Early Alzheimer's Disease, Functional Magnetic Resonance Imaging, Transcranial Direct Current Stimulation
Conditions
Keywords
High Definition Transcranial Direct Current Stimulation, Functional Magnetic Resonance Imaging, Neuropsychology, Early Alzheimer's Disease, Working Memory, Alzheimer's Disease Assessment Scale-Cognitive Subscale
Brief summary
This completed randomized trial evaluated the clinical and neural effects of high-definition transcranial direct current stimulation (HD-tDCS) combined with computerized cognitive training in patients with Alzheimer's disease. Participants were assigned to active HD-tDCS plus computerized cognitive training, computerized cognitive training control, or active HD-tDCS control. The study assessed whether combined neuromodulation and cognitive training produced greater cognitive and clinical benefit than either component condition, and whether treatment-related benefit was associated with changes in brain network organization.
Detailed description
Upon meeting the inclusion criteria and providing informed consent, each participant completed a series of cognitive, neuropsychological, and neuroimaging assessments at the hospital outpatient clinics or inpatient department before receiving the assigned intervention. Participants were randomly allocated to one of three parallel intervention arms: active anodal high-definition transcranial direct current stimulation (HD-tDCS) combined with computerized cognitive training, active anodal HD-tDCS combined with control cognitive training, or sham HD-tDCS combined with computerized cognitive training. Approximately 20 participants were assigned to each group. Participants were studied using a masked randomized design. Study participants and personnel responsible for clinical and neuropsychological outcome assessments remained masked to the assigned stimulation condition and allocation parameters. Only trained tDCS administrators had access to the randomization list; they had minimal contact with participants and had no role in cognitive or clinical assessments. Each participant received the assigned intervention for 10 sessions over 2 weeks. Active HD-tDCS was delivered using an anodal stimulation protocol. In the combined intervention arm, active HD-tDCS was paired with computerized cognitive training. In the active HD-tDCS control arm, active stimulation was paired with control cognitive training. Control cognitive training consisted of structured computer-based cognitive activities matched for session duration, computer exposure, task instructions, and participant contact, but used fixed or minimally adaptive task difficulty and did not include individualized performance-based progression. In the sham stimulation arm, computerized cognitive training was paired with sham HD-tDCS. Before intervention, trained investigators obtained baseline cognitive and neuropsychological assessments. The assessment battery included the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Montreal Cognitive Assessment (MoCA), associative memory measures, and additional tasks and questionnaires assessing general cognition, attention, executive function, language, memory, mood, and daily functioning. These measures included Digit Span, Stroop test, verbal fluency test, Symbol Digit Modalities Test, Auditory Verbal Learning Test, associative memory tasks, working memory tasks, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and other executive-function tasks. Stimulation tolerability and adverse events were also assessed. The baseline assessment was completed over approximately 2 days. Participants also underwent multimodal magnetic resonance imaging and electroencephalography recording to assess neural mechanisms related to the intervention. Follow-up evaluations were conducted after the intervention course, including clinical and neuropsychological assessments, stimulation tolerability assessment, and adverse-event monitoring. Post-intervention assessments, neuropsychological testing, multimodal MRI, and EEG recording were completed within 24 hours after the last stimulation session whenever feasible. Additional follow-up assessments were conducted approximately 1 month and 3 months after the last stimulation session using the same or comparable clinical and cognitive assessment battery. Participants were instructed to answer symptom and function questionnaires based on the relevant recent assessment period.
Interventions
OTHERHD-tDCS
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool that alters cortical excitability and activity via application of weak direct currents.HD-tDCS was administered using the Soterix 1×1 tDCS Low-Intensity Stimulator and the Soterix 4×1 Adapter. The selection of the electrode montage was based on computational models generating simulated current topography using HD Explore, which demonstrated good current distribution in the left dorsolateral prefrontal cortex (DLPFC). For left DLPFC stimulation, the anodal electrode was placed at the F3 position (using the International 10-20 EEG system), and the 4 return electrodes (cathodes) were placed at positions AFz, FCz, F7, and C5 (4-6 cm from the anode). The center position CZ was aligned with the vertex of the head. During anodal DLPFC stimulation, participants received stimulation at 2 mA for 30 minutes, including a 30-second ramp-up period at the start and a 30-second ramp-down period at the end.
