Mild Cognitive Impairment (MCI)LETHE-ATNCT07376135
LETHE-AT: a Personalized Multidomain Lifestyle Intervention for Individuals at Increased Risk of Memory Impairment.
A study testing A tailored hybrid multidomain lifestyle intervention group and Self-guided multimodal lifestyle advice group in people with Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD), run by Medical University of Vienna at 3 sites in Austria.
Trial summary
The goal of this clinical trial is to learn whether a hybrid multidomain lifestyle program can prevent cognitive decline and reduce dementia risk in community-dwelling adults in mid- to late life who are at increased risk of Alzheimer´s disease or related dementias but do not yet have significant cognitive impairment. Read more about this study
- Who is it for?
- Ages 55 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment (MCI), Subjective Cognitive Decline (SCD)
- What is being tested?
- A tailored hybrid multidomain lifestyle intervention group and Self-guided multimodal lifestyle advice group
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 3 sitesAustria
- Study dates
- 8 Jan 2026to 1 Nov 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 55 and 75 years at the time of screening.
- Fluency in German.
- All participants must be able and willing to provide written informed consent form (ICF) prior to any study-related procedures.
- Ownership of a compatible Android smartphone, or willingness and capability to use a study-provided Android smartphone for the duration of the study.
- Subjective cognitive decline and/or a positive first-degree family history of dementia.
- Willingness to make meaningful changes in at least three of six lifestyle domains: dietary counselling, physical activity, cognitive training, vascular risk management, social interaction, and sleep and relaxation.
- Cognitive performance at or slightly below age expectations, defined as an m-TICS (modified Telephone Interview for Cognitive Status) score ≥ 37/50, and a Montreal Cognitive Assessment (MoCA) ≥ 26/30.
Who cannot join
- Diagnosed or suspected dementia or substantial cognitive impairment, defined as an m-TICS score ≤ 36 or MoCA < 26, or current or previous use of Alzheimer´s disease or other dementia medication.
- Significant neurological disease, including but not limited to Parkinson´s disease, Huntington´s disease, normal pressure hydrocephalus, brain tumour, progressive supranuclear palsy, seizure disorder, subdural haematoma, multiple sclerosis, or a history of significant head trauma with persistent neurological sequelae or known structural brain abnormalities.
- Diminished decision-making capacity, inability to provide informed consent, inability to complete study assessments, or any condition preventing effective cooperation, as determined by clinical judgement.
- Severe impairment of vision, hearing, or communication abilities that would preclude participation in study procedure.
- Any medical or psychiatric condition affecting safe engagement, including but not limited to active malignancy, major depressive disorder, symptomatic cardiovascular disease, or revascularisation procedures within the past year.
- Current participation in another interventional trial, unless the study team determines this does not interfere with participation in the LETHE-AT.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Austria3 sites
Medical University of Innsbruck
Graz, Styria, 8010
Stephan Seiler, MD PhD, +43 316 385 83396, stephan.seiler@medunigraz.at
Stephan Seiler, Md PhD
Medical University of Innsbruck
Innsbruck, Tyrol, 6020
Atbin Djamshidian-Tehrani, MD PhD, +4351250424239, atbin.djamshidian-tehrani@i-med.ac.at
Atbin Djamshidian-Tehrani, MD PhD
Medical University of Vienna
Vienna
Niklas Rast MD, +49 1515 47 33 860, niklas.rast@meduniwien.ac.at
Elisabeth Stögmann, MD PhD
About this study
Official title: Digitally Supported Lifestyle Programme to Promote Brain Health Among Older Adults - the LETHE-AT Randomised-controlled, Multicentre Pilot Trial
The goal of this clinical trial is to learn whether a hybrid multidomain lifestyle program can prevent cognitive decline and reduce dementia risk in community-dwelling adults in mid- to late life who are at increased risk of Alzheimer´s disease or related dementias but do not yet have significant cognitive impairment.
The main question the study aims to answer are:
Read more
- Whether the structured hybrid multidomain lifestyle intervention is feasible (e.g., adherence and retention rate), and how well the digital components are accepted and implemented in the intervention group.
- Does the intervention reduces the overall burden of modifiable dementia risk factors and improves global cognitive performance compared with usual care.
Researchers will compare participants assigned to the tailored hybrid multidomain lifestyle intervention group with those in a self-guided multimodal lifestyle advice group.
