Alterations in Cognitive Function and Blood Biomarkers Following Transcranial Direct Current Stimulation in Patients with Amyloid Positron Emission Tomography-positive Alzheimer's Disease: a Preliminary Study

Overview

Journal Front Neurosci

Date 2024 Jan 5

PMID 38178837

Authors

Jinuk Kim

YoungSoon Yang

Affiliations

Soon will be listed here.

Abstract

Introduction: Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive cognitive decline. To address this, we conducted a randomized, double-blinded, sham-controlled study to investigate the therapeutic potential of transcranial direct current stimulation (tDCS) on patients with amyloid positron emission tomography (PET)- positive AD.

Methods: Participants already undergoing pharmacological treatment and testing positive for amyloid PET were divided into Active-tDCS ( = 8) and Sham-tDCS ( = 8) groups. For 12 weeks, participants or their caregivers administered daily bi-frontal tDCS (YMS-201B+, Ybrain Inc., Seongnam, Korea) at home (2 mA, 30 min). Pre- and post-intervention assessments included neuropsychological tests and blood sample measurements for oligomerized beta-amyloid.

Results: The Active-tDCS group demonstrated significant improvements in cognitive domains such as language abilities, verbal memory, and attention span and in frontal lobe functions compared to the Sham-tDCS group. Furthermore, the Active-tDCS group showed a marked reduction in post-intervention plasma Aβ oligomerization tendency level, suggesting changes in pivotal AD-associated biomarkers.

Discussion: Our results emphasize the potential therapeutic benefits of tDCS for mild AD patients with amyloid PET positivity and stress the urgency for broader research, considering the global challenges of dementia and the need to pursue innovative therapeutic strategies.

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References

Sanchez-Lopez A, De Raedt R, Puttevils L, Koster E, Baeken C, Vanderhasselt M . Combined effects of tDCS over the left DLPFC and gaze-contingent training on attention mechanisms of emotion regulation in low-resilient individuals. Prog Neuropsychopharmacol Biol Psychiatry. 2020; 108:110177. DOI: 10.1016/j.pnpbp.2020.110177. View

Hertrich I, Dietrich S, Blum C, Ackermann H . The Role of the Dorsolateral Prefrontal Cortex for Speech and Language Processing. Front Hum Neurosci. 2021; 15:645209. PMC: 8165195. DOI: 10.3389/fnhum.2021.645209. View

Ryu H, Yang D . The Seoul Neuropsychological Screening Battery (SNSB) for Comprehensive Neuropsychological Assessment. Dement Neurocogn Disord. 2023; 22(1):1-15. PMC: 9939572. DOI: 10.12779/dnd.2023.22.1.1. View

Charvet L, Shaw M, Bikson M, Woods A, Knotkova H . Supervised transcranial direct current stimulation (tDCS) at home: A guide for clinical research and practice. Brain Stimul. 2020; 13(3):686-693. DOI: 10.1016/j.brs.2020.02.011. View

Drzezga A, Lautenschlager N, Siebner H, Riemenschneider M, Willoch F, Minoshima S . Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study. Eur J Nucl Med Mol Imaging. 2003; 30(8):1104-13. DOI: 10.1007/s00259-003-1194-1. View

Gong Y, Chang L, Viola K, Lacor P, Lambert M, Finch C . Alzheimer's disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc Natl Acad Sci U S A. 2003; 100(18):10417-22. PMC: 193576. DOI: 10.1073/pnas.1834302100. View

An S, Lee B, Yu J, Lim K, Kim G, Lee R . Dynamic changes of oligomeric amyloid β levels in plasma induced by spiked synthetic Aβ. Alzheimers Res Ther. 2017; 9(1):86. PMC: 5645921. DOI: 10.1186/s13195-017-0310-6. View

Khedr E, Gamal N, El-Fetoh N, Khalifa H, Ahmed E, Ali A . A double-blind randomized clinical trial on the efficacy of cortical direct current stimulation for the treatment of Alzheimer's disease. Front Aging Neurosci. 2014; 6:275. PMC: 4191219. DOI: 10.3389/fnagi.2014.00275. View

Apatiga-Perez R, Soto-Rojas L, Campa-Cordoba B, Luna-Viramontes N, Cuevas E, Villanueva-Fierro I . Neurovascular dysfunction and vascular amyloid accumulation as early events in Alzheimer's disease. Metab Brain Dis. 2021; 37(1):39-50. DOI: 10.1007/s11011-021-00814-4. View

10.

Pyun J, Ryu J, Lee R, Shim K, Youn Y, Ryoo N . Plasma Amyloid-β Oligomerization Tendency Predicts Amyloid PET Positivity. Clin Interv Aging. 2021; 16:749-755. PMC: 8096417. DOI: 10.2147/CIA.S312473. View

11.

Zuin M, Cherubini A, Volpato S, Ferrucci L, Zuliani G . Acetyl-cholinesterase-inhibitors slow cognitive decline and decrease overall mortality in older patients with dementia. Sci Rep. 2022; 12(1):12214. PMC: 9288483. DOI: 10.1038/s41598-022-16476-w. View

12.

Meinzer M, Lindenberg R, Phan M, Ulm L, Volk C, Floel A . Transcranial direct current stimulation in mild cognitive impairment: Behavioral effects and neural mechanisms. Alzheimers Dement. 2014; 11(9):1032-40. DOI: 10.1016/j.jalz.2014.07.159. View

13.

Babapour Mofrad R, Scheltens P, Kim S, Kang S, Youn Y, An S . Plasma amyloid-β oligomerization assay as a pre-screening test for amyloid status. Alzheimers Res Ther. 2021; 13(1):133. PMC: 8311929. DOI: 10.1186/s13195-021-00873-w. View

14.

Hayden E, Teplow D . Amyloid β-protein oligomers and Alzheimer's disease. Alzheimers Res Ther. 2013; 5(6):60. PMC: 3978746. DOI: 10.1186/alzrt226. View

15.

Kim H, Na D . Normative data on the Korean version of the Boston Naming Test. J Clin Exp Neuropsychol. 1999; 21(1):127-33. DOI: 10.1076/jcen.21.1.127.942. View

16.

Leung J, Lee G, Lam Y, Chan R, Wu J . The use of the Digit Span Test in screening for cognitive impairment in acute medical inpatients. Int Psychogeriatr. 2011; 23(10):1569-74. DOI: 10.1017/S1041610211000792. View

17.

Mohammad D, Chan P, Bradley J, Lanctot K, Herrmann N . Acetylcholinesterase inhibitors for treating dementia symptoms - a safety evaluation. Expert Opin Drug Saf. 2017; 16(9):1009-1019. DOI: 10.1080/14740338.2017.1351540. View

18.

Arnaiz E, Jelic V, Almkvist O, Wahlund L, Winblad B, Valind S . Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. Neuroreport. 2001; 12(4):851-5. DOI: 10.1097/00001756-200103260-00045. View

19.

Zlokovic B . Neurodegeneration and the neurovascular unit. Nat Med. 2010; 16(12):1370-1. DOI: 10.1038/nm1210-1370. View

20.

Im J, Jeong H, Bikson M, Woods A, Unal G, Oh J . Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer's disease. Brain Stimul. 2019; 12(5):1222-1228. PMC: 6703942. DOI: 10.1016/j.brs.2019.06.003. View