Physiological changes in neurodegeneration - mechanistic insights and clinical utility

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / physiopathology
  • Amyotrophic Lateral Sclerosis* / metabolism
  • Amyotrophic Lateral Sclerosis* / physiopathology
  • Animals
  • Autonomic Nervous System* / physiopathology
  • Frontotemporal Dementia* / metabolism
  • Frontotemporal Dementia* / physiopathology
  • Humans
  • Hypothalamus* / metabolism
  • Hypothalamus* / physiopathology
  • Nerve Net* / physiopathology
  • Parkinsonian Disorders* / metabolism
  • Parkinsonian Disorders* / physiopathology
  • Sleep Wake Disorders* / physiopathology