O4‐06‐06: Modulating dietary fat and glycemic load affects CSF biomarkers and cognition in adults with MCI: The role of the Western diet in the pathophysiology of Alzheimer's disease
Year: 2010
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Insulin resistance and hyperinsulinemia are associated with an increased risk of amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD), potentially through effects on Aβ regulation, inflammation, dyslipidemia, and/or glucose metabolism. Diets high in saturated fats and simple carbohydrates that typify the “Western diet” reliably induce hyperinsulinemia and insulin resistance, and thus may serve as environmental triggers for AD. We examined the effects of dietary modulation of insulin sensitivity on cognition and cerebrospinal fluid (CSF) Aβ and insulin levels. Adults with amnestic MCI (n = 29, mean age = 67.6 y, SD = 6.8) and healthy adults (n = 20, mean age = 69.2 y, SD = 7.3) were randomized to one of two isocaloric diet conditions: a high saturated fat and high glycemic index (HSF/HGI; total fat 45%, 25% SF, >70 GI) diet, or a low saturated fat and low glycemic index (LSF/LGI; total fat 25%, <8%SF, <55 GI) for 4 weeks. Participants received cognitive testing and lumbar punctures for CSF collection before and following the diet intervention. The HSF/HGI diet increased fasting plasma insulin, LDL and total cholesterol, whereas the LSF/LGI diet lowered these parameters, with greater effects demonstrated for participants with MCI (p < 0.05). Changes in LDL were associated with increased CSF Aβ40 in the HSF/HGI condition and lowered CSF Aβ40 in the LSF/LGI condition. CSF Aβ42 levels increased for the MCI group consuming the HSF/HGI diet (p < 0.05). The lipoprotein-free fraction of CSF Aβ42, which may have potent neurotoxic effects, decreased with the LSF/LGI diet and increased with the HSF/HGI diet for both normal and MCI groups (p < 0.01). CSF insulin levels and the CSF-plasma insulin ratio decreased in the HSF/HGI group and increased in the LSF/LGI group, consistent with previous reports that inducing insulin resistance reduces insulin transport into the brain (ps<0.05). Greater reduction in CSF insulin levels was associated with increased lipoprotein-free CSF Aβ42 in the HSF/HGI condition (p < 0.05) and lowered lipoprotein-free CSF Aβ42 in the LSF/LGI condition (p < 0.05). Changes in CSF lipoprotein-free Aβ42 and CSF non-esterified fatty acids predicted performance on tests of memory and attention (ps<0.05). These results demonstrate a close association between diet composition and AD-related biomarkers that may have important implications for environmental modulation of AD risk.
Source: Alzheimer s & Dementia
Institutions: University of Washington, VA Puget Sound Health Care System
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2109284940