Digitally Supported Lifestyle Programme to Promote Brain Health Among Older Adults

Study Overview
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Brief Summary
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Previous research has shown that a healthy lifestyle, including a balanced diet, physical and social activity, and management of vascular risk factors can support both cardiovascular and brain health. In a landmark Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a multimodal lifestyle programme had clear benefits on older adults' cognition, functioning, and quality of life. The LETHE study utilises novel technologies and digital tools to deliver an optimised and more personalised FINGER-type multimodal lifestyle intervention. A total of 160 digitally skilled older adults (age 60-77) with risk factors for dementia but without substantial cognitive impairment will be recruited in Austria, Finland, Italy, and Sweden. Participants will be randomly assigned in a 1:1 ratio to the structured ICT-assisted multimodal lifestyle program (intervention group) or a self-guided lifestyle program (control group). Duration of the study and the intervention is 24 months. The multimodal lifestyle program covers the following domains: physical activity, nutrition, cognitive activity, vascular risk management, social interaction, sleep, and relaxation. The structured intervention program follows a hybrid model where regular in-person, individual and group-based intervention activities led by professionals are supported with activities in the LETHE mobile phone application. The self-guided (control) group receives relevant health advice and is recommended and encouraged to independently implement healthy lifestyle changes that are suitable and fit in with their daily routine. Control group will have access to a simplified version of the LETHE app without any structured, scheduled activities or personalized content. The primary objective of the LETHE trial is to test the feasibility of a digitally supported multimodal lifestyle program (i.e., retention rate, adherence to intervention), and assess change in dementia risk based on validated risk scores (CAIDE, LIBRA). Other objectives include testing the intervention effects on lifestyle and risk factors, cognition, function, health-related quality of life, health literacy, physical functioning, and dementia-related biomarkers. To this aim, a range of personal, lifestyle, and health-related data will be collected both actively and passively with the help of digital devices. Attitudes towards digital tools and experiences of trial participation will also be explored.

Detailed Description
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The LETHE pilot trial is a 24-month multicentre parallel-group randomised controlled trial conducted in Finland (Finnish Institute for Health and Welfare, THL), Austria (Medical University of Vienna, MUW), Sweden (Karolinska Institute, KI), and Italy (University of Perugia, UPG). LETHE is an academic-led trial (funded by EU Commission) where all four clinical centers are jointly and equally responsible for the planning and conduct of the trial. The recruitment goal is 160 participants (40 per country). Participants will be recruited e.g., through public announcements or advertisements (newspaper, social media) and at the local study centres. Interested individuals will first be pre-screened to check the key inclusion criteria related to e.g., age, digital skills and readiness, and risk factor profile (CAIDE dementia risk score). Persons who appear to meet the inclusion criteria (and no reasons for exclusion have arisen) are then invited for the actual screening assessment visit (organised remotely or in-person) where the eligibility criteria are checked in detail (including cognition). Exclusion criteria are assessed by a physician (for those who meet the inclusion criteria). Eligible individuals are invited to the baseline visit at the study centre. After completing all baseline assessments, participants are randomised in 1:1 ratio to the intervention group (structured ICT-assisted multimodal lifestyle intervention) and control group (self-guided multimodal lifestyle intervention). Randomisation will be balanced across sites. At the beginning of the study, all participants receive an Android smartphone (unless they have already a compatible phone which they prefer to use), first with a simplified version of the LETHE App installed where participants can complete a set of outcome assessment questionnaires (e.g., lifestyle-related). After randomisation, a visit is booked to hand out the Fitbit smartwatch (different versions for the intervention and control groups) and install the full study version of the App (also different for the different groups). The App and the smartwatch are used for both active and passive data collection throughout the trial, and to support the intervention delivery. The intervention group will be offered a structured and tailored multimodal lifestyle programme (based on the FINGER model) including regular in-person (face-to-face and remote) counselling and sessions led by professionals, as well as independent digital activities in the LETHE App. Sessions and activities are related to the following intervention components: physical activity, nutrition, cognitive activity, vascular risk management and monitoring, social interaction, sleep, and relaxation/stress management. Recommendations and plans are tailored. The LETHE App, which has been designed by the LETHE consortium for this project, has features such as e.g., a cognitive training program, on-demand exercise videos, calendar to schedule activities, advice and educational material, group chat, and possibility to set and monitor goals and self-monitor risk factors such as e.g., blood pressure. Participants in the self-guided group are instructed to build their own lifestyle programme based on general health and lifestyle recommendations that they will receive at the main study visits. They will also have access to a simplified version of the LETHE App with static educational content about healthy lifestyle, but without any structured and scheduled activities, interactive features, or personalised content. After baseline, all participants are invited to the study centre for three main study visits to collect outcome information, at month 6, 12, and 24. The outcome assessors are blinded to the group allocation and participants are not actively told to which group they were assigned. Data collection through the digital devices takes place continuously. The primary objective of the trial is to assess the feasibility of the digitally supported multimodal lifestyle intervention programme, i.e., assess retention rate (what proportion of participants completes the 24-month intervention period) and adherence to the intervention and engagement with the digital tools. Furthermore, changes in validated dementia risk scores (CAIDE, LIBRA) are assessed. Other objectives include testing the intervention effects on lifestyle and different risk factors of cognitive decline and dementia, cognitive performance, physical functioning, health-related quality of life, health literacy, and dementia-related fluid and imaging biomarkers. Participants' experiences of study participation and views on e.g., the usability and acceptability of the digital tools will also be explored (through interviews/focus groups).

