{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:23:25Z","timestamp":1772637805778,"version":"3.50.1"},"reference-count":18,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nova Palm Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Despite recent breakthroughs in pharmacological treatment for Alzheimer\u2019s disease, high costs and the complex procedure to monitor safety have limited access for many patients. Less invasive and more accessible non-pharmacological therapies that support neuroplasticity and slow cognitive decline are needed. Processing Inner Strength Toward Actualization (PISTA) stimulation applies structured tactile input to promote cortical\u2013subcortical activation. This study evaluated the long-term effects of PISTA on cognition and pain in older adults with mild cognitive impairment or early dementia. Methods: This single-arm, prospective trial enrolled 100 outpatients aged 47\u201370 years at outset (50 women, 50 men) with no control group. Participants received clinician-supervised PISTA stimulation three times weekly for 48 months. Each 30 min session delivered rhythmic tactile input calibrated to individual sensory thresholds. Cognitive performance was assessed monthly using the Mini-Mental State Examination (MMSE). Perceived pain was measured monthly with the Numeric Pain Rating Scale. Outcomes were analyzed using ANCOVA, adjusting for age, sex, and baseline cognitive status. Results: Cognitive scores improved significantly across all age strata, with a mean annual MMSE increase of 0.75 points (95% CI: 0.26\u20131.21; p &lt; 0.0025). Pain intensity decreased in parallel (mean reduction: 0.56 points; 95% CI: 0.34\u20130.78; p &lt; 0.001). Improvements in cognition and pain were moderately correlated (r = 0.38). The greatest combined benefits occurred in participants aged 55\u201362 years. No serious adverse events were observed during the 48-month trial. Conclusions: PISTA stimulation produced sustained improvement in cognition and reduced perceived pain, supporting its promising role as a safe, non-invasive adjunct for neurodegenerative cognitive decline. These findings suggest peripheral sensory activation as a promising driver of functional neuroplasticity and warrant verification in randomized, controlled trials.<\/jats:p>","DOI":"10.3390\/brainsci16030265","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T08:31:19Z","timestamp":1772181079000},"page":"265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral Sensory Stimulation for Long-Term Improvement in Mild Cognitive Decline: A Prospective Interventional Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Tom","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Chinese Medicine, Wuhe Chengnan Hospital, Bengbu 233300, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Social Work, Michigan State University, East Lansing, MI 48823, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Stang","sequence":"additional","affiliation":[{"name":"Department of Development and Science, Sili-Tec GmbH, 26135 Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-8983","authenticated-orcid":false,"given":"George","family":"Ayoub","sequence":"additional","affiliation":[{"name":"Department of Psychology, Santa Barbara City College, Santa Barbara, CA 93109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41398-020-0690-4","article-title":"Do Nonpharmacological Interventions Prevent Cognitive Decline? A Systematic Review and Meta-Analysis","volume":"10","author":"Yao","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e20128","DOI":"10.1097\/MD.0000000000020128","article-title":"Management of Cognitive Decline in Alzheimer\u2019s Disease Using a Non-Pharmacological Intervention Program","volume":"99","author":"Quail","year":"2020","journal-title":"Medicine"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sharew, N.T. (2022). The Effect of Multimodal Non-Pharmacological Interventions on Cognitive Function Improvement for People With Dementia: A Systematic Review. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.894930"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Luo, G., Zhang, J., Song, Z., Wang, Y., Wang, X., Qu, H., Wang, F., Liu, C., and Gao, F. (2023). Effectiveness of Non-Pharmacological Therapies on Cognitive Function in Patients with Dementia\u2014A Network Meta-Analysis of Randomized Controlled Trials. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1131744"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e70291","DOI":"10.2196\/70291","article-title":"Nonpharmacological Multimodal Interventions for Cognitive Functions in Older Adults With Mild Cognitive Impairment: Scoping Review","volume":"8","author":"Chan","year":"2025","journal-title":"JMIR Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"46","DOI":"10.5114\/areh.2025.149343","article-title":"Non-Pharmacological Interventions Targeting Working Memory in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis","volume":"39","author":"Sahaf","year":"2025","journal-title":"Adv. Rehabil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1001\/jama.2025.12923","article-title":"Structured vs Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function: The US POINTER Randomized Clinical Trial","volume":"334","author":"Baker","year":"2025","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e6061","DOI":"10.1002\/gps.6061","article-title":"The Relationship between Playing Musical Instruments and Cognitive Trajectories: Analysis from a UK Ageing Cohort","volume":"39","author":"Vetere","year":"2024","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13195-023-01214-9","article-title":"The Effect of Music Therapy on Cognitive Functions in Patients with Alzheimer\u2019s Disease: A Systematic Review of Randomized Controlled Trials","volume":"15","author":"Bleibel","year":"2023","journal-title":"Alzheimers Res. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/nyas.15079","article-title":"An Integrated Review of Music Cognition and Rhythmic Stimuli in Sensorimotor Neurocognition and Neurorehabilitation","volume":"1530","author":"Emmery","year":"2023","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_11","unstructured":"Witte, M., de Bradt, J., Aithal, S., Flynn, L., Karkou, V., Koch, S., Orkibi, H., Sajnani, N., Berberian, M., and Fietje, N. (2025). The Effects of Arts-Based Interventions in the Treatment and Management of Non-Communicable Diseases: An Umbrella Review and Meta-Analyses. Res. Sq."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"gnad171","DOI":"10.1093\/geront\/gnad171","article-title":"Sounds of Difference: A Typology of Reactions of People With Dementia to Individualized Music in the Presence of a Monitoring Person","volume":"64","author":"Jakob","year":"2024","journal-title":"Gerontologist"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e70032","DOI":"10.1002\/dmrr.70032","article-title":"Review of Associations of Diabetes and Insulin Resistance With Brain Health in Three Harmonised Cohort Studies of Ageing and Dementia","volume":"41","author":"Biswas","year":"2025","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_14","first-page":"402","article-title":"Physical Exercise, Cognition, and Brain Health in Aging","volume":"47","author":"Barha","year":"2024","journal-title":"Trends Neurosci."},{"key":"ref_15","unstructured":"(2025, September 20). Cognitive Health Initiative. Available online: https:\/\/www.novapalmfoundation.com\/cognitive-health-initiative."},{"key":"ref_16","unstructured":"(2025, September 20). How Does PISTA Work? PISTA Programs. Available online: https:\/\/www.pistatherapy.com\/method."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8588272","DOI":"10.1155\/2022\/8588272","article-title":"Effects of the Alpha, Beta, and Gamma Binaural Beat Brain Stimulation and Short-Term Training on Simultaneously Assessed Visuospatial and Verbal Working Memories, Signal Detection Measures, Response Times, and Intrasubject Response Time Variabilities: A Within-Subject Randomized Placebo-Controlled Clinical Trial","volume":"2022","author":"Rakhshan","year":"2022","journal-title":"Biomed. Res. Int."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ayoub, G. (2025). Vitamins, Vascular Health and Disease. Nutrients, 17.","DOI":"10.3390\/nu17182955"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/3\/265\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T09:19:23Z","timestamp":1772615963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/3\/265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":18,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["brainsci16030265"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16030265","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]}}}