Abstract
Alzheimer's disease (AD) and Parkinson's disease (PD) constitute a leading cause of disability and death worldwide. Millions of people are currently afflicted with AD and PD with numbers expected to double by mid-century, if effective disease-modifying treatments do not become available. There is no cure for AD or PD. Current Food and Drug Administration (FDA)-approved treatments are symptomatic which do not halt the progression of the disease and are associated with adversities. These limitations have prompted the emergence of alternative therapies although with moderate benefits but with least or no side effects. Music-based interventions (MBIs) are one of such alternative therapeutic options increasingly being considered for treating AD and PD. Not only experimental work but also clinical trials have shown benefits of MBIs. National clinical trial registry has documented successful completion of many clinical trials that involved the use of MBIs in AD and PD. The benefits of MBIs are attributed to the versatile features of music. Different components of music such as pitch and tempo, produce differential effects on brain chemistry, human emotions, brainwave patterns, and overall well-being. Postulated mechanisms fundamental to the benefits exerted by MBIs in treating AD and PD are discussed.
Keywords
Alzheimer’s disease, Dementia, Parkinson’s disease, Brainwaves, Musical tempo, Musical pitch, Rhythmic auditory stimulation
Abbreviations
AD: Alzheimer’s Disease; ADRD: Alzheimer’s Disease Related Dementias; ARIA: Amyloid Related Imaging Abnormalities; BDNF: Brain-Derived Neurotrophic Factor; BPSD: Behavioral and Psychological Symptoms of Dementia; bpm: Beats Per Minute; COMT: Catechol-O-Methyltransferase; FDA: Food and Drug Administration; PD: Parkinson’s Disease; MAO-B: Monoamine Oxidase B; MBI: Music-Based Interventions; NCT: National Clinical Trial; ND: Neurodegenerative Diseases; NGF: Nerve Growth Factor; NMDA: N-Methyl-D-Aspartate; NMT: Neurologic Music Therapy; RAS: Rhythmic Auditory Stimulation
Introduction
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases, impacting millions of people worldwide and the number of people living with AD/PD is expected to double by 2050 [1]. The most recent reports indicate that AD and Alzheimer’s disease related dementia (ADRD) are prevalent in >7 million Americans [2] and ~60 million people worldwide [3–5], while PD is prevalent in >1 million Americans and >10 million people worldwide [6,7]. By the mid-century, these numbers are projected to stagger by 14 million Americans and 153 million people worldwide suffering from AD/ADRD [5,8], and ~3 million Americans and >12 million people worldwide afflicted with PD [6,9], if effective disease-modifying treatments are not discovered [2,7]. Current U.S. Food and Drug Administration (FDA) approved treatments for AD include Acetylcholinesterase inhibitors (Donepezil, Rivastigmine, Galantamine), N-Methyl-D-Aspartate (NMDA) glutamate receptor modulators-alone (Memantine) or in combination (Memantine + Donepezil) known as or Namzaric, anti-insomnia drugs (Suvorexant or Belsomra), atypical anti-psychotic drugs (Brexpiprazole or Rexulti), and anti-amyloid antibodies (Lecanemab or Leqembi, Donanemab or Kisunla) (Table 1). As detailed in the most recent 2025 Alzheimer’s facts and Figures [2], Donepezil, Rivastigmine, Galantamine and Memantine (single or in combination) do not slow, stop or reverse the disease process or affect the course of the disease and may have side effects such as headaches and nausea. The anti-psychotic drug Brexpiprazole may increase the risk of psychosis and stroke while Suvorexant may impair alertness and motor coordination and worsen depression or suicidal thinking. Anti-amyloid treatments with Lecanemab and Donanemab can cause serious allergic reactions as well as amyloid-related imaging abnormalities (ARIA), infusion-related reactions, headaches and falls. Non-drug treatments, on the other hand, can reduce behavioral and psychological symptoms of dementia (BPSD) more effectively than pharmacological drugs [10].
|
Alzheimer’s Treatment |
Asymptomatic Changes Stages (0-2) |
Mild Cognitive Impairment (MCI) Stage 3 |
Mild Dementia Stage 4 |
Moderate Dementia Stage 5 |
Severe Dementia Stage 6 |
|
Donepezil (Aricept) |
|
|
Symptomatic Cognition |
SymptomaticCognition |
Symptomatic Cognition |
|
Rivastigmine (Excelon) |
|
|
Symptomatic Cognition |
Symptomatic Cognition |
Symptomatic Cognition |
|
Galantamine (Razadyne) |
|
|
Symptomatic Cognition |
Symptomatic Cognition |
|
|
Memantine (Nameda) |
|
|
|
Symptomatic Cognition |
Symptomatic Cognition |
|
Memantine + Donepezil (Namazaric) |
|
|
|
Symptomatic Cognition |
Symptomatic Cognition |
|
Suvorexant (Belsomra) |
|
|
BPSD |
BPSD |
|
|
Brexpiprazole (Rexulti) |
|
|
Mood Stabilization BPSD |
Mood Stabilization BPSD |
Mood Stabilization BPSD |
|
Lecanemab (Leqembi) |
|
Slow Disease Progression |
Slow Disease Progression |
|
|
|
Donanemab (Kisunla) |
|
Slow Disease Progression |
Slow Disease Progression |
|
|
|
AD: Alzheimer’s Disease; ADRD: Alzheimer’s disease related dementia; BPSD: Behavioral and Psychological Symptoms of Dementia |
|||||
FDA-approved drugs for PD consist of three major types of treatments including Dopamine replacement (Levodopa, Levodopa/Carbidopa), Dopamine agonists (Pramipexole, Ropinirole, Apomorphine, Rotigotine), Monoamine Oxidase B (MAO-B) inhibitors (Safinamide, Rasagiline, Selegiline). Catechol-O-Methyltransferase (COMT) inhibitors (Entacapone, Tolcapone, Opicapone), Combined Dopamine precursor, Dopamine decarboxylase inhibitor, COMT inhibitor (Stalevo), and Amantadine and Istradefylline for dyskinesia. The newer treatments include subcutaneous dopaminergic infusions (Vyalev, Onapgo), adaptive deep brain stimulation and focused ultrasound. Dopamine replacement drugs are associated with nausea, dizziness, orthostatic hypotension, swelling of ankles, anxiety, dyskinesia, confusion, hallucination, sleep disturbances [11,12]. MAO-B and COMT add on therapies are associated with diarrhea and liver dysfunction in addition to the side effects mentioned for as Dopamine replacement therapies [11,13]. Amantadine and Istradefylline pose a risk of kidney dysfunction in addition to above-mentioned adversities [14]. Deep brain stimulation leads to cognitive deficits [15] while focused ultrasound may lead to lingual dystonia and speech problems [16]. As evident, all approved therapies for treating AD/ADRD and PD provide only symptomatic relief and do not slow the progression of the diseases [17,18], making AD/ADRD and PD, clinically unmanageable [2,19]. Given these limitations [18, 19], non-pharmacological alternatives in treating NDs are emerging [20–22]. In that regard, Music based interventions (MBI/MBIs) are gaining increasing recognition as an effective non-pharmacological alternative in treating neurological disorders [23,24].
