Efficacy of music therapy as a non-pharmacological measure to support alzheimer's disease patients: a systematic review

Abstract

Background

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive memory degradation and language and behavior disorders. Apart from curative pharmacological therapies, music therapy (MT) has been diffusely used as an efficient and economical non-pharmacological treatment for AD patients in recent years.

Methods

Three databases (PubMed, Web of Science and PsycINFO) were searched to analyse the efficacy of MT in patients with AD. Keywords included "Alzheimer's disease", "AD", "Mild Cognitive Impairment", "MCI", "music" and "music therapy".

Results

Literatures between January 2013 and January 2023 were selected, with 42 literatures included in the study, which highlights the beneficial impact of MT on cognition (memory, attention, language), behavioural and psychological symptoms (anxiety, depression and agitation), quality of life, self-esteem and physical pain in AD patients.

Conclusion

MT is a promising non-pharmacological treatment approach for individuals living with AD. However, further evidences from prospective, randomised, blinded, uniform, and rigorous method-logical investigations in this field are required to conclusively validate MT's impact on this disease.

PROSPERO registration number

CRD420251034039.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1186/s12877-025-06073-7.

Introduction

Alzheimer's disease (AD) is a degenerative disease of the central nervous system (CNS), which is the most common form of dementia, including early-onset and late-onset AD [1]. It is characterised by cognitive decline, including memory impairment, aphasia, agnosia, visuospatial impairment, and neuropsychiatric symptoms, such as anxiety, depression, irritability, and apathy [1, 2]. With the further aging of the population in China, the incidence of AD is constantly rising, which brings more burden to patients, their families and the whole society [3, 4]. More than 50 million people worldwide have dementia, and this number is likely to reach 152 million by 2050, of which about 65% are AD [5]. The annual economic burden of AD exceeds $1 trillion [6]. An estimated 6.7 million Americans aged 65 and older live with AD today, which could grow to 13.8 million by 2060 [7]. In China, the number of people over 60 is expected to more than double from 2010 levels by 2050 [6]. Accordingly, the number of AD patients is expected to reach 27.7 million by 2050, which will cause a huge health and economic burden to the society and patients'families [8]. It can be seen that AD has become a major public health problem that the whole society is concerned about and needs to be solved urgently. Therefore, it is particularly important to intervene before the onset of AD, that is mild cognitive impairment (MCI).

AD has a variety of pathogenesis, such as abnormal tau protein metabolism, β-amyloid protein, inflammatory responses, and cholinergic and free radical damage [9]. Although there is no cure for AD, early detection and intervention can effectively slow the disease and improve patients'quality of life. Until now, there are two main AD treatments: pharmacological and non-pharmacological treatments. Pharmacolo-gical treatments for AD aim to improve cognition and relieve behavioural symptoms, such as anti-amyloid monoclonal antibodies (such as Lecanemab, Donanemab) to improve cognitive function, as well as fluoxetine and sertraline to control mental symptoms, which can only relieve symptoms, but cannot cure or prevent the disease [10–13]. However, non-pharmacological treatments are becoming more prominent as they are simple, safe, and inexpensive in treating AD without adverse effects before the onset of AD symptoms [14]. Many non-pharmacological treatment studies have achieved compelling results.

Currently, non-pharmacological treatments for AD include cognitive training [14, 15], exercise therapy [16], physical stimulation [17], music therapy (MT), acupuncture therapy, repetitive trans- cranial magnetic stimulation [18]and play therapy [8]. Among them, MT is considered a promising non-pharmacological treatment that can effectively improve AD patients' quality of life and self-esteem [19], which can improve the mood and pressure of patients by listening, singing, playing and other ways, and can evoke the sleepy memory of patients. Other studies have also shown that MT reduces cognitive decline, particularly in autobiographical, amyloid accumulation and glucose metabolism, ameliorate AD pathology, agitation and anxiety depression, aggressive behaviour, and episodic memory [20–26]. So, the ability to memorise music makes music a unique stimulus that effectively engages AD patients. Therefore, MT can be used as a potential approach to alleviate AD-related symptoms, which can enhance their cognitive function and mental well-being [27, 28].

MT also could improve sleep by increasing melatonin levels without the adverse effects of hormone therapy [29]. According to these studies, music is a form of psychotherapy that allows it to be implemented in various ways in AD patients. In addition, MT is a safe, efficient, compliant, and easy-to-implement treatment. This study aims to review a more comprehensive understanding of MT for AD and provide a theoretical reference for future research. In this study, the existing literature on MT involving individuals with AD dementia and MCI will be analysed to summarise the efficacy of MT in patients with AD and MCI.

Methods

Inclusion criteria

The inclusion criteria include: (1) AD or MCI patients (at least 65 years old), studies were selected if they reported a validated or medical diagnosis of AD or MCI; (2) The intervention must meet the definition of MT and must be validated by caregivers without a music therapist or conducted in a controlled environment to ensure adherence to the protocol; (3) Randomized controlled trial (RCT) or observational studies (including cohort and case–control studies); (4) Availability during the intervention and testing phases; (5) Literatures written in English, indexed in databases from January 2013 to January 2023.

Exclusion criteria

The exclusion criteria include: (1) Articles for which an abstract is not available; (2) Non-research articles such as conferences, newsletters, and reviews; (3) Duplicate articles; (4) Studies were excluded if they only included patients with Subjective Cognitive Decline (SCD) or other subtypes of dementia, such as Parkinson's disease (PD), Huntington disease (HD) or mixed dementia; (5) Studies which did not involve a music intervention; (6) The absence of music intervention-related outcome measures.

Search strategy

To highlight the most influential and cutting-edge research in AD, MCI, and MT, we focused on the last decade of research. The electronic databases PubMed, Web of Science and PsycINFO were searched using the terms "Alzheimer's disease", "OR", "AD", "Mild Cognitive Impairment", "MCI", "AND", "music"and"music therapy". Abstracts for all studies returned from the search were read and sorted according to inclusion and exclusion criteria. The initial included literatures were then carefully read, and those not meeting the criteria were further excluded according to the main body content.

Data extraction

Two researchers screened all potential literatures independently, reviewing and scoring all abstracts and titles. If the abstract and title met the criteria, we continued to evaluate the full text to further identify studies that met the inclusion criteria. In disagreement, the researchers engaged in a team discussion to approach a final decision. In this process, studies were synthesised according to the following characteristics: study design, sample age and gender, intervention style, intervention implementer, intervention duration and frequency, scale, and intervention outcome. A narrative synthesis approach was performed to examine the results.

Quality assessment

We used Grading of Recommendations, Assessment, Development and Evaluations (GRADE) to grade the evidence confidence of systematic reviews [30]. The system is widely used in medicine and public health and is a consistent and transparent approach [31]. The assessment tool classifies paper quality into three levels: high, medium and low, comprising 15 items, with the entire assessment tool worth 19 points. The two researchers used the system to rank articles and resolve disagreements to reach a consensus.

