The purpose of the present research is to evaluate the ability of non-invasive
transcranial electrical stimulation (TES) during slow-wave sleep (SWS) to enhance this
stage of sleep for people with mild cognitive impairment (MCI). A previous study of the
investigators have demonstrated, in a pilot study, that TES can acutely (i.e.,
immediately after TES) increase SWS duration in healthy people. In the present proposal,
the investigators aim to replicate and extend the pilot findings in seniors with MCI. It
is evidenced that decline in SWS duration with aging is associated for memory impairment
in seniors, which also creates risk for Alzheimer disease (AD). At the same time as
conducting TES to enhance SWS sleep in seniors with MCI, the investigators also aim to
explore changes in biomarkers associated with AD, including Aβ40 and Aβ42.
The investigators propose to conduct a sleep study using the Brain Electrophysiology
Laboratory (BEL) company's Sleep WISP device (described in detail below). The Sleep WISP
device is made up of three components: 1) 16-channel EEG amplifier with transcranial
electrical stimulation (TES) capabilities, 2) a 16-channel EEG headband and 3) a small
portable computer.
All participants will be provided a Sleep WISP device. Participation in the study
requires that participants use the Sleep WISP when they sleep. As participants sleep,
their sleep EEG will be measured and automatically scored by the computer to determine
stage of sleep. When SWS is detected, low-level current (.5-1 mA total) will be applied
through pre-set electrodes (four on the forehead and four at base of back of head). These
electrodes were used in our pilot study, showing that current applied through these
electrodes during SWS is able to increase total SWS sleep duration.
To evaluate the efficacy of the system, BEL will use a small, exploratory pilot sample of
10 employees and staff members to run the testing in Eugene, Oregon. After the 10 pilot
subjects at BEL with employees and staff and prior to the main study, the protocol and
system will be tested with older adults at each of the Wake Forest area (Winston-Salem,
North Carolina) and Portland-Eugene surrounding area (Oregon) as pilot sub-studies for
device usability feedback with seniors. These pilot subjects will only take part in the
acute portion of the parent sleep study, where the first night is acclimation (no TES),
the second night is TES or sham, and then a week later, they get TES or sham, for a total
of three nights for the pilot studies. This pilot study does not include the PAVL memory
test.
The greater study is divided into two phases.
Phase I involves up to nine sleep sessions. The first session is a baseline/acclimation
session. In the first session, participants will use the Sleep WISP device to passively
record sleep EEG (no TES) as baseline. The second session is performed the night
following the baseline session with randomized experiment condition (either placebo or
active TES session). Participants will be blinded for what condition they receive. The
final session will occur one week after the second session to receive the opposite
experiment condition to the second session. In the week between the second and final
sessions, participants will be asked to wear the device at night to record their EEG.
During this period, there will be no TES stimulation.
Phase II of the study can begin as early as the night following the completion of Phase
I. To participate in Phase II participants do not need to have participated in Phase I.
Phase II will follow a repeated-measures placebo-controlled design across six weeks. An
equal number of participants without MCI (control group) and with MCI (experimental
group) will be enrolled. Following screening and thorough training, participants will
wear the WISP device for 2 weeks and receive either sham or treatment TES every night. A
2 week washout period where participants do not use the device will follow. Finally,
participants will receive the remaining condition (sham or treatment) each night of the
last 2 weeks of participation. Participants will also be asked to wear an actigraphy
watch that measures sleep parameters based on movement each night in Phase II. A trained
phlebotomist will collect blood samples or nasal swab assays from participants before and
after each condition (sham and treatment; 4 total measurements) for Aβ detection.
In both Phases I and II, prior to sleep, participants will be presented with a
paired-associate verbal learning (PAVL) task. Participants will be required to learn the
list of words, to a pre-specified performance criterion. After waking from sleep in the
morning, participants will be tested with the same list, to assess retention of the
previously learned materials.
In our previous TES study of SWS enhancement, the investigators were able to show that
SWS can be enhanced immediately (short-term/acute) after TES. The study was performed in
the BEL sleep lab. Phase I of the proposed new study will extend the previous pilot study
results by using Sleep WISP device as participants with MCI sleep at home, which will
allow us to support home monitoring and acute treatment of disordered sleep for adults
with MCI. Phase II will assess whether SWS modulation over multiple nights will produce
cumulative enhancement of SWS in adults with MCI. In both study phases, the investigators
will also evaluate the cognitive consequences, specifically declarative memory, of
enhancing SWS.
Aim 1: Phase I aims to replicate our previous study (acute/short-term enhancement of SWS
and safety/feasibility) in seniors with MCI with the sleep WISP device.
Aim 2: Phase II aims to assess the ability of TES to cumulatively enhance SWS over
multiple sessions in seniors with MCI compared to healthy controls.
Aim 3: Evaluate SWS quality on a declarative memory task in older adults with MCI.