Participants assigned to the intervention group will receive a plan adjusted to their individual dementia risk profile. A physician trained in motivational interviewing will review their progress continuously.
The self-guided multimodal lifestyle advice group will receive rigid but comprehensible lifestyle health advice with reduced access to digital support tools.
Participants will:
- Complete an initial risk assessment that uses machine-learning triage to identify and prioritize their most important modifiable dementia risk factors.
- Receive personalized recommendations for gradual lifestyle change, including physical activity, nutrition, cognitive training, other dementia risk-factor management (e.g. hearing impairment), stress \& sleep management, and social activities.
- Use a smartphone and smartwatch to passively collect digital biomarkers and to complete questionnaires at regular intervals, so that physicians trained in motivational interviewing can adapt goals through shared decision making.
- Use a study app as the central access point for the program, including educational content, progress tracking, and gamified challenges with social comparison and incentives.
Read the detailed description
LETHE AT is an 18 month multicentre randomized controlled trial in Austria that evaluates a tailored hybrid multidomain lifestyle intervention programme in older adults with multiple dementia risk factors and is conducted at the Medical Universities of Vienna, Innsbruck, and Graz.
Previous multidomain lifestyle trials have shown that structured interventions targeting modifiable risk factors can attenuate cognitive decline and reduce dementia risk. These programme have used different delivery formats, including intensive face to face interventions (FINGER), fully digital approaches (Maintain Your Brain), and hybrid models (SMART and LETHE EU). LETHE-AT builds on this foundation by combining refined risk profiling and motivational interviewing (MI) with a centrally organized online and telephone prescreening process. This approach identifies cognitively unimpaired adults with a high burden of dementia risk factors and reduces avoidable on-site screening failures and participant disappointment.
Following the prescreening, comprehensive on-site screening is conducted at three Austrian memory clinics to enroll 300 participants. Eligibility is determined using predefined inclusion and exclusion criteria, including age 55-75 years, preserved cognition, subjective cognitive decline or a first-degree family history of dementia, the presence of at least three of 14 established modifiable dementia risk factors (e.g. hearing impairment, elevated LDL cholesterol), and sufficient motivation for lifestyle change as evaluated by physicians trained in MI.
Eligible participants are invited for a baseline visit, where dementia risk is quantified using LIBRA2 and ANU-ADRI, and a harmonized neuropsychological and functional assessment battery is administered by trained neuropsychologists.
The study population is then stratified by sex, age and study site and randomly assigned in a 1:1 ratio to the tailored hybrid multidomain lifestyle intervention group or to the self-guided multimodal lifestyle advice group.
At a subsequent in-person visit, all participants attend a structured onboarding session. In both groups, the smartphone, smartwatch and LETHE-App are introduced, standardized usage instructions are provided, and access to ongoing technical support is ensured.
In the MI-guided hybrid multidomain lifestyle intervention group, onboarding additionally includes an individual consultation with a trained MI-coach.
The 14 modifiable risk factors are mapped onto six lifestyle domains (diet, physical activity, cognitive engagement, sleep and stress, social interactions, and other risk-factor management) to guide content and provide a replicable coaching framework. Additionally, the modifiable risk profile is processed by a dedicated AI-based decision-support tool that generates tailored goal recommendations, and a complemental questionnaire captures personal preferences and constraints. Based on this information, participants and the MI coach select personal goals from a predefined list, with each goal allocated to one of the six lifestyle domains.
The intervention programme begins with a small set of high-priority goals and is gradually expanded, with the number and intensity of goals adapted over time to each participant's risk profile, capacity and circumstances. The intervention programme is harmonized across study sites and supported by manuals to ensure consistent delivery.
The LETHE-App is provided to both study arms and serves several purposes. First, it enables continuous assessment of digital markers (e.g., log-in patterns), complemented by digital biomarkers from the smartwatch (e.g., sleeping-time). Second, it delivers frequent questionnaires on system satisfaction and risk-factor status. In addition, the app offers reminders and review functions for personal goals and provides evidence-based lifestyle information for each domain, including content supplied by the Austrian Agency for Health and Food Safety (AGES). Further functions, such as gamification elements to support adherence and motivation to change, are planned for iterative development.
