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NCT Number: NCT05544201

Transcranial Alternating Current Stimulation (TACS) for Sleep Disturbances in Neurocognitive Disorders Due to Alzheimer's Disease

Background: Sleep disturbances are highly prevalent in ageing population and patients with age-related neurodegenerative diseases, which severely affect cognition and even lead to accumulated amyloid-β (Aβ). At present, non-pharmacological interventions for sleep disturbances in dementia patients are accepted as first line of treatment, of which the evidence from clinical trials is very limited. Encouraging results from recent studies on transcranial direct current stimulation (tDCS) showed moderate positive effects on sleep quality in preclinical Alzheimer's disease (AD). Compared to tDCS, high-definition transcranial alternating current stimulation (HD-tACS) enables the entrainment of neuronal activities with optimized focality through injecting small electric current with a specific frequency and has significant enhancement effects on slow wave activities.

Objectives: The investigators aim to 1) investigate and compare the safety, efficacy and sustainability of 40 Hz HD-tACS and HD-tDCS over left dorsolateral prefrontal cortex (DLPFC) in mild neurocognitive disorder due to AD (NCD-AD) patients with sleep disturbances; 2) examine the relationship between the changes in sleep quality, cognitive function and saliva Aβ levels.

Methods: Chinese right-handed mild NCD-AD patients with sleep disturbances (aged from 60 to 90 years) will be randomly assigned to a 4-week intervention of either HD-tACS, HD-tDCS, or sham HD-tCS, with 33 participants per arm. Before intervention, structural magnetic resonance imaging (MRI) data is used to construct individual realistic head model. Comprehensive assessments, including sleep quality, cognitive performance and saliva Aβ levels will be conducted at baseline, 4th week, 8th week, 12th week and 24th week. Program adherence and adverse effects will be monitored throughout intervention.

Data analysis: The primary outcomes will be the changes in sleep quality and memory performance with modality-driven paradigms (HD-tACS, HD-tDCS, sham HD-tCS), and comparisons of group differences across different time points. Secondary outcomes will be the changes objective sleep pattern, global cognition, saliva Aβ levels and quality of life. Intention-to-treat analysis will be carried out. Changes of efficacy indicators from baseline to each follow up point will be tested with mixed effect model.

Significance: This study aims to investigate the feasibility, safety and efficacy of HD-tACS and HD-tDCS over left DLPFC for sleep disturbances and cognitive dysfunction in mild NCD-AD patients. It wills also test the program adherence, tolerability and adverse effects of this innovative neurotechonology. Information will be helpful for in-depth understanding the relationship of "sleep disturbances-amyloid deposition" and guiding the further studies of sleep medicine and neurodegenerative diseases.

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Key information

Conditions

Brain Stimulation Aging Alzheimer Disease Brain Diseases Central Nervous System Diseases Cognition Disorders Cognitive Dysfunction Cognitive Impairment, Mild Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Parasomnias Sleep Disturbance Sleep Wake Disorders Tauopathies tACS

Age range

60 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

The Chinese University of Hong Kong

Hong Kong, 100000

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Chinese, aged from 60 to 90 years.
  • Mild neurocognitive disorder due to Alzheimer's disease (NCD-AD) is diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). NCD-AD patients are defined by the following criteria: (1) evidence of modest cognitive decline in at least one of six domains of cognition (memory, perceptual- motor, complex attention, language, executive function and social cognition), and with clinical features indicative of AD, identified with the Montreal Cognitive Assessment (MoCA) score range from 22 to 26; (2) no interference with independence in everyday activities; (3) and no better explanation by other psychiatric disorders. NCD-AD patients fulfill the criteria of NCD and have impaired episodic memory assessed by delayed recall.
  • Sleep disturbances are defined as a Pittsburgh Sleep Quality Index (PSQI) total score above 5.

Exclusion criteria

  • Previous diagnosis of other major neurocognitive disorders;
  • Past history of bipolar disorders or psychosis;
  • Physically frail affecting attendance to training sessions;
  • Already attending regular training, such as cognitive behavioral therapy;
  • Taking a psychotropic or other medication known to affect cognition (e.g. anti-dementia medication);
  • Significant communicative impairments.
  • History of major neurological deficit including stroke, transient ischemic attack or brain tumor.

Treatment and study plan

High-definition transcranial current stimulation

Device

High-definition transcranial current stimulation (HD-tCS) is delivered by a battery driven direct current stimulator (DC-Stimulator Plus, NeuroConn, Ilmenau, Germany) through a central anodal electrode surrounded by four return cathodal electrodes.

Primary outcomes

  1. Pittsburg Sleep Quality Index (PSQI)

    Time frame: 24 weeks

    The PSQI is a 19-item questionnaire that includes seven areas of subjective sleep quality and patterns in adults over the last month including the following components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, SDs, use of sleeping medications, and daytime dysfunction (Buysse et al., 1988). Each item in the scale is scored from 0 to 3 scale (0 = no difficulty; 3 = severe difficulty). The scores are added to yield a global score ranging from 0 to 21 (0 = no difficulty; 21 = severe difficulties in all areas). This scale has good reliability and validity psychometrics and is widely used in research: Cronbach's alpha (0.77 to 0.83), sensitivity (89.6%), specificity (86.5%)(Buysse et al., 1988). Greater score of PSQI indicates worse sleep quality.

  2. Delayed recall of words

    Time frame: 24 weeks

    Word-list learning test (WLLT), consisting of sixteen semantically non-associated words, is presented consecutively over three free trials of immediate recall, a 20-min delayed recall (to prevent recency effects) (Lu et al., 2018). The raw numbers of words recalled are used to assess the memory function.

Secondary outcomes

  1. Efficacy evaluated by attention function performance

    Time frame: 24 weeks

    Attention network function measured by computerized attention network test (ANT)

  2. Efficacy evaluated by executive function performance

    Time frame: 24 weeks

    Executive function is measured by category verbal fluency test (CVFT).

  3. Efficacy evaluated by saliva Aβ40 and Aβ42 levels

    Time frame: 24 weeks

    The levels of Aβ40 and Aβ42 in the saliva samples will be quantified by enzyme-linked immunosorbent assay (ELISA)-type assays (Aurin Biotech, Inc.).

Sponsors and collaborators

Lead sponsor

Chinese University of Hong Kong

Other

Registry information

Official study title

Gamma-band High-definition Transcranial Alternating Current Stimulation (HD-tACS) for Sleep Disturbances in Mild Neurocognitive Disorders Due to Alzheimer's Disease

Important dates

Study start
2022
Primary completion
2023
Study completion
2024
First posted
Sep 16, 2022
Registry last updated
Mar 18, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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