Results

Studies included and excluded

Nine hundred seventy-three literatures were identified in the study, as follows Figs. 1 and 2. Following duplicate removal, 642 literatures were considered potentially relevant and were screened for relevant content. A further 546 literatures were excluded based on the title and abstract, leaving 95 literatures to be retrieved for full-text assessment. In the next phase, 53 literatures were excluded based on the inclusion criteria, with 42 literatures left.

Fig. 1.

Mechanism of music therapy for Alzheimer's disease (AD)

Fig. 2.

Flowchart of systematic literature search

Quality assessment tool applied

All literatures have a high-quality and precise description of basic information about subjects, a clear description of intervention methods, and a detailed description of results (Table 1). Forty literatures were reported as a RCT, and one each of a single- subject design study and cohort study. All 42 literatures reported statistical analyses, and the results showed clear conclusions.

Table 1.

Quality evaluation of references

References	[32]	[33]	[34]	[35]	[36]	[37]	[38]	[39]	[40]	[41]	[42]	[43]	[44]	[45]	[46]	[47]	[48]	[49]	[50]	[51]	[52]
Study design criteria	4	5	5	3	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5
5-Trial
4-Cohort study
3-Single subject design study
2-Crossover study
1-Case series/Case report
Additional criteria (1 point each)
Clear experimental controls were used	0	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Prospective study completed	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Blinding of assessors used	0	0	1	0	1	1	1	1	0	0	0	0	1	0	1	1	1	0	0	0	1
Clear description of subjects/group	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Balanced baselines between groups or stable across single subject	0	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Target behaviors are observable and measurable	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Clear description of intervention methods	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Attrition rate explained or minimal (<20%)	1	1	0	1	1	1	1	1	1	1	1	1	1	1	1	1	1	0	1	1	1
Clear description of observable or measurable outcomes	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Statistical analysis described or conducted appropriately	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Appropriate reliability methods described or used	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Appropriate validity methods described or used	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Clear conclusions drawn from the results	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Clear description of follow-up and maintenance outcomes	1	0	1	0	1	1	0	1	0	1	1	0	0	1	0	1	1	0	0	0	0
Total score	15	17	18	15	19	19	18	19	17	18	18	17	18	18	18	19	19	16	17	17	18
References	[53]	[54]	[55]	[56]	[57]	[58]	[59]	[60]	[61]	[62]	[63]	[64]	[65]	[66]	[67]	[68]	[69]	[70]	[71]	[72]	[73]
Study design criteria	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5
5-Trial
4-Cohort study
3-Single subject design study
2-Crossover study
1-Case series/Case report
Additional criteria (1 point each)
Clear experimental controls were used	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Prospective study completed	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Blinding of assessors used	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0
Clear description of subjects/group	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Balanced baselines between groups or stable across single subject	1	1	1	1	0	1	0	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Target behaviors are observable and measurable	1	1	0	1	1	1	1	1	1	0	1	1	1	1	1	1	1	1	1	1	1
Clear description of intervention methods	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Attrition rate explained or minimal (<20%)	1	1	0	1	0	1	1	1	0	0	1	1	1	1	1	1	1	1	1	1	0
Clear description of observable or measurable outcomes	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Statistical analysis described or conducted appropriately	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Appropriate reliability methods described or used	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Appropriate validity methods described or used	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Clear conclusions drawn from the results	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
Clear description of follow-up and maintenance outcomes	0	0	0	0	1	1	0	0	1	1	0	1	0	0	0	1	1	1	1	1	1
Total score	17	18	15	18	16	18	16	17	17	16	17	18	17	17	17	18	18	19	19	19	17

Studies were then ranked as high (14–19 points), medium (7–13 points), and low quality (1–6 points)

Data synthesis

Seven aspects were summarized: study design, grouping, intervention implementers, intervention methods, duration and frequency, measurement methods, and outcomes (Table 2). The number of participants from each group in the 42 literatures ranged from 3 to 132. Among these, 22 literatures used the MMSE for cognitive screening. All of the literatures used musical interventions. The music was selected according to the patient's personal preferences or characteristics. Participants in all literatures included patients with AD or MCI. The studies varied regarding music implementation, music type, intervention duration, and intervention frequency. Some of previous studies had explored the effects of music on cognition or psychological behavior in AD patients. But this study was the first comprehensive and detailed summary of the benefits of MT for AD over the past decade.

Table 2.

