Key Points
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The effects of neurodegenerative syndromes extend beyond cognitive function to involve key physiological systems
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Key changes in eating and metabolism, autonomic function, sleep and motor function have been demonstrated across several neurodegenerative conditions
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Key neural structures that mediate physiological change across these conditions include neuroendocrine and hypothalamic pathways, reward pathways, motor systems and the autonomic nervous system
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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
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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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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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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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DOI: https://doi.org/10.1038/nrneurol.2018.23
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