Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT03456986 |
| Other study ID # |
1R43 AG059547-01 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 4, 2018 |
| Est. completion date |
September 30, 2021 |
Study information
| Verified date |
April 2018 |
| Source |
Perception Dynamics Institute |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The proposed SBIR Phase I study tests the feasibility of PATH neurotraining for improving
cognitive skills in older adults and, potentially, forestalling or protecting against
cognitive decline and dementia. The feasibility of PATH neurotraining will be evaluated by
comparing it with another cognitive training program, Brain HQ's Target Tracker, and
ascertaining the relative advantage(s) of PATH neurotraining for enhancing cognition in older
adults between 55 and 75 years of age whose cognition is either in the age-normative range or
in the mild cognitive impairment (MCI) range of standardized psychometric measures. MEG/MRI
source imaging will be used on 12 of the PATH group participants to determine whether the
behavioral results are verified by improvements in the dorsal, attention, and executive
control networks.
Description:
The goal of this study is to show that neurotraining in the center of the motion working
range (PATH) that improves the contrast sensitivity for direction discrimination (dorsal
stream activity significantly improves cognitive skills in older adults more than in those
who do training to improve orientation discrimination: ventral stream activity (sham
training). Brain training will be administered for 20 minutes three times a week for 12
weeks: Arm 1) PATH neurotraining and Arm 2) Sham training. The investigators predict that
older adults who do PATH neurotraining will improve their visual and cognitive skills,
improving attention, multitasking, processing speed, reading fluency, and working memory,
significantly more than those doing sham training. This prediction will be evaluated by
measuring whether older adults improve on standardized tests of cognitive skills following
PATH neurotraining more than older adults doing orientation discrimination training to
improve processing speed and attention. MEG brain imaging will be used to show that PATH
training improves the dorsal, attention, and executive control networks, as found previously,
more than does sham training. The investigators predict these improvements will be found in
both healthy adults and those with MCI.
The feasibility of rapid, effective brain training will be evaluated by using behavioral
methods to remediate age-related cognitive decline, and to treat the cognitive impairment
and/or behavioral symptoms associated with MCI, as well as to slow and/or reverse the course
of cognitive decline or to prevent it entirely. PATH neurotraining provides a computer-based
product to remediate the visual and cognitive difficulties of older adults rapidly and
effectively. The innovative PATH neurotraining improves the center of the motion working
range, whereas the sham training improves the center of the orientation discrimination
working range. The two brain training groups will be balanced, in terms of healthy older
adults and those with MCI. A subject will be considered to have MCI if the WAIS Working
Memory Index score is less than 50 percent, and the MOCA has a score of 19-25. These groups
will also be balanced in terms of age and reading speed, a sensitive measure of processing
speed.
Half of the older adults will complete the PATH neurotraining for 12 weeks and half will
complete sham training for 12 weeks. An additional 12 weeks will be needed to train staff,
recruit subjects, and complete the standardized tests and MEG imaging. The choice of which
adults will do each type of brain training will be randomized, to be determined by study
statistician Prof. John Shelley-Tremblay. After initial standardized testing, 12 adults doing
PATH training will be selected for pre-post MEG brain imaging.
Precise measurements using pre- and post- standardized tests of cognitive skills will be used
to validate the improved visual and cognitive (attention, processing speed, and memory)
performance reported previously in older adults. Standardized tests and MEG imaging on a
subset will be administered by staff before and after cognitive training to evaluate
improvements in cognitive skills following treatment (PATH neurotraining) and control (sham
training) interventions.
Evaluating improvements in cognitive skills of older adults will be grouped by subject type:
whether the adult is healthy or has MCI to determine which intervention improves cognitive
skills the most. The investigators predict that PATH neurotraining will significantly improve
(at p ≤ 0.05) reading speed, working memory and attention (cognitive flexibility) in older
adults more than after training on sham training. This will be evaluated by both: 1)
measuring whether older adults improve on the standardized tests listed above following brain
training, and 2) MEG brain source imaging to validate that dorsal stream, attention, and
executive control networks improve in function significantly following PATH neurotraining.
This study plans to study 40 older adults between the ages of 55 to 75, 20 in each group.
Older adults will be recruited by posting brochures, getting referrals from Dr. James Brewer
and Dr. Michael Lobatz, both who work with older adults having Alzheimer's Disease.
Training Procedures. Brain training exercises will be implemented in a high fidelity manner,
using a detailed written protocol that all Research Assistants (RAs) are trained to follow
meticulously, new PATH training movies and new motivational strategies. Staff will be hired
at UCSD following interviews with Cognitive Science undergraduates who answered an
advertisement on Handshake, the UCSD portal advertising for internships for UCSD students.
Hiring RAs for this project and a Senior RA (SRA) to monitor study will be done by the PI at
UCSD. Eleven RAs will be hired to administer standardized tests and both types of brain
training to older adults at Perception Dynamics Institute (PDI) having a clinic ideal for
collecting data in quiet surroundings with easy access for older adults. New training videos
aimed at older adults will be developed by Leslie Peters at Desert Bay Productions in
Encinitas.
The RAs will ensure each older adult is on task, completing the PATH neurotraining
(pathtoreading.com) designed to activate the dorsal brain pathways and Sham training designed
to activate the ventral brain pathways, and is progressing through each program in a timely
manner by examining their data. The PI, having extensive experience conducting controlled
validation studies, will be in charge of training all staff, running daily operations which
requires supervising standardized testing and administering the interventions.
