This multi-site study will be the first to evaluate the dose-dependent effects of t-PBM in amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer's Disease (AD) (CDR of 0.5-1, FAST 1-4; age 65-85) in a randomized clinical trial of 8 weeks of t-PBM vs. sham. At baseline, all subjects will complete initial neuropsychological testing. To elucidate mechanisms of action of t-PBM, prior to treatment, subjects will undergo neuroimaging related to critical features of AD: tau 18F MK-6240 load (PET), measures of brain bioenergetics (31P-MRS), and functional connectivity (rs-fMRI). After undergoing target engagement testing (t-PBM session performed during fMRI to detect BOLD changes with active t-PBM), subjects will then be randomized to t-PBM/sham and complete 24 t-PBM/sham treatments, \~11 min per day, 3 days per week, for 8 weeks. t-PBM will be administered via continuous, 808 nm wavelength laser delivery to the forehead bilaterally (at standard EEG electrode positions F4, F3).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
196
The NIR continuous wave (average irradiance = 300 mW/cm2) will be used. The duration or irradiation will be for \~11 minutes (666 seconds).
The sham mode (0 mW/cm2) will be used. The duration or sham "irradiation" will be for \~11 minutes (666 seconds).
PET tracer to be injected prior to PET imaging session, which will occur during baseline assessments
Massachusetts General Hospital
Boston, Massachusetts, United States
NYU Langone Health
New York, New York, United States
Nathan Kline Institute
Orangeburg, New York, United States
Change in Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS) Total Scale Index Score.
RBANS is s a brief, individually administered battery to measure cognitive decline or improvement. Total Scale Index Score Range = 40-160. A higher score indicates better performance.
Time frame: Baseline, Week 8
Change in Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS) Total Scale Index Score.
RBANS is s a brief, individually administered battery to measure cognitive decline or improvement. Total Scale Index Score Range = 40-160. A higher score indicates better performance.
Time frame: Baseline, Month 3
Addenbrooke's Cognitive Examination (ACE-III) Score
ACE-III is a screening test that is composed of tests of attention, orientation, memory, language, visual perceptual and visuospatial skills. The total range of raw score is 0-100. A higher score indicates more intact cognitive functioning.
Time frame: Baseline
Addenbrooke's Cognitive Examination (ACE-III) Score
ACE-III is a screening test that is composed of tests of attention, orientation, memory, language, visual perceptual and visuospatial skills. The total range of raw score is 0-100. A higher score indicates more intact cognitive functioning.
Time frame: Week 8
Addenbrooke's Cognitive Examination (ACE-III) Score
ACE-III is a screening test that is composed of tests of attention, orientation, memory, language, visual perceptual and visuospatial skills. The total range of raw score is 0-100. A higher score indicates more intact cognitive functioning.
Time frame: Month 3
Letter Comparison Test Score
The total range of score is 0-21. A higher raw score indicates better performance.
Time frame: Baseline
Letter Comparison Test Score
The total range of score is 0-21. A higher raw score indicates better performance.
Time frame: Week 8
Letter Comparison Test Score
The total range of score is 0-21. A higher raw score indicates better performance.
Time frame: Month 3
Pattern Comparison Test Score
The total range of score is 0-30. A higher raw score indicates better performance.
Time frame: Baseline
Pattern Comparison Test Score
The total range of score is 0-30. A higher raw score indicates better performance.
Time frame: Week 8
Pattern Comparison Test Score
The total range of score is 0-30. A higher raw score indicates better performance.
Time frame: Month 3
Stroop Color and Word Test (SCWT)
SCWT is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. This study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.
Time frame: Baseline
Stroop Color and Word Test (SCWT)
SCWT is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. This study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.
Time frame: Week 8
Stroop Color and Word Test (SCWT)
SCWT is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. This study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.
Time frame: Month 3
Difference in Score Between Trail Making Test-A (TMT-A) and Trail Making Test-B (TMT-B)
Trails Making Test (Trails) is a neuropsychological test of visual attention and task switching. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1-25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1-13) and letters (A-L); as in Part A, the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time it takes to connect the "trail" is recorded. Reported as B - A. Range = 0 - 100+ (measured in seconds). A higher B - A score indicates poorer performance.
Time frame: Baseline
Difference in Score Between Trail Making Test-A (TMT-A) and Trail Making Test-B (TMT-B)
Trails Making Test (Trails) is a neuropsychological test of visual attention and task switching. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1-25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1-13) and letters (A-L); as in Part A, the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time it takes to connect the "trail" is recorded. Reported as B - A. Range = 0 - 100+ (measured in seconds). A higher B - A score indicates poorer performance.
Time frame: Week 8
Difference in Score Between Trail Making Test-A (TMT-A) and Trail Making Test-B (TMT-B)
TMT is a neuropsychological test of visual attention and task switching. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1-25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1-13) and letters (A-L); as in Part A, the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time it takes to connect the "trail" is recorded. Reported as B - A. Range = 0 - 100+ (measured in seconds). A higher B - A score indicates poorer performance.
Time frame: Month 3
TMT-B T-Score
In TMT-B, the circles include both numbers (1-13) and letters (A-L); the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time is takes to connect the "trail" is recorded. Range = 0 - 100. A higher T-score indicates better performance
Time frame: Baseline
TMT-B T-Score
In TMT-B, the circles include both numbers (1-13) and letters (A-L); the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time is takes to connect the "trail" is recorded. Range = 0 - 100. A higher T-score indicates better performance
Time frame: Week 8
TMT-B T-Score
In TMT-B, the circles include both numbers (1-13) and letters (A-L); the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time is takes to connect the "trail" is recorded. Range = 0 - 100. A higher T-score indicates better performance
Time frame: Month 3
Face-Name Associative Memory Exam (FNAME-12) Score
FNAME-12 is an associative memory test where participants see a series of facial photos and names and are asked to remember the face-name pairs.
Time frame: Baseline
Face-Name Associative Memory Exam (FNAME-12) Score
FNAME-12 is an associative memory test where participants see a series of facial photos and names and are asked to remember the face-name pairs.
Time frame: Week 8
Face-Name Associative Memory Exam (FNAME-12) Score
FNAME-12 is an associative memory test where participants see a series of facial photos and names and are asked to remember the face-name pairs.
Time frame: Month 3
Letter Number Sequencing Score
this study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.
Time frame: Baseline
Letter Number Sequencing Score
this study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.
Time frame: Week 8
Letter Number Sequencing Score
this study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.
Time frame: Month 3
Change in Systemic Assessment for Treatment Emergent Events - Specific Inquiry (SAFTEE-SI) Score
SAFTEE-SI is a list of 55 symptoms. Participants indicate how bothersome each symptom has been for them by circling the appropriate number (0-none, 1-mild, 2-moderate, 3-severe). The total range of score is 0 - 165. The higher the score, the more severely bothersome the symptoms are.
Time frame: Baseline, up to Week 8
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