Sleep Disturbance and Emotion Regulation Brain Dysfunction as Mechanisms of Neuropsychiatric Symptoms in Alzheimer's Dementia

Inclusion Criteria:

   - Males and females of any racial or ethnic group, aged 50-90 (inclusive)

   - Subjective complaint of insomnia associated with daytime impairment or distress (ISI ≥
   10)

   - Subjective complaint of sleep disturbance ≥ 3 months in duration

   - Subjective complaint of Neuropsychiatric symptoms (Self-Report NPI distress total
   score ≥ 4 on any measure other than the sleep domain OR current symptoms from Study
   Partner NPI ≥ 1

   - Able to verbalize understanding of involvement in the research and provide written
   informed consent or provide assent co-signed by a LAR

   - Fluent and literate in English

   - Written, informed consent

   - Medications (including any dementia-related meds) stable for at least 4 weeks prior to
   study baseline

   - Research diagnosis of memory impairment based on the following:

   i) Global Clinical Dementia Rating (CDR) of 0.5 or 1.0. ii) Wechsler Memory
   Scale-Revised Logical Memory II subtest using the following rubric: < 11 for subjects
   with 16 or more years of education, ≤ 9 for 8-15 years of education, ≤ 6 for 0-7 years
   of education

   - MRI safety screen passed

   - Have a caregiver or study partner willing to aid in facilitating the protocol and
   ratings

   - Reside within approximately 60 miles of Stanford University

Exclusion Criteria:

   - less than 20 on the Mini-Mental State Examination (MMSE)

   - Acute or unstable chronic illness: including but not limited to: uncontrolled thyroid
   disease, kidney, prostate or bladder conditions causing excessively frequent urination
   (> 3 times per night); medically unstable congestive heart failure, angina, other
   severe cardiac illness as defined by treatment regimen changes in the prior 3 months;
   stroke with serious sequelae; cancer if < 1 year since end of treatment; asthma,
   emphysema, or other severe respiratory diseases uncontrolled with medications; and
   neurological disorders (with the exception of mild AD) such as Parkinson's disease and
   unstable epilepsy as defined by treatment regimen changes in the prior 3 months;
   unstable adult onset diabetes as defined by treatment regimen changes in the prior 3
   months.

   - Use of medication specifically prescribed for sleep disturbance or nighttime-only, low
   dose anti-depressants (e.g., doxepin, amitriptyline, trazodone used only at
   sub-therapeutic anti-depressant doses and taken only at bedtime) specifically
   prescribed for sleep disturbance and unwilling or unable to discontinue > two weeks
   (anti-depressants) or >1 week (sleep medications) prior to baseline data collection.

   - Current or lifetime history of bipolar disorder

   - History of psychosis preceding onset of memory impairments

   - Substance abuse or dependence

   - Excessive alcohol consumption (>14 drinks per week or > 4 drinks per occasion)

   - Current exposure to trauma, or exposure to trauma within the past 3 months

   - Presence of suicidal ideations representing high risk as measured by the
   Columbia-Suicide Severity Rating Scale (C-SSRS). Individuals are considered high risk
   if they have endorsement of either of the following:

      1. A positive endorsement, relative to the past 30 days, in the "Suicide Thoughts"
      section of item #4 (Have you had these thoughts and had some intention of acting
      on them) or item #5 (Have you started to work out or worked out the details of
      how to kill yourself? Do you intend to carry out this plan?

      2. A positive endorsement, relative to the past 90 days, in the "Suicide Behavior"
      section of item #6 (Have you ever done anything, started to do anything, or
      prepared to do anything to end your life?)

   - Mild traumatic brain injury (history of physical brain injury or blow to the head
   resulting in loss of consciousness >5 minutes)

   - Severe impediment to vision, hearing and/or hand movement, likely to interfere with
   the ability to complete the assessments, or are unable and/or unlikely to follow the
   study protocols

   - Current or expected cognitive behavioral therapy or other evidence based psychotherapy
   for another condition (e.g. depression)

   - History of falling and/or severe mobility impairment

   - Individuals who are not CPAP adherent or have untreated OSA of moderate severity or
   worse (AHI ≥ 15). CPAP adherence being defined as using the CPAP machine 70% of nights
   for a minimum of 4 hours per night.

   - Received Cognitive Behavior Therapy for Insomnia (CBT-I) or Desensitization Therapy
   for Insomnia (DTI) within the past year

   - Are not fully vaccinated for COVID-19 (e.g. 2 doses of Moderna or BioNTech, Pfizer
   vaccines; or 1 for Johnson and Johnson) and unwilling, if asked, to provide proof
   (e.g., CDC COVID-19 Vaccination Card, e-Health record, etc.)