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

Dimitrios Kapogiannis, Mark P. Mattson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)187-198
Number of pages12
JournalThe Lancet Neurology
Volume10
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

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