Alzheimer's Disease, Mild Cognitive Impairment
Conditions
Keywords
Aging, Alzheimer's Disease/Dementia, Cognitive Disorders, Imaging, Magnetic Resonance Imaging (MRI), Neurology, Physical Medicine & Rehabilitation, transcranial direct current stimulation
Brief summary
Remembering how to travel from one location to another is critical in everyday life, yet this vital ability declines with normal aging and can be further affected by conditions that disproportionately affect the elderly, such as vision loss or progressive dementia. Human and animal research has shown that two distinct memory systems interact during navigation. The first, referred to as allocentric navigation, is very flexible and uses spatial knowledge of key features or landmarks to develop and use a mental map of the environment. This approach involves brain regions that are critical for new learning and memory but that decline with age. The second, referred to as egocentric navigation, is inflexible and relies on habit memories that link specific features with specific directions. This approach relies on brain regions that are critical for automatic responses and that are relatively unaffected by age. The main problem is that allocentric navigation declines with age and is accompanied increased dependence on egocentric navigation. This change increases the risk of becoming disoriented or lost when traveling in unfamiliar areas or even when traveling new routes in familiar areas. Therefore, the main goal of this project is to examine whether non-invasive brain stimulation, specifically transcranial direct current stimulation, can improve allocentric navigation in healthy older adults and patients with mild cognitive impairment. Participants will complete two functional magnetic resonance imaging sessions while learning new environments. Before one of these sessions, participants will receive active brain stimulation over the parietal cortex. Before the other session, participants will receive sham brain stimulation over the parietal cortex. The effects of this stimulation will be evaluated using both an allocentric and an egocentric memory test. Physiologic effects will be evaluated using both task-based and resting-state MRI.
Interventions
DEVICETranscranial direct current stimulation (tDCS)
Active and/or sham; All participants receive both stimulation condition. Groups will be counterbalanced (half receiving active tDCS in the first session and sham in the second session; the other half receiving the opposite).
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blinded
Intervention model description
Transcranial Direct Current Stimulation
Eligibility
Sex/Gender
ALL
Age
50 Years to 88 Years
Healthy volunteers
Yes
Inclusion criteria
General inclusion criteria (all participants): * All medications stable for approximately 1-2 months; * No history of severe mental illness; * No current untreated alcohol or substance abuse/dependence; * English as native and preferred language; * MRI-compatible if taking part in fMRI studies * Able to give informed consent. MCI Inclusion Criteria: * Diagnosis of amnestic MCI based on criteria set forth by Petersen (2004). Additionally, other potential causes of cognitive deficit ruled out by the referring physician; Healthy older adults * intact cognitive functioning as measured by neuropsychological testing
Exclusion criteria
* History of neurological disease or injury * History of severe mental illness * Current untreated alcohol or substance abuse * Other conditions may exclude; please discuss with contact
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Accuracy in Centimeters From Target Location for Allocentric | Outcome assessed after each of 2 sessions (estimated within 1 week of each other) | 1 active tDCS; 1 sham tDCS for each measure. Participants touched a screen (using a ELO 19 touchscreen monitor) to document the location of the landmark. The distance between the actual vs. selected location served as the dependent measure. |
| Hippocampal BOLD Signal During Task-based fMRI | change between active and sham tDCS sessions (<1month) | BOLD signal change comparing active to sham tDCS during Allocentric navigation (i.e., active HD-tDCS \> sham HD-tDCS). Activation maps thresholded at p\<.01 with minimum cluster size of 5 voxels. |
| Dorsal Attention Network Connectivity During Resting-state fMRI | change between active and sham tDCS sessions (<1month) | Change in resting state functional connectivity strength between active and sham tDCS sessions. Strength is measured by Pearson r correlations between nodes, which are z-transformed, and summated. |
| Egocentric | Outcome assessed after each of the 2 sessions | Number of turns correctly recalled for each egocentric environment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cognitively Intact Older Adults All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). | 22 |
| Patients With Mild Cognitive Impairment All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). | 20 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Incidental MRI findings | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Cognitively Intact Older Adults | Total | Patients With Mild Cognitive Impairment |
|---|---|---|---|
| Age, Continuous | 72.15 years STANDARD_DEVIATION 7.14 | 70.8 years STANDARD_DEVIATION 6.89 | 69.5 years STANDARD_DEVIATION 6.55 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 39 Participants | 19 Participants |
| Region of Enrollment United States | 22 Participants | 42 Participants | 20 Participants |
| Sex: Female, Male Female | 12 Participants | 19 Participants | 7 Participants |
| Sex: Female, Male Male | 10 Participants | 23 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 13 / 21 | 17 / 22 | 15 / 20 | 12 / 20 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Accuracy in Centimeters From Target Location for Allocentric
1 active tDCS; 1 sham tDCS for each measure. Participants touched a screen (using a ELO 19 touchscreen monitor) to document the location of the landmark. The distance between the actual vs. selected location served as the dependent measure.