Official Title
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Digitally Supported Lifestyle Programme to Promote Brain Health Among Older Adults - the LETHE Pilot Trial

Conditions
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Cognitive Impairment, Cognitive Decline, Dementia

Intervention / Treatment
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* Behavioral: Structured ICT-assisted multimodal lifestyle intervention
* Behavioral: Self-guided multimodal lifestyle intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 60-77 years Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) Risk Score ≥ 6 points Cognitive performance at the mean level or slightly lower than expected for age, assessed with Mini-Mental State Examination (MMSE) and the Consortium to Establish a registry for Alzheimer's Disease (CERAD) verbal learning test (word list learning/recall) Proficiency in the local language (German, Italian, Finnish or Swedish) Ability and willingness to use an Android smartphone, access to and ability to use the internet (digital readiness) Existing compatible smartphone (Android) or willingness to use a new Android smartphone provided from the study Exclusion Criteria: Dementia or substantial cognitive impairment (e.g., memory clinic referral needed as judged by the study physician) Current or past use of medications for Alzheimer's disease or related diseases (e.g., cholinesterase inhibitors, memantine) Diminished decision-making capacity, not capable of consenting or completing study assessments, based on clinical judgement Other significant neurologic disease, including but not limited to Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent neurologic sequelae or known structural brain abnormalities Any condition affecting safe engagement in the intervention, e.g., malignant disease, major depression, symptomatic cardiovascular disease, revascularisation within 1 year previously Severe loss of vision, hearing, or communicative ability; conditions preventing cooperation as judged by the study physician Concomitant participation in an interventional trial (unless this will not interfere with the LETHE trial based on study staff's judgement)