Cohort study

References	Study design	Intervention Group/Exposure	Control group	Intervention conducted by	Intervention	Duration and frequency	Measures	Outcomes
[32]	Cohort Study	Male(5), female(9).Age: Mean/SD = 84.60/8.69	None	None	None	None	1. The scale for physical health2. The scale for valence3. Talking	1. Physical health increased2. Improve positive emotion3. Improvements in physical and cognitive abilities
[33]	Randomised Controlled Trial (RCT)	20 patients diagnosed with probable Alzheimer’s disease (AD). Age:Mean/SD = 84.2/6	20 residents in the same nursing homes. Age: Mean/SD = 82/10	The examiner	Musical reminiscence workshops	In three phases over two weeks	1. Mini-mental State Examination (MMSE) 2. The Geriatric Depression Scale (GDS) 3. A semi-structured questionnaire, the “TEMPau” 4. The IMAGE Test 5. The I-AM Test	Improvement in autobiographical memories
[34]	RCT	Patients with probable AD, SI(sing group)(n=33). Age: Mean/SE =78.8/7.43	Patients with probable AD, PI(painting group)(n=32). Age: Mean/SE = 80.2/5.71	A professional choir conductor accompanied by a psychologist	1. SI 2. PI	12 weekly two-hour SI or PI sessions during 3 months	1. The Numeric Rating Scale (NRS) 2. The SVS 3. The Brief Pain Inventory (BPI) 4. The State-Trait Anxiety Inventory (STAI) 5. GDS 6.The EuroQol-5 dimensions (EQ-5D) health survey 7. The Rosenberg Self-Esteem Scale 8. A complete battery of neuropsychological tests	1. Concerning verbal memory, FCRT total recall was stable over time for SI, and decreased for PI 2. Anxiety decreased, and quality of life and self-esteem increased post-intervention (However, self-esteem statistical analysis is meaningless) 3. A reduction of depressive symptoms with PI 4. Reduction of chronic pain
[35]	Single subject design study	3 AD patients with mild or moderate. Age: Mean = 80	Self-control	The researchers	Music therapy	Two times a week, each time was 45 minutes, for a total of 16 times	1. The autobiographical memory test (AMT) 2. GDS	1. Improvement in autobiographical memories 2. In terms of time, there was an improvement in directional force. However, it was not statistically significant
[36]	Controlled Trial	39 AD patients with mild to moderate AD (24 females, 15 males). Age: Mean/SE = 73.64/7.11	Self-control	1. A neuropsycholo-gist (CT) 2. A music therapist (ATM) 3. A neurologist (NE) 4. The caregivers	1. CT 2. AMT 3. NE	The CT and AMT lasted 12 weeks, two 45-minute group sessions a week, and NE also lasted 3 months.	1. The Word Fluency test (WFT) 2. The Short Story test (SST) 3. The Beck Depression Inventory (BDI) 4. STAI Y-1, STAI Y-2 5. Lubben Social Network Scale (LSNS)	1. Verbal initiative, the AMT and NE groups showed no significant changes, about 8 and 23% of patients treated by AMT improved in initiative and episodic memory 2. An increase in interpersonal relationships in the AMT and NE groups 3. A decrease in trait anxiety and depression in all groups
[37]	RCT	Active music therapy (AMT) and memantine (M), 45 Patients with probable AD (31 females). Age: Mean = 73.2	M	AMT	AMT and M	AMT included twice weekly sessions, each lasting 40 min, and lasted 24 weeks.	1. The Severe Impairment Battery Language (SIB-l) subscale score 2. Activities of Daily Living (ADL) scales 3. Neuropsychiatric Inventory (NPI) 4. MMSE 5. LSNS	1. Benefits in the M-AMT group for Depression and Appetite disorders 2. Improved psychiatric symptoms (the M-AMT group)
[38]	RCT	49 patients with AD (70% mild patients, 30% moderate patients). Age of group 1: Mean/SD = 83.93/8.01 Age of group 2: Mean/SD = 78.67/5.73	41 patients with AD (70% mild patients, 30% moderate patients). Age: Mean/SD = 80.02/5.78	The music facilitators	1. Group 1: AMI - active music intervention 2. Group 2: RM - receptive music intervention	Approximately 45 min and was performed twice a week for three months (12 sessions in total)	1. MMSE 2. NPI 3. GDS 4. Barthel Index (BI) 5. Tinneti Scale (TS)	1. AMI was found to improve Cognitive and motor functions, behavior, and ADL improved 2. RMI has only a stabilising effect on behaviour
[39]	RCT	Severe AD, a Passive music intervention group (10 women, age: Mean/SE = 81.1/11.0; three men, age: Mean/SE = 78.7/12.1), and an Interactive music intervention group (11 women, age: Mean/SE = 81.2/7.5; two men, age:Mean/SE = 76/7.1)	Severe AD (11 women, age: Mean/SE =  81/8.3; two men, age: Mean/SE = 84.5/4.95)	Music facilitators(two music therapists, four occupational therapists, and six nurses with knowledge of severe dementia symptoms)	1. A Passive music intervention group 2. An Interactive music intervention group	30 min once a week for ten weeks (10 sessions in total)	1. The autonomic nerve index and the Faces Scale (Short-term effects) 2. The Behavioral Pathology in AD Rating Scale (Long-term effects) 3. Video	1. Elicited pleasant emotional states 2. The behavioral psychological symptoms of both the active group and the passive group were improved (paranoid and delusional ideation, activity disturbance, and aggressiveness toward caregivers). 3. Reduced stress and increased relaxation 4. Improved QOL and increased activity in daily life 5. The interactive music intervention may directly stimulate cognitive and emotional function in individuals with cognitive reserve
[40]	Controlled Trial	25 AD patients. Age: Mean/SE = 78.38/6.7	Self-control	A professional music therapist	Music therapy	A duration of 60 min, through two activities that lasted 30 min each	1.Saliva samples (cortisol was quantified using the Enzyme-Linked ImmunoSorbent Assay (ELISA) immunoassay technique) 2. The HADS test	1. The levels of cortisol decrease 2. Symptoms of depression after therapy are improved, same as stress levels
[41]	Controlled Trial	53 Mild AD patients, 6 moderate AD patients. Age: Mean/SE = 77.2/7.1, participants were women(72.9%)	Self-control	The researchers	Cognitive training, music therapy, art therapy	A 32-hour therapy (2 hours×16 sessions)	1. MMSE 2. Clinical Dementia Rating (CDR) 3. A Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) 4. GDS 5. Beck Anxiety Inventory (BAI) 6. Seoul-Instrumental ADL (S-IADL) scale	1. Improve cognition 2. Maintain a more beneficial ADL function 3. Alleviate depression and anxiety
[42]	RCT	32 patients with probable AD. Age: Mean/SD = 78.44/1.00	21 patients with probable AD. Age: Mean/SD = 78.52/1.70	Two skilled and professionally educated occupational therapists	Multidomain cognitive stimulation including art, music, recollection and horticultural therapy	Each period of intervention lasting 1 h, repeated five times per week for six months	1. The Korean Boston Naming Test (K-BNT) 2. Word fluency 3. MMSE 4. Word list registration 5. Construction praxis 6. Word list recall 7. Word list recognition 8. Construction recall 9. GDS 10. The Quality of Life-AD (QOL-AD) scale 11. CDR	1. Better maintenance of cognitive abilities 2. Help in forming interpersonal relationships 3. Depression has a trend towards an improvement 4. The quality of life of caregivers has improved
[43]	RCT	18 mild AD patients. Age: Mean/SE = 80.60/5.12	17 mild AD patients. Age: Mean/SE = 77.88/5.49	A therapist who had over five years of occupational therapy experience	A nonpharmacolo-gical intervention (physical, horticultural, musical, art, and instrumental activity of daily living)	A total of 24 sessions--five times per week for one hour per session	1. Functional Independent Measure (FIM) 2. Korean MMSE 3. Subjective Memory Complaints Questionnaire (SMCQ) 4. Short-Form Geriatric Depression Scale-K (SGDS-K) 5. Geriatric Quality of Life-Dementia (GQOL-D)	1. Improved cognitive functions (subjective memory deterioration) 2. Reduced depression 3. Enhanced quality of life
[44]	Controlled Trial	7 AD patients. Age: Mean/SE = 86.14/4.63	7 AD patients. Age: Mean/SE = 81.29/7.99	Gerontologists	Musical listening session	20 min/week for two months	1. NPI 2. Biofeedback cardiovascular 3. Addenbrooke’s Cognitive Examination-Revised (ACE-R)	Although not statistically significant, it is observed that the severity of depression and apathy improved.
[45]	RCT	37 AD patients, 21 males and 16 females. Age: Mean/SE = 70.06/6.67	36 AD patients, 20 males and 16 females. Age: Mean/SE = 69.89/5.51	One doctor, five nurses, two psychologists and one nutritionist	Continuing care combined with music therapy	Listening to music for 30 minutes each in the morning, afternoon and evening for two years	1. The Western Aphasia Battery (WAB) 2. ADL scale 3. MMSE 4. The 100-point SF-36 scale	1. Improved the linguistic skills of elderly AD patients 2. Improved their self-care abilities 3. Improved their cognitive function
[46]	RCT	18 AD patients (12 women and 6 men). Age: Mean/SE = 75.83/5.85	18 healthy controls (11 women and 7 men). Age: Mean/SE = 73.61/6.27	Researchers	Music	In the ‘‘Music’’ condition, the participants were exposed during 2 min to their own chosen music.	1. The TEMPau test 2. Empty words 3. Grammatical complexity 4. Propositional density 5. Verbal fluency	1. Autobiographical recall improvement in AD patients 2. This linguistic enhancement 2.1. A greater reduction in the production of empty words. 2.2. A greater enhancement of grammatical complexity. 2.3. A greater enhancement of propositional density. 2.4. Enhancement in verbal fluency in AD patients
[47]	RCT	A singing group (mild AD=33, moderate AD=34, severe AD=33, age: Mean/SD = 68.9/7.1) a lyric reading group (mild AD=31, moderate AD=34, severe AD=34, age: Mean/SD = 70.3/8.3)	Conventional medicines combined with other daily care and support (mild AD=32, moderate AD=35, severe AD=32, age: Mean/SD = 69.9/7.9)	Therapists	1. A singing group 2. A lyric reading group	Twice daily, with one session in the morning and one session in the afternoon for three months, which lasted 30 - 40 min per session	1. MMSE 2. World Health Organization University of California-Los Angeles, Auditory Verbal Learning Test (WHO-UCLA AVLT) 3. NPI 4. BI 5. Verbal fluency test	1. Music therapy is more effective for improving verbal fluency and for alleviating psychiatric symptoms and caregiver distress than lyric reading in patients with AD 2. No significant effect was found for ADL 3. Music therapy has a positive effect on the ability of immediate and delayed word recall in mild AD patients
[48]	Controlled Trial	Music (18 AD patients, age: Mean/SD = 86.7/6.4) Cooking (19 AD patients, age: Mean/SD = 87.5/6)	Self-control	Two supervisors (including one psychologist)	1. Music 2. Cooking	A duration of one hour, twice a week, for four weeks (total 8 hours)	1. Assessing discourse content, emotional facial expressions and mood 2. STAI for Adults (STAI-A) 3. SIB 4. The Cohen-Mansfifield Agitation Inventory (CMAI) 5. NPI 6. Musical Expertise Questionnaire 7. MMSE	1. Positive changes in the patients’ emotional state 2. Decreased the severity of their behavioral disorders(agitated behaviors) 3. Reduced caregiver distress 4. No benefit on the cognitive status
[49]	Controlled Trial	32 AD patients, 8 males and 13 females. Age: Mean/SE = 81.1/9.1	Self-control	The same professionals	Video-music therapy (VMT)	Twice a week for a total of 12 times, with 6 times as one cycle, each separated by an interval of 5 months	1. MMSE 2. QOL-AD	The Patients with questionable, mild and moderate neurocognitive impairment (MMSE Stages 1, 2, 3) reported an improvement in their quality of life, whereas the Patients with severe deterioration (MMSE stage 4) did not report any change.
