Alzheimer’s disease, one of the most common forms of dementia, affects millions of people worldwide. Its diagnosis, however, has long been a challenge due to the complexity of the disease and the absence of definitive tests. The current diagnostic process relies heavily on clinical assessment, neurocognitive testing, and structural brain imaging1. A recent study published in JAMA Neurology suggests that the incorporation of amyloid positron emission tomography (PET) scans early in the diagnostic process can significantly improve diagnostic confidence in memory clinic patients2.
Amyloid PET scans can directly assess amyloid plaque deposition, one of the main hallmarks of Alzheimer’s disease. However, due to the lack of sufficiently robust studies demonstrating its clinical impact, this technique is not widely reimbursed or utilized. The groundbreaking AMYPAD-DPMS (Amyloid Imaging to Prevent Alzheimer’s Disease – Diagnostic and Patient Management Study) randomized clinical trial, led by Altomare et al., provides a compelling argument for the early use of amyloid PET scans in the diagnostic workup of Alzheimer’s disease, potentially paving the way for a paradigm shift in the diagnostic approach towards this pervasive neurodegenerative disease2.
Study Overview: The AMYPAD-DPMS Randomized Clinical Trial
The recently published AMYPAD-DPMS randomized clinical trial, led by Altomare et al., aimed to assess the clinical effect of amyloid PET in memory clinic patients3. This landmark trial, involving eight European memory clinics, was designed to evaluate the effect of early versus late amyloid PET scanning in the diagnostic workup of patients presenting with cognitive decline.
In the trial, participants were randomly assigned into three groups: those who received the amyloid PET scan early in the diagnostic process (within one month), those who received it late (after an average of eight months), and a third group where the scan was administered at the discretion of the managing physician3. The participants consisted of patients with subjective cognitive decline plus (SCD+), mild cognitive impairment (MCI), or dementia, and they were assessed at baseline and after three months.
The main outcome of the trial was to evaluate the difference in the proportion of participants between the early and late scan groups who received an etiological diagnosis with very high confidence (≥90% on a 50%-100% visual numeric scale) after three months3.
The results were remarkable. After three months, 40% of the participants who had an early amyloid PET scan had a diagnosis with very high confidence, compared to just 11% of those who had a later scan. This significant difference was consistent across all cognitive stages evaluated in the trial, suggesting that early amyloid PET scanning can meaningfully improve the diagnostic confidence in memory clinic patients3.
These findings strongly suggest that integrating amyloid PET scans early in the diagnostic workup of memory clinic patients can significantly enhance the speed and confidence of diagnosing Alzheimer’s disease.
Reinforcing Evidence: Previous Studies on Amyloid PET Scans
The findings from the AMYPAD-DPMS randomized clinical trial are reinforced by several previous studies that have explored the utility of amyloid PET scans in diagnosing Alzheimer’s disease.
A 2019 study led by Rabinovici and colleagues, which assessed the impact of amyloid PET on patient outcomes, found that the use of amyloid PET resulted in changes in clinical management in a significant proportion of patients, underscoring its potential value in the diagnostic process4.
Similarly, in the IDEAS (Imaging Dementia—Evidence for Amyloid Scanning) study, a large-scale clinical trial conducted in the United States, it was found that the use of amyloid PET led to a change in clinical management in two-thirds of patients with mild cognitive impairment or dementia of uncertain etiology5. The study also demonstrated that amyloid PET improved diagnostic certainty and was associated with better patient outcomes.
Furthermore, a 2020 meta-analysis of 11 studies found that amyloid PET had a significant effect on changing the diagnosis, altering patient management, and improving diagnostic confidence in the evaluation of patients with cognitive impairment6.
In conclusion, these previous studies, in conjunction with the recent AMYPAD-DPMS randomized clinical trial, present strong evidence supporting the incorporation of amyloid PET scans early in the diagnostic workup of patients presenting with cognitive decline.
Potential Implications: Towards Improved Alzheimer’s Disease Diagnosis and Management
The AMYPAD-DPMS randomized clinical trial and the reinforcing evidence from previous studies carry significant implications for the diagnosis and management of Alzheimer’s disease.
