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Original Contribution
June 2011

Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment

Author Affiliations

Author Affiliations: Geriatric Research, Education, and Clinical Center (Ms Bayer-Carter and Drs Green, VanFossen, Baker, Watson, Bonner, Callaghan, Plymate, Wilkinson, and Craft), Parkinson's Disease Research, Education, and Clinical Center (Dr Leverenz), and Departments of Neurology (Dr Walter) and Medicine (Dr Kahn), Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, and Departments of Psychiatry and Behavioral Science (Ms Bayer-Carter and Drs VanFossen, Baker, Watson, Bonner, Wilkinson, and Craft), Medicine (Drs Green, Tsai, Plymate and Kahn), Pathology (Drs Montine, Postupna, and Zhang), and Neurology (Drs Leverenz and Walter), University of Washington School of Medicine, and Fred Hutchinson Cancer Research Center (Dr Lampe), Seattle, Washington.

Arch Neurol. 2011;68(6):743-752. doi:10.1001/archneurol.2011.125

Objective  To compare the effects of a 4-week high–saturated fat/high–glycemic index (HIGH) diet with a low–saturated fat/low–glycemic index (LOW) diet on insulin and lipid metabolism, cerebrospinal fluid (CSF) markers of Alzheimer disease, and cognition for healthy adults and adults with amnestic mild cognitive impairment (aMCI).

Design  Randomized controlled trial.

Setting  Veterans Affairs Medical Center clinical research unit.

Participants  Forty-nine older adults (20 healthy adults with a mean [SD] age of 69.3 [7.4] years and 29 adults with aMCI with a mean [SD] age of 67.6 [6.8] years).

Intervention  Participants received the HIGH diet (fat, 45% [saturated fat, > 25%]; carbohydrates, 35%-40% [glycemic index, > 70]; and protein, 15%-20%) or the LOW diet (fat, 25%; [saturated fat, < 7%]; carbohydrates, 55%-60% [glycemic index, < 55]; and protein, 15%-20%) for 4 weeks. Cognitive tests, an oral glucose tolerance test, and lumbar puncture were conducted at baseline and during the fourth week of the diet.

Main Outcome Measures  The CSF concentrations of β-amyloid (Aβ42 and Aβ40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition.

Results  For the aMCI group, the LOW diet increased CSF Aβ42 concentrations, contrary to the pathologic pattern of lowered CSF Aβ42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF Aβ42, whereas the HIGH diet increased CSF Aβ42. The CSF apolipoprotein E concentration was increased by the LOW diet and decreased by the HIGH diet for both groups. For the aMCI group, the CSF insulin concentration increased with the LOW diet, but the HIGH diet lowered the CSF insulin concentration for healthy adults. The HIGH diet increased and the LOW diet decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. Delayed visual memory improved for both groups after completion of 4 weeks of the LOW diet.

Conclusion  Our results suggest that diet may be a powerful environmental factor that modulates Alzheimer disease risk through its effects on central nervous system concentrations of Aβ42, lipoproteins, oxidative stress, and insulin.