High-fat diets and cognition: effects and mechanisms

  • Fiona Ramage

    Student thesis: Doctoral ThesisDoctor of Philosophy

    Abstract

    Western diets high in fats and sugars have been gaining in popularity over the last few decades. Concerningly, their consumption is associated with the development of metabolic and cognitive dysfunction, as well as an increased risk of dementias such as Alzheimer’s disease. Clinical and preclinical research has aimed to determine how these diets cause cognitive impairment, but disease mechanisms are not yet fully understood.

    In the first part of this thesis, I aimed to replicate a previous study showing rapid cognitive deficits with brief exposure to a high-fat diet (HFD). I contrast the HFD to a high-fat, low-carbohydrate ketogenic diet (KD). Initial results showed a rapid effect of 1-5 days exposure to a HFD on body weight and adiposity, as well as deficits in hippocampal-dependent object recognition tasks absent in KD or control groups. However, rescoring behaviour videos while blinded suggested no diet-induced cognitive impairment and overall poor task performance. This finding was concerning, due to the poor reporting of blinding in neuroscience literature.

    In subsequent sections, I present a systematic review and meta-analysis of the effects of HFDs on cognition in rodents as well as a study of potential underlying mechanisms. This review was designed to summarise a vast field with often conflicting results, to better understand the impact of study design heterogeneity on HFD effects, as well as appraising study quality and risk of bias and their impact for the first time in nutritional neuroscience literature. In addition to capturing a huge amount of heterogeneity in study design and animal and diet models used, I contrast the impact of these variables on cognition with current views in the field. I also present evidence of issues such as pseudoreplication and publication bias. Finally, I present data on the impact of interventions/treatments on HFD-induced cognitive deficits, and the effects of HFDs on peripheral metabolism and hippocampal neuropathology, in a preliminary exploration of mechanisms of HFD-induced cognitive changes.
    Date of Award2023
    Original languageEnglish
    SponsorsBiotechnology and Biological Sciences Research Council
    SupervisorRos Langston (Supervisor), Malcolm Macleod (Supervisor), Jeremy Lambert (Supervisor) & Lynda M. Williams (Supervisor)

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