Topical Cellular/Tissue and Molecular Aspects Regarding Nonpharmacological Interventions in Alzheimer’s Disease—A Systematic Review
Abstract
:1. Introduction
1.1. Pathology of AD
1.2. Familial and Sporadic AD
2. Methods
3. Results
3.1. Acupuncture
Electroacupuncture
3.2. Cognitive Behavioral Therapy (CBT)
Counseling and Psychoeducation
3.3. Environmental Adjustment
3.4. Exercise/Physical Activity
Music and Dancing
3.5. Information Technology
Virtual Reality (VR)
3.6. Lifestyle Factors
3.6.1. Sensory Practices
3.6.2. Validation Therapy
3.7. Low-Dose Ionizing Radiation (LDIR)
3.8. Mechanical-Based Stimulation
3.9. Photobiomodulation (PBM)
3.10. Reminiscence Therapy (RT)
3.11. Repetitive Transcranial Magnetic Stimulation (rTMS)
3.12. Transcranial Direct Current Stimulation (tDCS)
Nonpharmacological Interventions in AD | Cellular/Tissue and Molecular Aspects | References |
---|---|---|
Acupuncture | Acupuncture in AD potentially modulates neurotransmitters and neuroinflammation, improving ADAS-cog and CIBIC-Plus scores. Data mining aids acupoint selection. | [78,79,80] |
Electroacupuncture | Electroacupuncture enhances MoCA scores in AD, possibly via cellular mechanisms such as neuroplasticity and molecular pathways like neurotransmitter modulation. | [78] |
Cognitive behavioral therapy (CBT) | CBT-I may improve cognitive function and potentially delay AD onset through the modulation of Aβ deposition at a molecular level. | [81] |
Counseling and psychoeducation | The intervention promotes healthy lifestyles and better coping strategies, with a potential cellular impact on BDNF expression, affecting mental health in mild AD. | [82,83,84,85] |
Environment adjustment | Interventions to combat loneliness may impact regional WM density in the brain cortex, potentially affecting AD development. Activities like aromatherapy with Salvia officinalis could influence acetylcholinesterase levels, offering molecular-level therapeutic potential. | [86,87,88,89,90,91,92,93,94,95,96,97] |
Exercise/Physical activity | Exercise-based nonpharmacological interventions show multifaceted benefits across cellular and molecular domains, impacting homeostasis, transcription, protein function, and BDNF release. Physical exercise modulates brain metabolic activity, enhances the release of Brain-Derived Neurotrophic Factor (BDNF), and possibly influences monocyte functions, potentially offering a holistic approach to managing AD. Exercise also affects cerebral blood flow and mitochondrial function, although its precise efficacy remains under debate. | [13,20,82,94,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134] |
Music and dancing | Music-based interventions, including active participation and passive listening, impact neuroplasticity, evoke positive emotions and influence cognitive function in Alzheimer’s disease (AD) patients. These interventions modulate brain structures linked to emotivity and decision-making via dopaminergic circuits and sympathetic arousal. Technological aids like functional MRI and EEG indicate differential neural responses to music, suggesting utility in AD management. Molecular changes, although not fully understood, appear to involve neurotransmitter pathways and neuroconnectivity, particularly in regions like the medial prefrontal cortex and posterior cingulate cortex. | [4,9,13,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149] |
Information technology | Technology, including mHealth and computer-based cognitive training, empowers Alzheimer’s patients and caregivers by enhancing cognition and psychosocial well-being. These interventions likely modulate neural pathways and cellular functions, although the exact molecular mechanisms remain underexplored. | [87,150,151,152,153,154,155,156,157,158,159,160] |
Virtual reality (VR) | VR and AR interventions in Alzheimer’s Disease (AD) likely impact neuroplasticity, cognitive function, and motor skills by modulating neural pathways. These immersive technologies may interact with molecular markers associated with cognitive and emotional regulation, although specific mechanisms warrant further study. | [117,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176] |
Lifestyle factors | Dietary interventions like the Mediterranean and ketogenic diets, as well as exercise, are suggested to modulate cognitive function possibly through anti-inflammatory and antioxidant pathways, impacting cellular and molecular mechanisms relevant to Alzheimer’s Disease. Further studies are needed for mechanistic insights. | [177,178,179,180] |
