Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment

A 24 Weeks Double-blind Latin-square Trial of Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment

Manipulation of the gut microbiota through dietary modification affects brain function, with improvement in patients with cognitive disorders. Combined effect of nutritional intervention with Mediterranean diet and probiotics with potentially healthy growth of germ, affect the evolution of mild cognitive impairment, by the modulation of components related with the axis microbiota-gut-brain: neuropeptides, short-chain fatty acids, markers for oxidative stress and inflammation.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Healthy diet (WHO recommendations); Dietary supplement: Mediterranean diet; Dietary supplement: Biopolis-MIX42

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Cordoba, Spain
    • Reina Sofia University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age> = 60 years with mild cognitive impairment (Clinical Dementia Rating (CRD) 0.5; Mini Mental Examiantion de Folstein (MMSE)> 23; Repeatable Battery for the Asessment of Neuropsychological Status (RBANS) <= 85)
• Drugs with a stable dose from a minimum of 4 weeks prior to screening (excluding psychopharmaceuticals and any other that could affect alertness and cognitive ability)
• Geriatric depression scale score <6
• Sufficient visual and auditory abilities to carry out the neuropsychological tests. Good health without diseases that prevent the completion of the study.
• A minimum educational training established for 6 years or similar work history.
• A familiar informant or close caregiver with a minimum contact with the patient established in 10 hours per week that can accompany the participant to the clinical visits

Exclusion Criteria:

• Any uncontrolled medical or neurological condition that, in the opinion of the researcher, could contribute to the subject's cognitive impairment (for example, substances abuse, vitamin B12 deficiency, abnormal thyroid function, stroke, or other Cerebral vascular disease, Lewy body dementia, frontotemporal dementia, TBI).
• A clinically significant psychiatric illness (eg, major depression, schizophrenia, or bipolar affective disorder) in the 6 months prior to screening.
• Transient ischemic attack or cerebrovascular accident or any unexplained loss of consciousness in 1 year before selection (in case of vascular deficit with cognitive sequelae that may still be reversible).
• Poorly controlled diabetes mellitus, due to a glycosylated haemoglobin (HbA1c) value of 8% in the selection.
• History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class 3 or 4), or clinically significant conduction disorders (unstable atrial fibrillation) within 1 year prior to screening.
• Uncontrolled hypertension defined as the mean of 3 measures of systolic blood pressure / diastolic blood pressure> 165/100 mmHg, and persistent systolic blood pressure / diastolic blood pressure > 180/100 mmHg in the 3 months prior to randomization which were considered by the researcher as an indicative of chronic uncontrolled hypertension.
• History of seizures in the 10 years prior the selection.
• Recent history (within 1 year of screening) of alcohol or substance abuse with positive urine test (looking for non-prescription drugs), alcohol or cannabinoids.
• Patients with chronic diseases will be excluded: severe psychiatric, chronic processes in need of treatment such as chronic kidney failure, chronic liver disease, neoplasms under treatment, chronic obstructive pulmonary disease, endocrinopathies susceptible to decompensation and digestive tract diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Healthy diet Arm; Healthy diet (WHO recommendations) + placebo	Dietary supplement: Placebo; Placebo; Dietary supplement: Healthy diet (WHO recommendations); Recommendations according to WHO
Placebo Comparator: Mediterranean diet Arm; Mediterranean diet + placebo	Dietary supplement: Placebo; Placebo; Dietary supplement: Mediterranean diet; Mediterranean diet: 22% Monounsaturated fat, 6% Polyunsaturated fat, 7% Saturated fat, 15% Protein, 50% Carbohydrates
Active Comparator: Mediterranean diet "plus" Arm; Mediterranean diet + Biopolis-MIX42 (1 capsule per day containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium long).	Dietary supplement: Mediterranean diet; Mediterranean diet: 22% Monounsaturated fat, 6% Polyunsaturated fat, 7% Saturated fat, 15% Protein, 50% Carbohydrates; Dietary supplement: Biopolis-MIX42; Biopolis-MIX42: a capsule containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium longum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive change	Cognitive change in Alzheimer's Disease Assessment Scale-Cognitive-Plus ("ADAS-Cog- Plus"). The total ADAS-Cog-plus score ranges from 0-70 with higher scores suggesting greater impairment.	Baseline and 24 weeks after each dietary intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiota pattern	Changes in the percentage of different families of Microbiota will be analysed during the study	Baseline and 24 weeks after each dietary intervention
Endotoxemia levels	Changes in the endotoxemia levels will be analysed during the study	Baseline and 24 weeks after each dietary intervention
Change in inflammatory marker	At time 0 and after 24 weeks of each intervention period and follow-up, the levels of high sesitivity C-reactive protein (hs-CRP) were determined in plasma in mg/dL.	Baseline and 24 weeks after each dietary intervention
Change in oxidative stress parameters	At time 0 and after 24 weeks of each intervention period and follow-up, the levels of advanced glycation end products (AGEs) were determined in serum in ug/mL: methylglioxal (MG) and N-carboxymethyllysine (CML). Likewise, carbonilated proteins in nmol/mg and lipid peroxidation levels in plasma in ug/mL.	Baseline and 24 weeks after each dietary intervention
Neurofunctional change	At time 0 and after 24 weeks of each intervention period and follow-up, neurofunctional changes were measured by emission tomography with 2-deoxy-2-[fluorine-18]fluoro- D-glucose (18F-FDG-PET)	Baseline and 24 weeks after each dietary intervention
Modulation of Microbiota-gut-nervous system	Changes in the plasma levels of molecules with activity on the nervous system were analysed during the study. At time 0 and after 24 weeks of each intervention period and follow-up, Gamma-Aminobutiric acid (GABA) in ng/mL and short-chain fatty acids (acetate, propionate and butirate) in ng/mL were determined in plasma.	Baseline and 24 weeks after each dietary intervention
Change in cytokine levels	At time 0 and after 24 weeks of each intervention period and follow-up, the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) were determined in plasma in pg/mL.	Baseline and 24 weeks after each dietary intervention
Neuropeptides modulation	Changes in the plasma levels of molecules with activity on the nervous system were analysed during the study. At time 0 and after 24 weeks of each intervention period and follow-up, Substance P (SP), Y Peptide (PYY), beta-amyloid in pg/mL were determined in plasma.	Baseline and 24 weeks after each dietary intervention

Collaborators and Investigators

• Sponsor: Pablo Pérez Martínez
• Investigators: Principal Investigator: Pablo Perez-Martinez, PhD, MD, IMIBIC/ Reina Sofia University Hospital / University of Cordoba

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2017
• Primary Completion (Actual): March 5, 2020
• Study Completion (Actual): March 5, 2020

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Microbiota; Probiotics; Mild Cognitive Impairment; Mediterranean diet
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: PI16/01777

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No