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Neurophysiological correlates of altered time awareness in Alzheimer’s disease and frontotemporal dementia

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Abstract

Background

Alterations in time awareness have been reported in dementia, particularly in Alzheimer's disease (AD) and frontotemporal dementia (FTD). However, the neurophysiological correlates underlying these alterations remain largely unexplored. This study aimed to investigate the neurophysiological correlates of altered time awareness in AD and FTD patients.

Methods

A total of 150 participants (50 AD patients, 50 FTD patients, and 50 healthy controls [HC]) underwent a standardized neuropsychological assessment, an altered time awareness survey, and transcranial magnetic stimulation (TMS) to assess cholinergic (short latency afferent inhibition—SAI), GABAergic (short interval intracortical inhibition—SICI), and glutamatergic (intracortical facilitation—ICF) circuits.

Results

In AD patients, the most frequent symptom was difficulty in ordering past events (52.0%), while FTD patients primarily struggled with estimating temporal intervals between events (40.0%). Significant differences were observed between HC and both patient groups, as well as between AD and FTD patients in their tendency to re-live past events. Binomial logistic regression analysis revealed that impairments in glutamatergic and cholinergic circuits significantly predicted the likelihood of participants manifesting altered time awareness symptoms.

Conclusions

This study provides novel insights into the neurophysiological correlates of altered time awareness in AD and FTD patients, highlighting the involvement of specific neurotransmitter circuits, particularly glutamatergic and cholinergic circuits. Further research is needed to explore the potential clinical implications and therapeutic targets arising from these findings.

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Data Availability

All study data, including raw and analysed data, and materials will be available from the corresponding author, A.B., upon reasonable request.

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Acknowledgements

AB was partially by Fondazione Cariplo (grant n° 2021-1516), and by the Fondation pour la Recherche sur Alzheimer.

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Authors and Affiliations

  1. Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy

    Valeria Bracca, Valentina Cantoni, Yasmine Gadola, Jasmine Rivolta, Alessandro Padovani, Barbara Borroni & Alberto Benussi

  2. Neurology Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia, Italy

    Maura Cosseddu, Rosanna Turrone, Salvatore Caratozzolo, Alessandro Padovani, Barbara Borroni & Alberto Benussi

  3. Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy

    Monica Di Luca

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  1. Valeria Bracca
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Contributions

VB and AB contributed to the study conception and design. All authors contributed to data collection and analysis. The first draft of the manuscript was written by VB and AB and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Alberto Benussi.

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In accordance with the Declaration of Helsinki, full written informed consent was obtained from all participants. The Brescia Hospital ethics committee approved the study protocol.

Competing interests

All authors report no competing interests relevant to the present manuscript.

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Bracca, V., Cantoni, V., Gadola, Y. et al. Neurophysiological correlates of altered time awareness in Alzheimer’s disease and frontotemporal dementia. Neurol Sci 44, 3515–3522 (2023). https://doi.org/10.1007/s10072-023-06877-8

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