Lifestyle Interventions to Prevent Cognitive Deficits in Subjects With Depressive Symptoms: From Mechanisms to Clinical Practice

NCT07009223 | Recruiting DMC

• 1 other identifier: CERP-2024-23685718
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical study is to investigate if lifestyle changes can help prevent cognitive decline and reduce depressive symptoms in people between the ages of 50 and 80 with depressive symptoms or a diagnosis of major depression, but without signs of cognitive decline. The main questions it aims to answer are:

• Does regular physical activity improve mood and memory in people who are depressed or have depressive symptoms?
• Does cognitive training help prevent mental difficulties in people at risk of cognitive decline?
• Do changes in diet and lifestyle alter the composition of the gut microbiota and immuno-related infiammatory factors? Researchers will compare three different treatment groups to see which intervention is most effective in improving mental and cognitive health. The participants:
• Will take part to online sessions on healthy eating based on the Mediterranean diet
• Some will do regular exercise, supervised by a personal trainer
• Others will do weekly cognitive training in small groups at the hospital
• They will provide blood and fecal samples and complete cognitive tests and clinical questionnaires at the beginning, at the end of the treatment (12 weeks), and after 3 months.

Conditions

Metabolome; Gut Microbiota; Depressive Symptoms; Major Depressive Disorder (MDD); Physical Activity; Inflammation

Keywords

Depression; Cognition; nutrition

Outcome Measures

Primary Outcomes (8)

• MADR Scale for Depression

  The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-administered scale designed to assess the severity of depressive symptoms. It consists of 10 items, each rated on a scale from 0 to 6, yielding a total score ranging from 0 to 60. Higher scores indicate greater severity of depression, meaning a worse clinical outcome.

  Baseline, Week 12, and 3-month follow-up (Week 24)

• PHQ-9

  The Patient Health Questionnaire-9 (PHQ-9) is a self-administered instrument used to assess the severity of depressive symptoms based on DSM criteria. It consists of 9 items, each rated from 0 (not at all) to 3 (nearly every day), resulting in a total score ranging from 0 to 27. Higher scores reflect more severe depressive symptoms, indicating a worse clinical outcome.

  Baseline, Week 12, and 3-month follow-up (Week 24)

• GDS-15

  The Geriatric Depression Scale - Short Form (GDS-15) is a self-report questionnaire designed to screen for depressive symptoms in older adults. It contains 15 yes/no items, with a total score ranging from 0 to 15. Higher scores indicate more severe depressive symptoms, representing a worse clinical outcome.

  Baseline, Week 12, and 3-month follow-up (Week 24)

• WHOQOL-BREF

  The World Health Organization Quality of Life - Bref (WHOQOL-BREF) is a self-report questionnaire developed by the WHO to assess quality of life across multiple domains. It contains 26 items rated on a 5-point Likert scale. Higher scores indicate a better quality of life, reflecting a more favorable outcome.

  Baseline, Week 12, and 3-month follow-up (Week 24)

• RBANS

  The Repeatable Battery for the Assessment of Neuropsychological (RBANS) is a neuropsychological battery composed of 12 subtests grouped into five domains: Immediate Memory, Visuospatial/Constructional, Language, Attention, and Delayed Memory. It yields index scores and a total scale score. Higher scores indicate better cognitive functioning, reflecting a more favorable clinical outcome.

  Baseline, Week 12, and 3-month follow-up (Week 24)

• TMT

  The Trail Making Test (TMT) evaluates processing speed (Part A) and executive function, including task switching (Part B). The outcome is the time (in seconds) required to complete each part. Lower completion times indicate better performance and cognitive flexibility.

  Baseline, Week 12, and 3-month follow-up (Week 24)

• DSST

  The Digit Symbol Substitution Test (DSST) evaluates attention, processing speed, and working memory. Participants match numbers and symbols in a limited time. Higher scores reflect better performance.

  Baseline, Week 12, and 3-month follow-up (Week 24)

• M-WCST

  The Modified Wisconsin Card Sorting (M-WCST) measures cognitive flexibility and executive function. Outcomes include number of categories completed and perseverative errors. More categories and fewer errors indicate better performance.

  Baseline, Week 12, and 3-month follow-up (Week 24)

Secondary Outcomes (2)

• Immunitary-related factors levels

  Baseline, Week 12, and 3-month follow-up (Week 24)

• Gut Microbiome Composition

  Baseline, Week 12, and 3-month follow-up (Week 24)

Study Arms (3)

Group 1: Control group (CON)

ACTIVE COMPARATOR

Behavioral: Mediterranean Diet

Group 2: CON + physical activity

EXPERIMENTAL

Behavioral: Mediterranean Diet; Behavioral: Physical Activity

Group 3: CON + Cognitive training

EXPERIMENTAL

Behavioral: Mediterranean Diet; Behavioral: Cognitive Training

Interventions

Mediterranean Diet BEHAVIORAL

Participants will receive only the educational intervention about the Mediterranean diet. The program consists of 4-5 online sessions conducted by a nutritionist.

Group 1: Control group (CON); Group 2: CON + physical activity; Group 3: CON + Cognitive training

Physical Activity BEHAVIORAL

In addition to educational sessions on the Mediterranean diet, there will be 2-3 weekly personalized exercise sessions, followed by a dedicated personal trainer at a partner gym. The treatment will last 12 weeks.

Group 2: CON + physical activity

Cognitive Training BEHAVIORAL

In addition to educational sessions on the Mediterranean diet, there will be one weekly cognitive training session in groups, supervised by qualified staff at the IRCCS FBF. The treatment will last for 12 weeks.

Group 3: CON + Cognitive training

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 50 and 80 years;
• Diagnosis of DDM according to DSM-5 or depressive symptoms (PHQ-9 or GDS-15 ≥ 5, the choice of test will be justified by the participant's age);
• Ability to provide written informed consent.

You may not qualify if:

• Active gastrointestinal disorders;
• Autoimmune disorders;
• Chronic inflammatory disorders;
• Diagnosis of dementia; cognitive impairment or mild functional impairment.
• Use of antibiotics and/or anti-inflammatory drugs in the 8 weeks prior to the screening visit.

Sponsors & Collaborators

• IRCCS Centro San Giovanni di Dio Fatebenefratelli: lead
• Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC): collaborator
• University of Milan: collaborator
• China Medical University, China: collaborator
• University College Cork: collaborator
• Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement: collaborator

Study Sites (1)

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Brescia, 25125, Italy

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Motor Activity; Inflammation; Depression

Interventions

Diet, Mediterranean; Exercise; Cognitive Training

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms

Intervention Hierarchy (Ancestors)

Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Health Services; Health Care Facilities Workforce and Services

Central Study Contacts

Elisa Mombelli

CONTACT

(+39) 030 35 01 598; emombelli@fatebenefratelli.eu

Moira Marizzoni, PhD

CONTACT

(+39) 030 35 01 563; mmarizzoni@fatebenefratelli.eu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2025
• First Posted: June 6, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): March 1, 2028
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

IT (1)