Participants attend in-person study visits at baseline, month 9 and month 18, where they undergo an extended neuropsychological test battery, standardized dementia risk assessment and blood sampling. Brain MRI is performed as part of an imaging sub-study, and blood samples are stored for analysis of conventional risk markers and exploratory dementia-related biomarkers.
Outcome assessors for cognition, imaging and laboratory measures are blinded to group allocation, and group assignment is not revealed in study documentation used for these assessments.
Intervention study visits consist of individual MI-based tele-health sessions of approximately 20 to 30 minutes, scheduled at roughly three-month intervals to review progress, troubleshoot barriers and adjust goals. A harmonized protocol is used across sites, and sessions focus on strengthening intrinsic motivation for lifestyle change by exploring ambivalence, linking behaviour change to personally meaningful values and reinforcing self-efficacy in initiating and maintaining lifestyle modifications.
Safety is monitored through brief adverse event questionnaires at scheduled time points and through spontaneous reports during visits or phone contacts. All study related events are documented and managed according to protocol, and the intervention is nonpharmacologic and consistent with current dementia prevention guidelines. Data are pseudonymized and stored on secure servers with restricted access and audit trails, and trial conduct follows Good Clinical Practice and standardized operating procedures with trained staff and a central data management plan.
The planned sample of 300 participants reflects the focus on feasibility outcomes such as counseling acceptability, adherence and retention. Analyses follow the intention to treat principle and use linear mixed effects models with group, time and their interaction adjusted for baseline values and prespecified covariates. Effect estimates are reported with 95 percent confidence intervals, and missing data are examined in planned sensitivity analyses. No formal interim efficacy analysis is planned.
- Being tested
- A tailored hybrid multidomain lifestyle intervention group, Self-guided multimodal lifestyle advice group
- Keywords
- dementia prevention, brain health, multidomain lifestyle intervention, Austria, multicenter, subjective cognitive decline, physical activity, cognitive training, wearable, smartwatch, App, risk reduction, randomized controlled trial, hybrid digital, dietary counselling, sleep, stress management, ANU-ADRI, LIBRA2, Neuropsychological Test Battery (NTB)
- Medical subject headings
- Cognitive Dysfunction, Motor Activity, Alzheimer Disease, Risk Reduction Behavior, Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A tailored hybrid multidomain lifestyle intervention groupBehavioural
The structured counselling intervention combines interactive face-to-face workshops with ongoing remote coaching through the LETHE-AT mobile app and regular (video)-telephone sessions to support sustained lifestyle changes. Each participant is individually guided throughout the intervention by a dedicated coach (physician or psychologist), trained in motivational interviewing techniques aimed at facilitating behavioural changes across targeted lifestyle domains.
Self-guided multimodal lifestyle advice groupBehavioural
Participants receive a reduced version of the LETHE-AT app with general health information only. No structured in-person or remote counselling is provided and no individualized digital content is unlocked. They are encouraged to implement lifestyle changes independently. Throughout the trial, participants complete the same in-app questionnaires, wear a Garmin Vivosmart 5, and receive routine laboratory result with advice to seek certain medical care if needed. A pure no-treatment arm is not included for ethical reasons.
| Study group | Role | What they receive |
|---|---|---|
| A self-guided multimodal lifestyle advice group | Sham comparator | Participants in the control arm receive a self-guided lifestyle advice programme via the LETHE-AT app and smartwatch, with standardized information across all lifestyle domains but without motivational interviewing, structured coaching or algorithm-based personalization. Receives: Behavioral: Self-guided multimodal lifestyle advice group |
| A tailored hybrid multidomain lifestyle intervention group | Active comparator | Participants in the intervention arm receive an MI-guided hybrid multidomain lifestyle intervention that integrates AI-based risk profiling, personalized goal setting and structured telehealth coaching with app- and smartwatch-supported self-management across six lifestyle domains. Receives: Behavioral: A tailored hybrid multidomain lifestyle intervention group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Operational feasibility: retention rate
Proportion of all randomized participants who complete the Month 18 assessment in each trial arm (percentage of all randomized participants; higher percentage = better retention).
Measured: Baseline to 18 months
Operational feasibility: adherence to the structured hybrid lifestyle intervention
Composite adherence score combining attendance at workshops and telehealth sessions, engagement with the LETHE-AT app (logins and completed modules), and proportion of days with successful smartwatch data uploads (higher values = better adherence).
