Alzheimer's Disease
Conditions
Keywords
Alzheimer's disease, Cognitive Training, Transcranial Magnetic Stimulation
Brief summary
This study looks at the potential benefits of combining cognitive training (mental exercises) together with transcranial magnetic stimulation (also known as TMS) to see if this can make a difference in the condition of people with Alzheimer's disease by improving their disease and the cognitive decline that goes along with it.
Detailed description
This study takes place in Boston, Massachusetts and Beth Israel Deaconess Medical Center. The treatment portion of the study requires patients to visit the BIDMC daily, Monday through Friday, for 6 weeks. All participants will receive real cognitive training, but half of our participants will receive active TMS treatment and half will receive a placebo TMS treatment. However, those receiving the placebo treatment will be offered the real treatment upon the completion of the study. This study goes up to approximately 4.5 months. TMS is a noninvasive way of stimulating the brain, which is not painful and does not involve any needles or any form of surgery. It acts by delivering a magnetic stimulation to a particular region of your brain and that, coupled with the cognitive training, is what is being looked at in this study. The investigators are examining if this combination of TMS and cognitive training will improve your memory function and other mental functions such as language, orientation, and thinking or judgment.
Interventions
DEVICERepetitive Transcranial Magnetic Stimulation (rTMS)
Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS.
BEHAVIORALNICE Cognitive Training
12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive sham cognitive training that follows the same procedures as the active group.
Sponsors
Neuronix Ltd
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Male or female age 55-90 * Diagnosed with mild to moderate AD according to DSM-IV criteria * Diagnosis of dementia of the Alzheimer's type according to the criteria established by the NINCDS-ADRDA * Normal or corrected normal ability to see and hear * Primary language is English
Exclusion criteria
* IQ below 85 * Any major structural abnormalities on MRI (eg. Infarction, intracerebral malformation) * Any symptoms of disease or abnormalities sufficient to cause memory impairment other than AD (eg. Normal pressure hydrocephalus, progressive supranuclear palsy) * Any functional psychiatric disorder (eg. Schizophrenia) * Chronic uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (eg. Cardiac malformation) * History of seizures, diagnosis of epilepsy * Metal implants excluding dental fillings or any of the following medical devices: pacemaker, implanted medication pump, vagal nerve stimulator, deep brain stimulator, TENS unit (unless removed completely for this study), cerebral spinal fluid shunt * Recent withdrawal from the following drugs: alcohol, barbiturates, benzodiazepines, meprobamate, chloral hydrate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | Pre treatment; 1 month post treatment | Assessment to measure the severity of all of the most important symptoms of Alzheimer's disease: loss of memory, language, praxis, and attention. The total scoring range is 0-70, with 0 representing the least impairment and 70 the most severe impairment. The results posted below represent a change in score from baseline. A positive change represents an improvement on the ADAS-Cog (change = 1 month score - baseline score). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Change (CGIC) | Pre-treatment, 1 month post treatment | The CGI is a three-item scale used to assess treatment response in psychiatric patients. The CGI-C subset measures the global improvement or change from baseline. Scores range from 0 to 7, with 0 indicating marked improvement and 7 indicating marked worsening. The scores below represent the percent change of the scores from baseline. |
| Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) | Pre-treatment, 1 month Post-treatment | 23 item scale to assess activities of daily living. Scores range from 0 to 78 with a higher score indicating less functional impairment. The scores reported below are the means of the actual scores from the assessments representing the percent change from baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active rTMS With Real Cognitive Training High frequency rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area).
Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day).
Sham participants will receive the same study procedures as patients receiving active rTMS.
NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus).
A particular cognitive exercise will start 200msec after the termination of each TMS train.
Sham participants receive real cognitive training that follows the same procedures as the active group. | 10 |
| Sham rTMS With Real Cognitive Training High frequency sham rTMS to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area).
Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day).
Sham participants will receive the same study procedures as patients receiving active rTMS.
NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus).
A particular cognitive exercise will start 200msec after the termination of each TMS train.
Sham participants receive real cognitive training that follows the same procedures as the active group. | 5 |
| Sham rTMS With Sham Cognitive Training High frequency sham rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area).
Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day).
Sham participants will receive the same study procedures as patients receiving active rTMS.
Sham Cognitive Training: subjects will undergo pseudo cognitive training with the sham rTMS following the same procedures as the active group | 6 |
| Total | 21 |
Baseline characteristics
| Characteristic | Active rTMS With Real Cognitive Training | Sham rTMS With Real Cognitive Training | Sham rTMS With Sham Cognitive Training | Total |
|---|---|---|---|---|
| Age, Continuous | 69.1 years | 68.6 years | 70 years | 69.24 years |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 2 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 10 | 5 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 1 / 6 |
Outcome results
Primary
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
Assessment to measure the severity of all of the most important symptoms of Alzheimer's disease: loss of memory, language, praxis, and attention. The total scoring range is 0-70, with 0 representing the least impairment and 70 the most severe impairment. The results posted below represent a change in score from baseline. A positive change represents an improvement on the ADAS-Cog (change = 1 month score - baseline score).
Time frame: Pre treatment; 1 month post treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS With Real Cognitive Training | Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | 1.79 percentage change | Standard Deviation 3.6 |
| Sham rTMS With Real Cognitive Training | Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | -0.20 percentage change | Standard Deviation 5.45 |
| Sham rTMS With Sham Cognitive Training | Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | -0.66 percentage change | Standard Deviation 2.91 |
Secondary
Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL)
23 item scale to assess activities of daily living. Scores range from 0 to 78 with a higher score indicating less functional impairment. The scores reported below are the means of the actual scores from the assessments representing the percent change from baseline.
Time frame: Pre-treatment, 1 month Post-treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active rTMS With Real Cognitive Training | Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) | Pre-Treatment | 72.67 percent change | Standard Deviation 5.07 |
| Active rTMS With Real Cognitive Training | Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) | Post-Treatment | 69.78 percent change | Standard Deviation 7.8 |
| Sham rTMS With Real Cognitive Training | Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) | Pre-Treatment | 73.60 percent change | Standard Deviation 3.36 |
| Sham rTMS With Real Cognitive Training | Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) | Post-Treatment | 71.20 percent change | Standard Deviation 5.93 |
| Sham rTMS With Sham Cognitive Training | Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) | Pre-Treatment | 65.75 percent change | Standard Deviation 6.8 |
| Sham rTMS With Sham Cognitive Training | Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) | Post-Treatment | 61.75 percent change | Standard Deviation 9.5 |
Secondary
Clinical Global Impression of Change (CGIC)
The CGI is a three-item scale used to assess treatment response in psychiatric patients. The CGI-C subset measures the global improvement or change from baseline. Scores range from 0 to 7, with 0 indicating marked improvement and 7 indicating marked worsening. The scores below represent the percent change of the scores from baseline.
Time frame: Pre-treatment, 1 month post treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS With Real Cognitive Training | Clinical Global Impression of Change (CGIC) | 3.25 percent change | Standard Deviation 0.72 |
| Sham rTMS With Real Cognitive Training | Clinical Global Impression of Change (CGIC) | 4.40 percent change | Standard Deviation 0.89 |
| Sham rTMS With Sham Cognitive Training | Clinical Global Impression of Change (CGIC) | 4.08 percent change | Standard Deviation 1.02 |