[50]	Controlled Trial	29 AD patients, 4 non-AD dementia subtypes patients. Age: Mean/SD = 79.1/8.0	Self-control	A professional conductor	Choir (consisted of a warm-up song rehearsal)	Three choir seasons, each lasting 3.5 months, during which there will be a two-hour meeting every week	1. MMSE 2. The Positive and Negative Affect Schedule(PANAS)	1. Attenuate cognitive decline 2. Reduce negative outcomes (isolation, anxiety)
[51]	RCT	20 AD patients (18 women and 2 men). Age: Mean/SE = 74.38/3.56	20 AD patients (19 women and 1 man). Age: Mean/SE = 75.15/4.23	Familiar caregiver	Listening to a familiar/unfami-liar song	Three sessions per week, approximately 2 - 4 minutes at each session. approximately three months	1. The SC questionnaire 2. MMSE 3. Frontal assessment short test (FAS)	Improvement in aspects of self-consciousness.
[52]	RCT	25 AD patients. Age: Mean/SE = 86.6/4.5	25 AD patients. Age: Mean/SE = 86.9/5.7	A trained music facilitator	Used percussion instruments with familiar music	A 60-minute group music session weekly for 12 weeks	1. The Hamilton Anxiety Rating Scale(HAMA) 2. GDS	1. Reduction in the anxiety level 2. The change in depressive symptoms between the two groups was nonsignificant
[53]	RCT	20 AD patients (10 women,10 men). Age: Mean/SE = 75.9/1.7	19 healthy people (9 women, 10 men). Age: Mean/SE = 73.5/1.7	The experimenter	Listened to two 4.5-minute blocks of self-selected music(happy/sad music)	40 minutes in total	1. BDI 2. The Iowa Music Background Questionnaire 3. CDR 4. self-report rating scales	Induced strong and lingering emotions in individuals with AD.
[54]	Controlled Trial	Singing group (31 mild AD patients). Age: Mean/SE = 78.8/7.43 Painting group(28 mild AD patients). Age: Mean/SE = 80.2/5.71	Self-control	1. A professional choir conductor 2. Psychologis-ts 3. A painting teacher	1. Singing 2. Painting	12 weekly 2-hour sessions during 3 months	1. EVIBE (in French: Evaluation Instantane´e du Bien-Etre) 2. NRS	1. Improvement in well-being 2. Not improvement in pain intensity
[55]	RCT	8 mild AD patients. Age: Mean/SE = 77.8/5.2	7 healthy older adults. Age: Mean/SE = 75.7/7.4	The experimenter	Learned and memorised lyrics that were either sung or spoken	Each session lasted for approximately 45 minutes, six sessions in total.	1. MMSE 2. GDS 3. Well-being scale 4. Token tests 5. Verbal fluency 6. The Montreal Battery of Evaluation of Amusia (MBEA)	Increased delayed recall.
[56]	Controlled Trial	7 AD patients (4 female, 3 male). Age: 70 to 85 years (median 77.0).	Self-control	The musician	A live musical violin intervention	A total of three musical interventions, a duration of 18 minutes for each intervention	1. Video 2. CMAI	- Facilitated the expression of positive behaviour (smiling, laughing, relaxing facial expression, initiating conversation, attention focused towards the direction of music, tapping feet to music, nodding, swaying to music).
[57]	Controlled Trial	45 AD and related dementia patients	Self-control	Familiar caregiver	A personal music player	6 months	1. The Agitation Behavior Mapping Instrument (ABMI) 2. CMAI 3. The Minimum Data Set-Aggressive Behavior Scale (MDS-ABS) 4. Directly observing residents’ behaviors 5. Interviewing	Decreased in agitated behaviors.
[58]	RCT	13 AD patients. Age: Mean/SE = 77.9/8.1	26 healthy people. Age: Mean/SE = 77.1/8.2	The researchers	Study the text in the context of different music	Two hours	1. MBEA 2. GDS 3. The Mattis Dementia Rating Scale 4. The digit symbol-coding subtest 5. The French version of Baddeley’s dual task	Evoked memories.
[59]	RCT	8 AD patients. Mean MMSE =  25.2/30; range 23–27	Six healthy controls	The researchers	Learn four different sets of 10 gestures in musical accompaniment or metronomic accompaniment	Estimated 15 min	1. Token test 2. Auditory attention 3. GDS 4. MMSE 5. Video	Reinforced the memory.
[60]	RCT	12 mild AD patients. Age: Mean/SD = 82.8/8.9	15 healthy controls. Age: Mean/SD = 77.1/7.2	The experimenter	Texts presented with either a musical or a nonmusical association or without association	A single experimental session lasting approximately one hour and a half	1. GDS 2. MBEA 3. The Wechsler Adult Intelligence Scale 4. The Free and Cued Selective Reminding Test (FCSRT) 5. The Hearing Handicap Inventory for the Elderly (HHIE) 6. The Dementia Rating Scale	Facilitated learning and enhances verbal episodic memory (in terms of the number of lines learned, immediate and delayed recall).
[61]	RCT	34 patients with dementia, 12 males, 22 females. Age: Mean/SD = 81.5/9.7	11 patients with dementia, 6 males, 5 females. Age: Mean/SE = 81.5/9.7	Caregivers	Listening music sessions	Six weeks, 360 listening sessions in total	1. MMSE 2. QOL-AD 3. The Vulnerability to Negative Affect Scale –Proxy version (VNADS) 4. The Music in Dementia Assessment Scale was used (MIDAS)	1. Improvements to quality of life 2. Increases in Interest, Responsiveness, Initiation, Involvement, and Enjoyment 3. Closest relationship also improved 4. Mood had improved
[62]	RCT	30 mild AD patients (10 males, 20 females). Age: Mean/SD = 70.4/7.5	30 mild AD patients (12 males,18 females). Age: Mean/SD = 69.1/7.2	The therapist	Music therapy and drug therapy	Per day for 30–50 min per session, three consecutive months	1. MMSE 2. The Montreal Cognitive Assessment (MoCA) 3. NPI	Improved cognitive function and behavior (the improvement in MMSE was significantly better, and the score of neuropsychiatric symptoms decreased).
[63]	RCT	10 AD patients (4 males and 6 females). Age: Mean/SD = 78.1/7.0	10 AD patients (2 males and 8 females). Age: Mean/SD = 77.0/6.1	Professional musicians	Group music therapy and practice singing at home(karaoke and a unique voice training method (the YUBA Method))	Once a week for six months	1. Functional magnetic resonance imaging (fMRI) 2. Raven's Colored Progressive Matrices (RCPM) 3. MMSE 4. Rivermead Behavioral Memory Test (RBMT) 5. NPI 6. BI 7. Instrumental ADL Scale (IADL) 8. Disability Assessment for Dementia (DAD) 9. Zarit Burden Interview (ZBI)	1. Decreased in the NPI score 2. A prolongation of the patients'sleep time 3. ADL had worsened 4. Increased psychomotor speed
[64]	Controlled Trial	132 patients with dementia (31 AD patients). Age: Mean = 89.6	Self-control	Two nationally board-certified music therapists	Singing, rhythm, and movement therapeutic activities	Three times a week for two weeks, lasting from 15 min to 1 h, a total of six sessions	1. The Cornell Scale for Depression (CSD) 2. The Algase Wandering Scale (AWS) 3. The Cohen Mansfifield Agitation Inventory (CMAI) 4. The Functional Assessment Screening Test (FAST)	Symptoms of depression and agitation were significantly reduced, and maintained these changes for at least two weeks post treatment.
[65]	A cross-over RCT	60 patients with dementia (67.2% AD patients). Age: Mean/SD = 75.83/8.76	Self-control	The caregivers	1. Validation therapy (VT) in a Psycho-educational program 2. Reminiscence therapy (RT) 3. Music therapy (MT)	1.VT: 24 seminars, lasted for 12 weeks and 2 hours each seminar 2. RT: lasted 60 minutes per session, once a day after breakfast 3. MT: 45 minutes per session, five times a week, once per day every morning after breakfast	1. MMSE 2. ACE-R 3.GDS 4. Functional rating scale for symptoms in dementia (FRSSD) 5. NPI	The most effective combination for the reduction of the hallucinations and the caregivers’ distress.
[66]	Controlled Trial	5 moderate AD patients. Age: Mean/SD = 89.6/5.1	Self-control	A physical therapist	A progressive physical exercise program accompanied by music	A session frequency of three times a week (30 min/session), three weeks in totally	1. Video 2. The Intrinsic Motivation Inventory (Dutch version) 3. The Credibility expectancy questionnaire 4. The observed emotion rating scale (OERS)	Music increases the patient's concentration
[67]	Controlled Trial	62 patients with dementia (22.6% AD patients, 53 female). Age: Mean/SD = 85.54/8.25	Self-control	Certified nursing assistants (CNAs) trained by music therapists	The singing and music-with-movement activities	Two weeks of music therapy three times a week, duration ranging from 10 to 15 min	1. CSD 2. Video 3. MIDAS	1. Depression symptoms significantly declinedbut appeared to stabilise following the 2-weeks music activity 2. Improvement in wellbeing
[68]	RCT	12 mild cognitive impairment patients (MCI). Age: Mean/SE = 72.83/7.93	12 MCI patients. Age: Mean/SE = 73.42/5.96	A music therapist	The protocol of Song-based Cognitive Stimulation Therapy (SongCST)	Ten weeks, two times/week, 60 minutes/session	1. MMSE-Dementia Screening (MMSE-DS) 2. MoCA 3. And CDR Scale Sum of Boxes (CDR-SOB) 4. BDI 5. QOL-AD	Executive/visuospatial function, delayed memory, and orientation significantly improved after intervention.
[69]	RCT	44 cognitive impairment patients. Age: Mean/SE = 84.09/5.60	40 cognitive impairment patients. Age: Mean/SE = 83.00/7.20	Music leaders,	A musical fitness programme (MFP) intervention	50 min per session, twice a week for 12 weeks	1. NPI nursing home version 2. CSD 3.30-s arm curl test 4. MMSE	Reduced neuropsychiatric symptoms and depression.
[70]	RCT	134 MCI patients, dancing group (n = 67) and playing musical instruments group (n = 67)	67 MCI patients	1. One or two professional dance instructors 2. One or two professional music instructors	1. Dancing 2. Playing musical instruments	1. Weekly 60-minute sessions for 40 weeks (dance) 2. Weekly 60-minute sessions for 40 weeks (music intervention)	1. The story memory and word list memory tests from the National Center for Geriatrics and Gerontology Functional Assessment Tool 2. MMSE 3. Nonmemory domain (Trail Making Tests A and B) scores	Improvements in general cognitive function
[71]	RCT	30 MCI patients. Age: Mean/SE = 74.62/5.05 years	9 MCI patients. Age: Mean/SE = 74.62/5.05	The instructor	Multitask movement music therapy (MMT)	Total of 12, 60 - min sessions over 3 months	1. Six physical function tests 2. The Frontal Assessment Battery (FAB) 3. Measured relative oxyhemoglobin concentrations using 45-multichannel functional near-infrared spectroscopy	1. Improved cognition 2. Activated the prefrontal area
[72]	RCT	32 MCI patients. Age: Mean/SE = 75.63/6.30	32 MCI patients. Age: Mean/SE = 76.81/5.36	Occupational therapists	Multimodal Cognitive Enhancement Therapy (MCET)	Three 3-hour sessions per week for eight weeks	1. MMSE 2. AD Assessment Scale-Cognitive Subscale 3. Revised Memory and Behavior Problems Checklist frequency scores 4. QOL-AD 5. GDS 6. DAD	Improved cognition, behavior, depression, and quality of life.
[73]	RCT	16 MCI patients. Age: Mean/SD = 71.25/4.56	Self-control	Researcher	Music-with-movement interventions	One-hour music therapy sessions three times a week for 12 weeks	1. MoCA 2. The Wechsler Intelligence Scale 3. The Spanish version of the digit span subtest 4. The Wechsler Memory Scale 5. The Text II tests 6. FAB 7. The Depression Questionnaire	Improved global cognitive state, attention, immediate memory, delayed memory, executive function, gait velocity, gait parameters.