Music-Based Interventions (MBIs)
MBIs are broadly classified into two major categories i.e. active and receptive MBIs [25,26], and a recently emerging third category known as “Neurologic Music Therapy” comprising of structured congregation of active and receptive MBIs [24,27–29]. Active MBIs consist of activities such as singing, drumming, playing musical instruments, moving/dancing to the music-tunes or improvising, etc. [30]. The rhythmic auditory stimulation (RAS) is a prominent feature of active MBIs, known to restore brain’s rhythms through the use of rhythmic cycles with defined beats per minute (bpm) [31, 32]. Unlike active MBIs, receptive passive listening of music, involves passive listening to live or recorded music chosen by a patient or therapist [33]. Neurologic Music Therapy (NMT) uses specific elements of all types of active and/or receptive MBIs such as rhythm, melody, dynamics, and tempo aimed at achieving non-musical therapeutic goals towards improving speech, cognitive, motor and other functional impairments in treating NDs [24,34,35]. There have been a considerable number of clinical trials that tested the effects of different types of MBIs in AD/ADRD and PD (Tables 3 and 4). With the exception of couple of studies, most MBI interventions were observed to exert positive effects.
|
Parkinson’s Treatment |
Early PD Stages 1 |
Mild PD Stage 2 |
Moderate PD Levo/Carbidopa wear out begins Stage 3 |
Severe PD Levo/Carbidopa desensitization Stage 4 |
Severe PD Stage 5 |
|
Levodopa (Inbrija) (Inhalation) |
Motor Symptoms |
Motor Symptoms |
|
|
|
|
Carbidopa/Levodopa (Sinemet, Dhivy), subcutaneous (Vyalev) |
Motor Symptoms |
Motor Symptoms |
|
|
|
|
Dopamine agonists (Mirapex, Requip, Apokin, Onapgo, Neupro) |
Motor Symptoms |
Motor Symptoms |
|
|
|
|
Monoamine Oxidase B inhibitors (Safinamide, Rasagiline, Selegiline) |
Motor Symptoms |
Motor Symptoms |
|
|
|
|
Catechol-O-Methyltransferase inhibitors (Comtan, Tasmar, Ongenty) |
Motor Symptoms |
Motor Symptoms |
|
|
|
|
Combined dopamine precursor, Dopamine decarboxylase inhibitor, COMT inhibitor (Stalevo) |
|
|
Overcome Levo/Carbidopa Ineffectiveness |
Overcome Levo/Carbidopa Desensitization |
Overcome Levo/Carbidopa Desensitization |
|
Amantadine and Istradefylline |
|
|
Add-on for Severe motor dyskinesia |
Add-on for Severe motor dyskinesia |
Add-on for Severe motor dyskinesia |
|
Deep Brain Stimulation |
|
|
Severe Motor Dyskinesia |
Severe Motor Dyskinesia |
Severe Motor Dyskinesia |
|
Focused Ultrasound |
|
|
|
Motor Deficits (Experimental) |
Motor Deficits (Experimental) |
|
PD: Parkinson’s Disease; MAO-B: Monoamine Oxidase B; COMT: Catechol-O-Methyltransferase |
|||||
|
NCT # |
Truncated Title |
Interventions |
Key Findings |
|
NCT04645017 |
Music Program to Older Adults with Declining Cognition |
BEHAVIORAL: Intergenerational Music Program |
Improved Emotional Well-being, Sociability, Quality of Life |
|
NCT05317910 |
Music Therapy on Anxiety of Caregivers of Alzheimer’s Patients |
OTHER: MUSIC CARE |
Increased cortical activity, Increased alpha and beta EEG power |
|
NCT05125536 |
The Effect of Music in Alzheimer's Patients |
OTHER: Music Therapy |
Decreased adaptation difficulty |
|
NCT04761497 |
Group Music Therapy on Alzheimer's Disease Patients |
Active & Passive Music Therapy, Watching Nature Videos |
Improved cognition, Reduced BPSD, Enhanced Functional State |
|
NCT03011723 |
Tailored Music Therapy for Dementia |
BEHAVIORAL: Resource Oriented Music Therapy |
Improved Emotional Well-being and Sociability |
|
NCT06596278 |
Memesto Wearable Music Therapy Device Reduces Agitation in AD |
DEVICE: Memesto |
Reduced Agitation |
|
NCT05309369 |
Musical Engagement of Brain Lobes in Alzheimer's Patients |
BEHAVIORAL: Preferred Music, Nature Sounds |
Improved Brain Connectivity (fMRI), Improved Clinical Global Impression |
|
NCT05153161 |
Memesto Wearable Device for Persons with Dementia |
DEVICE: Memesto |
Reduced Agitation |
|
NCT06765434 |
Effects of Personalized Music Listening in Advanced Alzheimer's |
Music (Dmitri Shostakovich's Jazz Waltz Suite), Personalized Music |
Improved Standardized Mini-Mental State Examination (SMMSE) Scores |
|
NCT03643003 |
Music Therapy for Persons with Dementia |
BEHAVIORAL: Music Therapy, Non-Music Verbal Interaction (Placebo) |
Feasibility and Acceptability of Music Therapy Successfully Demonstrated |
|
NCT00759863 |
LifeZig Personalized Music for Alzheimer's and Dementia |
BEHAVIORAL: LifeZig Music |
Improved Quality of Life |
|
NCT04308512 |
Care Coordination System for People with Dementia |
BEHAVIORAL: Active Nili device, Passive Nili system |
Feasibility and Acceptability of Nili Device Successfully Demonstrated |
|
NCT03907748 |
Home-Based Music and Reading Interventions for Dementia |