Sensory practices | Alternative therapies like aromatherapy and light therapy may modulate neurotransmitter levels and circadian rhythms, potentially ameliorating behavioral symptoms in Alzheimer’s Disease. | [20,143] |
Validation therapy | Psychosocial interventions may influence neurotransmitter systems and neuronal plasticity, potentially alleviating delusions and hallucinations in dementia patients. | [9,20] |
Low-dose ionizing radiation (LDIR) | Low-dose ionizing radiation (LDIR) in Alzheimer’s treatment may induce radiation hormesis, enhancing DNA repair, gene expression, antioxidant defense, and anti-inflammatory actions, while potentially improving synaptic and myelin integrity. | [181] |
Mechanical-based stimulation. | Whole-body vibration (WBV), transcranial ultrasound stimulation (TUSS), and auditory stimulation (AS) may impact neurotrophic and neurotransmission pathways. WBV enhances musculoskeletal and hormonal systems, TUSS affects cerebral circuitry and neuroplasticity, while AS modulates gamma brain waves. | [145,182,183,184,185] |
Photobiomodulation (PBM) | Low-level LASER therapy (LLLT) in Alzheimer’s Disease (AD) mainly targets mitochondrial function, modulating cytochrome c oxidase (CCO) and exerting antioxidant effects. It also impacts mitochondrial fission/fusion and neuroinflammation. | [186,187] |
Reminiscence therapy (RT) | Reminiscence therapy (RT) in AD focuses on stimulating remote memory. While not directly cellular or molecular, EEG signals suggest its neurophysiological relevance, impacting cognition and mood. | [9,10,30,82,123,170,188,189,190,191,192,193,194,195,196,197] |
Repetitive transcranial magnetic stimulation (rTMS) | Repetitive transcranial magnetic stimulation (rTMS) in AD shows promise at the cellular and molecular levels by reducing Aβ peptides, counteracting tau hyperphosphorylation, and modulating ApoE expression. It also influences BDNF levels and GABAergic synaptic strength, potentially rectifying imbalanced neural inhibition–excitation dynamics. | [179,180,187,198,199,200] |
Transcranial direct current stimulation (tDCS) | Transcranial direct current stimulation (tDCS) in Alzheimer’s Disease (AD) shows polarity-dependent effects, enhancing cognition and combating Aβ peptide deposits. It improves cerebral circulation, synaptic plasticity, and NMDA receptor activity, while also exerting antineuroinflammatory effects. | [187,202,203,204] |
4. Discussion
Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Keywords | Elsevier | PubMed | PMC | PEDro | Total |
---|---|---|---|---|---|
“Alzheimer’s disease” + “Video game therapy” | 0 | 0 | 0 | 0 | 0 |
“Alzheimer’s disease” + “Augmented reality therapy” | 0 | 0 | 0 | 0 | 0 |
“Alzheimer’s disease” + “Virtual reality therapy” | 0 | 0 | 19 | 0 | 19 |
“Alzheimer’s disease” + “Serious games therapy” | 0 | 0 | 0 | 0 | 0 |
“Alzheimer’s disease” + “Reminiscence therapy” | 1 | 6 | 96 | 0 | 103 |
“Alzheimer’s disease” + “Music therapy” | 0 | 16 | 249 | 0 | 265 |
“Alzheimer’s disease” + “Dancing therapy” | 0 | 0 | 0 | 0 | 0 |
“Alzheimer’s disease” + “Exercise therapy” | 2 | 22 | 241 | 0 | 265 |
Total | 3 | 44 | 605 | 0 | 652 |
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Aurelian, S.; Ciobanu, A.; Cărare, R.; Stoica, S.-I.; Anghelescu, A.; Ciobanu, V.; Onose, G.; Munteanu, C.; Popescu, C.; Andone, I.; et al. Topical Cellular/Tissue and Molecular Aspects Regarding Nonpharmacological Interventions in Alzheimer’s Disease—A Systematic Review. Int. J. Mol. Sci. 2023, 24, 16533. https://doi.org/10.3390/ijms242216533
Aurelian S, Ciobanu A, Cărare R, Stoica S-I, Anghelescu A, Ciobanu V, Onose G, Munteanu C, Popescu C, Andone I, et al. Topical Cellular/Tissue and Molecular Aspects Regarding Nonpharmacological Interventions in Alzheimer’s Disease—A Systematic Review. International Journal of Molecular Sciences. 2023; 24(22):16533. https://doi.org/10.3390/ijms242216533
Chicago/Turabian StyleAurelian, Sorina, Adela Ciobanu, Roxana Cărare, Simona-Isabelle Stoica, Aurelian Anghelescu, Vlad Ciobanu, Gelu Onose, Constantin Munteanu, Cristina Popescu, Ioana Andone, and et al. 2023. "Topical Cellular/Tissue and Molecular Aspects Regarding Nonpharmacological Interventions in Alzheimer’s Disease—A Systematic Review" International Journal of Molecular Sciences 24, no. 22: 16533. https://doi.org/10.3390/ijms242216533