Computer-based cognitive training (CCT) is a potentially important tool for individuals at risk of dementia. This trial will employ a computerized multi-domain adaptive training program. This program and training model have been demonstrated to be effective and beneficial in patients with vascular cognitive impairment. In the CCT intervention group, participants will undergo 2 weeks of computerized, multi-domain, adaptive training. The training domains include processing speed, attention, perception, long-term memory, working memory, calculation, executive control, reasoning, and problem-solving. Task rigor varies across domains and determines task grouping. Participants are required to complete 30 minutes of daily training(one session each of six 5-minute tasks).
OTHERSham tDCS
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool that alters cortical excitability and activity via application of weak direct currents.HD-tDCS was administered using the Soterix 1×1 tDCS Low-Intensity Stimulator and the Soterix 4×1 Adapter. The selection of the electrode montage was based on computational models generating simulated current topography using HD Explore, which demonstrated good current distribution in the left dorsolateral prefrontal cortex (DLPFC). For left DLPFC stimulation, the anodal electrode was placed at the F3 position (using the International 10-20 EEG system), and the 4 return electrodes (cathodes) were placed at positions AFz, FCz, F7, and C5 (4-6 cm from the anode). The center position CZ was aligned with the vertex of the head. For sham stimulation, participants received only the initial 30-second ramp-up to 2 mA, after which stimulation was immediately terminated.
BEHAVIORALControl cognitive training
Control cognitive training consisted of a structured, computer-based cognitive activity matched to the adaptive computerized cognitive training program for session duration, screen exposure, task instructions, and participant contact. The control tasks used fixed or minimally adaptive task difficulty and did not provide individualized, performance-based progression. This condition was designed to control for nonspecific effects of computer use, task engagement, therapist contact, and repeated cognitive activity, while minimizing the adaptive cognitive-training component.
Sponsors
Anhui Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Caregivers, subjects, and evaluators remain blind
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subject diagnosed with early Alzheimer's disease or related diseases according to NINCDS-ACDRADA criteria. * Subjects must have a MMSE score between 10 and 27,indicating mild cognitive impairment or dementia * CDR score ≤ 2 * Subject under treatment by IAChE for at least 3 months. * psychotropic treatments are tolerated if they were administered and unchanged for at least 3 months
Exclusion criteria
* CDR \> 2 * Any history or clinical signs of other severe psychiatric illnesses (like major depression,psychosis or obsessive compulsive disorder). * History of head injury,stroke,or other neurologic disease. * Organic brain defects on T1 or T2 images. * History of seizures or unexplained loss of consciousness. * Implanted pacemaker,medication pump,vagal stimulator,deep brain stimulator. * Family history of medication refractory epilepsy. * History of substance abuse within the last 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes assessed by Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) | changes from baseline at 14 days and 12 weeks post-treatment | This is an very common clinical motor estimating scale. including orientation, language, structure, application of concepts, immediate recall of words and recognition of words, with a full score of 70. Higher scores indicate worse symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| special-version working memory | changes from baseline at 14 days and 4,12 weeks post-treatment | the accuracy and reaction time in working memory task |
| Associative Memory | changes from baseline at 14 days and 4,12 weeks post-treatment | The changes in Associative Memory will constitute the major research outcome measure used to assess response to HD-tDCS. |
| MMSE(Mini Mental State Examination) | changes from baseline at 14 days and 4,12 weeks post-treatment | The full name of MMSE is mini-mental state examination, and the scale consists of 30 subject, include the following seven aspects: time orientation, place orientation,immediate memory,attention and calculation,delay memory,language, visual space.One point is awarded for each question correctly answered during MMSE evaluation. If subject give the wrong answer or don't know answe he/she awarded 0 score, scope of scale score of 0 to 30 points. The higher the score, the better. |
| LMT (Logic Memory Test) | changes from baseline at 7,14 days and 4,12 weeks post-treatment | The changes in LMT will constitute the secondary research outcome |
Countries
China
Outcome results
None listed