OTHER: Music Intervention, Reading Intervention (Placebo) |
Neither Music nor Reading Significantly Reduced BPSD |
|
NCT05508646 |
Group-Based Telehealth Music Therapy for Dementia |
BEHAVIORAL: Music Therapy, Personalized Music CD |
Reduced BPSD, Agitation, and Depression |
|
NCT04850807 |
Music & MEmory: A Pragmatic TRial for ALzheimer's Disease (METRIcAL) |
BEHAVIORAL: Music & Memory |
No Significant Difference in Study Outcomes than Controls |
|
NCT04157244 |
The Music, Sleep and Dementia Study |
BEHAVIORAL: Tailored Music Listening Intervention |
Interventional Feasibility and Acceptability, Improved Insomnia |
|
NCT07069530 |
Musical Therapeutic Intervention on Depression in Dementia Patients |
BEHAVIORAL: Receptive Music Therapy |
Improved Depression in Dementia Patients, Reduced Caregiver Burden |
|
NCT02833870 |
Non-Pharmacological Music Interventions in Alzheimer's Disease |
BEHAVIORAL: Music intervention, No Intervention (Placebo) |
Mood Upliftment but No Effect on Cognition |
|
NCT04769024 |
Virtual Reality Intervention for the Reduction of BPSD |
DEVICE: LUMEEN Virtual Reality, Non-Digital Stimulation (Placebo) |
Interventional Feasibility and Acceptability, Reduced BPSD |
|
NCT03284112 |
Old SCHOOL Hip-Hop: Improve Alzheimer's Disease |
BEHAVIORAL: Old SCHOOL Hip-Hop |
Reduced Auditory Hallucinations and Depression |
|
NCT02518243 |
Safe & Easy for Alzheimer's Disease and Related Pathologies |
OTHER: Non-Pharmacological Music Therapy |
Feasibility and Acceptability of Music Therapy Successfully Demonstrated |
|
NCT05627687 |
Caring Relationships Expression Study |
BEHAVIORAL: Heart Rate Variability Biofeedback, Music Listening Control |
Feasibility and Acceptability of Music Therapy Successfully Demonstrated |
|
NCT03333837 |
Improvisational Movement for People With Memory Loss |
BEHAVIORAL: Dance Group, Social Group |
Improved Quality of Life and balance, Increased Brain Network Efficiency |
|
NCT06530277 |
REMINDer - A Digital Environmental Enrichment Intervention |
BEHAVIORAL: Reminder (A Digital Environmental Enrichment) |
Improved Multi-Domain Health and Lifestyle Behaviors |
|
AD: Alzheimer’s Disease; ADRD: Alzheimer’s Disease Related Dementia; BPSD: Behavioral and Psychological Symptoms of Dementia |
|||
|
NCT # |
Truncated Title |
Interventions |
Key Findings |
|
NCT03434496 |
Music Role in PD Rehabilitation |
DEVICE: Gait Trainer 3 |
RAS Treadmill Training Significantly Improved Gait Performance |
|
NCT05421624 |
Amplifying Physical Activity through Music in Parkinson Disease |
DEVICE: Digital Music Therapeutic, Active-Control |
RAS Significantly Improved Walking Intensity and Stride-Lengths |
|
NCT00750945 |
Treadmill and Music Cueing for Gait Training in Parkinson's Disease |
Music and Treadmill Walking Program |
Treadmill and Music Cueing Improved Gait |
|
NCT04966689 |
Effect of Speech and Music-therapy in Parkinson's Disease (PD) |
BEHAVIORAL: Combined Speech and Music Therapy |
Voice Intensity, Shimmer Frequency Improved |
|
NCT04246476 |
Sing for Your Saunter |
BEHAVIORAL: Mentally Singing, Listening to Music |
Gait Speed and Stride Length Improved |
|
NCT04518917 |
Sing for Your Saunter PD-Dementia Supplement |
BEHAVIORAL: Mentally Singing, Listening to Music |
Improved Stride Length and Velocity |
|
NCT04891107 |
Feasibility of MR-005 in Parkinson’s Disease |
BEHAVIORAL: Walking with a Music-Rhythm-Modulating Wearable System |
Improved Walking, Functional Mobility, and Quality of Life |
|
NCT03253965 |
Effects of Auditory Cues on Gait in Parkinson's Disease |
Metronome Normal, Slow, Fast, No Auditory Cueing (Controls) |
Increase/Decrease Cadence in Response to Music, Longer Strides |
|
NCT05157074 |
Group Drum-Music Therapy for Parkinson's Disease |
BEHAVIORAL: Group Drumming Music Therapy |
Drum-RAS Enhanced Movement and Improved Quality of Life |
|
NCT05585489 |
Individualized Music-Based Cueing for Gait in Parkinson's Disease. |
OTHER: Gait Training with Musical Cue |
Musical Cues Improved Gait |
|
NCT02999997 |
Evaluation of Ronnie Gardiner Method in Parkinson's Disease |
BEHAVIORAL: Ronnie Gardiner Method (RGM) |
Improved Measures of Fall Fear and Quality of Life |
|
NCT06063161 |
Music Therapy to Prevent Delirium in Parkinson's Disease |
BEHAVIORAL: Music Therapy, Standard Care (Control) |
Partially Successful in Preventing Hospital Acquired Delirium |
|
NCT06896123 |
Dance Well Therapy: Evaluating Efficacy, Safety, and Feasibility |
BEHAVIORAL: Dance, Conventional Motor Therapy (Control) |
Found Feasible for Improving Motor, Cognitive, and Emotional Symptoms |
|
NCT05769972 |
Cognitive Rehabilitation with Virtual Reality, Computer-Stimulation |
DEVICE: Computer-Based Cognitive Rehabilitation, Music-Therapy |
Improved Default Mode Network Connectivity and Cognition |
|
NCT05446194 |
