12‐weeks of caloric restriction diet improves cortical cerebral blood flow in healthy middle‐age adults

Abstract

AbstractBackgroundCaloric restriction (CR) improves neuronal stress resistance in animals and improves cognitive performance in older adults (1‐3). Neuroinflammation is an increasingly recognized mechanism relevant to Alzheimer disease (AD). We investigated the effect of a 12‐week CR diet on imaging markers of dementia and neuroinflammation in midlife individuals with multiple sclerosis (MS), a prototype neuroinflammatory disease.MethodsIn a single‐blind randomized controlled trial, 10 participants with MS (8 women and 2 men, age: 45.5±10.67 and education: 16.4±2.5 years) were recruited from the Washington University John L. Trotter MS Center and randomly assigned to participate in either a 12‐week CR or control group on their regular diet. Participants fasted 2 days a week and during those days eating no more than 500 calories. Participants underwent MRI scanning at the time of recruitment and at the end of the 12‐week program. Volumetric analyses were conducted through FreeSurfer 7.1.1 (4), relative regional cerebral blood flow (rCBF) was obtained through ASL‐MRICloud (5), and hindered and restricted diffusion fractions (HF and RF) were calculated through the diffusion basis spectrum imaging (DBSI), representing tissue edema and inflammatory cell infiltration respectivelyResultsSix participants were obese, two were overweight and two had normal weight with an average BMI of 30.3±5.48 kg/m2 across participants. Following 12‐weeks of CR, participants showed an increase in normalized hippocampal volume (p:0.02) compared to those on regular diet. CR also resulted in improved cortical thickness in the bilateral medial orbitofrontal cortices compared to the control group (p:0.014). An average increase in relative perfusion (rCBF) in the bilateral inferior temporal gyri (p:0.02, & p:0.004) and bilateral fusiform gyri (p:0.008 & p:0.002) was observed in participants undergoing CR compared to those on a regular diet at the end of 12‐weeks (Figure 1 and 2). Being on a CR diet was associated with reduced HF and RF in the bilateral inferior longitudinal fasciculi (p:0.04 & p:0.002) indicating reduced edema and cellularity (6).ConclusionCR is associated with alterations in brain’s structure and function in terms of improved volumetric measurements, regional perfusion and reduced tissue inflammation, and hence implicated as a neuroprotective intervention in midlife persons.