Nutrition is an important modifiable risk factor of human cognitive health. Increasing data suggests that certain nutrients or food ingredients, such as plant polyphenols, have the potential to benefit cognitive abilities even in later life. In terms of polyphenols, Hydroxytyrosol (HT) has gained health benefit claims as a potential preventative antioxidant supplementation of neurodegenerative and amyloid-associated diseases while its pharmacological mechanisms suggest protection against cognitive decline. The primary objective of this study will be to evaluate the effects of HT-rich olive juice polyphenol supplementation alongside MeDi adherence compared with placebo alongside MeDi adherence in the prevention of cognitive decline among patients with Mild Cognitive Impairment associated with AD and non-AD pathology.
GR-based men and women aged 50 - 85
Willingness and ability to conform to the full protocol.
Ability to accept and sign the consent form.
Presence of a diagnostic classification of Mild Cognitive Impairment according to the National Institute on Aging and Alzheimer's Association (NIA-AA) framework MCI, which corresponds to stage 3 on the pre-dementia range.
Patients with mild, moderate, or severe dementia.
Current or recent (within the last 4 weeks) engagement with a strict dietary regime i.e., vegetarian / vegan / ketogenic / paleolithic / high protein / weight loss.
Any known issues with blood taking.
Any known bleeding disorders.
Parallel
Low-Dose Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement
Dietary supplementThis is a prospective, randomised, double-blind, three-arm, placebo-controlled with 1:1:1 randomisation and 52-week follow-up trial. The MEDIPHENO-HTrial study will enrol patients within the Mild Cognitive Impairment spectrum related to AD and non-AD type pathologies. Participants will be randomised to receive either 8 drops of the active HT-high phenolic supplement, or 16 drops of the active HT-high phenolic supplement or 8 drops of the matching placebo. The Mediterranean diet adherence support will be delivered identically to all groups to reduce dietary confounding.
High-Dose Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement
Dietary supplementThis is a prospective, randomised, double-blind, three-arm, placebo-controlled with 1:1:1 randomisation and 52-week follow-up trial. The MEDIPHENO-HTrial study will enrol patients within the Mild Cognitive Impairment spectrum related to AD and non-AD type pathologies. Participants will be randomised to receive either 8 drops of the active HT-high phenolic supplement, or 16 drops of the active HT-high phenolic supplement or 8 drops of the matching placebo. The Mediterranean diet adherence support will be delivered identically to all groups to reduce dietary confounding.
Placebo
Dietary supplementThis is a prospective, randomised, double-blind, three-arm, placebo-controlled with 1:1:1 randomisation and 52-week follow-up trial. The MEDIPHENO-HTrial study will enrol patients within the Mild Cognitive Impairment spectrum related to AD and non-AD type pathologies. Participants will be randomised to receive either 8 drops of the active HT-high phenolic supplement, or 16 drops of the active HT-high phenolic supplement or 8 drops of the matching placebo. The Mediterranean diet adherence support will be delivered identically to all groups to reduce dietary confounding.
Primary: Mean change on the Alzheimer's Disease (AD) Assessment Scale-Cognitive Subscale (ADAS-Cog) total score from baseline to Week 52 compared with placebo
The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on the cognitive performance of patients with MCI as measured by ADAS-Cog. ADAS-Cog ranges from 0-85 by summing the number of errors made on each task, so that higher scores indicate worse performance.
Key secondary: Mean change on the Montreal Cognitive Assessment Test (MoCA) total score from baseline to Week 52 compared with placebo
The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on the cognitive performance of patients with MCI as measured by MoCA. The total possible score for the test is 30 points by summing the number of correct responses given in each task, so higher scores indicate better performance.
- Mean change on Clinical Dementia Rating - Sum of boxes (CDR-SB) from baseline to Week 52 compared with placebo
\- The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on the CDR-SB, which ranges from 0 to 18, and is calculated by summing the ratings across each of the six domains (memory, orientation, judgment and problem-solving, community affairs, home and hobbies, and personal care), with higher scores indicating greater impairment.
Mean change on Mini-Mental State Examination (MMSE) from baseline to Week 52 compared with placebo
The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on the MMSE, which is a 30-point brief screening measure of cognitive status. Higher scores indicate better performance.
- Mean change on Geriatric Depression Scale-15 (GDS-15) from baseline to Week 52 compared with placebo.
\- The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on GDS-15, which consists of 15 items and is used to screen for depression in adults. GDS-15 assess mental health based on feelings over the past week, with higher scores on the measure denoting more severe levels of depressive symptoms.
Mean percentage change in plasma phosphorylated tau 217 (p-tau217) pg/mL from baseline to Week 52 compared with placebo.
Exploratory analyses will include blood biomarkers, p-tau217 pg/mL. Mean percentage change in plasma p-tau217 pg/mL from baseline to Week 52 compared with placebo.
Mean percentage change in plasma levels of beta-amyloid 1-42 (Aβ 1-42) pg/mL from baseline to Week 52 compared with placebo.
Exploratory analyses will include blood biomarkers, Aβ 1-42 pg/mL. Mean percentage change in plasma levels of Aβ 1-42 pg/mL from baseline to Week 52 compared with placebo.
Mean percentage change in plasma Glial Fibrillary Acidic Protein (GFAP) pg/mL concentration from baseline to Week 52 compared with placebo.
Exploratory analyses will include blood biomarkers, GFAP pg/mL. Mean percentage change in plasma GFAP pg/mL concentration from baseline to Week 52 compared with placebo.
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Panhellenic Federation of Alzheimer's Disease and Related Disorders
Lead sponsor
Palliative Care Centre "Panagia Glykofilousa", Greek Association of Alzheimer's Disease and Related Disorders, Plastira 65, Thessaloniki 542 50, Greece.
Collaborator
Levius Vita Foods srl
Collaborator
