An interventional study of A tailored hybrid multidomain lifestyle intervention group and Self-guided multimodal lifestyle advice group in Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD), sponsored by Medical University of Vienna. Not yet recruiting at 3 sites in Austria. Open to participants aged 55 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-01-29.
Sponsored by Medical University of Vienna · Not applicable, Interventional, and Prevention
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:
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:
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.
3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.
This study's planned enrollment of 300 is above the median of 64 across 2,794 interventional studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →Medical University of Vienna is the lead sponsor of 1,109 studies on the registry; 184 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Behavioral: Self-guided multimodal lifestyle advice group
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.
Behavioral: A tailored hybrid multidomain lifestyle intervention group
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.
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.
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).
Time frame: 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).
Time frame: Continuously assessed over 18 months
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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: Baseline, Month 9, 18 months
Change in global cognition assessed with the modified Neuropsychological Test Battery (mNTB)
All test raw scores are converted to z-scores (baseline mean = 0, SD = 1, with sign reversal where lower times indicate better performance): Wechsler Memory Scale - Fourth Edition (WMS-IV) Logical Memory (immediate and delayed recall, recognition) Rey Auditory Verbal Learning Test (RAVLT / VLMT; list learning, immediate and delayed recall, recognition) Rey-Osterrieth Complex Figure Test (copy, 3-minute and 30-minute delayed recall) Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Digit Span (forward, backward, sequencing) Test of Attentional Performance (TAP) - Alertness Test of Attentional Performance (TAP) - Divided Attention WAIS-IV Digit Symbol Substitution Test (DSST) Trail Making Test (TMT) Part A Trail Making Test (TMT) Part B (shitime B-A) Regensburg Word Fluency Test (semantic: animals; phonemic: letter P) Colour-Word Interference Test (German Stroop; colour naming, word reading, interference condition)
Time frame: Baseline (Month 0) to Month 18.
Change in dementia risk: LIBRA2
Change in dementia risk estimated with the Lifestyle for Brain Health index (LIBRA2; theoretical range -5.9 to +12.7; higher scores = less healthy lifestyle and higher estimated dementia risk).
Time frame: Baseline and Month 18.
Change in dementia risk: ANU-ADRI
Change in dementia risk estimated with the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI; theoretical range approximately -13 to +64; higher scores = higher estimated Alzheimer's disease risk).
Time frame: Baseline and Month 18.
Change in physical activity (German-PAQ)
Change in self-reported physical activity assessed with the Short German Physical Activity Questionnaire (German-PAQ; minutes per week of moderate-to-vigorous activity; higher values = more physical activity).
Time frame: Baseline, Month 9, Month 18.
Change in depressive symptoms (SDS)
Change in depressive symptoms assessed with the Zung Self-Rating Depression Scale (SDS; 20-80 points; higher scores = more depressive symptom burden).
Time frame: Baseline, Month 9, Month 18
Change in Mediterranean diet adherence (MEDAS)
Change in diet quality assessed with the 14-Item Mediterranean Diet Adherence Screener (MEDAS; 0-14 points; higher scores = better adherence to a Mediterranean-style diet).
Time frame: Baseline, Month 9, Month 18
Change in functional abilities (FAQ)
Change in instrumental activities of daily living assessed with the Functional Activities Questionnaire (FAQ; 0-30 points; higher scores = greater functional impairment in IADL).
Time frame: Baseline, Month 9, Month 18
Change in social engagement (LSNS-6)
Change in social networks assessed with the Lubben Social Network Scale-6 (LSNS-6; 0-30 points; higher scores = larger and more supportive social network).
Time frame: Baseline, Month 9, Month 18
Change in cognitive reserve (CRQi)
Change in cognitive reserve assessed with the Cognitive Reserve questionnaire index. (higher scores = greater lifetime cognitive reserve from education and stimulating activities)
Time frame: Baseline, Month 9, Month 18
Change in physical functioning (SPPB and grip strength)
Change in lower-extremity function assessed with the Short Physical Performance Battery (SPPB; 0-12 points; higher scores = better balance, gait and chair-rise performance) and change in hand grip strength measured in kilograms with a dynamometer.
Time frame: Baseline, Month 9, Month 18
Change in smoking dependence (FTND)
Change in nicotine dependence among current smokers assessed with the Fagerström Test for Nicotine Dependence (FTND; 0-10 points; higher scores = stronger nicotine dependence).
Time frame: Baseline, Month 9, Month 18
Change in alcohol consumption (AUDIT-C)
Change in alcohol use assessed with the Alcohol Use Disorders Identification Test - Consumption subscale (AUDIT-C; 0-12 points; higher scores = higher risk of hazardous drinking).
Time frame: Baseline, Month 9, Month 18
Change in AD-related blood biomarkers
Change in plasma Aβ42/40 ratio, phosphorylated tau (e.g. p-tau217) and neurofilament light chain (NfL) as markers of Alzheimer-related and neuroaxonal pathology (higher levels = greater pathology).
Time frame: Baseline and Month 18 (subsample).
Ten-year cardiovascular disease risk (Framingham Risk Score)
Change in 10-year cardiovascular risk estimated using the Framingham Risk Score (percentage probability based on age, blood pressure, lipids, smoking and diabetes status; higher values = higher predicted CVD risk).
Time frame: Baseline and Month 18.
Change in attitudes towards dementia risk reduction (selected MCLHB-DRR items)
Change in participants' motivation, perceived benefits, and perceived personal relevance of dementia risk reduction, assessed with selected items from the MCLHB-DRR scale (higher scores indicating more positive attitudes towards adopting risk-reducing behaviours).
Time frame: Baseline, 9 Months, 18 Months
Change in hippocampal volume (MRI)
Change in hippocampal volume measured on high resolution structural MRI.
Time frame: Near Baseline and near Month 18 (±2 months; optional MRI sub study)
Change in cortical thickness (MRI)
Change in cortical thickness measured on high resolution structural MRI.
Time frame: Near Baseline and near Month 18 (±2 months; optional MRI sub study)
Change in white matter integrity (MRI)
Change in white matter integrity measured on diffusion weighted MRI.
Time frame: Near Baseline and near Month 18 (±2 months; optional MRI sub study)
Change in resting state connectivity indices (MRI)
Change in resting state connectivity indices measured on resting state functional MRI.
Time frame: Near Baseline and near Month 18 (±2 months; optional MRI sub study)
Change in resting heart rate (Continuously)
Change in resting heart rate derived from continuous wrist photoplethysmography recorded day and night by the Garmin Vivosmart 5 smartwatch.
Time frame: Continuously for 18 months.
Change in Sleep Score (Continuously)
Change in Sleep Score derived from wearable identified sleep stages combined into a single Sleep Score (Garmin Vivosmart 5).
Time frame: Continuously for 18 months.
Change in minutes of moderate to vigorous activity (Continuously)
Change in minutes of moderate to vigorous activity captured by the Garmin Vivosmart 5 smartwatch.
Time frame: Continuously for 18 months.
Plan to share: 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.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Analytic code
Time frame: IPD and supporting information will be made available after publication of the primary results for a limited period to be specified in the final data sharing policy.
Access criteria: Access will be granted to qualified researchers upon reasonable request and subject to sponsor and ethics committee approval, according to the final data sharing policy.
Data sharing details ↗ · www.lethe.at
Start is estimated for Jan 2026; primary completion for Oct 2027, 20 months later.
Of 1,442 non-industry interventional studies with no phase under Cognitive Dysfunction, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 51. This study's planned 20 months is below that.
Counting every sponsor, half of 1,511 studies reached it within 27 months; a quarter within 12 and three quarters within 50.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.
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