches such as lifestyle intervention strategies, photobiomodulation and neurostimulation. The Task Force proposed a general strategy to accelerate the development of alternative treatment approaches, which would include increased partnerships and collaborations, improved trial designs, and further exploration of combination therapy strategies.
S. Gauthier ; P.S. Aisen ; J. Cummings ; M.J. Detke ; F.M. Longo ; R. Raman ; M. Sabbagh ; L. Schneider ; R. Tanzi ; P. Tariot ; M. Weiner ; J. Touchon ; B. Vellas ; and the EU/US CTAD Task Force ; ; (2020): Non-Amyloid Approaches to Disease Modification for Alzheimer’s Disease: An EU/US CTAD Task Force Report. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.18
RATIONALE FOR EARLY DIAGNOSIS OF MILD COGNITIVE IMPAIRMENT (MCI) SUPPORTED BY EMERGING DIGITAL TECHNOLOGIES
M.N. Sabbagh, M. Boada, S. Borson, M. Chilukuri, P.M. Doraiswamy, B. Dubois, J. Ingram, A. Iwata, A.P. Porsteinsson, K.L. Possin, G.D. Rabinovici, B. Vellas, S. Chao, A. Vergallo, H. Hampel
J Prev Alz Dis 2020;3(7):158-164Show summaryHide summary
Disease-modifying pharmacotherapies for Alzheimer’s Disease (AD) are currently in late-stage clinical development; once approved, new healthcare infrastructures and services, including primary healthcare, will be necessary to accommodate a huge demand for early and large-scale detection of AD. The increasing global accessibility of digital consumer electronics has opened up new prospects for early diagnosis and management of mild cognitive impairment (MCI) with particular regard to AD. This new wave of innovation has spurred research in both academia and industry, aimed at developing and validating a new “digital generation” of tools for the assessment of the cognitive performance. In light of this paradigm shift, an international working group (the Global Advisory Group on Future MCI Care Pathways) convened to elaborate on how digital tools may be optimally integrated in screening-diagnostic pathways of AD The working group developed consensus perspectives on new algorithms for large-scale screening, detection, and diagnosis of individuals with MCI within primary medical care delivery. In addition, the expert panel addressed operational aspects concerning the implementation of unsupervised at-home testing of cognitive performance. The ultimate intent of the working group’s consensus perspectives is to provide guidance to developers of cognitive tests and tools to facilitate the transition toward globally accessible cognitive screening aimed at the early detection, diagnosis, and management of MCI due to AD.
M.N. Sabbagh ; M. Boada ; S. Borson ; M. Chilukuri ; P.M. Doraiswamy ; B. Dubois ; J. Ingram ; A. Iwata ; A.P. Porsteinsson ; K.L. Possin ; G.D. Rabinovici ; B. Vellas ; S. Chao ; A. Vergallo ; H. Hampel (2020): Rationale for Early Diagnosis of Mild Cognitive Impairment (MCI) supported by Emerging Digital Technologies. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.19
EARLY DETECTION OF MILD COGNITIVE IMPAIRMENT (MCI) IN PRIMARY CARE
M.N. Sabbagh, M. Boada, S. Borson, M. Chilukuri, B. Dubois, J. Ingram, A. Iwata, A.P. Porsteinsson, K.L. Possin, G.D. Rabinovici, B. Vellas, S. Chao, A. Vergallo, H. Hampel
J Prev Alz Dis 2020;3(7):165-170Show summaryHide summary
Mild cognitive impairment (MCI) is significantly misdiagnosed in the primary care setting due to multi-dimensional frictions and barriers associated with evaluating individuals’ cognitive performance. To move toward large-scale cognitive screening, a global panel of clinicians and cognitive neuroscientists convened to elaborate on current challenges that hamper widespread cognitive performance assessment. This report summarizes a conceptual framework and provides guidance to clinical researchers and test developers and suppliers to inform ongoing refinement of cognitive evaluation. This perspective builds upon a previous article in this series, which outlined the rationale for and potentially against efforts to promote widespread detection of MCI. This working group acknowledges that cognitive screening by default is not recommended and proposes large-scale evaluation of individuals with a concern or interest in their cognitive performance. Such a strategy can increase the likelihood to timely and effective identification and management of MCI. The rising global incidence of AD demands innovation that will help alleviate the burden to healthcare systems when coupled with the potentially near-term approval of disease-modifying therapies. Additionally, we argue that adequate infrastructure, equipment, and resources urgently should be integrated in the primary care setting to optimize the patient journey and accommodate widespread cognitive evaluation.
