Problem Adaptation Therapy for Mild Cognitive Impairment and Depression (PATH-MCI)

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.

Study Overview

• Status: Completed
• Conditions: Depression; Cognitive Impairment
• Intervention / Treatment: Behavioral: PATH-MCI; Behavioral: Supportive Therapy

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University School of Medicine
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • White Plains, New York, United States, 10605
      • Weill Cornell Institute of Geriatric Psychiatry, Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PATH-MCI; Problem Adaptation Therapy for Mild Cognitively Impaired Adults (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.	Behavioral: PATH-MCI; Problem Adaptation Therapy for Mild Cognitively Impaired Adults (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.
Active Comparator: Supportive Therapy; Supportive Therapy focuses on: 1. Facilitating expression of affect; 2. Conveying to the patient that he or she is understood; 3. Offering empathy; and 4. Highlighting positive experiences. The ST manual aims to standardize nonspecific therapeutic factors.	Behavioral: Supportive Therapy; ST focuses on: 1. facilitating expression of affect; 2. conveying to the patient that he or she is understood; 3. offering empathy; and 4. highlighting positive experiences. The ST manual aims to standardize nonspecific therapeutic factors.; Other Names: ST

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Global Cognition Assessed by RBANS	Global cognition will be assessed by the Repeatable Battery for the Assessment of Neuropsychological Status Total Score (RBANS). The total score represents the simple sum of the five cognitive domain index scores (Immediate Memory, Visuospatial/Constructional, Language, Attention, and Delayed Memory). Total raw scores are converted based on the subjects age and a RBANS scoring manual. Higher scores indicate better functionality. The total scores range from 200 to 800.	Baseline, 12, 24, and 52 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Disability Function Assessed With WHODAS-II	The 12-item WHODAS-II (World Health Organization Disability Assessment Schedule) assesses functional impairment across six domains of daily living. Each item is scored on a 5-point Likert scale ranging from 0 (No difficulty), 1 (Mild Difficulty), 2 (Moderate Difficulty), 3 (Severe Difficulty) and 4 (Extreme difficulty or cannot do). Each individual item has a minimum score of 0 and a maximum of 4. The total raw score is computed by summing all 12 items, resulting in a possible score range of 0 to 48. Higher score reflect greater functional impairment. Lower scores indicate better functional status and less reported difficulty with daily activities.	Baseline, 6, 12, 24, 36, and 52 Weeks
Change in Depression Assessed by MADRS	Depression assessed by Montgomery Asberg Depression Rating Scale (MADRS) Total Score. The MADRS is a 10 item questionnaire assessing severity of depression by scoring participants on mood, anxiety, sleep, concentration, appetite, and suicidal thoughts. The lowest score is 0, no depression symptoms, and the highest possible score is 60, severe depression symptoms.	Baseline, 6, 12, 24, 36, and 52 Weeks
Change in Episodic Memory Assessed by Delayed Recall Subscale of RBANS	The Delayed Recall subscale of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) assesses memory function across multiple tasks. It includes the following components: List Recall Total Score (range: 0-10), List Recognition Total Score (range: 0-20), Story Recall Total Score (range: 0-12), and Figure Recall Total Score (range: 0-20). The raw scores from these four components are summed to yield a Delayed Memory Index raw total score ranging from 0 to 62, with higher scores indicating better memory performance. To facilitate standardized interpretation, raw total scores are converted to age-adjusted Index Scores using normative data provided in the RBANS manual. These Index Scores have a mean of 100 and a standard deviation of 15, and are normed by decade (e.g., 60-69, 70-79, 80-89). Higher Index Scores reflect better memory functioning relative to age-matched peers.	Baseline, 12, 24, and 52 Weeks
Change in Executive Function Assessed by Trail Making Test	Trail Making Test is a neuropsychological assessment where raw scores are converted into a scaled score range from 1 to 25. Participants with scores between 1 - 8 have impaired performance; Mid range scores typically fall between 10 - 16, and subjects who fair the best on this measure have scores ranging from 20 - 25.	Baseline, 12, 24, and 52 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Stress Reduction Assessed by Perceived Stress Scale	Perceived Stress Scale s the most widely used psychological instrument for measuring the perception of stress. It is a measure of the degree to which situations in one's life are appraised as stressful. The 10-item measure has 4 choice options; (0=Never, 1=Almost Never, 2=Sometimes, 3=Fairly Often, 4=Often). 4 items are reversed scored and the total score is summed across all items ranging from 0 to 40. Lower scores are better and indicate less stress.	Baseline, 6, 12, 24, 36, and 52 Weeks

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Johns Hopkins University; Montefiore Medical Center; National Institute on Aging (NIA)
• Investigators: Principal Investigator: Dimitris Kiosses, PhD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): September 19, 2024
• Study Completion (Actual): September 19, 2024

Study Registration Dates

• First Submitted: January 27, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimated): February 6, 2017

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: July 23, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Neurocognitive Disorders; Cognition Disorders; Mood Disorders; Cognitive Dysfunction; Depression; Depressive Disorder
• Other Study ID Numbers: 1603017114; 1R01AG050514 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be available as per NIH's data sharing policy.
• IPD Sharing Time Frame: Data will be available as per NIH's data sharing policy.
• IPD Sharing Access Criteria: Access criteria is determined by NIH and can be requested by applying online.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No