Mediterranean and Western diet effects on Alzheimer's disease biomarkers, cerebral perfusion, and cognition in mid-life: A randomized trial

Abstract

Introduction: Mid-life dietary patterns are associated with Alzheimer's disease (AD) risk, although few controlled trials have been conducted.

Methods: Eighty-seven participants (age range: 45 to 65) with normal cognition (NC, n = 56) or mild cognitive impairment (MCI, n = 31) received isocaloric diets high or low in saturated fat, glycemic index, and sodium (Western-like/West-diet vs. Mediterranean-like/Med-diet) for 4 weeks. Diet effects on cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral perfusion were assessed to determine whether responses differed by cognitive status.

Results: CSF amyloid beta (Aβ)_42/40 ratios increased following the Med-diet, and decreased after West-diet for NC adults, whereas the MCI group showed the reverse pattern. For the MCI group, the West-diet reduced and the Med-diet increased total tau (t-tau), whereas CSF Aβ₄₂ /t-tau ratios increased following the West-diet and decreased following the Med-diet. For NC participants, the Med-diet increased and the West-diet decreased cerebral perfusion.

Discussion: Diet response during middle age may highlight early pathophysiological processes that increase AD risk.

Keywords: Alzheimer's disease; cerebral perfusion; cerebrospinal fluid biomarkers; diet intervention.

FIGURE 1

Consort diagram of study enrollment

FIGURE 2

Diet effects on peripheral metabolism. A‐C) Total cholesterol, low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) levels were significantly reduced following the Mediterranean diet (Med‐diet) and increased following the Western diet (West‐diet) for both normal cognition (NC) and mild cognitive impairment (MCI) groups (all Ps < .001). D, Plasma glucose levels increased for the NC group and decreased for the MCI group following the West‐diet (P = .01), with no changes observed for groups following the Med‐diet. E Plasma insulin levels increased for the NC group and decreased for the MCI group following Med‐diet (P = .031). Insulin also tended to decrease for the MCI but not the NC group during the West‐diet (P = .051). F, The NC group showed increased HbA1c levels following the West‐diet, and the MCI group showed decreased levels (P = .049). Figures depict change scores for ease of interpretation, adjusted means from repeated measures analysis of covariance are included in Table S2. Error bars represent ± 1 standard error from the mean. Significance is set at ⁺ P < .10, *P < .05, ** P < .01, or *** P < .001

FIGURE 3

Diet effects on cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. A, CSF amyloid beta (Aβ)₄₀ decreased for normal cognition (NC) participants following the Mediterranean diet (Med‐diet) and increased following the Western diet (West‐diet; P = .026). B, The CSF Aβ_42/40 ratio increased for NC participants following the Med‐diet and decreased after the West‐diet (P = .014), and the mild cognitive impairment (MCI) participants showed a trend for the reverse pattern (P = .064). C, Total tau (t‐tau) was increased by the Med‐diet and reduced by the West‐diet for the MCI group (P = .044). D, The Aβ₄₂/t‐tau ratio was reduced following the Med‐diet for the MCI group and increased following the West‐diet (P = .036). Figures depict change scores for ease of interpretation, adjusted means from repeated measures analysis of covariance are included in Table S2. Error bars represent ± 1 standard error from the mean. Significance is set at ⁺ P < .10, *P < .05, ** P < .01, or *** P < .001

FIGURE 4

Diet effects on cerebral perfusion assessed with pseudo‐continuous arterial spin labeling (pcASL) magnetic resonance imaging (MRI). A, Rendering of the a priori anatomical mask used in the study constructed using WFU PickAtlas toolbox. The mask included the bilateral superior, inferior, middle and medial frontal cortices; superior, middle, and inferior temporal gyrus; posterior cingulate, precuneus, parahippocampal gyrus; amygdala; and hippocampus. B, The Mediterranean diet (Med‐diet) was associated with significantly greater cerebral perfusion following diet intervention compared to the Western diet (West‐diet) group in the (a) left inferior frontal cortex and the right temporal lobe (b), hippocampus (c), and precuneus (d). C, Normal cognition (NC) participants showed increased mean cerebral perfusion after the Med‐diet, and decreased perfusion after the West‐diet (P = .003). Although the mild cognitive impairment (MCI) group perfusion values also increased following the Med‐diet, this effect was variable and did not approach significance (P = .499). Figures depict change scores for ease of interpretation, adjusted means from repeated measures analysis of covariance are included in Table S2. Error bars represent ± 1 standard error from the mean. Significance is set at ⁺ P < .10, *P < .05, ** P < .01, or *** P < .001

FIGURE 5

Diet effects on cognition. Diet affected cognition differently for normal cognition (NC) and mild cognitive impairment (MCI) groups (diet x diagnosis x time F_[1,71] = 4.00, P = .049). No individual comparisons between groups achieved significance; the NC group's scores tended to improve for the Mediterranean diet (Med‐diet) and remain unchanged for the Western diet (West‐diet; P = .077), whereas the MCI group scores were unchanged. Figures depict change scores for ease of interpretation, adjusted means from repeated measures analysis of covariance are included in Table S2. Error bars represent ± 1 standard error from the mean. Significance is set at ⁺ P < .10, *P < .05, ** P < .01, or *** P < .001