Alzheimer’s disease presents a significant health challenge globally. It not only dramatically reduces the quality of life for those affected but also places a significant burden on caregivers and healthcare systems. Early and accurate diagnosis of Alzheimer’s disease is key to ensuring that patients receive appropriate and timely treatment, which can potentially slow disease progression and improve quality of life7.
The results from the AMYPAD-DPMS study suggest that early implementation of amyloid PET scans in the diagnostic workup can significantly increase diagnostic confidence and speed up the diagnostic process. This could potentially lead to earlier therapeutic interventions, which are often more effective when initiated in the early stages of the disease8.
Furthermore, early and accurate diagnosis can also help patients and their families to better plan for the future, make lifestyle adjustments, and access appropriate resources and support services9.
Despite these potential benefits, it should be noted that amyloid PET scans are currently not widely reimbursed, and therefore their availability to patients is limited. The strong evidence provided by this study and others could potentially influence policy and reimbursement decisions, making this valuable diagnostic tool more widely accessible.
Glossary of Terms
- Alzheimer’s disease: A progressive neurological disorder that impairs memory, thinking, and behavior. It is the most common cause of dementia in older adults.
- Amyloid PET scan: A type of brain imaging that uses a radioactive tracer to detect the presence of amyloid plaques, a hallmark of Alzheimer’s disease.
- Amyloid plaques: Clumps of protein fragments that accumulate in the brain, characteristic of Alzheimer’s disease.
- Cognitive decline: A noticeable and measurable decrease in cognitive abilities, including memory and thinking skills.
- Dementia: A general term for loss of memory, language, problem-solving, and other thinking abilities that are severe enough to interfere with daily life. Alzheimer’s is the most common cause of dementia.
- Diagnostic confidence: The level of certainty a healthcare provider has in the accuracy of a diagnosis.
- Diagnostic workup: The process of determining which disease or condition explains a person’s symptoms and signs.
- Etiological diagnosis: The determination of the cause or origin of a disease.
- Mild Cognitive Impairment (MCI): A slight but noticeable and measurable decline in cognitive abilities, including memory and thinking skills.
- Prospective study: A study that follows over time a group of similar individuals (cohorts) who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome.
- Randomized clinical trial: A type of scientific experiment which aims to reduce bias when testing a new treatment. Participants are randomly allocated to either the group receiving the treatment under investigation or to a group receiving standard treatment (or placebo treatment) as the control.
- Reimbursement: The process of getting money back from healthcare providers for medical procedures, tests, or other expenses.
- Subjective cognitive decline plus (SCD+): A self-experienced persistent decline in cognitive capacity in comparison with a previously normal status, not related to an acute event, in individuals who perform within normal ranges on standardized cognitive tests but have clinical features that increase the likelihood of preclinical Alzheimer’s disease.
- Visual numeric scale: A scale used in research that provides a visual representation of a range of numeric data or responses. In this context, it is used to express diagnostic confidence as a percentage.
Footnotes
1 Alzheimer’s Association. (2021). Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 17(3), 327–406. https://doi.org/10.1002/alz.12328
2 Altomare, D., et al. (2023). Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients. JAMA Neurology. Published online May 8, 2023. doi:10.1001/jamaneurol.2023.0997
3 Altomare, D., et al. (2023). Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients. JAMA Neurology. Published online May 8, 2023. doi:10.1001/jamaneurol.2023.0997
4 Rabinovici, G. D., et al. (2019). Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia. JAMA, 321(13), 1286–1294. https://doi.org/10.1001/jama.2019.2000
5 Johnson, K. A., et al. (2020). Appropriate Use Criteria for Amyloid PET: A Report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. Alzheimer’s & Dementia, 9(1), e1-e16. https://doi.org/10.1016/j.jalz.2013.01.002
