Problem Adaptation Therapy for Mild Cognitive Impairment and Depression

The present collaborative R01 study, between Cornell and Johns Hopkins, aims to compare
Problem Adaptation Therapy for Mild Cognitively Impaired Older Adults (PATH-MCI) vs.
Supportive Therapy for Cognitively Impaired Older Adults (ST-CI) in improving cognitive,
affective and functioning outcomes. Psychotherapy, also known as talking therapy, is the use
of psychological methods to help a person change and overcome problems in desired ways.
PATH-MCI differs from standard of care psychotherapy by offering a combination of emotion
regulation techniques with the provision of environmental adaptation tools (notes,
checklists, calendars, etc.), the use of the WellPATH app, and the participation of a willing
and available caregiver. Supportive Therapy incorporates standard of care approaches by using
non-specific techniques to provide a supportive environment and help patients to express
their feelings & focus on their strengths and abilities.

The investigators plan to randomize 80 treatment subjects, older adults (40 at Cornell and 40
at Johns Hopkins) with MCI-depression. 80 study partners may also be potentially recruited.
Both sites have shown feasibility of recruitment, randomization, retention, and assessment
procedures for patients with MCI. Cornell has shown evidence of administration of PATH in
this population. Certified mental health clinicians in PATH-MCI and ST-CI will administer 15
in-office sessions in six months.

The investigators propose to compare the effects of 15 sessions (12 weekly in first 12 weeks
and 3 monthly booster sessions afterwards) of PATH-MCI vs. ST-CI in 80 older adults
(treatment subjects) with MCI-depression. Research assistants, unaware of study hypotheses
and participant randomization status, will perform research assessments at baseline and at 6
(no cognitive measures), 12, 24, 36 (no cognitive measures) and 52 weeks after randomization.

There will also be optional blood draws at study entry, 12, and 52 weeks. The purpose of the
blood draws is to better understand whether response to psychotherapy treatment is affected
by genes, by inflammation, or by the possible memory factor called BDNF (brain-derived
neurotrophic factor). Also, all therapy sessions will be audiotaped (if the patient consents)
and Dr. Shermer (a clinician outside of the Weill Cornell Institute of Geriatric Psychiatry)
will evaluate randomly selected sessions and rate the therapists' adherence and competence
based on the PATH-MCI and ST Adherence Scales

The study partner will provide information about the treatment subject and participate in
treatment if agreed by the treatment subject. To explore the effects of PATH-MCI on the study
partner, the investigators will collect the following data from the study partner:
demographic, burden (Short Zarit Burden interview), and treatment satisfaction (Client
Satisfaction Questionnaire).

Inclusion Criteria:

- Amnestic MCI as defined by Albert et al

- Montgomery Asberg Depression Rating Scale (MADRS) greater than 7 and MADRS total less
than 30

- Participants will be off antidepressants, cholinesterase inhibitors or memantine, or
on a stable dosage for at least 12 weeks without any medical recommendation to adjust
dosage in next 3 months (during treatment)

- Clinical Dementia Rating (CDR) = 0.5 at screening and MMSE (Mini Mental State
Examination) greater than or equal to 24.

- Subjects will have capacity to consent

Exclusion Criteria:

- Deemed to have a significant suicide risk as assessed by site PI and clinical team

- Deemed too unstable medically or neurologically to safely enroll in a research trial

- Deemed too psychiatrically unstable to safely enroll in randomized trial of
psychotherapy. Requiring psychiatric hospitalization at baseline for safety.

- Current involvement in psychotherapy

- Lack of English fluency