Measured: Continuously assessed over 18 months
Secondary outcomes (5)
Change in health-related quality of life (SF-36)
Change in health-related quality of life assessed with the 36-Item Short Form Health Survey (SF-36; 0-100 points per domain; higher scores = better self-reported health status).
Measured: Baseline to 18 months
Change in health literacy (HLS-EU-Q16)
Change in health literacy assessed with the European Health Literacy Survey Questionnaire, 16-item version (HLS-EU-Q16; 0-16 points; higher scores = better general health literacy).
Measured: Baseline to 18 months
User acceptance of the digital solution (SUS)
Change in perceived usability of the app and digital devices assessed with the System Usability Scale (SUS; 0-100 points; higher scores = better perceived usability and acceptance).
Measured: 2 months past enrollment to 18 months
Change in perceived stress (PSS-14)
Change in perceived stress assessed with the Perceived Stress Scale-14 (PSS-14; 0-56 points; higher scores = more perceived stress during the past month).
Measured: Baseline, Month 9, 18 months.
Change in insomnia symptoms (ISI)
Change in insomnia symptoms assessed with the Insomnia Severity Index (ISI; 0-28 points; higher scores = more severe insomnia complaints).
Measured: Baseline, Month 9, 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2026
- Study start8 Jan 2026 (estimated)
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive Impairment (MCI)Studies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Collaborators
- Medical University of Graz, FH Joanneum Gesellschaft mbH, Medical University Innsbruck, Austrian Research Promotion Agency
- Responsible party
- Principal investigator, Elisabeth Stögmann, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07376135
- Sponsor's protocol ID
- MUW EK Nr: 1792/2025
- Other IDs
- 58285128 / 921935
- Acronym
- LETHE-AT
- Status last verified
- Nov 2025
- First submitted
- 14 Dec 2025
- Last updated
- 29 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (including baseline characteristics, primary and key secondary outcomes) underlying the main published results will be made available to qualified researchers upon reasonable request, after approval by the sponsor and the relevant ethics committees.
Publications
Kivipelto M, Solomon A, Ahtiluoto S, Ngandu T, Lehtisalo J, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Nissinen A, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): study design and progress. Alzheimers Dement. 2013 Nov;9(6):657-65. doi: 10.1016/j.jalz.2012.09.012. Epub 2013 Jan 17.
PubMed 23332672Yaffe K, Vittinghoff E, Dublin S, Peltz CB, Fleckenstein LE, Rosenberg DE, Barnes DE, Balderson BH, Larson EB. Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults: The SMARRT Randomized Clinical Trial. JAMA Intern Med. 2024 Jan 1;184(1):54-62. doi: 10.1001/jamainternmed.2023.6279.
PubMed 38010725Brodaty H, Chau T, Heffernan M, Ginige JA, Andrews G, Millard M, Sachdev PS, Anstey KJ, Lautenschlager NT, McNeil JJ, Jorm L, Kochan NA, Maeder A, Welberry H, San Jose JC, Briggs NE, Popovic G, Mavros Y, Almendrales Rangel C, Noble Y, Radd-Vagenas S, Flood VM, O'Leary F, Lampit A, Walton CC, Barr P, Fiatarone Singh M, Valenzuela M. An online multidomain lifestyle intervention to prevent cognitive decline in at-risk older adults: a randomized controlled trial. Nat Med. 2025 Feb;31(2):565-573. doi: 10.1038/s41591-024-03351-6. Epub 2025 Jan 28.
PubMed 39875685Frisoni GB, Altomare D, Ribaldi F, Villain N, Brayne C, Mukadam N, Abramowicz M, Barkhof F, Berthier M, Bieler-Aeschlimann M, Blennow K, Brioschi Guevara A, Carrera E, Chetelat G, Csajka C, Demonet JF, Dodich A, Garibotto V, Georges J, Hurst S, Jessen F, Kivipelto M, Llewellyn DJ, McWhirter L, Milne R, Minguillon C, Miniussi C, Molinuevo JL, Nilsson PM, Noyce A, Ranson JM, Grau-Rivera O, Schott JM, Solomon A, Stephen R, van der Flier W, van Duijn C, Vellas B, Visser LNC, Cummings JL, Scheltens P, Ritchie C, Dubois B. Dementia prevention in memory clinics: recommendations from the European task force for brain health services. Lancet Reg Health Eur. 2023 Jan 31;26:100576. doi: 10.1016/j.lanepe.2022.100576. eCollection 2023 Mar.
