---
title: "High-definition 0.75 Hz so-tDCS for older adults with SCD and sleep disturbance: randomized trial"
id: "plos-one-13-personalized-assessment-of-high-definition-slow-oscillatory-transcranial-direct"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-13-personalized-assessment-of-high-definition-slow-oscillatory-transcranial-direct"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0360573"
published_at: "2026-10-13T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# High-definition 0.75 Hz so-tDCS for older adults with SCD and sleep disturbance: randomized trial
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-13-personalized-assessment-of-high-definition-slow-oscillatory-transcranial-direct
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0360573)
- **Published At:** 2026-10-13T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The protocol describes a randomized, double-blind, sham-controlled clinical trial testing high-definition **slow-oscillatory transcranial direct current stimulation** (so-tDCS) in older adults with **subjective cognitive decline (SCD)** and sleep disturbances. - Investigators will enroll right-handed Chinese participants age 60–80 with HK-MoCA >26, SCD (SCC score >1), and PSQI >5; exclusions include major neurodegenerative, neurological, or psychiatric diagnoses. - Participants will be randomized 1:1 to active or sham high-definition so-tDCS; the active intervention is 0.75 Hz, 2 mA, 20 minutes per session, three sessions per week for four weeks (total 12 sessions); sham delivers 30 seconds of stimulation then no sustained current. - Primary outcomes: changes in electrode–skin impedance measured via a wearable Galvanic Skin Response (GSR) sensor, self-reported **subjective cognitive complaints** (10‑item SCC questionnaire), and **subjective sleep quality** measured by the **Pittsburgh Sleep Quality Index** (PSQI). - Secondary outcomes: actigraphy-derived sleep-wake metrics (Philips Actiwatch 2), domain-specific cognitive performance including intra-individual variability of reaction time (ICV-RT from ANT), and salivary **Aβ** (Aβ42 and Aβ40 quantified by ELISA-type assays) at baseline and week 4. - Imaging: High-resolution 3.0T structural MRI (MPRAGE) will be used for screening and to localize stimulation targets (left DLPFC/F3) and control baseline brain features. - Randomization will be computer-generated by an independent statistician; participants and outcome assessors will be blinded. - The trial will record neurophysiological impedance signals in real time to evaluate safety, dosing interpretation, and predictive value for individual responses. - Ethics approval is in place (Joint CUHK NTEC-CREC); the protocol is registered (ClinicalTrials.gov Identifier: NCT07433738). - The source did not report detailed analytic plans, specific statistical thresholds, sample size justification beyond 40 participants per arm, or longer-term biomarker follow-up beyond week 12.
## Clinical Analysis & Structured Key Points
Personalized assessment of high-definition slow-oscillatory transcranial direct current stimulation (so-tDCS) in older adults with sleep and subjective cognitive complaints: A study protocol for a randomized clinical trial | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Background Subjective cognitive decline (SCD) is increasingly recognized as an early and potentially modifiable stage in the trajectory of neurodegenerative diseases. In older adults with SCD, untreated sleep disturbances may accelerate the neurodegenerative process, potentially via mechanisms involving amyloid-beta accumulation, and contribute to more rapid cognitive deterioration. Currently, non-pharmacological treatment options that concurrently manage SCD and sleep disturbances remain scarce. High-definition slow-oscillatory transcranial direct current stimulation (so-tDCS) is an emerging, frequency-specific neuromodulation technique designed to enhance brain health and cognition. Methods and design This is a randomized, double-blind, sham-controlled clinical trial. Right-handed Chinese older adults with SCD and sleep disturbances will be randomly assigned to receive either high-definition 0.75 Hz so-tDCS or sham stimulation over a 4-week intervention period, with 40 participants per group. Outcome measures, including galvanic skin response, subjective cognitive complaints, sleep quality, salivary amyloid-beta levels, and domain-specific cognitive performance, will be evaluated at four time points: baseline, week 4 (immediately post‑intervention), and follow‑up at weeks 8 and 12. Conclusions Personalized neurophysiological signals, namely electrode-skin impedance, will be monitored using state-of-the-art measurement during so-tDCS. The successful implement of this signal will provide researchers with access to an “add-on” setting that enables them to easily, quickly and quantitatively evaluate real-time neurophysiological signals, thereby facilitating the incorporation of transcranial brain stimulation into clinical practice. Trial registration ClinicalTrials.gov Identifier: NCT07433738 Citation: Lu H, Ni X, Yang NS, Yuen YS, Gong Y, Ma SL (2026) Personalized assessment of high-definition slow-oscillatory transcranial direct current stimulation (so-tDCS) in older adults with sleep and subjective cognitive complaints: A study protocol for a randomized clinical trial. PLoS One 21(10): e0360573. https://doi.org/10.1371/journal.pone.0360573 Editor: Xianwei Che, Hangzhou Normal University, CHINA Received: April 9, 2026; Accepted: September 22, 2026; Published: October 13, 2026 Copyright: © 2026 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: Data cannot be shared publicly because of personal medical information. Data are available from the CUHK Data Access / Ethics Committee (contact