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Longitudinal cognitive and functional changes in primary progressive aphasia

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Abstract

Objective

The variants of primary progressive aphasia (PPA) are predominantly diagnosed on the basis of specific profiles of language impairments. Deficits in other cognitive domains and their evolution over time are less well documented. This study examined the cognitive profiles of the PPA variants over time and determined the contribution of cognition on functional capacity.

Methods

Longitudinal performance on the Addenbrooke’s Cognitive Examination-III (ACE-III) total and cognitive subdomains were investigated in 147 PPA individuals (41 logopenic [lv-PPA], 44 non-fluent [nfv-PPA], and 62 semantic variants [sv-PPA]). The relative contribution of ACE-III subdomain scores to overall functional capacity over time was identified using mixed and hierarchical regression modelling.

Results

The annual rate of global ACE-III decline was twice that in lv-PPA than in nfv-PPA and sv-PPA, despite lv-PPA performing intermediate to the other variants at baseline assessment. Notably, attention and visuospatial subdomains declined faster in lv-PPA than in nfv-PPA and sv-PPA; and memory impairment was more severe in lv-PPA than in nfv-PPA at all time points. Functional decline was comparable across PPA variants; however, the contribution of cognition on functional capacity varied across variants and over time.

Conclusion

The cognitive profiles of the PPA variants are distinct at baseline and over time. Crucially, cognitive decline in lv-PPA was more widespread and pervasive than in nfv-PPA and sv-PPA. Our findings also demonstrate the complex interplay between cognition and functional capacity. This study underscores the importance of routinely assessing cognition and functional capacity in PPA to improve diagnostic accuracy and provide targeted support services.

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Data availability

The syntax and code used for this project have been made available for review on the Open Science Framework website (https://osf.io/63vhz/). The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank all the participants and their carers for their time and contribution to this study. We acknowledge the statistical assistance of Jim Matthews from the Sydney Informatics Hub, a Core Research Facility of the University of Sydney.

Funding

This work was supported in part by funding to ForeFront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neuron disease, from the National Health and Medical Research Council (NHMRC) (GNT1037746) and the Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders Memory Program (CE11000102). MI is supported by an Australian Research Council Future Fellowship (FT160100096), JRB was supported by an NHMRC Early Career Fellowship (GNT1072451), and OP is supported by an NHMRC Senior Research Fellowship (GNT1103258). The authors certify that no actual or potential conflict of interest in relation to this study exists.

Author information

Authors and Affiliations

  1. School of Psychology, The University of Sydney, Sydney, Australia

    David Foxe, Muireann Irish, James Carrick & Olivier Piguet

  2. Brain and Mind Centre, The University of Sydney, 94 Mallett St, Sydney, NSW, 2006, Australia

    David Foxe, Muireann Irish, Anne Hu, James Carrick, John R. Hodges, Rebekah M. Ahmed, James R. Burrell & Olivier Piguet

  3. School of Mathematics and Statistics, The University of Sydney, Sydney, Australia

    Anne Hu

  4. Central Medical School and Brain and Mind Centre, The University of Sydney, Sydney, Australia

    Rebekah M. Ahmed

  5. Concord Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia

    James R. Burrell

Authors
  1. David Foxe
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  2. Muireann Irish
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  3. Anne Hu
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  4. James Carrick
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  5. John R. Hodges
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  6. Rebekah M. Ahmed
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  7. James R. Burrell
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  8. Olivier Piguet
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Contributions

DF, MI, and OP contributed to the design and conceptualisation of the study, analysis and interpretation of data, and drafting and revising the manuscript. AH contributed to analysing and interpreting the data and improving the study design. JC, JRH, RMA, and JRB contributed to the acquisition and interpretation of data and revising the manuscript.

Corresponding author

Correspondence to Olivier Piguet.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

Human Research Ethics Committee of South Eastern Sydney Local District and the University of New South Wales.

Consent to participate

All participants or their person responsible provided written informed consent in accordance with the Declaration of Helsinki.

Supplementary Information

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Foxe, D., Irish, M., Hu, A. et al. Longitudinal cognitive and functional changes in primary progressive aphasia. J Neurol 268, 1951–1961 (2021). https://doi.org/10.1007/s00415-020-10382-9

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  • DOI: https://doi.org/10.1007/s00415-020-10382-9

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