PubMed 36895446Rosenberg A, Untersteiner H, Guazzarini AG, Bodenler M, Bruinsma J, Buchgraber-Schnalzer B, Colombo M, Crutzen R, Diaz A, Fotiadis DI, Hilberger H, Huber S, Kaartinen N, Kassiotis T, Kivipelto M, Lehtisalo J, Loukas VS, Lotjonen J, Pirani M, Thunborg C, Hanke S, Mangialasche F, Mecocci P, Stogmann E, Ngandu T; on behaf of the LETHE Consortium. A digitally supported multimodal lifestyle program to promote brain health among older adults (the LETHE randomized controlled feasibility trial): study design, progress, and first results. Alzheimers Res Ther. 2024 Nov 21;16(1):252. doi: 10.1186/s13195-024-01615-4.
PubMed 39574193Livingston G, Huntley J, Liu KY, Costafreda SG, Selbaek G, Alladi S, Ames D, Banerjee S, Burns A, Brayne C, Fox NC, Ferri CP, Gitlin LN, Howard R, Kales HC, Kivimaki M, Larson EB, Nakasujja N, Rockwood K, Samus Q, Shirai K, Singh-Manoux A, Schneider LS, Walsh S, Yao Y, Sommerlad A, Mukadam N. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024 Aug 10;404(10452):572-628. doi: 10.1016/S0140-6736(24)01296-0. Epub 2024 Jul 31. No abstract available.
PubMed 39096926
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Digitally Supported Lifestyle Programme to Promote Brain Health Among Older Adults - the LETHE-AT Randomised-controlled, Multicentre Pilot Trial
- ClinicalTrials.gov ID
- NCT07376135
- Acronym / sponsor ID
- LETHE-AT / MUW EK Nr: 1792/2025
- Keywords
- dementia prevention, brain health, multidomain lifestyle intervention, Austria, multicenter, subjective cognitive decline, physical activity, cognitive training
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Collaborators
- Medical University of Graz, FH Joanneum Gesellschaft mbH, Medical University Innsbruck, Austrian Research Promotion Agency
- Study start
- 8 Jan 2026 (estimated)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Nov 2027 (estimated)
- First posted
- 29 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn whether a hybrid multidomain lifestyle program can prevent cognitive decline and reduce dementia risk in community-dwelling adults in mid- to late life who are at increased risk of Alzheimer´s disease or related dementias but do not yet have significant cognitive impairment.
The main question the study aims to answer are:
- Whether the structured hybrid multidomain lifestyle intervention is feasible (e.g., adherence and retention rate), and how well the digital components are accepted and implemented in the intervention group.
- Does the intervention reduces the overall burden of modifiable dementia risk factors and improves global cognitive performance compared with usual care.
Researchers will compare participants assigned to the tailored hybrid multidomain lifestyle intervention group with those in a self-guided multimodal lifestyle advice group.
Participants assigned to the intervention group will receive a plan adjusted to their individual dementia risk profile. A physician trained in motivational interviewing will review their progress continuously.
The self-guided multimodal lifestyle advice group will receive rigid but comprehensible lifestyle health advice with reduced access to digital support tools.
Participants will:
- Complete an initial risk assessment that uses machine-learning triage to identify and prioritize their most important modifiable dementia risk factors.
- Receive personalized recommendations for gradual lifestyle change, including physical activity, nutrition, cognitive training, other dementia risk-factor management (e.g. hearing impairment), stress \& sleep management, and social activities.
- Use a smartphone and smartwatch to passively collect digital biomarkers and to complete questionnaires at regular intervals, so that physicians trained in motivational interviewing can adapt goals through shared decision making.
- Use a study app as the central access point for the program, including educational content, progress tracking, and gamified challenges with social comparison and incentives.
Detailed description
LETHE AT is an 18 month multicentre randomized controlled trial in Austria that evaluates a tailored hybrid multidomain lifestyle intervention programme in older adults with multiple dementia risk factors and is conducted at the Medical Universities of Vienna, Innsbruck, and Graz.