AD Alzheimer’s disease, MCI mild cognitive impairment patients, Mean±SD mean± standard deviation, MC Matched Controls, MMSE Mini-Mental State Examination, GDS Geriatric Depression Scale, NRS the Numeric Rating Scale,  BPI the Brief Pain Inventory, STAI the State-Trait Anxiety Inventory, EQ-5D The EuroQol-5 dimensions health survey, SI sing group, PI painting group, AMT The autobiographical memory test, WFT the Word Fluency test, SST the Short Story test, BDI The Beck Depression Inventory, LSNS Lubben Social Network Scale, SIB-I the Severe Impairment Battery Language subscale score, ADL Activities of Daily Living, BI Barthel Index, TS Tinneti Scale, CDR Clinical Dementia Rating, KDSQ-C a Korean Dementia Screening Questionnaire-Cognition, BAI Beck Anxiety Inventory, K-BNT the Korean Boston Naming Test, FIM Functional Independent Measure, SMCQ Subjective Memory Complaints Questionnaire, SGDS-K Short-Form Geriatric Depression Scale-K, GQOL-D Geriatric Quality of Life-Dementia, NPI-Q the Neuropsychiatric Inventory Questionnaire, ACE-R Addenbrooke’s Cognitive Examination-Revised, WAB the Western Aphasia Battery, WHO World Health Organization, UCLA University of California-Los Angeles, AVLT Auditory Verbal Learning Test, CMAI the Cohen-Mansfifield Agitation Inventory, PANAS the Positive and Negative Affect Schedule, FAS frontal assessment short test, HAMA The Hamilton Anxiety Rating Scale, MBEMA the Montreal Battery of Evaluation of Amusia, ABMI the Agitation Behavior Mapping Instrument, MDS-ABS the Minimum Data Set-Aggressive Behavior Scale, FCSRT the Free and Cued Selective Reminding Test, HHIE the Hearing Handicap Inventory for the Elderly, WAIS-III Wechsler Adult Intelligence Scale, 3rd Edition, ELISA Enzyme-Linked Immunosorbent Assay, VNADS The Vulnerability to Negative Affect Scale –Proxy version, MIDAS the Music in Dementia Assessment Scale, MoCA the Montreal cognitive assessment, fMRI functional magnetic resonance imaging, RCPM Raven's Colored Progressive Matrices, RBMT Rivermead Behavioral Memory Test, DAD Disability Assessment for Dementia, ZBI Zarit Burden Interview, CSD The Cornell Scale for Depression, AWS The Algase Wandering Scale, FAST The Functional Assessment Screening Test, FRSSD Functional rating scale for symptoms in dementia, OERS the observed emotion rating scale, FAB the Frontal Assessment Battery

