Mediterranean and Western diet effects on Alzheimer's disease biomarkers, cerebral perfusion, and cognition in mid-life: A randomized trial

Alzheimers Dement. 2022 Mar;18(3):457-468. doi: 10.1002/alz.12421. Epub 2021 Jul 26.


Introduction: Mid-life dietary patterns are associated with Alzheimer's disease (AD) risk, although few controlled trials have been conducted.

Methods: Eighty-seven participants (age range: 45 to 65) with normal cognition (NC, n = 56) or mild cognitive impairment (MCI, n = 31) received isocaloric diets high or low in saturated fat, glycemic index, and sodium (Western-like/West-diet vs. Mediterranean-like/Med-diet) for 4 weeks. Diet effects on cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral perfusion were assessed to determine whether responses differed by cognitive status.

Results: CSF amyloid beta (Aβ)42/40 ratios increased following the Med-diet, and decreased after West-diet for NC adults, whereas the MCI group showed the reverse pattern. For the MCI group, the West-diet reduced and the Med-diet increased total tau (t-tau), whereas CSF Aβ42 /t-tau ratios increased following the West-diet and decreased following the Med-diet. For NC participants, the Med-diet increased and the West-diet decreased cerebral perfusion.

Discussion: Diet response during middle age may highlight early pathophysiological processes that increase AD risk.

Keywords: Alzheimer's disease; cerebral perfusion; cerebrospinal fluid biomarkers; diet intervention.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease* / cerebrospinal fluid
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Cerebrovascular Circulation
  • Cognition / physiology
  • Cognitive Dysfunction* / cerebrospinal fluid
  • Diet, Mediterranean*
  • Diet, Western*
  • Humans
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • tau Proteins