Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 May 14;37(1):151.
doi: 10.1007/s40520-025-03062-z.

Targeting brain health in subjective cognitive decline: insights from a multidomain randomized controlled trial

Elena Rolandi  1   2 , Alessandra Dodich  3 , Sara Mandelli  4 , Nicola Canessa  5   6 , Clarissa Ferrari  7 , Federica Ribaldi  8   9 , Giulio Munaretto  10 , Claudia Ambrosi  11 , Roberto Gasparotti  11 , Davide Violi  12 , Sandro Iannaccone  13 , Alessandra Marcone  13 , Andrea Falini  13   14 , Giovanni B Frisoni  8   9 , Samantha Galluzzi  15 , Chiara Cerami  5 , Enrica Cavedo  10
Affiliations
Randomized Controlled Trial

Targeting brain health in subjective cognitive decline: insights from a multidomain randomized controlled trial

Elena Rolandi et al. Aging Clin Exp Res. .

Abstract

Background: Multidomain lifestyle interventions are a promising approach to prevent cognitive decline, but their effects in subjective cognitive decline (SCD) remain controversial. We investigated the effects of lifestyle interventions on cognition and brain integrity in these at-risk individuals.

Methods: One-hundred twenty-eight older adults with SCD were randomly assigned to either Active Control Intervention (ACI), i.e. health education; Partial Intervention (PI), i.e. tramiprosate supplementation (100 mg/die) and dietary advice; or Multilevel Intervention (MI), i.e. PI plus computerized cognitive training and physical exercise, for one year. Neuropsychological assessment and MRI were performed at baseline and at 1-year follow-up. Analyses of covariance were used to measure the effects of interventions on predefined outcomes.

Results: The MI group significantly improved in attention-executive functioning (p = 0.003) compared to ACI (Cohen's d: 0.47, 95% CI 0.13-0.79). In addition, depressive symptoms (Cohen's d: - 0.48, 95% C.I. - 0.81 to - 0.14) and memory concerns (Cohen's d: - 0.77, 95% C.I. - 1.12 to - 0.41) decreased in the MI and PI respectively, relative to the ACI. The MI group also showed increased resting-state (i.e., intrinsic) brain activity in the right fronto-parietal executive network. No significant intervention effects on brain structural or vascular outcomes were found.

Conclusion: The study shows that a multidomain lifestyle intervention can enhance attention-executive function, ameliorate depressive symptoms and increase functional connectivity in SCD. These findings support the role of lifestyle interventions in public health strategies to mitigate cognitive decline risk.

Trial registration: The trial has been registered at the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on December 9th, 2017 ( https://www.

Clinicaltrials: gov/ct2/show/NCT03382353 ).

Keywords: Dementia prevention; Lifestyle; Multidomain interventions; Subjective cognitive decline; fMRI.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval and consent to participate: The study was performed in accordance with the guidelines of the Declaration of Helsinki. The study protocol was approved by the local ethics committees (Ethic Committee of the IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli and Ethic Committee of the San Raffaele hospital). Written informed consent was collected for all of the participants before screening evaluation. The principles of good clinical practice were observed in conducting the study.

Figures

Fig. 1
Fig. 1
CONSORT flowchart
Fig. 2
Fig. 2
Mean change and confidence interval (CI) in composite score of attention-executive functions from baseline to 12 months. Dark, grey, and dotted lines indicate Multiple Intervention (MI), Partial Intervention (PI), and Active Control Intervention (ACI), respectively
Fig. 3
Fig. 3
Mean change and confidence interval (CI) in depressive symptoms and memory complaints from baseline to 12 months. Dark, grey, and dotted lines indicate Multiple Intervention (MI), Partial Intervention (PI), and Active Control Intervention (ACI), respectively
Fig. 4
Fig. 4
Effect of the MI on the intensity of intrinsic brain activity in the middle-superior frontal sector of the right fronto-parietal executive network
See this image and copyright information in PMC

References

    1. World Health Organization and Alzheimer’s Disease International. Dementia: a public health priority 2012:112.
    1. Rolandi E, Zaccaria D, Vaccaro R et al (2020) Estimating the potential for dementia prevention through modifiable risk factors elimination in the real-world setting: A population-based study. Alzheimers Res Ther 12:94. 10.1186/s13195-020-00661-y - PMC - PubMed
    1. Livingston G, Huntley J, Liu KY et al (2024) Dementia prevention, intervention, and care: 2024 report of the lancet standing commission. Lancet. 10.1016/S0140-6736(24)01296-0 - PubMed
    1. Fratiglioni L, Marseglia A, Dekhtyar S (2020) Ageing without dementia: can stimulating psychosocial and lifestyle experiences make a difference? Lancet Neurol 19:533–543. 10.1016/S1474-4422(20)30039-9 - PubMed
    1. Kivipelto M, Mangialasche F, Ngandu T (2018) Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease. Nat Rev Neurol 14:653–666. 10.1038/s41582-018-0070-3 - PubMed

Publication types

Associated data