via Research Office: ro-grants@cuhk.edu.hk ) for researchers who meet the criteria for access to confidential data. Funding: The author(s) received no specific funding for this work. Competing interests: All authors declare no competing interest. Introduction As the world undergoes rapid population aging, issues surrounding brain health and cognitive longevity have become a core concern in clinical consultations and rehabilitation practices [ 1 ]. Over the past decade, research focus has shifted from objective cognitive dysfunction to subjective cognitive decline (SCD), increasingly recognized as the earliest symptomatic stage of age-related neurodegenerative diseases [ 2 ]. With SCD affecting a considerable proportion of older adults (prevalence typically 20–50%) [ 3 ], evidence from longitudinal studies suggests that up to ~60% of individuals with SCD may progress to mild cognitive impairment (MCI) or dementia over a 15-year period [ 4 , 5 ]. Untreated SCD is frequently comorbid with sleep disturbances or major depression in the ageing population [ 6 , 7 ]. Notably, the prevalence of sleep disturbances among older adults with SCD has been reported to be as high as 64% [ 8 ]. Two additional cohort studies found that sleep disturbances were associated with severe subjective cognitive complaints [ 9 , 10 ]. Moreover, sleep disturbances can markedly impair the glymphatic function system and reduce clearance of amyloid-beta (A β ), thereby increasing the risk of Alzheimer’s disease (AD) [ 11 ]. Accordingly, the coexistence of SCD and sleep disturbances in older adults may accelerate the progression of neurodegeneration, potentially leading to an earlier transition to MCI or dementia [ 12 , 13 ]. In light of SCD’s status as an early risk stage for neurodegeneration, effective management of SCD and its comorbidities assumes greater clinical importance, given their established association with an increased risk of accelerated cognitive decline. While early intervention in SCD remains essential and clinically valuable, the substantial heterogeneity of SCD and its comorbidities poses significant therapeutic challenges and hinders effective management. The heterogeneity of SCD can be decomposed into two main levels: (1) Inter-individual level: SCD refers to a diagnostically heterogeneous population, with individuals varying widely in their patterns of subjective cognitive complaints (domain-specific vs. global) [ 1 ], types of comorbidities, and degree of neuropathological load (e.g., A β deposition) [ 14 , 15 ]. (2) Intra-individual level: This concerns personalized indicators of treatment outcomes. Intra-individual variability (IIV), reflecting the short-term fluctuation or variation in brain signals and cognitive performance, has recently been applied in published clinical trials as a sensitive measure and predictor of treatment response [ 16 , 17 ]. In the context of heterogeneity, growing evidence shows that the disturbed cortical slow oscillations can interfere with domain-specific cognitive function, A β synthesis and glymphatic clearance systems [ 18 , 19 ], leading to cognitive dysfunction and A β accumulation in aged mice [ 20 ], and human adults with SCD [ 21 ], sleep disorders [ 22 ] and dementia [ 23 ]. Particularly, recent findings highlight that those slow oscillations ( 26 [ 17 ]. Subjective cognitive decline (SCD) is evaluated by a 10-item questionnaire that covers subjective cognitive complaints (SCC) in the core cognitive domains [ 30 ]. Participants will answer yes/no questions referring to the presence of cognitive deficits in the last six months. The answers of SCC are codified as 0 (absence of complaints) or 1 (presence of complaints). Answers will be summed up, and the total of complaints will be obtained ranging from 0 to 10. In this study, the status of SCD is defined as SCC total score > 1. Sleep disturbances or poor sleep quality is assessed and defined with a total score of the Pittsburgh Sleep Quality Index (PSQI) greater than 5 [ 31 ]. No impairments in the activities of daily living. Exclusion criteria include: Previous diagnosis of age-related neurodegenerative diseases, such as Alzheimer’s disease and Parkinson disease. History of neurological diseases including brain tumor, and stroke. History of psychiatric disorders including schizophrenia and depression. Presence of positive neurological diseases, such as stroke, brain tumor, dementia. Physically unable to attend the sessions of intervention. Currently enrolled in another intervention study. Currently taking a psychiatric or other medication that may affect sleep quality and cognition. Ethical consideration Strict ethical standards will be upheld throughout the clinical trial, including the provision of informed consent and the protection of participants’ anonymity, privacy, and confidentiality. Participants will be eligible for recruitment only if they are considered mentally fit to sign informed consent. No personally identifiable information, including name, dates of birth, or mobile phone numbers, will be disclosed in any reports or publications. Participants may withdraw from this study at any time, and such withdrawal will not affect their access to future services or care. Ethics approval has been obtained from the Joint Chinese University of Hong Kong New Territories East Cluster Clinical Research Ethics Committee (Joint CUHK NTEC-CREC) (Ref. No.: 2025.118). The protocol has been registered with the CCT Clinical Trials Registry of the Chinese University of Hong Kong and linked to ClinicalTrials.gov (Identifier: NCT07433738). The trial will be reported in accordance with the requirements of major international academic journals. The study will be conducted in compliance with the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH-GCP). Pre-intervention