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Baseline MRI atrophy predicts 2-year cognitive outcomes in early-onset Alzheimer’s disease

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Abstract

Background

MRI atrophy predicts cognitive status in AD. However, this relationship has not been investigated in early-onset AD (EOAD, < 65 years) patients with a biomarker-based diagnosis.

Methods

Forty eight EOAD (MMSE ≥ 15; A + T + N +) and forty two age-matched healthy controls (HC; A − T − N −) from a prospective cohort underwent full neuropsychological assessment, 3T-MRI scan and lumbar puncture at baseline. Participants repeated the cognitive assessment annually. We used linear mixed models to investigate whether baseline cortical thickness (CTh) or subcortical volume predicts two-year cognitive outcomes in the EOAD group.

Results

In EOAD, hemispheric CTh and ventricular volume at baseline were associated with global cognition, language and attentional/executive functioning 2 years later (p < 0.0028). Regional CTh was related to most cognitive outcomes (p < 0.0028), except verbal/visual memory subtests. Amygdalar volume was associated with letter fluency test (p < 0.0028). Hippocampal volume did not show significant associations.

Conclusion

Baseline hemispheric/regional CTh, ventricular and amygdalar volume, but not the hippocampus, predict two-year cognitive outcomes in EOAD.

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Data availability

The summary tables that support the findings of this study are available on request from the corresponding author, AL.

Code availability

Code used in this study is available on request from the corresponding author, AL.

Abbreviations

AD:

Alzheimer’s disease

Aβ:

Amyloid-β

bankssts:

Banks of the superior temporal sulcus

BDAE:

The Boston Diagnostic Aphasia Examination

BNT:

Boston Naming Test

CERAD:

Consortium to Establish a Registry for Alzheimer’s disease

CSF:

Cerebrospinal fluid

CTh:

Cortical thickness

DFR:

Delayed free recall

Digits-B:

Digits span backwards

Digits-F:

Digits span forwards

DTR:

Delayed total recall

EOAD:

Early-onset AD

LFT:

Letter fluency test

FCSRT:

Free and Cued Selective Reminding Test

FDG-PET:

Fluorodeoxyglucose positron emission tomography

FL:

Free learning

GC:

Global composite

HC:

Healthy controls

HCB:

Hospital Clínic de Barcelona

LM:

Linear model

LME:

Linear mixed-effects model

LOAD:

Late-onset AD

MMSE:

Mini-Mental State Examination

MRI:

Magnetic resonance imaging

MTL:

Medial temporal lobe

NIA-AA:

National Institute on Aging-Alzheimer’s Association

SF:

Semantic fluency test

TL:

Total learning

TMT-A:

Trail Making Test-A

VOSP:

Visual object and space perception battery

WAB:

Western Aphasia Battery

WAIS:

Wechsler Adult Intelligence Scale

YOE:

Years of education

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Acknowledgements

The authors thank patients, their relatives and healthy controls for their participation in the research. We acknowledge support for the project provided by Spanish Ministry of Science and Innovation-Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, “Una manera de hacer Europa”, CERCA Programme/Generalitat de Catalunya and Departament de Salut—Generalitat de Catalunya (PERIS 2016-2020). We also are indebted to the Magnetic Resonance Image core facility of the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) for the technical help.

Funding

This work was supported by Spanish Ministry of Science and Innovation-Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, “Una manera de hacer Europa” [PI19/00449 to Dr. Lladó (AL)] and CERCA Programme/Generalitat de Catalunya. AL also received funding from Departament de Salut—Generalitat de Catalunya (PERIS 2016–2020 SLT008/18/00061). Roser Sala-Llonch received funding from the Biomedical Imaging Group, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. Nuria Guillén received funding from a PFIS grant (FI20/00076). Oscar Ramos received funding from a PFIS grant (FI18/00121). This work has been partially performed thanks to the 3T Equipment of Magnetic Resonance at IDIBAPS (project IBPS15-EE-3688 co funded by MCIU and by ERDF).

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Author notes

  1. Roser Sala-Llonch and Albert Lladó have contributed equally to this work.

Authors and Affiliations

  1. Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    José Contador, Agnès Pérez-Millan, Nuria Guillen, Adrià Tort-Merino, Mircea Balasa, Neus Falgàs, Jaume Olives, Magdalena Castellví, Beatriz Bosch, Guadalupe Fernández-Villullas, Oscar Ramos-Campoy, Anna Antonell, Raquel Sanchez-Valle & Albert Lladó

  2. Institute of Neurosciences. Department of Biomedicine, Faculty of Medicine, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

    Agnès Pérez-Millan & Roser Sala-Llonch

  3. Atlantic Fellow for Equity in Brain Health, Global Brain Heath Institute, Trinity College Institute of Neuroscience, Dublin, Ireland

    Mircea Balasa

  4. Atlantic Fellow for Equity in Brain Health, Global Brain Heath Institute, Department of Neurology, University of California, San Francisco, CA, USA

    Neus Falgàs

  5. Department of Neurology, Memory & Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA

    Neus Falgàs

  6. Department of Neurology, Fundació Sanitària Mollet, Mollet del Vallés, Barcelona, Spain

    Sergi Borrego-Écija

  7. Image Diagnostic Centre Radiology Department, Hospital Clínic de Barcelona, Magnetic Resonance Image Core facility Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Nuria Bargalló

  8. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Spain

    Raquel Sanchez-Valle & Albert Lladó

  9. Biomedical Imaging Group, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain

    Roser Sala-Llonch

Authors
  1. José Contador
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  2. Agnès Pérez-Millan
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  3. Nuria Guillen
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  4. Adrià Tort-Merino
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  5. Mircea Balasa
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  10. Beatriz Bosch
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  11. Guadalupe Fernández-Villullas
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  16. Roser Sala-Llonch
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  17. Albert Lladó
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Corresponding author

Correspondence to Albert Lladó.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Approval was obtained from Hospital Clínic Ethics Committee. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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Contador, J., Pérez-Millan, A., Guillen, N. et al. Baseline MRI atrophy predicts 2-year cognitive outcomes in early-onset Alzheimer’s disease. J Neurol 269, 2573–2583 (2022). https://doi.org/10.1007/s00415-021-10851-9

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