Results of studies that met inclusion criteria

Cognitive

Fourteen people with dementia in nursing homes in the UK showed cognitive improvements after using a mobile app to recall music that triggered autobiographical or memory associations [32]. Ninety AD patients in 6 nursing homes were randomized to active group music intervention and group music listening, and the cognitive deficits were greatly improved, and the effect of the former intervention was greater than that of the latter [33]. Similar to this study, a RCT in Japan showed that active music intervention restored residual cognitive function with MT [34]. Fifty-nine AD patients in the US demonstrated that MT improved cognition in patients with mild to moderate AD [35]. Fifty-three community AD patients were randomized to receive multi-domain cognitive stimulation including art, music, recall, and gardening therapy. Compared to the control group, patients in the intervention group showed significant cognitive improvements in both identifying and recalling words [36]. Thirty-three dementia patients in another community had reduced MMSE scores after participating in an 18-month "Voice of Motion" intervention (P < 0.05) [37], which was similar to the result of another study [38]. Similar to the UK study, an electronic device for song cognitive stimulation therapy was developed in South Korea to perform a 10-week cognitive intervention on 24 MCI patients, which resulted in significant improvement in MMSE scores after 10 weeks [39]. Another Japanese team conducted single-blind RCT on 201 MCI patients. Patients were randomly assigned to dance, play a musical instrument, and receive health education. After 40 weeks, the dance group had improved memory function compared to the control group, while no difference was observed in the music group. However, MMSE scores increased in both groups compared with the control group [40], which was consistent with another report [41]. A double-blind RCT in Korea randomized 55 patients with MCI or dementia to an intervention or placebo group. Members of the intervention group completed 16 weeks of multimodal cognitive enhancement therapy, including cognitive training, cognitive stimulation, actual orientation, physical, recall therapy, and MT. Patients in the intervention group had significant increases in MMSE and AD Assessment Scale-Cognitive subscale scores, as did the Memory Checklist scores [42]. Another RCT also used MT to intervene patients with MCI, and the results showed that music intervention had significant effects on overall cognitive status, attention, immediate memory, delayed memory, executive function, gait speed, right and left stride length in patients with MCI [43]. Cognitive deficits in people with dementia are well known, but there is no difference in music perception between people with dementia and people without dementia [44]. Similar to the intervention in the UK study, recall MT was also used to treat AD patients in France, and the results were found to improve the quantity and quality of autobiographical memory in AD patients [45], which was consistent with the results of the Chinese team using computer combined MT [46]. In another RCT, 190 AD patients were randomized to either singing or reading poetry. After 3 months, those in the singing group had greater verbal fluency and improved both immediate and delayed memory [47]. In another multicenter RCT in France involving 59 patients with mild AD, participants were randomized to singing or painting. After 12 weeks, verbal memory remained stable in the singing group and decreased in the painting group (P < 0.05) [48], and similar results were obtained in the Italian cognitive training trial. After active music intervention, the initiative and memory of AD patients remained stable [49]. In Korea, an intervention program consisting of five categories of activities (physical, gardening, music, art and instrumental) was conducted in patients with mild AD, and participants in the intervention group showed cognitive improvement [50]. In addition, a study of 20 AD patients treated with recall MT showed a significant increase in self-awareness [51]. Another study showed that MT can improve the language ability and memory function of AD patients [52]. In addition, some studies had reported that singing lyrics had no effect on immediate memory in AD patients, but had a promotion effect on delayed memory [53]. Other studies have shown that recall MT can help protect episodic memory in AD patients [54]. A case study in Canada showed that music could be used as an aid for AD individuals to learn non-verbal information [55]. A psychological study in Japan used singing to treat 10 patients with AD, and the intervention group showed an increase in psychomotor speed compared with 10 patients with AD who received neuropsychological assessment only [56]. In a dementia nursing home, exercise therapy with musical accompaniment significantly improved attention in moderate AD patients, resulting in an overall participation rate of 84.1% [57]. A RCT study in France had slightly different results from previous studies, which reported improvements in both immediate and delayed memory in AD patients using music [58]. To sum up, MT has the potential to improve cognitive function.