assessments Magnetic resonance imaging. High-resolution structural MRI (MRI) scans will be collected at the Prince of Wales Hospital using a 3.0 Tesla Siemens MAGNETOM Prisma MRI scanner for detecting the major neurological diseases, such as stroke, brain tumor. T1-weighted magnetization prepared rapid gradient echo (MPRAGE) sequence is applied to optimize the grey-white contrast. The MPRAGE sequence yields high-quality isotropic images with the voxel size of 1 mm × 1 mm × 1 mm. The detailed parameters of this sequence are axial acquisition with a 256 × 256 × 192 matrix, field of view (FOV)=230 mm, repetition time (TR)=2070 ms, echo time (TE)=3.93 ms, thickness = 1 mm, no gap, flip angle = 15 ◦ . All MRI scans will be imported to BrainSuite for quantitative analysis [ 32 ]. Surface-based morphometric measures, including cortical volume, thickness and folding, are employed as brain features to precisely localize the stimulation target, correlate with neurophysiological signals and control the baseline brain features in two randomized groups. Randomization and masking. As shown in Fig 2 , eligible participants will be randomly assigned in a 1:1 ratio to one of two intervention groups: 1) High-definition so-tDCS; 2) Sham tDCS. To ensure balanced allocation across treatment groups, a randomization assignment will be generated prior to enrollment using an online system by a statistician who is not involved in the study design. Both outcome assessors and participants will be blinded to group allocation. Download: PNG larger image TIFF original image Fig 2. The Consolidated Standards of Reporting Trials (CONSORT) flow diagram for the clinical trial of slow-oscillatory transcranial direct current stimulation. Abbreviations: so-tDCS = Slow-oscillatory transcranial direct current stimulation; MRI = Magnetic resonance imaging. https://doi.org/10.1371/journal.pone.0360573.g002 Intervention strategies Apparatus and treatment setting. The so-tDCS is delivered by a battery driven direct current stimulator (DC-Stimulator Plus, NeuroConn, Ilmenau, Germany). The high-definition setting is applied by placing an anodal electrode over the center of the treatment target and placing four cathodal electrodes surrounding the anodal electrode. Each electrode in the “4 × 1” montages had a diameter of 1.2 cm. We place the anodal electrode over the center of left dorsolateral prefrontal cortex (DLPFC) (i.e., F3 according to the international 10–20 EEG system) as used in previous studies that investigated preserved cognition [ 33 ] and placed the four return electrodes around anodal electrode. For safety and health considerations, single use sponge electrodes (1.2 cm) will be applied in this study. Participants will be instructed to relax during the intervention of high-definition so-tDCS. Stimulation modalities. High-definition so-tDCS: 20 minutes at 0.75 Hz 2 milliamps [ 33 ]. Sham high-definition so-tDCS: With a same setting of high-definition as active so-tDCS, the stimulation of sham so-tDCS only lasts for 30 seconds. The electrodes will be left in place for a further 20 minutes. The purpose of this sham procedure is to mimic transient skin sensation of tingling induced by current stimulation, but without producing any sustainable effects. Intervention schedule The duration of the intervention is four weeks, with three sessions per week, 20 minutes per session. All participants will receive a total of 12 sessions of high-definition so-tDCS. Outcome assessments Primary outcomes. Skin impedance in so-tDCS: Neurophysiological signal recorded and measured by a built-in wearable Galvanic Skin Response (GSR) sensor. GSR sensor is placed on the fingers to detect the impedance of the skin when the participant is receiving so-tDCS intervention. Subjective cognitive complaints (SCC): a 10-item questionnaire that covers subjective complaints in the core cognitive domains [ 30 ]. Participants will answer ten yes/no questions relating to the presence of cognitive complaints in the last six months. The answers of SCC are codified as 0 (no complaints) or 1 (presence of complaints). Answers will be summed up, and the total of complaints will be obtained ranging from 0 to 10. Subjective sleep quality: The 19-item self-reported questionnaire of the Pittsburgh Sleep Quality Index (PSQI) is used to assess subjective sleep quality [ 31 ]. The 19 items produce seven component scores. The total score of these components yields a measure of subjective sleep quality that can be used to determine the status of sleep disturbances. The cutoff score of sleep disturbances is 5 or more [ 34 ]. Secondary outcomes. Actigraphic records were used to quantify sleep-wake cycle and estimate the objective sleep efficiency [ 35 , 36 ]. The actigraphy device (Philips Actiwatch 2) is about the size of a wristwatch and is usually worn on the wrist continuously for multiple days and nights, which can be used as an objective measurement of sleep quality and sleep-wake cycle in older adults. Intra-individual variability of reaction time (IIV-RT), representing the within-person fluctuations, is calculated based on the performance of attention network test (ANT). For correcting the increased RT in elderly, Intraindividual coefficient of variation of reaction time (ICV-RT) is used for assessing the IIV-RT enumerated with the formula: ICV-RT = (Standard deviation of RT/mean RT) × 100 [ 17 ]. The levels of salivary A β : At the baseline and 4 th week, salivary samples will be collected at a consistent time of day to avoid circadian effects and will be kept on ice during the collection. The levels of A β 42 and A β 40 in the plasma samples will be quantified by enzyme-linked immunosorbent assay (ELISA)-type a
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