Previous multidomain lifestyle trials have shown that structured interventions targeting modifiable risk factors can attenuate cognitive decline and reduce dementia risk. These programme have used different delivery formats, including intensive face to face interventions (FINGER), fully digital approaches (Maintain Your Brain), and hybrid models (SMART and LETHE EU). LETHE-AT builds on this foundation by combining refined risk profiling and motivational interviewing (MI) with a centrally organized online and telephone prescreening process. This approach identifies cognitively unimpaired adults with a high burden of dementia risk factors and reduces avoidable on-site screening failures and participant disappointment.
Following the prescreening, comprehensive on-site screening is conducted at three Austrian memory clinics to enroll 300 participants. Eligibility is determined using predefined inclusion and exclusion criteria, including age 55-75 years, preserved cognition, subjective cognitive decline or a first-degree family history of dementia, the presence of at least three of 14 established modifiable dementia risk factors (e.g. hearing impairment, elevated LDL cholesterol), and sufficient motivation for lifestyle change as evaluated by physicians trained in MI.
Eligible participants are invited for a baseline visit, where dementia risk is quantified using LIBRA2 and ANU-ADRI, and a harmonized neuropsychological and functional assessment battery is administered by trained neuropsychologists.
The study population is then stratified by sex, age and study site and randomly assigned in a 1:1 ratio to the tailored hybrid multidomain lifestyle intervention group or to the self-guided multimodal lifestyle advice group.
At a subsequent in-person visit, all participants attend a structured onboarding session. In both groups, the smartphone, smartwatch and LETHE-App are introduced, standardized usage instructions are provided, and access to ongoing technical support is ensured.
In the MI-guided hybrid multidomain lifestyle intervention group, onboarding additionally includes an individual consultation with a trained MI-coach.
The 14 modifiable risk factors are mapped onto six lifestyle domains (diet, physical activity, cognitive engagement, sleep and stress, social interactions, and other risk-factor management) to guide content and provide a replicable coaching framework. Additionally, the modifiable risk profile is processed by a dedicated AI-based decision-support tool that generates tailored goal recommendations, and a complemental questionnaire captures personal preferences and constraints. Based on this information, participants and the MI coach select personal goals from a predefined list, with each goal allocated to one of the six lifestyle domains.
The intervention programme begins with a small set of high-priority goals and is gradually expanded, with the number and intensity of goals adapted over time to each participant's risk profile, capacity and circumstances. The intervention programme is harmonized across study sites and supported by manuals to ensure consistent delivery.
The LETHE-App is provided to both study arms and serves several purposes. First, it enables continuous assessment of digital markers (e.g., log-in patterns), complemented by digital biomarkers from the smartwatch (e.g., sleeping-time). Second, it delivers frequent questionnaires on system satisfaction and risk-factor status. In addition, the app offers reminders and review functions for personal goals and provides evidence-based lifestyle information for each domain, including content supplied by the Austrian Agency for Health and Food Safety (AGES). Further functions, such as gamification elements to support adherence and motivation to change, are planned for iterative development.
Participants attend in-person study visits at baseline, month 9 and month 18, where they undergo an extended neuropsychological test battery, standardized dementia risk assessment and blood sampling. Brain MRI is performed as part of an imaging sub-study, and blood samples are stored for analysis of conventional risk markers and exploratory dementia-related biomarkers.
Outcome assessors for cognition, imaging and laboratory measures are blinded to group allocation, and group assignment is not revealed in study documentation used for these assessments.
Intervention study visits consist of individual MI-based tele-health sessions of approximately 20 to 30 minutes, scheduled at roughly three-month intervals to review progress, troubleshoot barriers and adjust goals. A harmonized protocol is used across sites, and sessions focus on strengthening intrinsic motivation for lifestyle change by exploring ambivalence, linking behaviour change to personally meaningful values and reinforcing self-efficacy in initiating and maintaining lifestyle modifications.
Safety is monitored through brief adverse event questionnaires at scheduled time points and through spontaneous reports during visits or phone contacts. All study related events are documented and managed according to protocol, and the intervention is nonpharmacologic and consistent with current dementia prevention guidelines. Data are pseudonymized and stored on secure servers with restricted access and audit trails, and trial conduct follows Good Clinical Practice and standardized operating procedures with trained staff and a central data management plan.
