Effects of Hydroxytyrosol-Rich Olive Polyphenol Dietary Supplement Combined With Mediterranean Diet Adherence on the Cognitive Health of Patients With Mild Cognitive Impairment

Panhellenic Federation of Alzheimer's Disease and Related Disorders141 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

141

Conditions

Mild Cognitive Impairment (MCI)

Interventions

This 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 SupplementDIETARY_SUPPLEMENT

PlaceboDIETARY_SUPPLEMENT

Eligibility

Sex: ALLMin age: 50 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. * MoCA score of ≥18 and ≤ 26. Or * MMSE (Mini-Mental State Examination) score of ≥26 and ≤ 28. * No active suicide ideation based on the Columbia-Suicide Severity Rating Scale. * Absence of severe depressive symptomatology based on the Geriatric Depression Scale-15. * Not using any laxative drugs for at least three days prior to the screening visit. * Information about APOE status Exclusion Criteria: * 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. * Any known allergy to olives, inability to tolerate gluten or multiple allergies/intolerances that would significantly limit food intake. * Average alcohol use of \>21 glasses per week for men and \>14 glasses per week for women (on average for the last six months). * History of psychiatric illness including intellectual disability, schizophrenia, bipolar disorder, severe, active depression and alcoholism. * Neurologic conditions such as vascular dementia, movement disorders, history of conditions such as anaemia and cancer in the last five years, renal or liver failure, malignant tumours, or organ transplant. * Coffee consumption greater than 5 cups per day. * Body mass index \> 35 kg/ m2. * Not taking a stable dose of statins for at least 3 months before the recruitment visit. Taking antibiotics in the 1 week preceding the recruitment visit. * Pregnancy or lactation. * Participation in another clinical trial during the last 30 days prior to the recruitment visit. * Subject taking supplements that may affect lipoprotein metabolism, \>1 g of fish oil/day, antioxidant supplements, cannabidiol (CBD) oil.

Outcomes

Primary Outcomes

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.

Time frame: From baseline to Week 52

Secondary Outcomes

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.

Time frame: From baseline to Week 52

- 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.

Time frame: From baseline to Week 52

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.

Time frame: From baseline to Week 52

- 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.

Time frame: From baseline to Week 52

- Mean change on Short Anxiety Screening Test (SAST-10) from baseline to Week 52 compared with placebo

The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on SAST-10, which is a brief questionnaire designed to assess anxiety. SAST-10 scores range from 10 to 40, with higher scores on the measure denoting more severe levels of anxiety symptoms.

Time frame: From baseline to Week 52

- Mean change on Functional Rating Scale of Symptoms of Dementia (FRSSD) from baseline to Week 52 compared with placebo.

The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on FRSSD. The scale ranges from 0 (fully independent) to 42 (fully dependent), with lower scores indicating better daily functioning.

Time frame: From baseline to Week 52

- Mean change on Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale for use in Mild Cognitive Impairment (ADCS-MCI-ADL) from baseline to Week 52 compared with placebo.

The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on ADCS-MCI-ADL, which is a brief questionnaire designed to capture functional abilities (with recall "In the past 4 weeks"). The 18-item ADCS-ADL-MCI is scored from 0 to 53 based on the subject's degree of independence in performing specific tasks. Lower scores on the measure denote more substantial impairment.

Time frame: From baseline to Week 52.

- Mean change on Quality of life in Alzheimer's disease (QoL-AD) from baseline to Week 52 compared with placebo.

The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on QoL-AD, which is a brief 13-item questionnaire designed to assess quality of life. QoL-AD range from 13 to 52, with higher scores indicating better quality of life.

Time frame: From baseline to Week 52.

- Mean change on - Pittsburgh Sleep Quality Index (PSQI) from baseline to Week 52 compared with placebo.

The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on PSQI, which is a questionnaire designed to assess Sleep quality. PSQI range from 0 to 21, with higher scores indicating poor sleep.

Time frame: From baseline to Week 52.

- Mean change in LDL-C mg/dL cholesterol from baseline to Week 52 compared with placebo.

The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on LDL-C mg/dL cholesterol.

Time frame: From baseline to Week 52

- Mean change in HDL-C mg/dL cholesterol from baseline to Week 52 compared with placebo.

The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on HDL-C mg/dL cholesterol.

Time frame: From baseline to Week 52

Effects of Hydroxytyrosol-Rich Olive Polyphenol Dietary Supplement Combined With Mediterranean Diet Adherence on the Cognitive Health of Patients With Mild Cognitive Impairment

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts