A Multi-domain Intervention for Healthy Aging (MultiMusic)

A Multi-domain Intervention to Constrast Cognitive Decline in Healthy Aging

This study aims to investigate the long-term impact of a non-pharmacological intervention including several activities (e.g., physical activity, choir, learning programs, horticulture, etc.) to prevent cognitive impairment in community-dwelling elderly individuals with aspects of frailty. The main questions it aims to answer are:

• Does engaging in multiple activities, including music, slow the degeneration of perceptual and cognitive functions?
• Is it possible to foster beneficial brain changes even during aging?
• Can regularly attending social contexts reduce the risk of loneliness and provide fulfillment in later life? Researchers will compare participants involved in the multidomain intervention, including music, to another active group carrying out several activities but without music, and to a passive control group.

Participants will:

• Participate in the programs for 9 months;
• Be tested three times (before and after the intervention, and at a 6-month follow-up);
• Keep a weekly diary of the actual time spent in their activities.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteer Study
• Intervention / Treatment: Other: Multidomain Intervention; Other: General activities

Detailed Description

Brain-Derived Neurotrophic Factor (BDNF) plays a crucial role in neuroplasticity, supporting brain health throughout life and even during aging. This longitudinal study investigates the impact of a 9-month multidomain intervention, including choral practice, on BDNF levels, as well as audiometric and neuropsychological outcomes, in older adults, who are also assessed for their multidimensional frailty, based on their physical, cognitive, and nutritional conditions. BDNF levels, along with geriatric, neuropsychological, audiometric, and neurophysiological measures, are collected via saliva samples both pre- and post-intervention. For the longitudinal analyses of BDNF, up to 60 elderly individuals will be recruited from several recreational centers located in Southern Italy. Of these, one group will engage in a multidomain program that includes choir, physical, intellectual, and manual activities. The other two control groups will engage either in sporadic non-musical activities or no activity, or in various non-musical activities. Participation in all activities will be monitored via diaries.

The researchers' primary goal is to investigate whether engaging in physical, cognitive, and social activities can enhance neuroplasticity, as measured by BDNF levels, to counteract aspects of multidimensional frailty (as assessed by the multidimensional prognostic score, MPI) in the aging population. Secondly, the researchers aim to relate changes in BDNF levels to perceptual and cognitive functions and psychosocial well-being. Although previous studies point out the positive effects of musical training and active aging on brain health, the scarcity of longitudinal research on BDNF effects in older individuals leaves the issue open. Moreover, the researchers aim to test whether non-invasive, accessible saliva-based BDNF measurements, despite some reliability limitations, could offer indications of neuroprotection in aging.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elvira Brattico, Professor; Phone Number: +390805714702; Email: elvira.brattico@uniba.it

Study Locations

• Italy
  • Bari, Italy, 70121
    • Recruiting
    • University of Bari
    • Contact: Mariangela Lippolis; Phone Number: +393284154560; Email: mariangela.lippolis@uniba.it
  • Bari, Italy, 70122
    • Recruiting
    • Centro Servizi per la famiglia Libertà
    • Contact: Mariella Cataldo; Phone Number: (+39) 080 558 0129; Email: csfliberta@occusol.org
  • Bari, Italy, 70125
    • Recruiting
    • ANAS Puglia (Associazione Nazionale di Azione Sociale)
    • Contact: Luigi Favia; Phone Number: +39 327 758 6556; Email: anaspromozionesocialepuglia@gmail.com
  • Bari
    • Adelfia, Bari, Italy, 70010
      • Recruiting
      • Musica In Gioco
      • Contact: Andrea Gargiulo, Prof.; Phone Number: +393381931953; Email: MusicaInGioco@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age ≥ 65
• Living independently

Exclusion Criteria:

• Musical expertise
• Severe cognitive or functional impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multidomain group; Participants who undergo regularly a series of activities involving different domains (e.g., physical activity, choir, horticulture etc.).	Other: Multidomain Intervention; The intervention is distinguished by its multidomain approach combining cognitive, social, and musical activities through choir participation, targeting holistic cognitive and emotional benefits, unlike active controls (general activities) and passive controls (no activities).
Active Comparator: Active control group; Participants who undergo regularly a series of activities but not musical acivities	Other: General activities; Participants will carry out a series of physical, manual and/or intellectual activities (e.g., horticulture, physical activities, theatre, learning programs etc.) but not musical activities
No Intervention: Passive control group; Participants who undergo any activity or just sporadic activities

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain-Derived Neurotrophic Factor (BDNF)	BDNF levels detected in saliva	Baseline, 9 months and 6 months follow-up
Cognitive functioning	Assessed using the Montreal Cognitive Assessment (MoCA) (Nasreddine et al., 2005), a widely used screening tool for cognitive impairment that evaluates multiple cognitive domains, including attention, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Description of the task: The MoCA consists of 30 items, covering various cognitive tasks such as word recall, trail-making, and visuospatial exercises. Unit of Measure: Raw score, ranging from 0 to 30, where higher scores indicate better cognitive functioning. A score below 26 typically indicates mild cognitive impairment. Interpretation: Higher scores reflect better cognitive performance. The measure is commonly used to detect cognitive deficits and track cognitive changes over time.	Baseline, 9 months and 6 months follow-up
Fluid Intelligence	Assessed with computerized Matrix Reasoning (Condon & Revelle 2014; Chan & Kosinski, 2015), a test that contains stimuli that are similar to those used in Raven's Progressive Matrices. Task Description: The stimuli are 3 × 3 arrays of geometric shapes with one of the nine shapes missing. Participants are instructed to identify which of the six geometric shapes presented as response choices will best complete the stimuli. In each round the stimulus disappears after 120 s, leaving only the response options visible for the participant. Unit of Measure: The score is calculated as a standardized z-score, with a mean of 0 and no fixed minimum or maximum value. Scores can be both positive or negative, depending on the participant's performance relative to the sample distribution. Interpretation: Higher positive scores indicate better-than-average performance in reasoning ability, while negative scores indicate below-average performance. This measure is suitable for evaluating individual	Baseline, 9 months and 6 months follow-up
Hearing Threshold	Assessed using a liminal tonal audiometric test, which determines the participant's minimum acoustic intensity perceivable at different tonal field frequencies. Description of the task: Participants are tested across a range of frequencies in a soundproof booth to identify the lowest intensity level at which they can detect a tone. Unit of Measure: Hearing threshold in decibels hearing level (dB HL), measured for each frequency. Lower thresholds (i.e., lower dB HL values) indicate better hearing sensitivity. Interpretation: Lower dB HL values indicate better hearing ability. The results are used to identify any hearing loss and its severity at specific frequencies.	Baseline, 9 months and 6 months follow-up
Intelligibility	Assessed using speech audiometry, which evaluates the participant's ability to recognize and understand spoken words in a controlled environment. Description of the task: Participants are presented with vocal material (e.g., phonemes, logotomes, words, sentences) in a silent booth and must repeat what they hear. Unit of Measure: Percentage of correctly recognized words, where higher percentages indicate better speech intelligibility. Interpretation: Higher percentages indicate better verbal recognition and understanding. This measure helps assess speech comprehension in quiet conditions.	Baseline, 9 months and 6 months follow-up
Speech in noise ability	Assessed using a Matrix Sentence Test, which evaluates speech comprehension under noisy conditions. Description of the task: Participants are presented with 5-word sentences along with a background noise (competition noise) and must repeat the sentences. The test adapts after each response by adjusting the difficulty (increasing or decreasing the noise level) until the participant reaches a 50% comprehension threshold. Unit of Measure: Signal Reception Threshold (SRT) in decibels (dB). The SRT represents the difference between the word volume and the noise volume at which the participant understands 50% of the words. Interpretation: Lower SRT values indicate better speech comprehension under noisy conditions.	Baseline, 9 months and 6 months follow-up
Auditory brainstem responses (ABR)	Measure of the neural activity along the auditory pathway in response to a brief acoustic stimulus. Description of the task: Short-duration acoustic stimuli (100 μs clicks) are presented independently to each ear at 90 dBnHL, with filters set at 100 and 3000 Hz. The resulting waveforms represent the activity of the auditory nerve and brainstem. Unit of Measure: Latencies of waves I-V in milliseconds (ms). Longer latencies may indicate abnormalities in the auditory pathway. Interpretation: Normal latencies indicate typical auditory nerve and brainstem function. Abnormal latencies may suggest issues such as hearing loss or neural conduction delays.	Baseline, 9 months and 6 months follow-up
P300 auditory cortical potentials	Measures higher-level auditory processing and cognitive responses to auditory stimuli. Description of the task: Tones (50 ms) are presented at a rate of 1.1/s, with standard stimuli occurring 80% of the time and target stimuli randomly occurring 20% of the time. Participants are required to detect and respond to the target stimuli. The P300 response is recorded using electrodes in the same montage as for the ABR. Unit of Measure: P300 latency in milliseconds (ms) and P300 amplitude in microvolts (µV). Shorter latencies and higher amplitudes indicate better cognitive and auditory processing. Interpretation: Shorter P300 latencies and higher amplitudes suggest more efficient auditory and cognitive processing. Prolonged latencies or reduced amplitudes may indicate deficits in auditory or cognitive functions.	Baseline, 9 months and 6 months follow-up
Multidimensional Frailty	Assessed using the Selfy-MPI (Pilotto et al., 2019), a self-administered digital tool via the Portable-MPI app. Description: The Selfy-MPI evaluates frailty across several dimensions, including: Functional status and independence: Measured by ADLs and IADLs. Mobility: Assessed through self-reported ability to move independently. Cognitive condition: Evaluated with a brief cognitive test. Nutritional status: Measured using the Mini Nutritional Assessment (MNA). Comorbidity: Assessed using the Cumulative Illness Rating Scale (CIRS). Medication use: Evaluated via the ATC classification for polypharmacy. Living situation: Assessed by questions on living arrangements. Unit of Measure: Composite score ranging from 0 to 1, where: 0-0.33: Low frailty risk 0.34-0.66: Moderate frailty risk 0.67-1.00: Severe frailty risk Interpretation: Higher scores indicate greater frailty.	Baseline, 9 months and 6 months follow-up
Socio-psychological well being	Assessed using the Flourishing Scale (Diener et al., 2010), a self-report measure that evaluates various domains, including relationships, purpose in life, and self-esteem. Description of the task: Participants rate 8 statements related to different aspects of their well-being (e.g., "I lead a purposeful and meaningful life") on a scale from 1 (Strongly disagree) to 7 (Strongly agree). Unit of Measure: The total score ranges from 8 to 56, with higher scores indicating greater psychological flourishing and well-being. Interpretation: Higher scores reflect better overall well-being, life satisfaction, and psychological functioning.	Baseline, 9 months and 6 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical activity	Assessed using the Global Physical Activity Questionnaire (GPAQ), developed by Armstrong & Bull (2006) for the World Health Organization (WHO) to measure physical activity levels across different domains of daily life. Description of the task: The GPAQ collects self-reported information on physical activity in three domains: Work-related physical activity Travel to and from places (active transport) Recreational physical activity It also includes a section on sedentary behavior. Unit of Measure: Physical activity is reported in Metabolic Equivalent of Task (MET) minutes per week. Sedentary behavior is reported in minutes per day spent sitting. Interpretation: Higher MET minutes indicate greater physical activity levels, while higher sedentary minutes indicate lower activity and greater sedentary behavior.	Baseline, 9 months and 6 months follow-up