M.N. Sabbagh ; M. Boada ; S. Borson ; M. Chilukuri ; B. Dubois ; J. Ingram ; A. Iwata ; A.P. Porsteinsson ; K.L. Possin ; G.D. Rabinovici ; B. Vellas ; S. Chao ; A. Vergallo ; H. Hampel (2020): Early Detection of Mild Cognitive Impairment (MCI) in Primary Care. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.21
EARLY DETECTION OF MILD COGNITIVE IMPAIRMENT (MCI) IN AN AT-HOME SETTING
M.N. Sabbagh, M. Boada, S. Borson, P.M. Doraiswamy, B. Dubois, J. Ingram, A. Iwata, A.P. Porsteinsson, K.L. Possin, G.D. Rabinovici, B. Vellas, S. Chao, A. Vergallo, H. Hampel
J Prev Alz Dis 2020;3(7):171-178Show summaryHide summary
Emerging digital tools have the potential to enable a new generation of qualitative and quantitative assessment of cognitive performance. Moreover, the ubiquity of consumer electronics, such as smartphones and tablets, can be harnessed to support large-scale self-assessed cognitive screening with benefit to healthcare systems and consumers. A wide variety of apps, wearables, and new digital technologies are either available or in development for the detection of mild cognitive impairment (MCI), a risk factor for dementia. Two categories of novel methodologies may be considered: passive technologies (which monitor a user’s behavior without active user input) and interactive assessments (which require active user input). Such examinations can be self-administered, supervised by a caregiver, or conducted by an informant at home or outside of a clinical setting. These direct-to-consumer tools have the potential to sidestep barriers associated with cognitive evaluation in primary care, thus improving access to cognitive assessments. Although direct-to-consumer cognitive assessment is associated with its own barriers, including test validation, user experience, and technological concerns, it is conceivable that these issues can be addressed so that a large-scale, self-assessed cognitive evaluation that would represent an initial cognitive screen may be feasible in the future.
M.N. Sabbagh ; M. Boada ; S. Borson ; P.M. Doraiswamy ; B. Dubois ; J. Ingram ; A. Iwata ; A.P. Porsteinsson ; K.L. Possin ; G.D. Rabinovici ; B. Vellas ; S. Chao ; A. Vergallo ; H. Hampel (2020): Early Detection of Mild Cognitive Impairment (MCI) in an At-Home Setting. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.22
DEVELOPMENT OF AN UPSA SHORT FORM FOR USE IN LONGITUDINAL STUDIES IN THE EARLY ALZHEIMER’S DISEASE SPECTRUM
T.E. Goldberg, P.D. Harvey, D.P. Devanand, R.S.E. Keefe, J.J. Gomar
J Prev Alz Dis 2020;3(7):179-183Show summaryHide summary
BACKGROUND: In individuals with only mild or very mild cognitive attenuations (i.e., so-called pre-clinical AD), performance-based measures of function may be superior to informant-based measures because of increased sensitivity, greater reliability, and fewer ceiling effects.
Objective: We sought to determine if a performance-based measure of everyday function would demonstrate adequate psychometric properties and validity in the context of serial assessment over a one-year period in patients with Mild Cognitive Impairment (MCI) and early stage Alzheimer’s disease (AD).
Design: Participants were assessed with the performance-based measure at baseline, six weeks, and one year.
Setting: A specialized center for the assessment and treatment of AD.
Participants: Three groups of subjects participated: a healthy subjects (HS) older cognitively intact group (N=43), an MCI group (N=20), and an AD group (N=26).
Measurements: A three subtest short form of the UCSD Performance-Based Skills Assessment (UPSA) (called the UPSA-3) was the measure of interest. It consisted of the Communication, Planning, and Finance subtests.
Results: Mixed model repeated measures were used to assess performance over time. Large group effects were present (HS>MCI>AD). Additionally, the AD and MCI groups demonstrated declines over one year, while the HS group remained stable (group x time interaction p=.11). The MCI/AD group demonstrated adequate test-retest reliability and did not demonstrate ceiling or floor effects.
Conclusion: Our data indicate that the UPSA-3 is suitable for clinical trials in that it has adequate ecological coverage and reasonable psychometric properties, and perhaps most importantly, demonstrates validity in serial assessments.
