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Nat Rev Neurol. 2018 May;14(5):259-271. doi: 10.1038/nrneurol.2018.23. Epub 2018 Mar 23.

Physiological changes in neurodegeneration - mechanistic insights and clinical utility.

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Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, Australia.
Memory and Cognition Clinic, Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, Australia.
Dementia Research Unit, School of Medical Sciences, The University of New South Wales, Sydney, Australia.
Transgenic Animal Unit, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia.
Neuroscience Research Australia, Sydney, New South Wales, Australia.
Department of Neurology and Department of Pathology, University of California San Francisco Memory and Aging Center, San Francisco, CA, USA.
Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia.
School of Psychology, University of Sydney, Sydney, Australia.


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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