Auditory Stimulation of Slow Wave Sleep and Memory in Mild Cognitive Impairment and Older Adults

Alzheimer's disease is a degenerative disorder associated with aging and presents a
significant human and financial burden. Amnestic mild cognitive impairment (aMCI) is a
disorder of impaired memory and is a precursor to Alzheimer's disease. Current treatments are
symptomatic and do not slow disease progression. There is increasing evidence linking sleep
and cognition, such that decreased sleep, particularly slow wave sleep (physiologically slow
wave activity; SWA), is associated with impaired cognitive performance. Not only does SWA
decrease with aging, it is much less in people with aMCI than cognitively normal elderly.
Interventions that improve sleep may also improve cognition. Auditory stimulation using
sounds played through headphones or speakers during sleep have been shown to increase SWA and
memory in young adults. Because this method plays sounds at fixed intervals, its ability to
enhance SWA may be limited. Investigators have developed an improved method that measures
slow waves during sleep in real time and delivers the sound at a particular phase of the slow
wave (phase locked loop; PLL). Given that people with aMCI have low SWA, this method may be
able to improve cognition by enhancing SWA. Our objective is to determine whether the PLL
method of auditory stimulation can increase SWA and improve cognition in people with aMCI.
Investigators propose a randomized sham-controlled cross-over study of auditory stimulation
that population.

The specific aims are:

1. to determine a dose and duration of stimulation required to increase SWA by 10% in
people with aMCI;

2. to determine the effect of the stimulus on cognitive performance in people with aMCI
using word pair recall and the NIH Toolbox cognitive battery, which includes tests in
multiple cognitive domains.

Investigators will recruit 15 participants with aMCI identified through the Northwestern
University Cognitive Neurology and Alzheimer's Disease Center Clinical Core. Participants
will undergo 2 separate nights of polysomnography (stimulation and sham) and cognitive
testing on stimulation and sham visits. There will be approximately 1 week between overnight
visits. The order of stimulation and sham will be randomized. Results study will be used to
determine the optimal stimulation parameters, provide preliminary data on its potential
effect, and guide design of future studies.

Inclusion Criteria:

1. Men and women age ≥60 years;

2. Amnestic MCI group: Diagnosis of aMCI based on change in cognition compared to the
individual's previous level, impairment of episodic memory, preserved independence in
functional abilities, and no evidence of impairment in social or occupational
functioning;

3. Healthy Older Adults Group: Intact cognitive profile based on neuropsychology testing
within 1 standard deviation for age and education status.

4. regular reported sleep and wake times

Exclusion Criteria:

1. moderate-severe sleep apnea defined by apnea-hypopnea index ≥15 events/hour or
periodic limb movement index ≥15/hour on the screening home sleep test;

2. unstable medical or psychiatric disorder;

3. currently doing rotating shift work or night work;

4. history of seizures or taking medications that may lower the seizure threshold;

5. current use of any sedative/hypnotics or stimulants, gabapentin, pregabalin, tricyclic
antidepressants, and trazodone or other psychoactive medications that may alter slow
wave sleep; however, stable (3 months or longer) use of antidepressants will be
allowed.

6. hearing loss