Cognitive Reserve	Assessed using the Cognitive Reserve Index Questionnaire (CRIq), developed by Nucci, Mapelli & Mondini (2012), a tool designed to estimate an individual's cognitive reserve based on their lifetime activities. Description of the task: The CRIq collects self-reported information across three domains: Education (CRI-E): Years of formal education and training. Working activity (CRI-W): Type and duration of work experience, categorized by cognitive demand. Leisure time activities (CRI-L): Participation in cognitively stimulating activities during leisure time (e.g., reading, social engagement, cultural activities). Unit of Measure: The questionnaire provides a total Cognitive Reserve Index (CRI) score, along with sub-scores for each domain (CRI-E, CRI-W, CRI-L). The total score is standardized, with higher values indicating greater cognitive reserve. Interpretation: Higher CRI scores suggest a higher level of cognitive reserve, which is associated with better cognitive functioning and r	Baseline, 9 months and 6 months follow-up
Melody Discrimination	Assessed using the Melody Discrimination Test (MDT), an adaptive task based on a three-alternative forced-choice (3-AFC) melodic discrimination paradigm, developed by Harrison et al. (2017). The test evaluates participants' ability to discriminate between similar melodies by identifying the melody with a single altered note. Description of the task: In each trial, participants hear three versions of the same melody. Two of the versions (lures) have the same interval structure, while the third version (the odd-one-out) contains a single altered note. Participants are required to identify the odd-one-out melody by first identifying the most similar pair and then selecting the melody that is different. The difficulty of the items is adaptively adjusted by manipulating the length of the melodies. In this study, the test consists of 18 items. Unit of Measure: Standardized z-score, with a mean of 0 and no fixed minimum or maximum value. Scores can be positive or negative, depending on the	Baseline, 9 months and 6 months follow-up
Mistuning Perception	Assessed using the Mistuning Perception Test (MPT) (Larrouy-Maestri et al., 2019), which evaluates the ability to detect mistuning in musical extracts. Description of the task: In each trial, participants are presented with two versions of a musical excerpt-one "in tune" and one "out of tune"-and must identify the out-of-tune version. The stimulus material consists of short excerpts (6-12 s in length) from pop music performances (obtained from MedleyDB; Bittner et al., 2017) for which the vocal track was pitch-shifted relative to the instrumental tracks. Each musical extract has a vocalist singing the main melodic line and an instrumental accompaniment. Out-of-tune extracts are produced by adding a constant pitch shift to the vocal line Unit of Measure: Standardized z-score with a mean of 0, where scores can be positive or negative. Interpretation: Higher scores indicate better mistuning perception.	Baseline, 9 months and 6 months follow-up
Emotion Discrimination	Assessed using the Emotion Discrimination Test (EDT) (MacGregor & Müllensiefen, 2019), an adaptive test that evaluates the ability to distinguish emotions conveyed by musical fragments. In each trial, participants are presented with two versions of a melody and must identify which fragment corresponds to a specific target emotion (anger, happiness, sadness, or tenderness). Excerpts differ between trials in terms of musical features such as length, instrument, melody, target emotion and comparison emotion, and item difficulty is assessed with regard to the contribution of these features. Unit of Measure: Standardized z-score, with a mean of 0, where scores can be positive or negative. Interpretation: Higher scores indicate better ability to discriminate emotions in music.	Baseline, 9 months and 6 months follow-up
Rhythmic Ability	Assessed using the Rhythm Ability Test (RAT) (MacGregor et al., 2022), an adaptive test that evaluates rhythmic perception. Participants hear a rhythm composed of high-pitched and low-pitched sounds and must select the image that correctly represents the rhythm, where sounds are visually indicated by squares of different colors in two rows. Description of the task: The rhythms are made up of high-pitched and low-pitched sounds. High-pitched and low-pitched sounds are represented in each picture with two rows of squares of two different colors placed at the top row (to indicate high-pitched sounds) and at the bottom row (to indicate low-pitched sounds). The tasks are presented according to a progressive increasing difficulty, and the stimuli are made up of 4, 8, and 16 sounds (quarter, eights, sixteenths notes). Unit of Measure: Standardized z-score, with a mean of 0, where scores can be positive or negative. Interpretation: Higher scores indicate better rhythmic ability.	Baseline, 9 months and 6 months follow-up