Time frame: Outcome assessed after each of 2 sessions (estimated within 1 week of each other)
Population: Computer errors caused missing data for a subset (n=4) of participants; those data have simply been omitted from analyses below.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Intact ACTIVE tDCS | Accuracy in Centimeters From Target Location for Allocentric | 13.24 Centimeters (cm) | Standard Deviation 3.96 |
| MCI ACTIVE tDCS | Accuracy in Centimeters From Target Location for Allocentric | 15.38 Centimeters (cm) | Standard Deviation 2.13 |
| Cognitively Intact SHAM tDCS | Accuracy in Centimeters From Target Location for Allocentric | 14.22 Centimeters (cm) | Standard Deviation 2.78 |
| MCI SHAM tDCS | Accuracy in Centimeters From Target Location for Allocentric | 15.03 Centimeters (cm) | Standard Deviation 1.77 |
Comparison: RM ANCOVA (covarying order) for cognitively intact groupsp-value: 0.048ANCOVA
Comparison: RM ANCOVA (covarying order) for MCI groupp-value: 0.063ANCOVA
Primary
Dorsal Attention Network Connectivity During Resting-state fMRI
Change in resting state functional connectivity strength between active and sham tDCS sessions. Strength is measured by Pearson r correlations between nodes, which are z-transformed, and summated.
Time frame: change between active and sham tDCS sessions (<1month)
Population: Participants from each group were excluded due to movement artifact that invalidated fMRI data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Intact ACTIVE tDCS | Dorsal Attention Network Connectivity During Resting-state fMRI | 29.41 arbitrary units | Standard Deviation 7.09 |
| MCI ACTIVE tDCS | Dorsal Attention Network Connectivity During Resting-state fMRI | 30.93 arbitrary units | Standard Deviation 11.97 |
| Cognitively Intact SHAM tDCS | Dorsal Attention Network Connectivity During Resting-state fMRI | 30.39 arbitrary units | Standard Deviation 8.2 |
| MCI SHAM tDCS | Dorsal Attention Network Connectivity During Resting-state fMRI | 31.47 arbitrary units | Standard Deviation 9.89 |
p-value: <0.001ANCOVA
p-value: 0.046ANCOVA
Primary
Egocentric
Number of turns correctly recalled for each egocentric environment
Time frame: Outcome assessed after each of the 2 sessions
Population: Participants from each group were excluded due to movement artifact that invalidated fMRI data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Intact ACTIVE tDCS | Egocentric | 9.05 Correct turns | Standard Deviation 3.53 |
| MCI ACTIVE tDCS | Egocentric | 8.21 Correct turns | Standard Deviation 3.08 |
| Cognitively Intact SHAM tDCS | Egocentric | 9.85 Correct turns | Standard Deviation 3.6 |
| MCI SHAM tDCS | Egocentric | 7.47 Correct turns | Standard Deviation 2.53 |
Comparison: Repeated Measures ANCOVA (covarying stimulation order)p-value: 0.497ANCOVA
p-value: 0.599ANCOVA
Primary
Hippocampal BOLD Signal During Task-based fMRI
BOLD signal change comparing active to sham tDCS during Allocentric navigation (i.e., active HD-tDCS \> sham HD-tDCS). Activation maps thresholded at p\<.01 with minimum cluster size of 5 voxels.
Time frame: change between active and sham tDCS sessions (<1month)
Population: Participants from each group were excluded due to movement artifact that invalidated fMRI data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Intact ACTIVE tDCS | Hippocampal BOLD Signal During Task-based fMRI | .089 Percent signal change | Standard Deviation 0.12 |
| MCI ACTIVE tDCS | Hippocampal BOLD Signal During Task-based fMRI | .037 Percent signal change | Standard Deviation 0.123 |
| Cognitively Intact SHAM tDCS | Hippocampal BOLD Signal During Task-based fMRI | .143 Percent signal change | Standard Deviation 0.134 |
| MCI SHAM tDCS | Hippocampal BOLD Signal During Task-based fMRI | .107 Percent signal change | Standard Deviation 0.117 |
Comparison: Change between active and sham tDCS sessions for allocentric blocksp-value: 0.27ANCOVA
p-value: <0.001ANCOVA