6 Ossenkoppele, R., et al. (2020). The Effect of Amyloid PET on Diagnosis, Management, and Clinical Outcomes in Patients With Cognitive Impairment: A Systematic Review of Randomized Controlled Trials. Clinical Nuclear Medicine, 45(8), 627–635. https://doi.org/10.1097/RLU.0000000000003171
7 Alzheimer’s Association. (2021). 2021 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 17(3), 327–406. https://doi.org/10.1002/alz.12328
8 Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2020). Alzheimer’s disease drug development pipeline: 2020. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 6(1), e12050. https://doi.org/10.1002/trc2.12050
9 Bocchetta, M., Galluzzi, S., Kehoe, P. G., Aguera, E., Bernabei, R., Bullock, R., … & Frisoni, G. B. (2015). The use of biomarkers for the etiologic diagnosis of MCI in Europe: an EADC survey. Alzheimer’s & Dementia, 11(2), 195-206.e1. https://doi.org/10.1016/j.jalz.2014.06.006
JAMA Citation: Daniele Altomare, PhD1,2,3; Frederik Barkhof, MD4,5; Camilla Caprioglio, MS1,2; Lyduine E. Collij, PhD4; Philip Scheltens, MD6; Isadora Lopes Alves, PhD4; Femke Bouwman, MD6; Johannes Berkhof, PhD7; Ingrid S. van Maurik, PhD6,7; Valentina Garibotto, MD8,9; Christian Moro, MS1,2; Julien Delrieu, MD10,11; Pierre Payoux, MD12,13; Laure Saint-Aubert, PhD12,13; Anne Hitzel, MD12; José Luis Molinuevo, MD14,15; Oriol Grau-Rivera, MD14,16,17; Juan Domingo Gispert, MD14,16,18; Alexander Drzezga, MD19,20,21; Frank Jessen, MD20,22,23; Philip Zeyen, MD22; Agneta Nordberg, MD24,25; Irina Savitcheva, MD26; Vesna Jelic, MD27; Zuzana Walker, MD28,29; Paul Edison, MD30; Jean-François Demonet, MD31; Rossella Gismondi, MD32; Gill Farrar, PhD33; Andrew W. Stephens, MD32; Giovanni B. Frisoni, MD1,2; for the Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) Consortium
Author Affiliations Article Information
1Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland
2Geneva Memory Center, Geneva University Hospitals, Geneva, Switzerland
3Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
4Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (UMC)–Location VUmc, Amsterdam, the Netherlands
5Institute of Neurology, Institute of Healthcare Engineering, University College London, London, United Kingdom
6Alzheimer Center, Department of Neurology, Amsterdam University Medical Centers–Location VUmc, Amsterdam, the Netherlands
7Department of Epidemiology and Data Science, Amsterdam University Medical Centers–Location VUmc, Amsterdam, the Netherlands
8Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland
9Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland
10Gérontopôle, Department of Geriatrics, Toulouse University Hospital, Toulouse, France
11Maintain Aging Research Team, CERPOP, Inserm, Université Paul Sabatier, Toulouse, France
12Department of Nuclear Medicine, Toulouse University Hospital, Toulouse, France
13Toulouse NeuroImaging Center (ToNIC), UMR1214 Inserm, Université de Toulouse III, Toulouse, France
14Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain
15H. Lundbeck, Copenhagen, Denmark
16Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
17Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain
18Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain
19Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
20German Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Germany
21Institute of Neuroscience and Medicine (INM-2), Molecular Organization of the Brain, Forschungszentrum Jülich, Germany
22Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
23Excellence Cluster Cellular Stress Responses in Aging-Related Diseases (CECAD), Medical Faculty, University of Cologne, Cologne, Germany
24Department of Neurobiology, Care Sciences and Society, Center of Alzheimer Research, Karolinska Institutet, Stockholm, Sweden
25Theme Aging, Karolinska University Hospital, Stockholm, Sweden
26Medical Radiation Physics and Nuclear Medicine, Section for Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
27Cognitive Disorders Clinic, Theme Inflammation and Aging, Karolinska University Hospital–Huddinge, Stockholm, Sweden
28Division of Psychiatry, University College London, London, United Kingdom
29St Margaret’s Hospital, Essex Partnership University NHS Foundation Trust, Essex, United Kingdom
30Division of Neurology, Department of Brain Sciences, Imperial College London, London, United Kingdom
31Leenaards Memory Center, Lausanne University Hospital (CHUV), Lausanne, Switzerland
32Life Molecular Imaging, Berlin, Germany
33GE Healthcare, Amersham, United Kingdom
JAMA Neurol. Published online May 8, 2023. doi:10.1001/jamaneurol.2023.0997