The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS).

BACKGROUND: The effect of diet on age-related brain atrophy is largely unproven. OBJECTIVES: We aimed to explore the effect of a Mediterranean diet (MED) higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy. METHODS: This 18-mo clinical trial longitudinally measured brain structure volumes by MRI using hippocampal occupancy score (HOC) and lateral ventricle volume (LVV) expansion score as neurodegeneration markers. Abdominally obese/dyslipidemic participants were randomly assigned to follow 1) healthy dietary guidelines (HDG), 2) MED, or 3) Green-MED diet. All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28 g walnuts/d (+440 mg/d polyphenols). The Green-MED group consumed green tea (3-4 cups/d) and Mankai (Wolffia-globosa strain, 100 g frozen cubes/d) green shake (+800 mg/d polyphenols). RESULTS: Among 284 participants (88% men; mean age: 51 y; BMI: 31.2 kg/m2; APOE-ε4 genotype = 15.7%), 224 (79%) completed the trial with eligible whole-brain MRIs. The pallidum (-4.2%), third ventricle (+3.9%), and LVV (+2.2%) disclosed the largest volume changes. Compared with younger participants, atrophy was accelerated among those ≥50 y old (HOC change: -1.0% ± 1.4% compared with -0.06% ± 1.1%; 95% CI: 0.6%, 1.3%; P < 0.001; LVV change: 3.2% ± 4.5% compared with 1.3% ± 4.1%; 95% CI: -3.1%, -0.8%; P = 0.001). In subjects ≥ 50 y old, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared with HDG (HOC: -0.8% ± 1.6% compared with -1.3% ± 1.4%; 95% CI: -1.5%, -0.02%; P = 0.042; LVV: 2.3% ± 4.7% compared with 4.3% ± 4.5%; 95% CI: 0.3%, 5.2%; P = 0.021). Similar patterns were observed among younger subjects. Improved insulin sensitivity over the trial was the parameter most strongly associated with brain atrophy attenuation (P < 0.05). Greater Mankai, green tea, and walnut intake and less red and processed meat were significantly and independently associated with reduced HOC decline (P < 0.05). Elevated urinary concentrations of the polyphenols urolithin-A (r = 0.24; P = 0.013) and tyrosol (r = 0.26; P = 0.007) were significantly associated with lower HOC decline. CONCLUSIONS: A Green-MED (high-polyphenol) diet, rich in Mankai, green tea, and walnuts and low in red/processed meat, is potentially neuroprotective for age-related brain atrophy.This trial was registered at clinicaltrials.gov as NCT03020186.

Association of peripheral blood pressure with gray matter volume in 19- to 40-year-old adults.

OBJECTIVE: To test whether elevated blood pressure (BP) relates to gray matter (GM) volume (GMV) changes in young adults who had not previously been diagnosed with hypertension (systolic BP [SBP]/diastolic BP [DBP] ≥140/90 mm Hg). METHODS: We associated BP with GMV from structural 3T T1-weighted MRI of 423 healthy adults between 19 and 40 years of age (mean age 27.7 ± 5.3 years, 177 women, SBP/DBP 123.2/73.4 ± 12.2/8.5 mm Hg). Data originated from 4 previously unpublished cross-sectional studies conducted in Leipzig, Germany. We performed voxel-based morphometry on each study separately and combined results in image-based meta-analyses (IBMA) to assess cumulative effects across studies. Resting BP was assigned to 1 of 4 categories: (1) SBP <120 and DBP <80 mm Hg, (2) SBP 120-129 or DBP 80-84 mm Hg, (3) SBP 130-139 or DBP 85-89 mm Hg, (4) SBP ≥140 or DBP ≥90 mm Hg. RESULTS: IBMA yielded the following results: (1) lower regional GMV was correlated with higher peripheral BP; (2) lower GMV was found with higher BP when comparing individuals in subhypertensive categories 3 and 2, respectively, to those in category 1; (3) lower BP-related GMV was found in regions including hippocampus, amygdala, thalamus, frontal, and parietal structures (e.g., precuneus). CONCLUSION: BP ≥120/80 mm Hg was associated with lower GMV in regions that have previously been related to GM decline in older individuals with manifest hypertension. Our study shows that BP-associated GM alterations emerge continuously across the range of BP and earlier in adulthood than previously assumed. This suggests that treating hypertension or maintaining lower BP in early adulthood might be essential for preventing the pathophysiologic cascade of asymptomatic cerebrovascular disease to symptomatic end-organ damage, such as stroke or dementia.