Vestibulopathy, Imbalance, and Gait Disturbances in Parkinson Disease |
DEVICE: Non-Invasive Neuromodulation Devices |
Improved both Balance and Gait |
|
NCT02753621 |
Parkinsonism: A Controlled Study of Group Singing in Parkinson Disease |
BEHAVIORAL: Group Singing, Discussion Group (Control) |
Improved Emotional Well-Being |
|
NCT01151111 |
Relaxation Guided Imagery for Treatment of Parkinson's Disease |
BEHAVIORAL: Relaxation Guided Imagery |
Improved Motor Fluctuations |
|
NCT03228888 |
Rhythmic-Auditory Stimulation (RAS) in Parkinson's Patients |
OTHER: Rhythmic Acoustic Stimuli for Gait Training |
Improved Motor Functions and Gait |
|
NCT02457832 |
Motor Training in PD |
BEHAVIORAL: Adapted Tango Dancing, with Behavioral Control |
Improved Physical Functions and Quality of Life |
|
NCT01939717 |
A Randomized Controlled Pilot Trial of Dancing in Parkinson's Disease |
OTHER: Dance Group |
A Safe, Feasible intervention that Improved Quality of Life |
|
NCT01757509 |
A Randomized Controlled Dancing Trial in Parkinson's Disease |
OTHER: Dance Intervention Group |
Improved Motor Functions, Balance, Gait, Rigidity, and Bradykinesia |
|
NCT03316365 |
Effects of Rhythmic Auditory Stimulation on Parkinson's Gait |
OTHER: Rhythmic Auditory Stimulation (RAS) |
Improved Gait, Reduced Falls, and Boosted Motor Performance |
|
PD: Parkinson’s Disease; RAS: Rhythmic Auditory Stimulation
|
|||
Potential Mechanisms of Actions of MBIs
As therapeutic potential of music continues to grow, it is integral to understand the biological mechanisms by which music influences health. MBIs are postulated to work mainly through neurochemical, neuroplastic, brain-entraining and emotional mechanisms [36].
Neurochemical mechanisms
MBIs influence brain neurochemistry by modulating key neurotransmitters (Dopamine, Serotonin, Endorphins, Endocannabinoids), neurohormones (Oxytocin, Cortisol, Melatonin, Adrenaline/Epinephrine, Prolactin) and neurotrophic factors—Brain-Derived neurotrophic Factor (BDNF), and Nerve Growth Factor (NGF) [27,37,38]. MBIs influence induction of key neurotransmitters such as dopamine and serotonin during happy and pleasurable musical experiences [39]. Dopamine is a key neurotransmitter involved in the brain's reward and pleasure system involving dopaminergic brain regions i.e. nucleus accumbens, ventral tegmental area, caudate, ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex [40,41]. The caudate is known to be involved during the anticipation and the nucleus accumbens during the experience of peak emotional responses to music, indicating that intense pleasure in response to music can lead to dopamine release in the striatal system [42]. Moreover, the anticipation of such abstract reward is postulated to result in dopamine release in an anatomical pathway distinct from the pleasure-pathways such as limbic system comprised of nucleus accumbens, ventral tegmental area, amygdala, hippocampus, and cortex [43]. Thus, music-induced dopamine release is associated not only with pleasure and motivation but also with cognition [44]. Serotonin is a neurotransmitter that not only induces the feelings of well-being and happiness, but also is implicated in mood, anxiety, depression, psychosis and cognition [45,46]. Listening to pleasant music was shown to elevate serotonin while listening to unpleasant music was shown to elevate adrenocorticotropic hormone, and sad music was associated with the induction of prolactin [47]. In addition to the pleasantness, “relaxing serene consonance” along with the tempo range between 60–80 is known to facilitate the induction of serotonin and oxytocin [39,48]. Oxytocin is the hormone associated with social bonding and trust. Shared musical experiences can stimulate oxytocin release, fostering social bonding [37,45]. Listening to soothing music can increase oxytocin levels [39,49]. Music-based interventions may increase serotonin levels, helping to balance emotions, stress, anxiety and depression, enhancing social connectedness.
Endorphins are body's natural opioids that reduce cell excitability and neurotransmission thus leading to the reduction of pain and feeling of well-being [50]. Endorphins are released in response to music impacting reduction in the feeling of pain [51], promoting neurological healing [52]. Music therapy has been shown to elevate serum melatonin levels in patients with Alzheimer's disease [53]. Pleasurable and relaxing music listening is associated with the upregulation of neurotrophic factors such as BDNF and NGF related to neuroregeneration and synaptic plasticity [27]. On the other hand, techno-music with high tempo is shown to induce Adrenalin/Norepinephrine, Cortisol, Adrenocorticotropic hormone, and growth hormone [54]. Thus, MBIs play a critical role in neuroprotection and general well-being.
