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Diabetic patients treated with metformin during early stages of Alzheimer’s disease show a better integral performance: data from ADNI study

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Abstract

We evaluated the effect of the antidiabetic drug metformin on patients enrolled in the ADNI study considering patients with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD). Employing data from this observational study, we performed a principal component analysis focusing on the cognitive sphere by evaluating data from neuropsychological tests included in a modified version of the Alzheimer’s Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite (ADCS-PACC). Second, we included the levels of amyloid-β, tau, and phosphorylated tau in CSF. We found that MCI metformin-treated patients were globally characterized as subjects with a better cognitive performance and CSF biomarkers profile than the mean population of MCI patients. On the other hand, control subjects and type 2 diabetes patients (T2D) were paired by age, gender, ApoE allele, and years of education, defining three groups: MCI, MCI + T2D, and MCI + T2D + metformin. We evaluated the effect of T2D and metformin treatment employing the PACC score and composites defined from standardized ADNI variables to evaluate the memory and learning function. We found that MCI + T2D patients had a worse cognitive performance than MCI patients, but this deleterious effect was not observed in MCI + T2D + metformin patients. These cognitive variations were associated with changes in cortical thickness and hippocampal volume. Finally, no differences were found in metabolic plasmatic parameters (glycemia, cholesterol, triglycerides). Our study—employing different strategies for data analysis from the global study ADNI—shows a beneficial effect of metformin treatment on cognitive performance, CSF biomarkers profile, and neuroanatomical measures in MCI due to AD patients.

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Acknowledgements

The authors gratefully acknowledge the scientific contribution of Ezequiel Surace, PhD; Juan Beauquis, MD, PhD; Angeles Vinuesa, PhD; and Patricio Chrem Mendez MD.

Funding

This work was supported by Williams, René Barón, and Florencio Fiorini Foundations, ANPCyT PICT Grants: 2016–1046, 2016–1572, 2019–3419 and UBACyT 2018 Grant. The funding sources had no involvement in the study design nor the collection, analysis and interpretation of data. CP is recipient of CONICET Fellowship. FS is CONICET Researcher.

Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12–2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of Southern California.

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Authors and Affiliations

  1. Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina

    Carlos Pomilio, Nicolás González Pérez & Flavia Saravia

  2. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

    Carlos Pomilio, Nicolás González Pérez & Flavia Saravia

  3. Centro de Memoria y Envejecimiento, FLENI, Buenos Aires, Argentina

    Ismael Calandri, Lucía Crivelli & Ricardo Allegri

  4. Departamento de Neurociencias, Universidad de La Costa (CUC), Barranquilla, Colombia

    Ricardo Allegri

  5. Laboratorio de Biología Molecular, FLENI, Buenos Aires, Argentina

    Gustavo Sevlever

  6. Banco de Cerebros FLENI, Buenos Aires, Argentina

    Gustavo Sevlever

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  1. Carlos Pomilio
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  2. Nicolás González Pérez
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  4. Lucía Crivelli
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  7. Flavia Saravia
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The ADNI Alzheimer’s Disease Neuroimaging Initiative

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Correspondence to Flavia Saravia.

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Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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Pomilio, C., Pérez, N.G., Calandri, I. et al. Diabetic patients treated with metformin during early stages of Alzheimer’s disease show a better integral performance: data from ADNI study. GeroScience 44, 1791–1805 (2022). https://doi.org/10.1007/s11357-022-00568-6

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