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  • Review Article
  • Published:

Physiological changes in neurodegeneration — mechanistic insights and clinical utility

Nature Reviews Neurology volume 14, pages 259–271 (2018)Cite this article

Subjects

Key Points

  • The effects of neurodegenerative syndromes extend beyond cognitive function to involve key physiological systems

  • Key changes in eating and metabolism, autonomic function, sleep and motor function have been demonstrated across several neurodegenerative conditions

  • Key neural structures that mediate physiological change across these conditions include neuroendocrine and hypothalamic pathways, reward pathways, motor systems and the autonomic nervous system

  • Evidence from human and animal studies suggests that these changes can arise presymptomatically and worsen with disease progression, offering a potential avenue for developing biomarkers to track disease progression

  • Further research is required to determine whether physiological changes simply result from the neurodegeneration process or also modify the neurodegenerative process, thereby providing a novel therapeutic target

Abstract

The effects of neurodegenerative syndromes extend beyond cognitive function to involve key physiological processes, including eating and metabolism, autonomic nervous system function, sleep, and motor function. Changes in these physiological processes are present in several conditions, including frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer disease and the parkinsonian plus conditions. Key neural structures that mediate physiological changes across these conditions include neuroendocrine and hypothalamic pathways, reward pathways, motor systems and the autonomic nervous system. In this Review, we highlight the key changes in physiological processing in neurodegenerative syndromes and the similarities in these changes between different progressive neurodegenerative brain conditions. The changes and similarities between disorders might provide novel insights into the human neural correlates of physiological functioning. Given the evidence that physiological changes can arise early in the neurodegenerative process, these changes could provide biomarkers to aid in the early diagnosis of neurodegenerative diseases and in treatment trials.

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Figure 1: Physiological changes documented in neurodegenerative syndromes.
Figure 2: Network connections of the hypothalamus.
Figure 3: Potential interplay between physiological changes, neural networks, underlying pathology and clinical phenotype.
Figure 4: Time course of the development of physiological changes in relation to cognitive and motor changes in neurodegenerative syndromes.

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Acknowledgements

This work was supported by funding received by ForeFront (a collaborative research group dedicated to the study of frontotemporal dementia and amyotrophic lateral sclerosis) from the National Health and Medical Research Council of Australia (NHMRC) programme (grant 1037746 to L.M.I., J.R.H. G.H. and M.C.K.) and the Australian Research Council Centre of Excellence in Cognition and its Disorders Memory Program (CE110001021 to J.R.H. and O.P.) and other grants and/or sources (NHMRC project grants 1003139 and 1081916, and a Royal Australasian College of Physicians Vincent Fairfax family fellowship). The authors are grateful to the research participants involved with the ForeFront research studies. R.M.A. is an NHMRC Early Career Fellow (1120770). Y.D.K. is an NHMRC R. D. Wright Biomedical Career Development Fellow (112564). O.P. is an NHMRC Senior Research Fellow (1103258). G.H. is an NHMRC Senior Principal Research Fellow (1079679).

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Authors and Affiliations

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

    Rebekah M. Ahmed, Steve Vucic, John R. Hodges, Glenda Halliday & Matthew C. Kiernan

  2. Memory and Cognition Clinic, Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, Australia

    Rebekah M. Ahmed & Matthew C. Kiernan

  3. Dementia Research Unit, School of Medical Sciences, The University of New South Wales, Sydney, Australia

    Yazi D. Ke & Lars M. Ittner

  4. Transgenic Animal Unit, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia

    Lars M. Ittner

  5. Neuroscience Research Australia, Sydney, New South Wales, Australia

    Lars M. Ittner

  6. Department of Neurology and Department of Pathology, University of California San Francisco Memory and Aging Center, San Francisco, CA, USA

    William Seeley

  7. Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia

    John R. Hodges & Olivier Piguet

  8. School of Psychology, University of Sydney, Sydney, Australia

    Olivier Piguet

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Ahmed, R., Ke, Y., Vucic, S. et al. Physiological changes in neurodegeneration — mechanistic insights and clinical utility. Nat Rev Neurol 14, 259–271 (2018). https://doi.org/10.1038/nrneurol.2018.23

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