Neuroplasticity
MBI interventions can enhance neuroplasticity and promote beneficial gene expression related to brain repair and function [27]. Music has a distinctive ability to simultaneously activate multiple brain regions and pathways [55]. Studies suggest that MBIs engage multiple cortical and subcortical networks, comprehending perceptual, sensorimotor, cognitive, and emotional processing of musical stimuli [27, 56, 57]. Positron emission tomography and functional magnetic resonance imaging have revealed that listening to pleasurable music activates cortical and subcortical cerebral areas where emotions are processed [58]. Music-mediated induction of BDNF can activate neurogenesis and neuronal proliferation, resulting in synaptic re-modelling and boosting cognition [59, 60]. Music is known to facilitate neuroplasticity, protect against cognitive decline, and promote stress resilience via enhancement of neurogenesis, synaptic plasticity, and neurotrophic factor expression (BDNF, NGF) [61]. Music-induced neuroplastic changes can occur across the lifespan, producing long-term effects strengthening of neural pathways through experience and practice, possibly extending over decades [62,63].
Brain entrainment
Brain entrainment to musical rhythm is conceptualized to underlie the process of the perception of music [64]. Music utilizes temporal sensitivity of auditory system and its coupling to neuronal networks to facilitate the process of brain entrainment [65]. Music can stimulate motor, cognitive and emotive networks entraining listeners in real time [66]. Globally increasing burden of neurological disorders such as AD and PD often experiences psychiatric symptoms with changed brainwave patterns [29]. Therefore, the brain-entraining ability of music is considered to have clinical application in rebalancing altered brainwaves of neurodegenerative diseases [29]. Music-mediated rebalancing of altered brainwaves is mainly achieved through musical reward and pleasure [67,68] and through rhythmic auditory stimulation in the form of tempo or beats per minute (bpm) [69,70]. The slow soothing music >60 bpm tempo activates theta brainwaves [71] and decreases delirium duration [72]. The reward and pleasurable music with ~80–120 bpm activates alpha waves [71,73,74], music with >120–150 bpm stimulates beta waves [75], while music with >150 bpm activates gamma waves [71]. Moreover slow-tempo music facilitates strong brain synchronization [76], and different music tempi modulate different emotional states [71].
Emotional stabilization
Neurological disorders often begin with emotional, behavioral and psychological disturbances [77]. Considering the ability of music in influencing human emotions [71], music can play a big role by exerting calming and emotional stabilizing effects [78]. Tempo is an important musical element that affects human's emotional processes when listening to music [71,79]. Slow-tempo (~60 bpm) relaxing music is shown to increase oxytocin promoting socialization and decrease cortisol leading to reduced anxiety [80]. While medium tempo (~60–120 bpm) music produces cheerful/happy/pleasure effects and fast tempo (>150 bpm) music produces excitement [79,81,82]. Alzheimer's disease (AD) is associated with impaired emotional memory and music has been shown to enhance emotional memory [83]. Thus, music offers a promising alternative for improving emotional state, quality of life and overall well-being [84], and reduce depressive symptoms [35]. Overall, music has been perceived as a positive intervention with potential psycho-emotional benefits [85].
Conclusions
Music-based interventions (MBIs) significantly impact the brain by modulating neurotransmitters, brainwave activity and emotions. Different components of MBIs affect differentially by inducing selective neurotransmitters, activating specific brainwaves, and exerting different emotions, together facilitating brain's neuroplasticity, improving brain-network connectivity and emotional stabilization.
Author Contributions
All authors contributed equally.
Conflict of Interests
Author declares no conflict of interest.
Funding Statement
Neelima Chauhan (Fulbright-Nehru Academic and Professional Excellence Awardee; Grant #APE 2023-24 USIEF) gratefully acknowledges the support provided by the Fulbright U.S. Scholar Program, U.S. Department of State and United States-India Educational Foundation (USIEF) Fulbright Commission.
Acknowledgements
Authors gratefully acknowledges the support provided by the U.S. Department of State and United States-India Educational Foundation (USIEF) Fulbright Commission, India. Its contents are solely the responsibility of the author and do not represent official views of Fulbright Program, USIEF. Authors also acknowledge the support provided by the Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA.
References
2. 2025 Alzheimer's disease facts and figures. Alzheimer's & Dementia. 2025;21(4):e70235.
3. Ji Z, Chen Q, Yang J, Hou J, Wu H, Zhang L. Global, regional, and national health inequalities of Alzheimer's disease and Parkinson's disease in 204 countries, 1990-2019. Int J Equity Health. 2024 Jun 19;23(1):125.
4. Wang F, Li D, Gao X, Zhang X, Shi X, Guo Y. Alzheimer's and dementia: Diagnosis, assessment, and disease monitoring global, regional, and national burden of Alzheimer's disease and other dementias (ADODs) and their risk factors, 1990-2021: A systematic analysis for the Global Burden of Disease study 2021. Alzheimers Dement (Amst). 2025 May 27;17(2):e70126.
5. Zhong S, Xiao C, Li R, Lan Y, Gong C, Feng C, et al. The global, regional, and national burdens of dementia in 204 countries and territories from 1990 to 2021: A trend analysis based on the Global Burden of Disease Study 2021. Medicine (Baltimore). 2025 Mar 14;104(11):e41836.
6. Su D, Cui Y, He C, Yin P, Bai R, Zhu J, et al. Projections for prevalence of Parkinson's disease and its driving factors in 195 countries and territories to 2050: modelling study of Global Burden of Disease Study 2021. BMJ. 2025;388:e080952.
