Using Metformin and Lifestyle Changes to Prevent Dementia in Older Adults

Multimodal METformin and FINGER Lifestyle Intervention to Prevent Cognitive Impairment and Disability in Older Adults at Risk for Dementia: a Phase IIb Multi-national Randomised, Controlled Trial

This study is testing if combining the diabetes drug metformin with healthy lifestyle changes can help older adults aged 60-79 lower their risk of developing dementia.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 600 (estimated)
• Ages: 60 Years to 79 Years
• Sex: All
• Sponsor: Imperial College London (Academic / other)
• Drugs / interventions: aducanumab
• Locations: 3 sites (Helsinki and 2 other locations)
• Trial ID: NCT05109169 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of the FINGER 2.0 multidomain intervention, which combines healthy lifestyle changes with the diabetes drug metformin, in reducing the risk of dementia among older adults. Participants aged 60-79 with specific cognitive and cardiovascular risk factors will be randomized into either the FINGER 2.0 intervention group or a self-guided lifestyle intervention group. The primary objective is to assess changes in cognitive function through a series of neuropsychological tests, while secondary objectives include evaluating individual cognitive domains and overall functioning. Data collection will include personal health information and blood samples to explore interactions between metformin and lifestyle changes.

Who should consider this trial

Good fit: Ideal candidates are older adults aged 60-79 with cardiovascular risk factors and mild cognitive impairment.

Not a fit: Patients with diagnosed dementia or significant cognitive impairment will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the risk of dementia and improve the quality of life for older adults at risk.

How similar studies have performed: Previous studies have shown promise in using lifestyle interventions for dementia prevention, but the combination with metformin is a novel approach.

Eligibility criteria

Inclusion Criteria:

* Main inclusion criteria (all participants)

  1. Age 60-79 years.
  2. Cardiovascular Risk Factors, Aging and Dementia (CAIDE) Risk Score ≥6 points.
  3. Cognitive performance at the mean level or slightly lower than expected for age according to local population norms based on the Montreal Cognitive Assessment (MoCA) test and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) verbal learning test.
  4. Proficiency in the local language (English, Finnish or Swedish)
* Inclusion criteria for metformin/placebo treatment (only for participants in the FINGER 2.0 multimodal lifestyle-based intervention arm)

  1. No diagnosed diabetes or known contraindications to metformin treatment.
  2. Elevated adiposity (BMI≥25 kg/m2 OR waist circumference \> 102 cm in men and \> 88 cm in women) OR mildly impaired fasting glucose (6.1-6.9 mmol/l).

Exclusion Criteria:

* Main exclusion criteria (all participants)

  1. Dementia or substantial cognitive impairment (e.g., memory clinic referral needed as judged by the study physician).
  2. Current or past use of medications for Alzheimer's Disease or related diseases (e.g., cholinesterase inhibitors, memantine, aducanumab).
  3. Diminished decision-making capacity, not capable of consenting or completing study assessments, based on clinical judgement.
  4. Other known significant neurologic disease (including e.g., Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, brain tumour, progressive, supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent neurologic sequelae or known structural brain abnormalities).
  5. Any other condition affecting safe engagement in the intervention (e.g., malignant disease, major depression, symptomatic cardiovascular disease, revascularisation within the previous year).
  6. Severe loss of vision, hearing, or communicative ability; conditions preventing cooperation.
  7. Coincident participation in the active phase of another intervention trial.
  8. A member of the household already enrolled in the MET-FINGER trial
* Exclusion criteria for metformin/placebo treatment (only for participants in the FINGER 2.0 multimodal lifestyle-based intervention group)

  1. Use of metformin for any indication.
  2. History of intolerance to metformin used for any indication.
  3. Diabetes diagnosed or suspected at baseline (e.g., HbA1c≥6.5%, fasting glucose ≥7 mmol/l, or 2HPG≥11.1 mmol/l).
  4. Metformin contraindications, e.g., history/presence of known renal or liver disease, congestive heart failure, alcohol abuse, calculated Glomerular Filtration Rate\<60 ml/min.

Where this trial is running

Helsinki and 2 other locations

• Finnish Institute of Health and Welfare - THL — Helsinki, Finland (Recruiting)
• Karolinska Institutet — Solna, Sweden (Recruiting)
• Ageing Epidemiology Research Unit, Imperial College London — London, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Tiia Ngandu, MD, PhD — Finnish Institute of Health and Welfare, Finland
• Study coordinator: Miia Kivipelto, MD, PhD

Conditions Cognitive Decline; Cognitive Impairment; Dementia; Dementia prevention; FINGER multidomain lifestyle intervention; Metformin; World-Wide FINGERs; Drug repurposing