Is insulin resistant brain state a central feature of the metabolic-cognitive syndrome?

Vincenza Frisardi, Vincenzo Solfrizzi, Cristiano Capurso, Bruno P. Imbimbo, Gianluigi Vendemiale, Davide Seripa, Alberto Pilotto, Francesco Panza

Research output: Contribution to journalArticlepeer-review


Cumulative evidence suggests that metabolic syndrome (MetS) may be important in the development of mild cognitive impairment, vascular dementia, and Alzheimer's disease (AD). As such, these patients might be described as having "metabolic-cognitive syndrome" -MetS plus cognitive impairment of degenerative or vascular origin. While peripheral insulin resistance appears to be of primary pathophysiological importance in MetS, the definitions of MetS and its components do not include any reference to insulin resistance or hyperinsulinemia. In the present article, we discuss the role of these factors in the development of cognitive decline and dementia, including underlying mechanisms that influence amyloid-β (Aβ) peptide metabolism and tau protein hyperphosphorylation, the principal neuropathological hallmarks of AD. In AD, an age-related desynchronization of biological systems results, involving stress components, cortisol and noradrenaline, reactive oxygen species, and membrane damage as major candidates that precipitates an insulin resistant brain state (IRBS) with decreased glucose/energy metabolism and the increased formation of hyperphosphorylated tau protein and Aβ. Unfortunately, it is very difficult to include the measurement of peripheral insulin resistance in the current MetS criteria or the identification of IRBS for the metabolic-cognitive syndrome. However, since inflammation has been suggested among the MetS components, we propose IRBS as an additional feature of the metabolic-cognitive syndrome to also identify a molecular profile in patients at high risk of developing predementia or dementia syndromes.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalJournal of Alzheimer's Disease
Issue number1
Publication statusPublished - 2010


  • Amyloid-β peptide metabolism
  • hyperinsulinemia
  • hyperphosphorylated tau protein
  • insulin resistance
  • insulin resistant brain state
  • metabolic syndrome
  • type 2 diabetes mellitus

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology
  • Medicine(all)


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