7. Luo Y, Qiao L, Li M, Wen X, Zhang W, Li X. Global, regional, national epidemiology and trends of Parkinson's disease from 1990 to 2021: findings from the Global Burden of Disease Study 2021. Front Aging Neurosci. 2025 Jan 10;16:1498756.
8. Twiss E, McPherson C, Weaver DF. Global Diseases Deserve Global Solutions: Alzheimer's Disease. Neurol Int. 2025 Jun 14;17(6):92.
9. Li M, Ye X, Huang Z, Ye L, Chen C. Global burden of Parkinson's disease from 1990 to 2021: a population-based study. BMJ Open. 2025 Apr 27;15(4):e095610.
10. Watt JA, Goodarzi Z, Veroniki AA, Nincic V, Khan PA, Ghassemi M, et al. Comparative Efficacy of Interventions for Aggressive and Agitated Behaviors in Dementia: A Systematic Review and Network Meta-analysis. Ann Intern Med. 2019 Nov 5;171(9):633–42.
11. Müller T. Update on the Present and Future Pharmacologic Treatment of Parkinson's Disease. Neurol Ther. 2025 Oct;14(5):1769–81.
12. Fernandes MM, Nogueira LOS, Rabelo ISM, Dallé LDC, Corso AMS, Santos FM, et al. Efficacy and Safety of Novel Continuous Subcutaneous Levodopa Infusion Therapies ND0612 and ABBV-951 for Parkinson's Disease: A Systematic Review. J Geriatr Psychiatry Neurol. 2025 Sep;38(5):326–38.
13. Khalid MB, Shahzad F, Siddiqui MR, Abedin MZU, Hulou S, Shami B, et al. Comparative efficacy and safety of irreversible (rasagiline) and reversible (safinamide) monoamine oxidase inhibitors as add-on therapy for Parkinson's disease. J Neurol. 2025;272(7):486.
14. Torres-Yaghi Y, Qian J, Cummings H, Shimoda H, Ito S, Batson S, et al. Comparative Safety of Istradefylline Among Parkinson Disease Adjunctive Therapies: A Systematic Review and Meta-analysis of Randomized Controlled Studies. Clin Neuropharmacol. 2025 Jan-Feb 01;48(1):7–12.
15. Reich MM, Hsu J, Ferguson M, Schaper FLWVJ, Joutsa J, Roothans J, et al. A brain network for deep brain stimulation induced cognitive decline in Parkinson's disease. Brain. 2022 May 24;145(4):1410–21.
16. Rosales RL, Endaya NJ. The tongue muscles: Clinical applications in lingual dystonia. Toxicon. 2025 Jul;262:108382.
17. Stancu P, Hentsch L, Seeck M, Zekry D, Graf C, Fleury V, et al. Neurology of Aging: Adapting Neurology Provision for an Aging Population. Neurodegener Dis. 2025;25(1):14–20.
18. Lasheen NN, Allam S, Elgarawany A, Aswa DW, Mansour R, Farouk Z. Limitations and potential strategies of immune checkpoint blockade in age-related neurodegenerative disorders. J Physiol Sci. 2024;74(1):46.
19. Langeskov-Christensen M, Franzen E, Grondahl Hvid L, Dalgas U. Exercise as medicine in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2024;95(11):1077–88.
20. Mantovani E, Martini A, Purgato M, Tamburin S. Pharmacological and non-pharmacological treatments for impulsive-compulsive behaviors in Parkinson's disease. Cochrane Database Syst Rev. 2025;10(10):CD015046.
21. Elbek JA, Norgaard B, Pedersen T, Thuesen J. Non-pharmacological rehabilitation for people living with advanced Parkinson's disease: A scoping review of interventions. Parkinsonism Relat Disord. 2025;133:107317.
22. Goldman JG. Non-motor Symptoms and Treatments in Parkinson's Disease. Neurol Clin. 2025;43(2):291–317.
23. Lee AW, Hirani R, Ogulnick J, Tiwari RK, Etienne M. Emerging Therapies for Neurological Disorders: A Clinical Review of MANAGED (Music, Art, Nature-Based, Animal-Assisted, Game, Essential Oil, Dance) Care. NeuroSci. 2025;6(2)51.
24. Wei Y, Qiao Z. Neurologic Music Therapy's Impact on Neurological Disorders. J Neurosci Res. 2024;102(12):e70000.
25. de Witte M, Nategh L, Antipas H, Westphal A, Lautenschlager NT, Baker FA, et al. The effects of music-based interventions on behavioural and psychological symptoms of people living with dementia: a systematic review and network meta-analysis protocol. Aging Ment Health. 2024;28(12):1726–32.
26. Zhang J, Lu Y, Mehdinezhadnouri K, Liu J, Lu H. Impact of music-based interventions on subjective well-being: a meta-analysis of listening, training, and therapy in clinical and nonclinical populations. Front Psychol. 2025;16:1608508.
27. Kunikullaya UK, Pranjic M, Rigby A, Pallas-Ferrer I, Anand H, Kunnavil R, et al. The molecular basis of music-induced neuroplasticity in humans: A systematic review. Neurosci Biobehav Rev. 2025;175:106219.
28. Ramaswamy M, Philip JL, Priya V, Priyadarshini S, Ramasamy M, Jeevitha GC, et al. Therapeutic use of music in neurological disorders: A concise narrative review. Heliyon. 2024;10(16):e35564.
29. Sahu M, Ambasta RK, Das SR, Mishra MK, Shanker A, Kumar P. Harnessing Brainwave Entrainment: A Non-invasive Strategy To Alleviate Neurological Disorder Symptoms. Ageing Res Rev. 2024;101:102547.
30. Schneider L, Gosse L, Montgomery M, Wehmeier M, Villringer A, Fritz TH. Components of Active Music Interventions in Therapeutic Settings-Present and Future Applications. Brain Sci. 2022 May 10;12(5):622.