Measures To Evaluate Effectiveness of Training to Improve Visual and Cognitive Skills.
Behavioral Measure: Standardized testing of cognitive skills will be conducted at PDI by UCSD
undergraduate Cognitive Science students trained by the PI, as done previously. All
participants will undergo a review of their medical history and everyday activities impacted
as they aged using a 9-item questionnaire described in Human Subjects. Since these are timed
tests with test items not able to be memorized for future testing, practice effects are
minimized. Cognitive assessments, which take about one hour to administer, will be evaluated
before and after training by standardized tests for adults to measure:
1. Attention using Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference
test (10 minutes).
2. Reading Speed using Computer-Based Reading Rate task (reading 6 words of text on screen)
from interesting story at increasing speeds to measure 2 reading rate thresholds using a
double-staircase procedure, after being trained by watching ReadingRate movie. (5
minutes).
3. Processing Speed Index (Wechsler Adult Intelligence Scale (WAIS)-4 Coding and Symbol
Search subtests) and Working Memory Index (WAIS-4 Digit Span and Letter-Number
Sequencing subtests), (10 minutes).
4. Visual Working Memory (VWM) using Test of Information Processing Skills, having two
distractor tasks, a counting task and repeating a short sentence, having to animal names
at end of test (10 minutes).
Biomarker Measure: MEG Imaging will be used to provide a Biomarker to show that only
improving dorsal stream function improves cognitive skills in older adults. To establish the
feasibility of PATH neurotraining to improve cognitive function in older adults, Prof.
Ming-Xiong Huang will record voxel-wise MEG source magnitude images, from 12 older adults to
determine the cortical areas improving in function following PATH neurotraining and following
sham training. MEG brain imaging, using the Fast-VESTAL procedure (Huang et al. 2016, 2017,
2018), showed that this movement-discrimination training improved time-locked activity in the
dorsal stream, attention, and executive control networks. MEG images covering the whole
brain, for each frequency band, following the Fast-VESTAL procedure, to measure time-locked
signals during a working memory N-back task will be used to evaluate improvements in brain
function. The N-back task is one of the most frequently used WM paradigms (Gevins and
Cutillo, 1993) to investigate the neural basis of WM processes. Two MEG exams will be
performed for each participant, one before and another after the PATH or sham training.
N-back Working Memory Task. Participants will undergo MEG recordings while performing an
N-back WM task. The task entails on-line monitoring, updating, and manipulation of remembered
information. During the task, the participant is required to monitor a series of letters
(both upper and lower case) presented for 500 ms in the middle of the screen. A fixation
cross is presented during the 3000 ms interstimulus interval. The participant is instructed
to respond only when a letter is presented that matches (i.e. target) the one presented n
trials previously, while not to responding to the unmatched stimuli (non-target). Two load
conditions will be used (1-back and 2-back), which place increasing demands on WM processes.
About 50 trials per load condition will be collected for each participant. Performance will
be recorded using an MEG-compatible response pad, in which index finger blocks-and-unblocks a
laser-beam. The outputs of the response pad including reaction times will be recorded in the
MEG file. The percent correct responses to target and non-target stimuli will be measured.
Different from the conventional MEG approach in which sensor waveforms are averaged with
respect to the onset of the stimuli, the sensor covariance matrices for individual trials
will be calculated. Then a total sensor-waveform covariance matrix of the target condition
will be calculated by averaging across the covariance matrices from individual trials for the
target stimuli. Then the covariance matrices across trials will be averaged. Using the total
covariance matrix, voxel-wise MEG source magnitude images that cover the whole brain will be
obtained for each subject, and each frequency band, following the Fast-VESTAL procedure, see
Method in (Huang et al., 2014) and Appendix in (Huang et al., 2016), measuring time-locked
signals during a working memory N-back task to evaluate improvements in brain function. An
Objective Pre-whitening Method will be applied to remove correlated environmental noise and
objectively select the dominant eigen-modes of sensor-waveform covariance matrix (Huang et
al., 2014).
Another goal is to study the neuronal correlates of potential cognitive dysfunctions observed
using behavioral measures in older adults. Voxel-wise correlation analyses will also be
performed to examine the association of N-back source images and neuropsychological scores.
All subjects will be combined together for the correlation analyses. In each frequency band,
the MEG source images in the MNI-152 space (following the spatial smoothing and logarithm
transformation) will be formed into three 4D data sets: Dimensions 1-3 represent the x-, y-,
and z-coordinates, and the fourth dimension represents all subjects. A total of eight data
sets will be created for 1- and 2-back conditions, and for four frequency bands. Next, along
the fourth dimension, voxel-wise repeated measure correlation analyses (Bakdash and Marusich,
2017) will be performed between MEG source images and each of the neuropsychological scores.
For each frequency band, the 1- and 2-back conditions will be treated as repeated measures in
such analyses. In this study, we will only examine the neuropsychological scores that show
statistical group differences. The repeated measure correlation analyses creates r-value
correlation maps, and cluster analysis that will be used to control for family-wise errors at
a corrected p<0.01 level for the r-value maps, similar to the correction procedure for the
F-value maps.
