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Differential associations of clinical features with cerebrospinal fluid biomarkers in dementia with Lewy bodies and Alzheimer’s disease

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Abstract

Aim

To explore associations of cerebrospinal fluid biomarkers of neurodegeneration and amyloidosis with caregiver burden, cognition and functionality in dementia with Lewy bodies (DLB) paired with late-onset Alzheimer’s disease (AD) and healthy older people.

Methods

Consecutive outpatients with DLB were matched with outpatients with AD according to sex, cognitive scores and dementia stage, and with cognitively healthy controls according to age and sex to investigate associations of cerebrospinal fluid amyloid-β (Aβ42,Aβ40,Aβ38), tau, phospho-tau Thr181, ubiquitin, α-synuclein and neurofilament light with caregiver burden, functionality, reverse digit span, a clock drawing test, Mini-Mental State Examination (MMSE) and Severe MMSE, adjusted for sex, age, education, dementia duration and APOE-ε4 alleles.

Results

Overall, 27 patients with DLB (78.98 ± 9.0 years-old; eleven APOE-ε4 +) were paired with 27 patients with AD (81.50 ± 5.8 years-old; twelve APOE-ε4 +) and 27 controls (78.98 ± 8.7 years-old; four APOE-ε4 +); two-thirds were women. In AD, Aβ42/Aβ38 and Aβ42 were lower, while tau/Aβ42 and phospho-tau Thr181/Aβ42 were higher; α-synuclein/Aβ42 was lower in DLB and higher in AD. The following corrected associations remained significant: in DLB, instrumental functionality was inversely associated with tau/phospho-tau Thr181 and tau/Aβ42, and reverse digit span associated with α-synuclein; in AD, instrumental functionality was inversely associated with neurofilament light, clock drawing test scores inversely associated with phospho-tau Thr181/Aβ42 and α-synuclein/Aβ42, and Severe MMSE inversely associated with tau/Aβ42 and tau/phospho-tau Thr181.

Conclusions

Cerebrospinal fluid phospho-tau Thr181 in DLB was similar to AD, but not Aβ42. In associations with test scores, biomarker ratios were superior to isolated biomarkers, while worse functionality was associated with axonal degeneration only in AD.

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Data availability

All data generated during this study have been published and are freely available for download from Mendeley Data at https://doi.org/10.17632/39xyyjdsf3.1.

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Acknowledgements

This work was sponsored by FAPESP – The State of São Paulo Research Foundation (grant #2015/10109-5 and grant #2015/18125-0). The sponsor had no role in study design, in data collection, in the analysis and interpretation of the data, in the writing of the report, or in the decision to submit the paper for publication.

Author information

Authors and Affiliations

  1. Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), Rua Botucatu 740, Vila Clementino, São Paulo, SP, 04023-900, Brazil

    Fabricio Ferreira de Oliveira, Marjorie Câmara Miraldo, Eduardo Ferreira de Castro-Neto, Sandro Luiz de Andrade Matas, Paulo Henrique Ferreira Bertolucci & Maria da Graça Naffah-Mazzacoratti

  2. Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

    Sandro Soares de Almeida

Authors
  1. Fabricio Ferreira de Oliveira
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  2. Marjorie Câmara Miraldo
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  3. Eduardo Ferreira de Castro-Neto
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  4. Sandro Soares de Almeida
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  5. Sandro Luiz de Andrade Matas
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  6. Paulo Henrique Ferreira Bertolucci
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Corresponding author

Correspondence to Fabricio Ferreira de Oliveira.

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Conflict of interest

The authors have no conflicts of interest to report. All authors have read the paper and agreed to be listed as authors, having approved it and validated the accuracy of the data. Individual author contributions include, as follows: Fabricio Ferreira de Oliveira, MD, MSc, PhD, is a medical researcher of the Department of Neurology and Neurosurgery of the Federal University of São Paulo—UNIFESP, a Member of the Committee of Experts of the European Science Foundation, of the American Academy of Neurology Global Strategies Subcommittee, of the Awards Committee of the International Parkinson and Movement Disorder Society (MDS, 2021–2023), and of the Executive Committee of the ISTAART Biofluid Based Biomarkers Professional Interest Area (Alzheimer’s Association, 2018–2025); he has received research support from CAPES—Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and FAPESP—The State of São Paulo Research Foundation, and serves as a healthcare council member for Gerson Lehrman Group, for Atheneum Partners, for Guidepoint, and for Lionbridge; he was involved in conceptualization, methodology, formal analysis, investigation, data curation, writing of the original draft, review and editing, visualization, and project administration. Marjorie Câmara Miraldo, MSc, is a researcher at the Department of Neurology and Neurosurgery of the Federal University of São Paulo—UNIFESP; she was involved in methodology, formal analysis, investigation, data curation, review and editing of the draft. Eduardo Ferreira de Castro-Neto, MSc, PhD, is a researcher at the Department of Neurology and Neurosurgery of the Federal University of São Paulo—UNIFESP; he was involved in methodology, formal analysis, resources, review and editing of the draft. Sandro Soares de Almeida, MSc, PhD, is a researcher at the Department of Biophysics of the Federal University of São Paulo—UNIFESP, and has received grants from CNPq—Conselho Nacional de Desenvolvimento Científico e Tecnológico and FAPESP—The State of São Paulo Research Foundation; he was involved in conceptualization, methodology, validation, formal analysis, resources, data curation, review and editing of the draft. Sandro Luiz de Andrade Matas, MD, MSc, PhD, is a medical researcher at the Department of Neurology and Neurosurgery of the Federal University of São Paulo—UNIFESP; he was involved in methodology, investigation, resources, review and editing of the draft. Paulo Henrique Ferreira Bertolucci, MD, MSc, PhD, is a full professor of the Department of Neurology and Neurosurgery of the Federal University of São Paulo—UNIFESP; he has received grants from CAPES—Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and FAPESP—The State of São Paulo Research Foundation, and serves as a consultant for Janssen, Lundbeck, Novartis, Pfizer and Support; he was involved in conceptualization, methodology, formal analysis, resources, review and editing of the draft, project administration and funding acquisition. Maria da Graça Naffah-Mazzacoratti, MSc, PhD, is a full professor of the Department of Neurology and Neurosurgery of the Federal University of São Paulo—UNIFESP, and has received grants from CAPES—Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CNPq—Conselho Nacional de Desenvolvimento Científico e Tecnológico, and FAPESP—The State of São Paulo Research Foundation; she was involved in conceptualization, methodology, formal analysis, resources, review and editing of the draft, supervision, project administration and funding acquisition.

Ethical approval

This study is part of the research project 0370/2015 (CAAE 43868615.5.0000.5505) approved by the Ethics Committee of Hospital São Paulo, Federal University of São Paulo (UNIFESP), in June 2015, following the tenets of the Declaration of Helsinki.

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This study only included human participants.

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de Oliveira, F.F., Miraldo, M.C., de Castro-Neto, E.F. et al. Differential associations of clinical features with cerebrospinal fluid biomarkers in dementia with Lewy bodies and Alzheimer’s disease. Aging Clin Exp Res 35, 1741–1752 (2023). https://doi.org/10.1007/s40520-023-02452-5

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