Three-year changes of cortical 18F-FDG in amnestic vs. non-amnestic sporadic early-onset Alzheimer’s disease
To examine and compare longitudinal changes of cortical glucose metabolism in amnestic and non-amnestic sporadic forms of early-onset Alzheimer’s disease and assess potential associations with neuropsychological performance over a 3-year period time.
Eighty-two participants meeting criteria for early-onset (< 65 years) sporadic form of probable Alzheimer’s disease and presenting with a variety of clinical phenotypes (47 amnestic and 35 non-amnestic forms) were included at baseline and followed up for 1.44 ± 1.23 years. All of the participants underwent a work-up at baseline and every year during the follow-up period, which includes clinical examination, neuropsychological testing, genotyping, cerebrospinal fluid biomarker assays, and structural MRI and 18F-FDG PET. Vertex-wise partial volume-corrected glucose metabolic maps across the entire cortical surface were generated and longitudinally assessed together with the neuropsychological scores using linear mixed-effects modeling as a function of amnestic and non-amnestic sporadic forms of early-onset Alzheimer’s disease.
Similar evolution patterns of glucose metabolic decline between amnestic and non-amnestic forms were observed in widespread neocortical cortices. However, only non-amnestic forms appeared to have a greater reduction of glucose metabolism in lateral orbitofrontal and bilateral medial temporal cortices associated with more severe declines of neuropsychological performance compared with amnestic forms. Furthermore, results suggest that glucose metabolic decline in amnestic forms would progress along an anterior-to-posterior axis, whereas glucose metabolic decline in non-amnestic forms would progress along a posterior-to-anterior axis.
We found differences in spatial distribution and temporal trajectory of glucose metabolic decline between amnestic and non-amnestic early-onset Alzheimer’s disease groups, suggesting that one might want to consider treating the two forms of the disease as two separate entities.
KeywordsSporadic early-onset Alzheimer’s disease Longitudinal glucose metabolism Positron emission tomography Cognition Linear mixed-effects modeling
The authors thank the participants and their families for their kind participation in the present study. We would also like to thank all the members of the Lille Young Onset Dementia study group for their respective contributions to the prospective COMAJ study. Lastly, we especially thank Dr. Jérôme Declerck (Siemens Molecular Imaging) for his advice on PET imaging.
This work was also supported through the LABEX (excellence laboratory, program investment for the future) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to Alzheimer disease), and the LiCEND.
This research was funded by Siemens Healthineers as part of a French CIFRE grant for a neuroimaging PhD thesis (CONVENTION CIFRE No. 2015/1047).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest. Rachid Fahmi is full-time employee of Siemens Medical Solutions USA, Inc.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The present study was approved by a local investigational review board (CPP Ile-de-France VI Groupe Hospitalier Pitié-Salpêtrière; reference 110-05). This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
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