Collaborators and Investigators

• Sponsor: University of Bari

Publications and helpful links

General Publications

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• Nazam F, Shaikh S, Nazam N, Alshahrani AS, Hasan GM, Hassan MI. Mechanistic insights into the pathogenesis of neurodegenerative diseases: towards the development of effective therapy. Mol Cell Biochem. 2021 Jul;476(7):2739-2752. doi: 10.1007/s11010-021-04120-6. Epub 2021 Mar 9.
• Nettiksimmons J, Simonsick EM, Harris T, Satterfield S, Rosano C, Yaffe K; Health ABC Study. The associations between serum brain-derived neurotrophic factor, potential confounders, and cognitive decline: a longitudinal study. PLoS One. 2014 Mar 26;9(3):e91339. doi: 10.1371/journal.pone.0091339. eCollection 2014.
• Moon SY, Kim S, Choi SH, Hong CH, Park YK, Na HR, Song HS, Park HK, Choi M, Lee SM, Chun BO, Lee JM, Jeong JH. Impact of Multidomain Lifestyle Intervention on Cerebral Cortical Thickness and Serum Brain-Derived Neurotrophic Factor: the SUPERBRAIN Exploratory Sub-study. Neurotherapeutics. 2022 Sep;19(5):1514-1525. doi: 10.1007/s13311-022-01276-x. Epub 2022 Aug 1.
• Mizoguchi Y, Yao H, Imamura Y, Hashimoto M, Monji A. Lower brain-derived neurotrophic factor levels are associated with age-related memory impairment in community-dwelling older adults: the Sefuri study. Sci Rep. 2020 Oct 5;10(1):16442. doi: 10.1038/s41598-020-73576-1.
• Marie, D., Müller, C. A., Altenmüller, E., Van De Ville, D., Jünemann, K., Scholz, D. S., ... & James, C. E. (2023). Music interventions in 132 healthy older adults enhance cerebellar grey matter and auditory working memory, despite general brain atrophy. Neuroimage: reports, 3(2), 100166.
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• Bugos JA, Bidelman GM, Moreno S, Shen D, Lu J, Alain C. Music and Visual Art Training Increase Auditory-Evoked Theta Oscillations in Older Adults. Brain Sci. 2022 Sep 27;12(10):1300. doi: 10.3390/brainsci12101300.
• Bonetti L, Bruzzone SEP, Paunio T, Kantojarvi K, Kliuchko M, Vuust P, Palva S, Brattico E. Moderate associations between BDNF Val66Met gene polymorphism, musical expertise, and mismatch negativity. Heliyon. 2023 Apr 18;9(5):e15600. doi: 10.1016/j.heliyon.2023.e15600. eCollection 2023 May.
• Alain C, Moussard A, Singer J, Lee Y, Bidelman GM, Moreno S. Music and Visual Art Training Modulate Brain Activity in Older Adults. Front Neurosci. 2019 Mar 8;13:182. doi: 10.3389/fnins.2019.00182. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 23, 2024
• First Submitted That Met QC Criteria: January 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 5, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: aging; neuroplasticity; multidomain intervention; BDNF; music training
• Other Study ID Numbers: ET-23-27

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share anonymized derived data, including salivary BDNF levels and neurophysiological data, but not the biological saliva samples due to logistical limitations, ethical constraints regarding participant consent, and the adequacy of the derived data to support further analyses. This ensures transparency while respecting ethical and practical considerations.

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