High Saturated-Fat Diet May Promote Cognitive Decline

A high saturated-fat, high glycemic-index diet may promote age-related cognitive impairment, if CSF levels of beta amyloid 1-42 are any indication. This conclusion—and it may be a considerable leap—is based on data from a newly published study in the Archives of Neurology (subscription required). The general assumption of the study authors, from the University of Washington, is that a declining CSF level of beta amyloid 1-42 is indicative of the road to Alzheimer disease (AD)—an assumption that is generally supported by animal models and some clinical data.

In this randomized, double-blind study, 49 elderly adults consumed a high or low saturated-fat diet for 4 weeks. In those with normal cognition (n = 20), the "low diet" decreased CSF levels of beta amyloid 1-42, and the "high diet" increased CSF beta amyloid. In the 29 subjects with amnestic mild cognitive impairment (aMCI), the CSF levels of beta amyloid rose with the low diet and didn't change with the high diet. CSF levels of apolipoprotein, which (putatively) clears beta amyloid from the CNS, increased with the low diet and declined with the high diet.

Variable	Normal Cognition		aMCI
	Low Diet	High diet	Low Diet	High Diet
Beta-amyloid 42	↓	↑	↑	—
Apolipoprotein E	↑	↓	↑	↓

The authors conclude that the observed pattern of a rising CSF level of beta amyloid 1-42 with the high-fat diet in cognitively normal subjects is a sign of these individuals are approaching a "tipping point" toward the CNS deposition of amyloid and the formation of amyloid-laden plaques in the brain. Conversely the rising beta-amyloid level in aMCI patients who consumed a low-fat diet indicates that this group is moving back toward the "tipping point," the authors argue, and away from the AD-consistent pattern of lower CSF beta amyloid.

The authors' explanation for their results amounts to considerable speculation, which nevertheless may be correct. What is potentially troubling, however, about their data is that CSF levels of tau (both total and phosphorylated) did not change in any group. Rising CSF levels of tau, along with declining levels of beta amyloid 1-42, have been proposed as an "AD signature." This pattern was observed in 72% of subjects with MCI in a heavily publicized study from last year (which was also printed in the Archives of Neurology).

CSF = cerebrospinal fluid.

Photograph of atrophied brain from person with AD: National Institute on Alcohol Abuse and Alcoholism.