Behavioural and psychological symptoms

The results of different individualized interventions in Japan showed that active music intervention could greatly improve the behavioral and psychological symptoms of AD patients [34]. A total of 59 AD patients in Korea received comprehensive cognitive therapy. Before and after treatment, the average score of geriatric depression scale decreased (P < 0.001). The mean Beck Anxiety Scale score also decreased (P = 0.001) [35]. Community singing in 33 dementia patients for 18 months also further improved cognitive function in terms of reducing negative emotions [37]. In South Korea, multimodal cognitive enhancement therapy showed improvement in behavioral problems Checklist scores in patients with dementia (effect size = 0.38, P = 0.046) compared with placebo [42]. Studies in France and Korea found that singing and painting therapy reduced anxiety and depression symptoms in MCI and AD patients (P < 0.05) [48, 50]. Cognitive training, active MT, and neuroeducation in a single-blind RCT study all improved mood and social relationships in AD patients [49]. The Chinese AD Center also found that AD patients' psychiatric symptoms were greatly relieved [52], similar to neuropsychological and fMRI studies in Japan [56]. In the US, 20 AD patients and 19 healthy people were asked to listen to 4.5 min of self-selected music, and their emotional changes were measured, which found that both groups of people were stimulated by strong emotional changes due to music. Perhaps music can be used as an emotional guide for AD patients, thus promoting their healthy mentality [59]. The French RCT study also provided evidence for the effectiveness of MT. Forty-eight dementia patients were randomly assigned to a music group or a cooking group. After 4 weeks of intervention, the blinded evaluation showed that both interventions promoted positive changes in mood and reduced the severity of behavioral disorders [60]. Other study has reported improvements in motivation and engagement after 6 weeks of dementia caregivers using music to intervene with dementia patients [61]. Similar to this study, there are studies that use live music to intervene in AD patients and promote positive behaviors in AD patients [62]. A nursing home music intervention study used the Cornell Depression Scale to measure depressive symptoms in 62 patients with dementia before and after intervention. After 2 weeks, depressive symptoms decreased significantly [63]. A RCT study in Italy combined active MT with medication in patients with AD, and the combination significantly improved neuropsychiatric symptoms compared with medication alone [64]. A research team in Spain conducted 60 min of MT for 25 MCI patients, and used scales to measure participants' anxiety and depression levels before and after the trial. The results showed that the application of MT significantly reduced depression and anxiety [65]. In a quasi-experimental study of 14 AD patients who were randomly assigned to listen to music, 7 received a music intervention and the other 7 served as a control group. After 2 months of intervention, members of the intervention group showed a decrease in apathy and a significant decrease in neuropsychiatric questionnaire scores [66]. A team in Taipei randomly assigned 50 men with AD to a percussion-music group or a control group. After 12 weeks of music lessons, the intervention group had significantly lower levels of anxiety (P < 0.001) [67]. A 6 month pilot study of 45 severe AD patients who received a personalized music intervention showed a reduction in agitation and aggression [68]. Another nursing home music intervention treatment of 132 moderate to severe AD patients, repeated measures of variance analysis confirmed that MT could significantly reduce symptoms of depression and agitation [69]. Another study in China used a music fitness program in elderly people with MCI in long-term care facilities. After 12 weeks of intervention, music fitness program was effective in reducing neuropsychiatric symptoms and depression (P < 0.05) [70]. A Greek cross-over RCT using three non-pharmacological interventions in mental health education, validation therapy, recall therapy, and MT, found that MT was effective in reducing hallucination in 60 AD patients who were randomly assigned to one of the 3 groups for 3 weeks [71]. Therefore, MT can greatly improve the behavioral and psychological symptoms of AD patients, especially anxiety and depression.

Quality of life

MT had a positive impact on the daily lives of AD patients in the UK [32], similar to group music interventions in Spain [33]. Personalized MT in Japan can restore residual cognitive and emotional functioning in AD patients. Therefore, MT may be useful in helping people with severe AD relate to others and improve quality of life [34]. Multi-domain cognitive stimulation therapy had improved the quality of life of AD patients, as well as the quality of life of caregivers [36]. A RCT study in Seoul, South Korea, after the intervention, the scores of the AD patients on the self-rated quality of life scale increased significantly [42]. A RCT study in France found that painting and MT improved the quality of life of AD patients [48]. The Italian RCT found that MT led to improvements in social relationships [49]. Another recall based occupational therapy program in South Korea resulted in significant improvements in quality of life for patients with mild AD [50]. Singing training in Japan significantly prolonged the sleep time of AD patients and improved their quality of life [56]. An Australian study reported an improvement in quality of life after 6 weeks of music treatment with dementia [61]. Video analysis and paired sample t-test showed that residents who participated in exercise music had a significant improvement in well-being (P = 0.003) in the US [63]. MT combined with medication showed that it could improve appetite and their quality of life in AD patients [63]. Thirty-two AD patients in Italy who received 6 sessions of video MT showed improvement in quality of life in mild and moderate patients, but no change in quality of life in severe patients [72]. A community study in France randomly assigned 59 patients with mild AD to sing or paint, and observed significant improvements in well-being in both groups after the intervention [73]. In conclusion, MT is worthy of being an effective intervention strategy for AD patients to improve their quality of life.

Other efficacy

In addition, Pongan E et al. reported that MT could reduce physical pain in AD patients and increase self-esteem in AD patients, although the latter was not statistically significant [48]. The other potential benefits of MT deserve further investigation and verification.