31. de l'Etoile SK, Bennett C, Zopluoglu C. Infant Movement Response to Auditory Rhythm. Percept Mot Skills. 2020;127(4):651–70.
32. Kong YY, Cruz R, Jones JA, Zeng FG. Music perception with temporal cues in acoustic and electric hearing. Ear Hear. 2004;25(2):173–85.
33. Phillips CS, Kim J, Ganesh A, Stuifbergen AM. Impact of Active Versus Receptive Music Interventions on Psychosocial and Neurological Outcomes in People with Multiple Sclerosis: A Systematic Review. J Integr Complement Med. 2025 Oct;31(10):889–903.
34. Harjunen L, Ostman K, Pohl P. Scoping review of the music-based movement therapy Ronnie Gardiner Method. Disabil Rehabil. 2025;47(9):2185–98.
35. van der Steen JT, van der Wouden JC, Methley AM, Smaling HJA, Vink AC, Bruinsma MS. Music-based therapeutic interventions for people with dementia. Cochrane Database Syst Rev. 2025;3(3):CD003477.
36. Koelsch S, Bradt J. A neuroscientific perspective on pain-reducing effects of music: Implications for music therapy and mental well-being. Ann N Y Acad Sci. 2025;1550(1):71–6.
37. Chanda ML, Levitin DJ. The neurochemistry of music. Trends Cogn Sci. 2013;17(4):179–93.
38. T Zaatar M, Alhakim K, Enayeh M, Tamer R. The transformative power of music: Insights into neuroplasticity, health, and disease. Brain Behav Immun Health. 2023 Dec 12;35:100716.
39. Dukic H. Music, Brain Plasticity and the Resilience: the Pillars of New Receptive Therapy. Psychiatr Danub. 2018;30(Suppl 3):141–47.
40. Menon V, Levitin DJ. The rewards of music listening: response and physiological connectivity of the mesolimbic system. Neuroimage. 2005;28(1):175–84.
41. Blood AJ, Zatorre RJ. Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc Natl Acad Sci U S A. 2001;98(20):11818–23.
42. Salimpoor VN, Benovoy M, Larcher K, Dagher A, Zatorre RJ. Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nat Neurosci. 2011;14(2):257–62.
43. Chen WG, Iversen JR, Kao MH, Loui P, Patel AD, Zatorre RJ, et al. Music and Brain Circuitry: Strategies for Strengthening Evidence-Based Research for Music-Based Interventions. J Neurosci. 2022;42(45):8498–507.
44. Volkos P, Stachteas P, Linardakis M, Skouradaki E, Baritaki S, Koutonen S, et al. Effects on plasma oxytocin and dopamine levels through a five-minute audiovisual stimulus of Greek Syrtaki: An intervention-control primary care study. Explore (NY). 2025;21(6):103263.
45. Speranza L, Pulcrano S, Perrone-Capano C, di Porzio U, Volpicelli F. Music affects functional brain connectivity and is effective in the treatment of neurological disorders. Rev Neurosci. 2022 Mar 24;33(7):789–801.
46. Schmitt JA, Wingen M, Ramaekers JG, Evers EA, Riedel WJ. Serotonin and human cognitive performance. Curr Pharm Des. 2006;12(20):2473–86.
47. Evers S, Suhr B. Changes of the neurotransmitter serotonin but not of hormones during short time music perception. Eur Arch Psychiatry Clin Neurosci. 2000;250(3):144–7.
48. Nilsson U. The anxiety- and pain-reducing effects of music interventions: a systematic review. AORN J. 2008;87(4):780–807.
49. Nilsson U. Soothing music can increase oxytocin levels during bed rest after open-heart surgery: a randomised control trial. J Clin Nurs. 2009;18(15):2153–61.
50. Listed NA. Opioids, Opioid Antagonists. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes, Digestive and Kidney Diseases-2012; 2012.
51. Arnold CA, Bagg MK, Harvey AR. The psychophysiology of music-based interventions and the experience of pain. Front Psychol. 2024;15:1361857.
52. Basile G. Beneficial effects of music in the healing process of traumatic injuries: perceptual control of suffering and possible abatement of disability conditions. Clin Ter. 2023;174(6):531–36.
53. Kumar AM, Tims F, Cruess DG, Mintzer MJ, Ironson G, Loewenstein D, et al. Music therapy increases serum melatonin levels in patients with Alzheimer's disease. Altern Ther Health Med. 1999;5(6):49–57.
54. Gerra G, Zaimovic A, Franchini D, Palladino M, Giucastro G, Reali N, et al. Neuroendocrine responses of healthy volunteers to 'techno-music': relationships with personality traits and emotional state. Int J Psychophysiol. 1998;28(1):99–111.
55. Vuust P, Heggli OA, Friston KJ, Kringelbach ML. Music in the brain. Nat Rev Neurosci. 2022 May;23(5):287–305.
56. Pranjić M, Braun Janzen T, Vukšić N, Thaut M. From Sound to Movement: Mapping the Neural Mechanisms of Auditory-Motor Entrainment and Synchronization. Brain Sci. 2024 Oct 25;14(11):1063.
57. Kunikullaya Ubrangala K, Kunnavil R, Sanjeeva Vernekar M, Goturu J, Vijayadas, Prakash VS, et al. Effect of Indian Music as an Auditory Stimulus on Physiological Measures of Stress, Anxiety, Cardiovascular and Autonomic Responses in Humans-A Randomized Controlled Trial. Eur J Investig Health Psychol Educ. 2022;12(10):1535–58.
58. Pauwels EK, Volterrani D, Mariani G, Kostkiewics M. Mozart, music and medicine. Med Princ Pract. 2014;23(5):403–12.
59. Wang J, Wang J, Wang Y, Chai Y, Li H, Miao D, et al. Music with Different Tones Affects the Development of Brain Nerves in Mice in Early Life through BDNF and Its Downstream Pathways. Int J Mol Sci. 2023 May 1;24(9):8119.
