Diet and Alzheimer’s Connections : Cracking the Code

Metabolic dysregulation conditions such as obesity, hypertension, type 2 diabetes, and hypercholesterolemia have increased due to the rising consumption of saturated fats, simple carbohydrates, and sodium, which are characteristic features of the Western diet. These conditions may promote pathological brain aging, with type 2 diabetes decreasing cerebral perfusion and increasing the risk for Alzheimer’s disease and other dementias. A high intake of saturated fats and simple carbohydrates is associated with an increased risk of Alzheimer’s disease, while diets low in these factors are associated with a lower risk. The common feature of insulin resistance among vascular risk factors suggests that the interface between insulin resistance and vascular function may be a critical mechanistic pathway, increasing the risk for Alzheimer’s disease and vascular dementia. This recent study compared the effects of a Western-like diet and a Mediterranean-like diet on metabolic parameters, cerebral perfusion assessed with magnetic resonance imaging, and cognition, observing striking differences between the groups with mild cognitive impairment and normal cognition in response to diet, which may highlight key early pathophysiological processes.

Participants were screened prior to starting the experiment and were randomly assigned to either the Med-diet or West-diet group. The caloric assignment for each group was determined using the basal metabolic rate calculated with the Mifflin St. Jeor equation. Both diets were designed to maintain body weight stability during the 4-week intervention. The Med-diet was modeled after a Mediterranean diet and was low in saturated fats, low in glycemic index (GI), low in sodium (Na+), and high in healthy fats, fruits, vegetables, and whole grains. The West-diet was high in saturated fats, high in GI, high in Na+, and had a higher total sodium intake compared to the Med-diet. Compliance was assessed using daily food journals and participants were contacted once a week to confirm compliance. Measures were collected again at the end of week 4.

To test for differences within the group, participants were involved in lumbar puncture’s to collect CSF from participants, which was then assayed for amyloid beta, total tau, phosphorylated tau, and CSF Aβ40 using kits from Fujirebio. Blood biomarkers such as lipids, insulin, glucose, and HbA1c were measured, as well as APOE genotyping. Cognitive tests were conducted pre- and post-diet intervention, which included tests of delayed episodic memory and the Dot Counting Test of executive function. Participants also underwent MRI with a 3T Siemens Skyra scanner and a 32 channel head coil, which included high-resolution T1-weighted structural images and pcASL MRI to assess cerebral blood flow. Scans from 49 participants with complete data that passed quality control inspections were included in a whole-brain voxel-wise analysis.

In a study with 157 participants screened, 87 were randomized to either the Med-diet or West-diet arm. 41 participants completed the Med-diet arm and 43 participants completed the West-diet arm. There were no differences in demographic characteristics or in body mass index between the assigned diet groups. The MCI group had lower 3MS scores than the NC group with no other significant demographic differences noted.

The study found that both NC and MCI groups had a decrease in total cholesterol levels after a Mediterranean diet and an increase after a Western diet while fasting plasma glucose levels remained unchanged after the Mediterranean diet and decreased after the Western diet in the MCI group but increased in the NC group. Insulin levels increased in the NC group and decreased in the MCI group following the Mediterranean diet, and decreased for the MCI group during the Western diet. Aβ40 levels decreased after the Mediterranean diet and increased after the Western diet in the NC group, but were unchanged in the MCI group. The CSF Aβ42/40 ratio increased in the NC group following the Mediterranean diet and reduced following the Western diet, while the MCI group showed a trend for the reverse pattern. t-tau levels increased following the Mediterranean diet and decreased after the Western diet for the MCI group but were unchanged for the NC group. The Med-diet > West-diet yielded clusters of significance in the left inferior frontal cortex, right middle temporal gyrus, and parahippocampal gyri, posterior cingulate, precuneus, and hippocampus regions for cerebral blood perfusion.

The study provides evidence that dietary patterns have a significant impact on metabolic function, cerebrovascular health, Alzheimer’s disease (AD) pathology, and cognitive function. Adherence to a Western-like dietary pattern may increase the risk of AD for middle-aged adults without cognitive impairment, while a Mediterranean-like diet promotes metabolic and brain health. However, a Western-like diet may have beneficial effects for adults with Mild Cognitive Impairment. Future studies are needed to confirm these results and identify the specific mechanisms underlying these effects. Overall, these findings suggest that diet could be an important tool for preventing or modulating disease progression in AD that helps with : Cracking the Code .

References of the article and images:

Hoscheidt S, Sanderlin AH, Baker LD, et al. Mediterranean and Western diet effects on Alzheimer’s disease biomarkers, cerebral perfusion, and cognition in mid-life: A randomized trial. Alzheimer’s Dement. 2022;18:457–468. https://doi.org/10.1002/alz.12421