T.E. Goldberg ; P.D. Harvey ; D.P. Devanand ; R.S.E. Keefe ; J.J. Gomar (2019): Predictive factors of in-hospital mortality in older adults with community-acquired bloodstream infection. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2019.51
TARGETING LIFESTYLE BEHAVIOR TO IMPROVE BRAIN HEALTH: USER-EXPERIENCES OF AN ONLINE PROGRAM FOR INDIVIDUALS WITH SUBJECTIVE COGNITIVE DECLINE
L.M.P. Wesselman, A.K. Schild, A.M. Hooghiemstra, D. Meiberth, A.J. Drijver, M.v. Leeuwenstijn-Koopman, N.D. Prins, S. Brennan, P. Scheltens, F. Jessen, W.M. van der Flier, S.A.M. Sikkes
J Prev Alz Dis 2020;3(7):184-194Show summaryHide summary
Background: Online programs targeting lifestyle have the potential to benefit brain health. We aimed to develop such a program for individuals with subjective cognitive decline (SCD). These individuals were reported to be at increased risk for dementia, and report both an intrinsic need for brain health information and motivation to participate in prevention strategies. Co-creation and user-evaluation benefits the adherence to and acceptance of online programs. Previously, we developed a prototype of the online program in co-creation with the users .
Objectives: We now aimed to evaluate the user-experiences of our online lifestyle program for brain health.
Design: 30-day user test; multi-method.
Setting: Participants were recruited in a memory clinic and (online) research registries in the Netherlands (Alzheimer Center Amsterdam) and Germany (Center for memory disorders, Cologne).
Participants: Individuals with SCD (N=137, 65±9y, 57% female).
Measurements: We assessed user-experiences quantitatively with rating daily advices and usefulness, satisfaction and ease of use questionnaires as well as qualitatively using telephone interviews.
Results: Quantitative data showed that daily advices were rated moderately useful (3.5 ±1.5, range 1-5 points). Participants (n=101, 78%) gave moderate ratings on the programs’ usability (3.7±1.3, max 7), ease of learning (3.6±1.9) and satisfaction (4.0±1.5), and marginal ratings on the overall usability (63.7±19.0, max 100). Qualitative data collected during telephone interviews showed that participants highly appreciated the content of the program. They elaborated that lower ratings of the program were mainly due to technical issues that hindered a smooth walk through. Participants reported that the program increased awareness of lifestyle factors related to brain health.
Conclusions: Overall user-experience of the online lifestyle program was moderate to positive. Qualitative data showed that content was appreciated and that flawless, easy access technique is essential. The heterogeneity in ratings of program content and in program use highlights the need for personalization. These findings support the use of online self-applied lifestyle programs when aiming to reach large groups of motivated at-risk individuals for brain health promotion.
L.M.P. Wesselman ; A.K. Schild ; A.M. Hooghiemstra ; D. Meiberth ; A.J. Drijver ; M.v. Leeuwenstijn-Koopman ; N.D. Prins ; S. Brennan ; P. Scheltens ; F. Jessen ; W.M. van der Flier ; S.A.M. Sikkes (2020): Targeting Lifestyle Behavior to Improve Brain Health: User-Experiences of an Online Program for Individuals with Subjective Cognitive Decline. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.9
FUTILITY ANALYSES IN ALZHEIMER’S DISEASE (AD) CLINICAL TRIALS: A RISKY BUSINESS
P.S. Aisen, R. Raman
J Prev Alz Dis 2020;3(7):195-196Show summaryHide summary
P.S. Aisen ; R. Raman (2020): Futility Analyses in Alzheimer’s Disease (AD) Clinical Trials: A Risky Business. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.20
IMPACT OF THE COVID-19 OUTBREAK ON THE CLINICAL AND RESEARCH ACTIVITIES OF MEMORY CLINICS: AN ALZHEIMER’S DISEASE CENTER FACING THE COVID-19 CRISIS
P.J. Ousset, B. Vellas
J Prev Alz Dis 2020;3(7):197-198Show summaryHide summary
P.J. Ousset ; B. Vellas ; (2020): Impact of the Covid-19 Outbreak on the Clinical and Research Activities of Memory Clinics: An Alzheimer’s Disease Center Facing the Covid-19 Crisis. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.17
THE EU/US TASK FORCE’S FUTURE FOR ANTI-AMYLOID TRIALS: FAITES VOS JEUX
J Prev Alz Dis 2020;3(7):199-200Show summaryHide summary
L.S. Schneider (2020): The EU/US Task Force’s Future for Anti-Amyloid Trials: Faites Vos Jeux. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.29