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 77 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are randomised 1:1 to two parallel arms: structured ICT-assisted multimodal lifestyle intervention (intervention group) self-guided multimodal lifestyle intervention (control group)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Structured ICT-assisted multimodal lifestyle intervention<br>Participants assigned to this study arm follow an intensive structured, digitally supported multimodal lifestyle intervention programme (combination of individual and group-based in-person consultations/sessions and digital activities in the LETHE mobile phone App). Intervention duration is 2 years. | Behavioral: Structured ICT-assisted multimodal lifestyle intervention<br>* The structured lifestyle intervention programme, partly tailored and personalised to individual needs, covers the following domains: physical activity, nutrition, cognitive activity, cardiovascular risk management, social interaction, sleep, and relaxation / stress management. The programme includes regular scheduled in-person sessions (group-based + individual) which are supported with independent digital activities in the LETHE App. The App has features such as e.g., a cognitive training programme, on-demand exercise videos, calendar to schedule activities, advice and educational material, group chat, and possibility to set and monitor goals and self-monitor risk factors such as e.g., blood pressure.<br>|
| Sham Comparator: Self-guided multimodal lifestyle intervention<br>Participants assigned to this study arm receive regular health advice in connection with the study visits (and through a simplified version of the LETHE mobile phone App), and are recommended and encouraged to independently implement healthy lifestyle changes that are suitable and fit in with their daily routine. Intervention duration is 2 years. | Behavioral: Self-guided multimodal lifestyle intervention<br>* Participants are advised to build their own healthy lifestyle programme based on standard healthy lifestyle advice that they will receive at individual consultations with the study physician/nurse as part of the study visits and through the simplified version of the LETHE app. The control group app does not include any structured / scheduled activities or personalised content.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility: retention rate | Percentage of participants completing the 24-month trial period in each study arm. Higher percentage indicates a better outcome. | 24 months | 
| Feasibility: adherence to the structured multimodal lifestyle intervention | Attendance at scheduled intervention sessions (percentage), usage of / engagement with the digital devices (LETHE App, Fitbit smartwatch). Possible values range from a minimum of 0, with higher values indicating better adherence and more active engagement. | Continuously measured during 24 months | 
| Change in dementia risk scores (LIBRA and CAIDE), units on a scale | Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score and Change in the LIfestyle for BRAin health (LIBRA) score are validated tools to estimate late-life dementia risk based on a combination of non-modifiable and modifiable risk factors (CAIDE) or modifiable factors only (LIBRA). Total score ranges from 0 to 15 (CAIDE) and from -5.9 to +12.7 (LIBRA). Higher scores indicate higher risk. | Baseline, 12 months, 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in healthy lifestyle, unit on a scale | Change in Healthy Lifestyle Index (brief score developed in the FINGER trial), a composite score based on self-reported data on exercise, diet, vascular factors, and cognitive/social activity (range 0-24, with a higher score indicating a better outcome) | Baseline, 12 months, 24 months | 
| Change in cognition: composite z-score based on an extended Neuropsychological Test Battery (NTB), unit on a scale | The NTB used in this study is adapted from the FINGER trial and includes the following tests: Wechsler Memory Scale Revised, WMS-III, WMS-R, logical memory, immediate WMS-R logical memory, delayed WMS-R visual paired associates, immediate WMS-R visual paired associates, delayed WMS-R Digit Span, total Rey Auditory Verbal Learning Test, RAVLT, learning (free recall) RAVLT, delayed recall CERAD category fluency Category fluency (fruits and vegetables) Trail Making Test (TMT) A Trail Making Test (TMT) B, shifting score B-A Stroop Test, shortened 40-stimulus version, condition 2 Stroop Test, condition 3, interference score 3 - 2 Wechsler Adult Intelligence Scale (WAIS) Digit Symbol Substitution Test (DSST) Higher z-score indicates better outcome (better cognitive performance). | Baseline, 12 months, 24 months | 
| Change in stress-related symptoms (Perceived Stress Scale, PSS-14), unit on a scale | PSS is a 14-item self-report scale assessing stress-related symptoms. Values ranging 0-56, with lower scores indicating a better outcome. | Baseline, 12 months, 24 months | 
| Change in sleep problems (Insomnia Severity Index, ISI), unit on a scale | The Insomnia Severity Index (ISI) is a validated seven item assessment tool to assist in the clinical evaluation of insomnia complaints. Values ranging 0-28, with lower scores indicating a better outcome. | Baseline, 12 months, 24 months | 
| Change in health-related quality of life (RAND-36), unit on a scale | The RAND-36 is comprised of 36 items that assess eight health concepts. The scale values are ranging 0-100, with higher scores indicating a better outcome. | Baseline, 12 months, 24 months | 
| Change in health literacy (short version of the European Health Literacy Survey Questionnaire, HLS-EU-Q16), unit on a scale. | Health literacy will be assessed with the 16-item short version of the European Health Literacy Survey Questionnaire. Each item has four response categories (very difficult, fairly difficult, fairly easy and very easy), and higher scores indicate better health literacy. | Baseline, 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention, Risk reduction, Brain health, Lifestyle intervention, Digital intervention, eHealth, Telemedicine