The planned sample of 300 participants reflects the focus on feasibility outcomes such as counseling acceptability, adherence and retention. Analyses follow the intention to treat principle and use linear mixed effects models with group, time and their interaction adjusted for baseline values and prespecified covariates. Effect estimates are reported with 95 percent confidence intervals, and missing data are examined in planned sensitivity analyses. No formal interim efficacy analysis is planned.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A self-guided multimodal lifestyle advice group | Sham comparator | Behavioral: Self-guided multimodal lifestyle advice groupParticipants in the control arm receive a self-guided lifestyle advice programme via the LETHE-AT app and smartwatch, with standardized information across all lifestyle domains but without motivational interviewing, structured coaching or algorithm-based personalization. |
| A tailored hybrid multidomain lifestyle intervention group | Active comparator | Behavioral: A tailored hybrid multidomain lifestyle intervention groupParticipants in the intervention arm receive an MI-guided hybrid multidomain lifestyle intervention that integrates AI-based risk profiling, personalized goal setting and structured telehealth coaching with app- and smartwatch-supported self-management across six lifestyle domains. |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age between 55 and 75 years at the time of screening.
- Fluency in German.
- All participants must be able and willing to provide written informed consent form (ICF) prior to any study-related procedures.
- Ownership of a compatible Android smartphone, or willingness and capability to use a study-provided Android smartphone for the duration of the study.
- Subjective cognitive decline and/or a positive first-degree family history of dementia.
Key exclusion criteria (6 listed)
- Diagnosed or suspected dementia or substantial cognitive impairment, defined as an m-TICS score ≤ 36 or MoCA < 26, or current or previous use of Alzheimer´s disease or other dementia medication.
- Significant neurological disease, including but not limited to Parkinson´s disease, Huntington´s disease, normal pressure hydrocephalus, brain tumour, progressive supranuclear palsy, seizure disorder, subdural haematoma, multiple sclerosis, or a history of significant head trauma with persistent neurological sequelae or known structural brain abnormalities.
- Diminished decision-making capacity, inability to provide informed consent, inability to complete study assessments, or any condition preventing effective cooperation, as determined by clinical judgement.
- Severe impairment of vision, hearing, or communication abilities that would preclude participation in study procedure.
- Any medical or psychiatric condition affecting safe engagement, including but not limited to active malignancy, major depressive disorder, symptomatic cardiovascular disease, or revascularisation procedures within the past year.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| A tailored hybrid multidomain lifestyle intervention groupThe structured counselling intervention combines interactive face-to-face workshops with ongoing remote coaching through the LETHE-AT mobile app and regular (video)-telephone sessions to support sustained lifestyle changes. Each participant is individually guided throughout the intervention by a dedicated coach (physician or psychologist), trained in motivational interviewing techniques aimed at facilitating behavioural changes across targeted lifestyle domains. | Behavioural | A tailored hybrid multidomain lifestyle intervention group |
| Self-guided multimodal lifestyle advice groupParticipants receive a reduced version of the LETHE-AT app with general health information only. No structured in-person or remote counselling is provided and no individualized digital content is unlocked. They are encouraged to implement lifestyle changes independently. Throughout the trial, participants complete the same in-app questionnaires, wear a Garmin Vivosmart 5, and receive routine laboratory result with advice to seek certain medical care if needed. A pure no-treatment arm is not included for ethical reasons. | Behavioural | A self-guided multimodal lifestyle advice group |
Primary outcome
Operational feasibility: retention rate
Time frame: Baseline to 18 months
Proportion of all randomized participants who complete the Month 18 assessment in each trial arm (percentage of all randomized participants; higher percentage = better retention).
Operational feasibility: adherence to the structured hybrid lifestyle intervention
Time frame: Continuously assessed over 18 months
Composite adherence score combining attendance at workshops and telehealth sessions, engagement with the LETHE-AT app (logins and completed modules), and proportion of days with successful smartwatch data uploads (higher values = better adherence).
5 secondary outcomes
Change in health-related quality of life (SF-36)
Time frame: Baseline to 18 months
Change in health literacy (HLS-EU-Q16)
Time frame: Baseline to 18 months
User acceptance of the digital solution (SUS)
Time frame: 2 months past enrollment to 18 months
Change in perceived stress (PSS-14)
Time frame: Baseline, Month 9, 18 months.
Change in insomnia symptoms (ISI)
Time frame: Baseline, Month 9, 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2026.