60. Chen W, Zheng J, Shen G, Ji X, Sun L, Li X, et al. Music Therapy Alleviates Motor Dysfunction in Rats With Focal Cerebral Ischemia-Reperfusion Injury by Regulating BDNF Expression. Front Neurol. 2021;12:666311.
61. Hanampa-Maquera M, Lourenco RC, Bailey A, Camarini R. Hormetic pathways in environmental enrichment in animal models and humans. Prog Brain Res. 2025;295:189–227.
62. Reybrouck M, Vuust P, Brattico E. Neural Correlates of Music Listening: Does the Music Matter? Brain Sci. 2021;11(12) :1553.
63. Reybrouck M, Vuust P, Brattico E. Brain Connectivity Networks and the Aesthetic Experience of Music. Brain Sci. 2018 Jun 12;8(6):107.
64. Tichko P, Page N, Kim JC, Large EW, Loui P. Neural Entrainment to Musical Pulse in Naturalistic Music Is Preserved in Aging: Implications for Music-Based Interventions. Brain Sci. 2022 Dec 7;12(12):1676.
65. Grahn JA, Bauer AR, Zamm A. Is neural entrainment to rhythms the basis of social bonding through music? Behav Brain Sci. 2021;44:e73.
66. Trost W, Trevor C, Fernandez N, Steiner F, Fruhholz S. Live music stimulates the affective brain and emotionally entrains listeners in real time. Proc Natl Acad Sci U S A. 2024;121(10):e2316306121.
67. Suwabe K, Fukuie T, Soya H. Enriched Exercise Environment Boosting Exercise Effects on the Brain: Beneficial Effects of Music. Adv Neurobiol. 2025;44:343–69.
68. Noda Y, Noda T. The Influence of Music on Mental Health Through Neuroplasticity: Mechanisms, Clinical Implications, and Contextual Perspectives. Brain Sci. 2025 Nov 20;15(11):1248.
69. Koshimori Y, Thaut MH. Rhythmic auditory stimulation as a potential neuromodulator for Parkinson's disease. Parkinsonism Relat Disord. 2023;113:105459.
70. Ross JM, Forman L, Gogulski J, Hassan U, Cline CC, Parmigiani S, et al. Sensory Entrained TMS (seTMS) Enhances Motor Cortex Excitability. Hum Brain Mapp. 2025;46(10):e70267.
71. Yang Z, Su Q, Xie J, Su H, Huang T, Han C, et al. Music tempo modulates emotional states as revealed through EEG insights. Sci Rep. 2025;15(1):8276.
72. Khan BA, Khan SH, Perkins AJ, Heiderscheit A, Unverzagt FW, Wang S, et al. Slow-Tempo Music and Delirium/Coma-Free Days Among Older Adults Undergoing Mechanical Ventilation: A Randomized Clinical Trial. JAMA Intern Med. 2025;185(12):1442–53.
73. Bauer AK, Kreutz G, Herrmann CS. Individual musical tempo preference correlates with EEG beta rhythm. Psychophysiology. 2015;52(4):600–4.
74. Leite JAA, Dos Santos MAC, da Silva RMC, Andrade AO, da Silva GM, Bazan R, et al. Alpha and beta cortical activity during guitar playing: task complexity and audiovisual stimulus analysis. Somatosens Mot Res. 2020;37(4):245–51.
75. Rivera-Tello S, Romo-Vazquez R, Gonzalez-Garrido AA, Ramos-Loyo J. Musical tempo affects EEG spectral dynamics during subsequent time estimation. Biol Psychol. 2023;178:108517.
76. Weineck K, Wen OX, Henry MJ. Neural synchronization is strongest to the spectral flux of slow music and depends on familiarity and beat salience. Elife. 2022 Sep 12;11:e75515.
77. Maristany AJ, Sa BC, Murray C, Subramaniam AB, Oldak SE. Psychiatric Manifestations of Neurological Diseases: A Narrative Review. Cureus. 2024;16(7):e64152.
78. Li Y, Peng Y, Ma S. The efficacy of music therapy for post-stroke depression: A meta-analysis. Medicine (Baltimore). 2025;104(43):e44949.
79. Liu Y, Liu G, Wei D, Li Q, Yuan G, Wu S, et al. Effects of Musical Tempo on Musicians' and Non-musicians' Emotional Experience When Listening to Music. Front Psychol. 2018;9:2118.
80. Ooishi Y, Mukai H, Watanabe K, Kawato S, Kashino M. Increase in salivary oxytocin and decrease in salivary cortisol after listening to relaxing slow-tempo and exciting fast-tempo music. PLoS One. 2017;12(12):e0189075.
81. Listed NA. Effects of music tempo on performance, psychological, and physiological variables during 20 km cycling in well-trained cyclists. Percept Mot Skills. 2013;117(2):484–97.
82. Wu R, Huang Y, Jin X. Development and validation of a standardized emotional music database based on multidimensional affective ratings. Front Psychol. 2025;16:1695114.
83. Moltrasio J, Rubinstein W. The soundtrack of memory: the effect of music on emotional memory in Alzheimer's disease and older adults. Memory. 2025;33(10):1266–80.
84. Leale I, Vinciguerra C, Di Stefano V, Brighina F, Battaglia G. Effectiveness of Telecoaching and Music Therapy in Neurological Disorders: A Narrative Review and Proposal for a New Interventional Approach. Healthcare (Basel). 2025 Apr 4;13(7):826.
85. Gardener SH, Mukaetova-Ladinska EB, Perera NA. The Effect of Music Therapy on Psychological Outcomes for Neurological Conditions: A Systematic Review. Medicina (Kaunas). 2025 Sep 5;61(9):1611.