Discussion

Cognitive decline mainly manifests itself in memory decline in AD, and decline in autobiographical memory is one of the most common symptoms in AD patients [74, 75]. Autobiographical memory decline can have a devastating impact on the sense of identity of people with AD. MT may act as a guardian of memory in AD, preventing profound memory loss. The therapeutic value of MT in the treatment of AD must be interpreted within a two-dimensional framework of neuroplastic remodelling and psychosocial compensation [76]. In the present study, we found that the ameliorative effect of MT on situational memory is highly compatible with the theory of limbic system activation proposed by Särkämö et al [77]: functional MRI evidence suggests that receptive music interventions significantly enhance neural activity in the right angular gyrus and left lingual gyrus of the brain [78], and that this mechanism of neural plasticity may retard the process of spatiotemporal spreading of the characteristic tau protein pathology of AD. In particular, the preservation of autobiographical memory by MT can be explained by the findings of Jacobsen's team [22], where it has long been known that the neural encoding of music in healthy adults involves the caudal anterior cingulate cortex (ACC) and the ventral anterior supplementary motor area (pre-SMA). And these two areas are among the last brain regions to degenerate in AD, with little apparent cortical atrophy or metabolic decompensation, providing a neurobiological explanation for the preservation of musical responsiveness in patients with advanced AD. In addition, MT could effectively improve language skills in patients with mild AD and reduce psychiatric symptoms and caregiver distress in patients with moderate or severe AD [52]. These studies were consistent with our findings. The language of AD patients is weakened or abolished [79], and the power of music and its non-verbal nature can provide a unique communication medium. Overcoming language barriers contributes to the health and self-esteem of people with AD and their social interactions and communication with family, friends, and caregivers. With the decline of cognitive ability in AD patients, social behavior will also decrease, which can further aggravate depression. These factors will gradually impair the patient's relationships and social engagement. MT allows AD patients with social isolation to interact socially, thus strengthening the participants' sense of achievement, belonging, self-confidence and identity.

The role of MT in modulating behavioural psychiatric symptoms of dementia (BPSD) stems from its synergistic regulatory mechanisms on multimodal neural circuits. Functional PET studies have confirmed that rhythmic music stimulation induces an increase in dopamine release through the substantia nigra-striatal pathway [80], a process that is closely associated with elevated D2 receptor occupancy in the nucleus ambiguus [80], providing a molecular basis for the improvement of aggressive behaviour. Animal experiments indicate that music exposure restores homeostasis of the hypothalamic–pituitary–adrenal axis, prevents oxidative stress, and counteracts neurotrophic factor deficits, which in turn suppresses depressive-like behaviour [80]. Salivary biomarker assays confirm that music improves mood states by reducing concentrations of cortisol, a biomarker of psychological disorders, and thereby improving mood states [81]. Notably, music selectively mediates activation of the auditory cortex and propagates through the coherent temporal window to the subcortical nucleus of the bed nucleus of the stria terminalis-nucleus ambiguus (BNST-NAc) reward circuit, evoking strong emotions [82]. At the same time, MT creates a therapeutic atmosphere and environment that can alleviate the anxiety and aggression, most commonly expressed by these patients and meet the social and emotional needs of people with dementia.

MT also plays an important role in creating new ways of communicating for people with AD and their carers. One study suggested that using young people to organise MT for patients with cognitive decline facilitated intergenerational communication [83]. Familiar music interventions can also allow family members to rebuild the emotional intimacy and meaningful interactions that have been lost due to AD, clearly improving the quality of life of patients and their families.

Sleep disturbance is a primary disease burden of AD, which is related to the pathophysiology of AD. It can exacerbate memory, behavioural, and cognitive complications in AD patients. Our study found that the beneficial effects of music on sleep outcomes include decreased nighttime sleep disturbance, increased daytime alertness, and improved sleep quality. Sachdeva S. et al. also showed that music promotes glymphatic solute clearance by increasing interstitial space, thereby reducing fluid transport resistance and improving sleep quality [84].

It's worth noting that active music intervention (AMI) can promote socialisation, participation and self-expression to a greater extent than other interventions. MT for MCI patients can also improve their cognition, behaviour, psychology and quality of life to some extent, which helps to reduce the progression of MCI to AD with more severe symptoms. In addition, MT is more effective when combined with other non-pharmacological interventions, and continuous MT has a long-term effect on people with AD and their carers.

Strengths and limitations

This study has some highlights. On one hand, we summarized the effect of MT on the five aspects of AD for the first time, and provided theoretical suggestions for the prevention and management of AD. On the other hand, literatures in this study have a long time span, including different countries, races, genders, ages, and AD patients with different degrees, which can better summarize the intervention effects of MT and combination therapy on AD at home and abroad, and provide a strong basis and theoretical support for the future development of effective and safe non-invasive AD treatment.

Despite the overall high quality of the included studies, there are some limitations. The significant heterogeneity between studies may affect the generalisability of the conclusions, as evidenced by differences in baseline characteristics of participants (e.g. stage of the AD process from early to late stage) and intervention parameters (e.g. duration of receptive MT from 1 h to 2 years). 36% of the trials had a non-randomised controlled design, which may introduce a risk of selection bias. However, only 36% of the studies explicitly implemented assessor blinding, which may lead to measurement bias in subjective scales. In addition, the small sample size (n < 10) of five studies may lead to insufficient statistical power and overestimation of the intervention effect. Twenty-two studies over-relied on screening tools such as the MMSE, lacked in-depth assessment of specific cognitive domains (such as episodic memory, executive function), and the use of objective biomarkers was minimal. In addition, most studies were short-term interventions (study duration ≤ 3 months), which limits the interpretation of long-term effects and dose–response relationships, and limitations in population selection (86% of studies focused on the AD population) make the generalisation of results to patients with mixed dementia uncertain. These methodological and design limitations need to be addressed in future standardised multicentre trials to increase the clinical translation value of the evidence.

Conclusion

As a non-pharmacological intervention, MT helps AD patients to promote memory and thinking skills and improve emotional and behavioural problems. This has important implications for the current life of dementia patients, helping them delay the disease process, improving their quality of life and extending healthy life. Therefore, MT is a promising non-pharmacological treatment approach for AD patients.

Future directions

With the increasing economic and disease burden of AD patients, MT's non-invasiveness, cheapness, safety and effectiveness will surely accelerate its widespread application in AD-like neurological diseases.

Abbreviations

AD

Alzheimer's disease

CNS

Central nervous system

MCI

Mild Cognitive Impairment

MT

Music Therapy

RCT

Randomized controlled trial

SCD

Subjective Cognitive Decline

PD

Parkinson's disease

HD

Huntington disease

GRADE

Grading of Recommendations, Assessment, Development and Evaluations

ACC

Anterior cingulate cortex

Pre-SMA

Supplementary motor area

BPSD

Behavioral and psychological symptoms of dementia

AMI

Active music intervention

Authors’ contributions

JC is responsible for the study concept and design. JW, CL, YD, CM, GW, YW, TH and JZ are responsible for data acquisition, analysis, and interpretation. JW, CL and YD drafted the manuscript. JC supervised and revised the study. All authors contributed to discussions in the manuscript. All authors read and approved the final manuscript.

Funding

This study was supported by grants from Key Laboratory Open Fund of Ministry of Education College Student Innovation and Entrepreneurship Project(S202410488180X, 202310488043X), Occupational Hazard Identification and control Key laboratory of Hubei Province open fund(OHIC2024G07, OHIC2024Z04), Ministry of Education (2023 KF002), Health Commission of Hubei Province scientific research project (WJ2023M107).

Data availability

All data generated or analysed during this study are included in this published article [and its supplementary information files]. The colour drawings produced in this study were drawn on Biobender with permission to publish.

Declarations

Ethics approval and consent to participate

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.