- Background: PubMed 23332672Kivipelto M, Solomon A, Ahtiluoto S, Ngandu T, Lehtisalo J, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Nissinen A, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): study design and progress. Alzheimers Dement. 2013 Nov;9(6):657-65. doi: 10.1016/j.jalz.2012.09.012. Epub 2013 Jan 17.
- Background: PubMed 38010725Yaffe K, Vittinghoff E, Dublin S, Peltz CB, Fleckenstein LE, Rosenberg DE, Barnes DE, Balderson BH, Larson EB. Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults: The SMARRT Randomized Clinical Trial. JAMA Intern Med. 2024 Jan 1;184(1):54-62. doi: 10.1001/jamainternmed.2023.6279.
- Background: PubMed 39875685Brodaty H, Chau T, Heffernan M, Ginige JA, Andrews G, Millard M, Sachdev PS, Anstey KJ, Lautenschlager NT, McNeil JJ, Jorm L, Kochan NA, Maeder A, Welberry H, San Jose JC, Briggs NE, Popovic G, Mavros Y, Almendrales Rangel C, Noble Y, Radd-Vagenas S, Flood VM, O'Leary F, Lampit A, Walton CC, Barr P, Fiatarone Singh M, Valenzuela M. An online multidomain lifestyle intervention to prevent cognitive decline in at-risk older adults: a randomized controlled trial. Nat Med. 2025 Feb;31(2):565-573. doi: 10.1038/s41591-024-03351-6. Epub 2025 Jan 28.
- Background: PubMed 36895446Frisoni GB, Altomare D, Ribaldi F, Villain N, Brayne C, Mukadam N, Abramowicz M, Barkhof F, Berthier M, Bieler-Aeschlimann M, Blennow K, Brioschi Guevara A, Carrera E, Chetelat G, Csajka C, Demonet JF, Dodich A, Garibotto V, Georges J, Hurst S, Jessen F, Kivipelto M, Llewellyn DJ, McWhirter L, Milne R, Minguillon C, Miniussi C, Molinuevo JL, Nilsson PM, Noyce A, Ranson JM, Grau-Rivera O, Schott JM, Solomon A, Stephen R, van der Flier W, van Duijn C, Vellas B, Visser LNC, Cummings JL, Scheltens P, Ritchie C, Dubois B. Dementia prevention in memory clinics: recommendations from the European task force for brain health services. Lancet Reg Health Eur. 2023 Jan 31;26:100576. doi: 10.1016/j.lanepe.2022.100576. eCollection 2023 Mar.
- Background: PubMed 39574193Rosenberg A, Untersteiner H, Guazzarini AG, Bodenler M, Bruinsma J, Buchgraber-Schnalzer B, Colombo M, Crutzen R, Diaz A, Fotiadis DI, Hilberger H, Huber S, Kaartinen N, Kassiotis T, Kivipelto M, Lehtisalo J, Loukas VS, Lotjonen J, Pirani M, Thunborg C, Hanke S, Mangialasche F, Mecocci P, Stogmann E, Ngandu T; on behaf of the LETHE Consortium. A digitally supported multimodal lifestyle program to promote brain health among older adults (the LETHE randomized controlled feasibility trial): study design, progress, and first results. Alzheimers Res Ther. 2024 Nov 21;16(1):252. doi: 10.1186/s13195-024-01615-4.
- Background: PubMed 39096926Livingston G, Huntley J, Liu KY, Costafreda SG, Selbaek G, Alladi S, Ames D, Banerjee S, Burns A, Brayne C, Fox NC, Ferri CP, Gitlin LN, Howard R, Kales HC, Kivimaki M, Larson EB, Nakasujja N, Rockwood K, Samus Q, Shirai K, Singh-Manoux A, Schneider LS, Walsh S, Yao Y, Sommerlad A, Mukadam N. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024 Aug 10;404(10452):572-628. doi: 10.1016/S0140-6736(24)01296-0. Epub 2024 Jul 31. No abstract available.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (including baseline characteristics, primary and key secondary outcomes) underlying the main published results will be made available to qualified researchers upon reasonable request, after approval by the sponsor and the relevant ethics committees.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing A tailored hybrid multidomain lifestyle intervention group and Self-guided multimodal lifestyle advice group in people with Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD), run by Medical University of Vienna at 3 sites in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Niklas Rast (+4915154733860, niklas.rast@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Operational feasibility: retention rate (time frame: Baseline to 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07376135, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2026.