Cited by 594Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease

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Kapogiannis, Dimitrios, Mattson, Mark P·2011·The Lancet Neurology

Abstract

Epidemiological, neuropathological, and functional neuroimaging evidence implicates global and regional disruptions in brain metabolism and energetics in the pathogenesis of cognitive impairment. Nerve cell microcircuits are modified by excitatory and inhibitory synaptic activity and neurotrophic factors. Ageing and Alzheimer's disease cause perturbations in cellular energy metabolism, level of excitation or inhibition, and neurotrophic factor release, which overwhelm compensatory mechanisms and result in dysfunction of neuronal microcircuits and brain networks. A prolonged positive energy balance impairs the ability of neurons to adapt to oxidative and metabolic stress. Results from experimental studies in animals show how disruptions caused by chronic positive energy balance, such as diabetes, lead to accelerated cognitive ageing and Alzheimer's disease. Therapeutic interventions to allay cognitive dysfunction that target energy metabolism and adaptive stress responses (such as neurotrophin signalling) have been effective in animal models and in preliminary studies in humans.

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Authors
Kapogiannis, D., & Mattson, M. P.
Affiliations
National Institute on Aging (US)
Corresponding author
Mattson, Mark P
Venue
The Lancet Neurology
Publisher
Elsevier BV
Published
2011-02
Volume
10
Issue
2
Pages
187-198
ISSN
1474-4422 (ISSN-L)
OpenAlex
W2168489336
Cited by
594
References
138
Citations by year
2026: 47 · 2025: 38 · 2024: 35 · 2023: 42 · 2022: 56 · 2021: 43 · 2020: 44 · 2019: 37 · 2018: 38 · 2017: 35 · 2016: 29 · 2015: 24 · 2014: 35 · 2013: 30 · 2012: 42
FWCI
2.92
Type
journal article
Language
en
Open access
Locations
  • The Lancet Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (Z99 AG999999, Z01 AG000332)
  • National Institute on Aging (ZIAAG000313, Z01AG000312, ZIAAG000330, ZIAAG000331, Z01AG000313, Z01AG000327, Z01AG000317, ZIAAG000312, Z01AG000315, ZIAAG000975, Z01AG000314)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Alzheimer's disease, cognitive impairment, brain energy metabolism, excitation-inhibition balance, neurotrophic factors, neurotrophin signaling, oxidative stress, metabolic stress, positive energy balance, diabetes mellitus, cognitive aging, brain networks
MeSH terms
Alzheimer Disease, Animals, Brain, Cognition Disorders, Energy Metabolism, Humans, Nerve Net

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