Cognitive changes of older adults with an equivocal amyloid load
Observational and interventional studies addressing the link between amyloid (Aβ) burden and cognitive decline are increasing, but a clear definition of amyloid positivity is still lacking. This may represent a great stake for therapeutic studies enrolling Aβ + patients only. The main objective of this study was to define a population with “equivocal” amyloid status, and evaluate their cognitive changes.
Sixty-five participants over 75 years old, from the Control group of the interventional MAPT study, at risk to develop Alzheimer’s disease, were included. Participants were classified into three groups in terms of amyloid load: Aβ +, Aβ − and Equivocal participants (according to visual reading, global standardized uptake (SUVR) cut-offs, or a k-mean clustering method). The cognitive changes over time (memory, executive functions, attention and processing speed) of this Equivocal group were then compared to Aβ + and Aβ − participants.
When classified by visual read, Equivocal participants’ memory scores were comparable to the Aβ- participants, and greater than in Aβ + participants over time. Secondary analyses, using SUVR cut-offs classification, showed different trajectories with Equivocal participants being comparable to the Aβ + participants, and lower than Aβ-, on executive performance over time.
This original work pointed out a population that may be of great interest for interventional studies, raising the question of how amyloid status should be defined and integrated in such studies. These findings should be replicated in future studies on larger datasets, to confirm what methodological approach would be the most suitable to highlight this specific neuroimaging entity.
KeywordsAmyloid imaging Memory Executive functions Equivocal cases
This study was supported by grants from the French Ministry of Health (PHRC 2008), and the Institut de Recherche Pierre Fabre. The promotion of this study was supported by the University Hospital Center of Toulouse. Biological sample collection was supported by Exhonit Therapeutics. The AV45-MAPT study was supported by Avid radiopharmaceuticals/Eli Lilly and Company. Authors would like to thank all the members of the MAPT/DSA Study Group.
This work was funded by grants from the Gérontopôle of Toulouse, the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute, Exhonit Therapeutics SA, and Avid Radiopharmaceuticals Inc.
Compliance with ethical standards
Conflicts of interest
Prof. P. Payoux served on the scientific advisory board of Avid Radiopharmaceuticals and GEHC. Dr. J. Delrieu served on the scientific advisory board of Avid Radiopharmaceuticals. Prof. B. Vellas served on the scientific advisory board of Avid Radiopharmaceuticals. Other authors (Dr K. Pothier, Dr L. Saint-Aubert, Dr C. Hooper, Dr de Souto Baretto) declare that they have no conflict of interest.
Research involving human participants and/or animals
All procedures performed in studies involving human participants were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 2.Ma Y, Zhang S, Li J, Zheng DM, Guo Y, Feng J, Ren WD (2014) Predictive accuracy of amyloid imaging for progression from mild cognitive impairment to Alzheimer disease with different lengths of follow-up: a meta-analysis. Medicine 93:27Google Scholar
- 3.Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, … Park DC (2011) Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. J Alzheimer’s Assoc 7(3):280–292CrossRefGoogle Scholar
- 4.Kemppainen NM, Aalto S, Wilson IA, Nagren K, Helin S, Bruck A et al. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology. 2007;68:1603–1606. https://doi.org/10.1212/01.wnl.0000260969.94695.56 CrossRefGoogle Scholar
- 5.Baker JE, Lim YY, Pietrzak RH, Hassenstab J, Snyder PJ, Masters CL, Maruff P (2017) Cognitive impairment and decline in cognitively normal older adults with high amyloid-β: A meta-analysis. Alzheimer’s Dement 6:108–121Google Scholar
- 8.Fleisher AS, Chen K, Liu X, Roontiva A, Thiyyagura P, Ayutyanont N, Doraiswamy PM (2011) Using positron emission tomography and florbetapir F 18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease. Arch Neurol 68(11):1404–1411CrossRefGoogle Scholar
- 15.Vellas B, Carrie I, Gillette-Guyonnet S, Touchon J, Dantoine T, Dartigues JF, Bories L (2014) MAPT study: a multidomain approach for preventing Alzheimer’s disease: design and baseline data. J Prevent Alzheimer’s Dis 1(1):13Google Scholar
- 16.Andrieu S, Guyonnet S, Coley N, Cantet C, Bonnefoy M, Bordes S, Desclaux F (2017) Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial. Lancet Neurol 16(5):377–389CrossRefGoogle Scholar
- 19.Landau SM, Horng A, Jagust WJ, Alzheimer’s Disease Neuroimaging Initiative (2018) Memory decline accompanies subthreshold amyloid accumulation. Neurology 5:10–1212Google Scholar
- 25.McMillan CT, Chételat G. Amyloid “accumulators”: the next generation of candidates for amyloid-targeted clinical trials? [published online March 23, 2018]. Neurology. https://doi.org/10.1212/WNL.0000000000005362