LETHE-AT: a Personalized Multidomain Lifestyle Intervention for Individuals at Increased Risk of Memory Impairment.

NCT07376135 | Not Yet Recruiting

• 2 other identifiers: MUW EK Nr: 1792/202558285128 / 921935
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Mild Cognitive Impairment (MCI); Subjective Cognitive Decline (SCD)

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); telemedicine; Alzheimer Disease; Cognition Disorders; mild cognitive impairment; multimodal intervention; multicomponent intervention; motivational interviewing; health coaching; mHealth; eHealth

Outcome Measures

Primary Outcomes (2)

• 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).

  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).

  Continuously assessed over 18 months

Secondary Outcomes (5)

• Change in health-related quality of life (SF-36)

  Baseline to 18 months

• Change in health literacy (HLS-EU-Q16)

  Baseline to 18 months

• User acceptance of the digital solution (SUS)

  2 months past enrollment to 18 months

• Change in perceived stress (PSS-14)

  Baseline, Month 9, 18 months.

• Change in insomnia symptoms (ISI)

  Baseline, Month 9, 18 months

Other Outcomes (22)

• Change in global cognition assessed with the modified Neuropsychological Test Battery (mNTB)

  Baseline (Month 0) to Month 18.

• Change in dementia risk: LIBRA2

  Baseline and Month 18.

• Change in dementia risk: ANU-ADRI

  Baseline and Month 18.

Study Arms (2)

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.

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.

Behavioral: A tailored hybrid multidomain lifestyle intervention group

Interventions

A tailored hybrid multidomain lifestyle intervention group BEHAVIORAL

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.

A tailored hybrid multidomain lifestyle intervention group

Self-guided multimodal lifestyle advice group BEHAVIORAL

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.

A self-guided multimodal lifestyle advice group

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University Innsbruck: collaborator
• Austrian Research Promotion Agency: collaborator
• Medical University of Vienna: lead
• Medical University of Graz: collaborator
• FH Joanneum Gesellschaft mbH: collaborator

Study Sites (3)

Medical University of Innsbruck

Graz, Styria, 8010, Austria

Location

Medical University of Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Medical University of Vienna

Vienna, Austria

Location

Related Publications (6)

• 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.

  PMID: 23332672 BACKGROUND

• Yaffe 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.

  PMID: 38010725 BACKGROUND

• Brodaty 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.

  PMID: 39875685 BACKGROUND

• Frisoni 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.

  PMID: 36895446 BACKGROUND

• Rosenberg 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.

  PMID: 39574193 BACKGROUND

• Livingston 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.

  PMID: 39096926 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Motor Activity; Alzheimer Disease; Risk Reduction Behavior; Cognition Disorders

Condition Hierarchy (Ancestors)

Neurocognitive Disorders; Mental Disorders; Behavior; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Central Study Contacts

Niklas Rast

CONTACT

+4915154733860; niklas.rast@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants will not be actively told to what group they have been assigned (intervention or control). Outcome assessors will be blinded to the group allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician Investigator

Study Record Dates

• First Submitted: December 14, 2025
• First Posted: January 29, 2026
• Study Start: January 8, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: January 29, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

AU (3)