A multidomain intervention against cognitive decline in an at-risk-population in Germany: Results from the cluster-randomized AgeWell.de trial.

Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024;20(1):615-628

Plain language summary

Due to ageing populations, there is a rapid increase in people living with dementia. A number of modifiable risk factors have been identified, including obesity, excessive alcohol consumption, diabetes mellitus, depression, physical inactivity, smoking and social isolation. The aim of this cluster-randomised controlled trial, including 1030 participants at risk of developing dementia aged 60-77, was to evaluate the effectiveness of a multidomain intervention which included optimisation of nutrition and medication, and physical, social, and cognitive activity for two years compared to standard care. There was no benefit of the intervention for the primary outcome global cognitive performance. The intervention had a positive effect on the secondary outcome health-related quality of life but did not have any significant effect on quality of life, depressive symptoms, social inclusion, activities of daily living and instrumental activities of daily living. The study period coincided with the COVID-19 pandemic. Significantly more participants than controls reported perceived COVID-19-related restrictions with regards to nutrition, whilst there was no such differences between groups for physical, cognitive or social activity. Better adherence to the nutrition and social activity components of the programme were associated with better global cognitive performance, whilst there was no association with physical and cognitive activity.

Expert Review

Conflicts of interest: None

Take Home Message:
  • Nutrition counselling based on the guidelines of the German Society for Nutrition, in association with other lifestyle counselling and optimisation of medication, does not improve GCP.

Evidence Category:
  • X A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
  • B: Systematic reviews including RCTs of limited number
  • C: Non-randomized trials, observational studies, narrative reviews
  • D: Case-reports, evidence-based clinical findings
  • E: Opinion piece, other

Summary Review:

The aim of this study was to evaluate the effectiveness of the AgeWell.de programme which targets modifiable risk factors for dementia.


  • Cluster-randomised, controlled trial (clustered by participating general practitioners).
  • Intervention: nutritional counselling (based on the guidelines by the German Society for Nutrition), enhancement of physical and social activity, cognitive training, and the management of cardiovascular risk factors (overweight, smoking). Baseline individual face-to-face session with study nurse, followed by contact with the nurse after 2, 4 and 8 months, second face-to-face session with the nurse at 12 months and further contacts at 16 and 20 months. Endpoint assessments at 24 months.
  • Controls: standard care.
  • Sample size: 1030 adults aged 60-77 at increased risk of dementia, of which 819 completed the study and were included in the analysis.
  • Primary outcome: global cognitive performance (GCP)
  • Secondary outcomes: mortality, nursing home placement, activities of daily living (ADL), instrumental activities of daily living (IADL), quality of life (QOL), health-related (QOL), depressive symptoms, and social inclusion.


  • No significant difference in GCP, p=0.874. No difference in ADL (p=0.374), IADL (p=0.746), QOL (p=0.964), depressive symptoms (p=0.090) and social inclusion (p=0.495).
  • Improvement in health-related QOL (AME = 0.198, 95% CI: 0.069, 0.328, p=0.003).
  • Results for mortality and nursing home placement are not reported.
  • Part of the study took place during the COVID-19 pandemic. More participants (9%) than controls (3.7%) reported perceived COVID-19-related restrictions with regards to nutrition (p=0.004). No such difference was observed for perceived restrictions regarding physical activity (p=0.328), cognitive activity (p=0.262) or social activity (p=0.192).


  • The authors concluded that the multidomain intervention had no beneficial effects on GCP and that higher-intensity interventions and more ambitious goals may be needed.

Clinical practice applications:
  • Nutrition counselling based on the guidelines of the German Society for Nutrition, in association with other lifestyle counselling and optimisation of medication, does not improve GCP.

Considerations for future research:
  • Studies using more intensive and individualised interventions may evaluate whether such strategies are more beneficial for improving GCP.
  • Studies of specific subgroups, e.g. based on lifestyle or medical risk factors, may help find more specific populations and interventions to help improve GCP.


INTRODUCTION We investigated the effectiveness of a multidomain intervention to preserve cognitive function in older adults at risk for dementia in Germany in a cluster-randomized trial. METHODS Individuals with a Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score ≥ 9 aged 60 to 77 years were recruited. After randomization of their general practitioner (GP), patients received a multidomain intervention (including optimization of nutrition and medication, and physical, social, and cognitive activity) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance (composite z score, based on domain-specific neuropsychological tests). RESULTS Of 1030 participants at baseline, n = 819 completed the 24-month follow-up assessment. No differences regarding global cognitive performance (average marginal effect = 0.010, 95% confidence interval: -0.113, 0.133) were found between groups at follow-up. Perceived restrictions in intervention conduct by the COVID-19 pandemic did not impact intervention effectiveness. DISCUSSION The intervention did not improve global cognitive performance. HIGHLIGHTS Overall, no intervention effects on global cognitive performance were detected. The multidomain intervention improved health-related quality of life in the total sample. In women, the multidomain intervention reduced depressive symptoms. The intervention was completed during the COVID-19 pandemic.

Lifestyle medicine

Fundamental Clinical Imbalances : Neurological
Patient Centred Factors : Antecedents/Ageing
Environmental Inputs : Diet ; Psychosocial influences
Personal Lifestyle Factors : Nutrition ; Psychological
Functional Laboratory Testing : Not applicable

Methodological quality

Jadad score : 3
Allocation concealment : Not applicable