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

This is an interventional treatment trial for Alzheimer Disease Read More

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.)