Award Title: Problem Adaptation Therapy For Individuals with Mild to Moderate Dementia and Depression. The PATHFINDER Trial
Funder: Department of Health and Social Care

Abstract: Depression is very common in people with Alzheimer’s disease and other dementias, causing them distress as well as reducing their quality of life and that of their carers. Unfortunately, antidepressant drugs do not have clear effectiveness in these patients and it appears that the most commonly available psychological therapies such as cognitive behavioural therapy or CBT are also not useful. Psychological therapy based upon the principle of problem-solving therapy, in which patients and their carers are helped to find ways to compensate for memory difficulties and to change their environment, relationships and engagement in activity in order to support a positive mood state has been reported to be helpful in the very early stages of dementia. But this has only been shown so far in an American university-based healthcare setting, with people who were mildly affected by dementia and with the use of experienced and expensive therapists. We want to investigate whether this approach can be successfully applied in an NHS setting and with patients who are representative of those seen with dementia and depression in the NHS._x000D_
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Working with the Alzheimer’s Society and NHS staff from the memory services and community mental health teams who already work with people who are mildly and moderately affected by dementia, we will adapt an existing form of problem-solving therapy called Problem Adaptation Therapy (PATH). The two most important adaptations that we will make are to develop a form of PATH that can be delivered by existing NHS staff rather than specialist psychological therapists and to make the therapy available in a form that is helpful for people who are mildly and moderately affected by dementia because this is the group who have the greatest need for an effective depression treatment in the NHS._x000D_
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In the first phase of the project we will develop a manual that can be used by carers, under the supervision and guidance of NHS staff, to apply the principles of PATH to the person with dementia that they live with or care for. We will test the acceptability of this and the willingness of patients and their carers to be involved in a subsequent trial._x000D_
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In the second phase we will carry out a randomised clinical trial, comparing 12 weeks of the modified PATH treatment with current treatment offered as usual within the NHS. We will measure outcomes at 0, 3, 6 and 12 months. The most important outcome of the trial will be improvement in symptoms of depression at 6 months in participants with dementia, but we will also measure quality of life, activities of daily living, cognitive function, anxiety symptoms, satisfaction with therapy and cost-effectiveness of the intervention. In addition, we will examine mental health and perceptions of burden in carers. Our PPI co-applicants suggested that the primary outcome should be at 6 months rather than 3 months (immediately after the intervention ends) as benefits would need to be seen at this later time point in order to justify the investment of time and energy required from participating carers in PATH. We will continue to follow participants for a year to look for evidence of sustained benefits of the therapy._x000D_
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If the intervention is successful at reducing depression in people with mild and moderate dementia, this would be the first evidence-based effective treatment available for this important problem, which could quickly be rolled out within NHS services and made available to patients.

Lay Abstract: PHASE 1 (months 1-12): Adapt intervention based on PATH for delivery in the NHS through interviews with 15-20 patient-carer dyads and 4 professionals' workshops. Assess acceptability to patients, carers and therapists, and likely uptake and adherence. Proceed to Phase 2 if credibility and expectancy scores are >70%, >70% participants complete 2 sessions, ratings are satisfactory on Client Satisfaction Questionnaire (CSQ [35]) and >5 modifiable problems are identified per person._x000D_
PHASE 2 (months 13-54): Assess clinical and cost effectiveness of adapted PATH for depression in dementia in a 6-centre single-blind parallel 2-arm RCT with an internal pilot in the first 12 months to assess feasibility of recruitment and acceptability of randomisation. Continue to full RCT if recruit 125 patients (75% of target)._x000D_
SETTING: Community._x000D_
PARTICIPANTS: 333 people with mild to moderate dementia recruited from Memory Services and CMHTs._x000D_
INCLUSIONS: Mild to moderate Alzheimer's disease (AD) or mixed AD/vascular dementia (SMMSE 10+) with clinically significant depression (score of 8+ on Cornell Scale for Depression in Dementia [CSDD (4)]); sufficiently fluent in English to engage with PATH; identified carer who spends 1hr+ per day on at least 3 days/week with the participant. Psychotropics allowed if dose has not changed in previous 4 weeks and no plan to change during next 12 weeks of PATH._x000D_
INTERVENTION: PATH adapted for people with dementia plus TAU. Psychiatric nurses, occupational therapists, assistant psychologists and psychological wellbeing practitioners from Memory Services, CMHTs and IAPTs will be trained to deliver 10 manualised sessions over 12 weeks under regular supervision from clinical psychologists. Random sessions will be assessed for treatment fidelity._x000D_
COMPARATOR: TAU within which participants will have access to psychotropics, supportive and other therapies at discretion of responsible clinicians._x000D_
RANDOMISATION: 1:1 stratified randomisation via CTU online system._x000D_
PRIMARY OUTCOME: Change in CSDD score from baseline to 6 months._x000D_
SECONDARY OUTCOMES: Patients: CSDD at 3 and 12 months; change in disease-specific health-related quality of life with DEMQOL and DEMQOL-proxy (27), generic quality of life with EQ-5D (28); function with Bristol Activities of Daily Living Scale (29); cognitive function with SMMSE (20); anxiety with Rating Anxiety in Dementia scale (30); cost-effectiveness with Client Service Receipt Inventory (31); satisfaction with CSQ. Carers: Burden with Zarit Burden Inventory (32); mental health with General Health Questionnaire-12 (33)._x000D_
TIMING OF OMs: Assessment at 0, 3, 6 (primary endpoint) and 12 months post-randomisation by blind outcome assessors._x000D_
SAMPLE SIZE: 333 participants will allow detection of a minimum clinically important difference of 2.0 points on the CSDD (an effect size of 0.4 SD) with a 2-sided alpha of 5% and 90% power, assuming 20% loss to follow-up at 6 months._x000D_
TIMETABLE: 1-9 months: Ethical/research approval, adapt intervention, train clinicians. 7-12 months: Assess acceptability, RCT set-up. 13-36 months: RCT recruitment with internal pilot in months 13-24. 37-48 months: Follow-up. 49-54 months: Database lock, analyses, dissemination._x000D_
OUR TEAM: Has experience of successfully delivering multi-site trials, with expertise in dementia (RHo/GL/RD/PB/SB/CF/PW/AT/VO/RG), developing psychotherapy manuals (GL/VO/KL/PW/RG), qualitative research (VL/VO/GL), statistics (NF) and health economics (RHu).

Research Activity Codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health Categories: MENTAL HEALTH;NEUROLOGICAL