LMN diet, rich in polyphenols and polyunsaturated fatty acids, improves mouse cognitive decline associated with aging and Alzheimer's disease

Behav Brain Res. 2012 Mar 17;228(2):261-71. doi: 10.1016/j.bbr.2011.11.014. Epub 2011 Nov 22.


We examined whether LMN diet, reported to induce neurogenesis in adult mice, was able to antagonize the age-related behavioural impairment and neuropathology in wild type (WT) mice and Tg2576 mice, a mouse model of Alzheimer's disease (AD). Thirteen-month-old mice (once the amyloid (Aβ) plaques were formed) were fed with the LMN diet for 5 months, and in the last 2 months of the regimen they received a battery of behavioural tests. In general, both aging and (to a higher extent) Tg2576 genotype deteriorated sensorimotor reflexes, exploratory behaviour in the hole board, activity (but not anxiety) in the elevated plus-maze, ambulation in the home cage during the dark phase, and spatial learning in the Morris water maze. LMN diet did not affect the detrimental effects observed in sensorimotor reflexes, but clearly reversed the effects of both aging and Tg2576 genotype. This behavioural amelioration was correlated with a 70% increase in cellular proliferation in subventricular zone (SVZ) of the brain, but did not correlate with a decrease of amyloid plaques. In contrast, administration of LMN diet to 10 months old mice (before the plaques are formed) strongly suggested a putative delay in the formation of plaques, as indicated by a decreasing tendency of soluble and fibrillar Aβ levels in hippocampus which correlated with a decrease in Aβ (1-40, 1-42) plasma content. Herein we describe for the first time that LMN diet rich in polyphenols, dry fruits and cocoa, was able to decrease behavioural deterioration caused by aging and Tg2576 genotype and to delay the Aβ plaque formation. These results corroborate the increasing importance of polyphenols as human dietary supplements in amelioration of the cognitive impairment during aging and neurological disorders such as AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging*
  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Protein Precursor / genetics
  • Analysis of Variance
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation / drug effects
  • Cognition Disorders / diet therapy*
  • Cognition Disorders / etiology*
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Fatty Acids, Unsaturated / administration & dosage*
  • Humans
  • Learning / drug effects
  • Learning / physiology
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Transgenic
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Muscle Strength / drug effects
  • Muscle Strength / genetics
  • Mutation / genetics
  • Plaque, Amyloid
  • Polyphenols / administration & dosage*
  • Postural Balance / drug effects
  • Postural Balance / genetics
  • Reaction Time / drug effects
  • Reaction Time / genetics
  • Reflex / drug effects
  • Reflex / genetics
  • Sensory Gating / drug effects
  • Sensory Gating / physiology


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Fatty Acids, Unsaturated
  • Polyphenols
  • Bromodeoxyuridine