Mechanisms of interventions targeting modifiable factors for dementia risk reduction

The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia, exploring preventative strategies is critical. Lifestyle-based interventions show promise in preventing or delaying dementia onset. However, understandi...

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Published in:Molecular neurodegeneration Vol. 20; no. 1; pp. 75 - 22
Main Authors: Matton, Anna, Stephen, Ruth, Daniilidou, Makrina, Barbera, Mariagnese, Alanko, Vilma, Ballin, Marcel, Ford, Jamie, Hemiö, Katri, Lehtisalo, Jenni, Rocha, Sabsil López, Mangialasche, Francesca, Ngandu, Tiia, Rosenberg, Anna, Saadmaan, Gazi, Udeh-Momoh, Chinedu, Uusimäki, Kerttu, Solomon, Alina, Kivipelto, Miia
Format: Journal Article
Language:English
Published: London BioMed Central 23.06.2025
BioMed Central Ltd
BMC
Subjects:
Alzheimer's disease
Biomarkers - metabolism
Biomedical and Life Sciences
Biomedicine
Dementia - prevention & control
Development and progression
Exercise - physiology
Humans
Life Style
Molecular Medicine
Neurology
Neurosciences
Review
Risk Factors
Risk Reduction Behavior
ISSN:1750-1326, 1750-1326
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Abstract The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia, exploring preventative strategies is critical. Lifestyle-based interventions show promise in preventing or delaying dementia onset. However, understanding the complex and multifactorial mechanisms underlying dementia, and how interventions target these pathways, is essential for developing personalized and effective strategies. In this review, we examined the current evidence of the mediating pathways in dementia risk reduction. We focused on mechanisms investigated in single-domain interventions on physical exercise, cognitive training, diet, metabolic/cardiovascular or psycho-social risk factors in line with those combined in the landmark FINGER trial. Additionally, we synthesized existing literature on mechanisms of action in multimodal interventions combining multiple lifestyle changes. Most evidence was identified in relation to neuroimaging biomarkers with positive effects for all intervention components. The evidence among fluid biomarkers of Alzheimer’s disease and related disorders (ADRD) (amyloid-beta peptide (Aβ), tau and neurofilament light chain (Nfl)) vascular markers, inflammatory markers, and neurotrophins were less conclusive, though physical exercise consistently appeared to impact several of these pathways. The findings of this review underscore the potential of lifestyle-based interventions in modulating several different types of pathophysiological pathways associated with dementia. As the number of dementia cases reach epidemic proportions, a multifaceted approach is needed. We propose that the next critical step in dementia prevention/risk reduction is to refine existing intervention tools and develop an adaptive platform that integrates different lifestyle interventions tailored to individual risk profiles and needs. Understanding the underlying mechanisms and biomarkers related to modifiable risk factors will be instrumental to optimising these interventions.
AbstractList Abstract The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia, exploring preventative strategies is critical. Lifestyle-based interventions show promise in preventing or delaying dementia onset. However, understanding the complex and multifactorial mechanisms underlying dementia, and how interventions target these pathways, is essential for developing personalized and effective strategies. In this review, we examined the current evidence of the mediating pathways in dementia risk reduction. We focused on mechanisms investigated in single-domain interventions on physical exercise, cognitive training, diet, metabolic/cardiovascular or psycho-social risk factors in line with those combined in the landmark FINGER trial. Additionally, we synthesized existing literature on mechanisms of action in multimodal interventions combining multiple lifestyle changes. Most evidence was identified in relation to neuroimaging biomarkers with positive effects for all intervention components. The evidence among fluid biomarkers of Alzheimer’s disease and related disorders (ADRD) (amyloid-beta peptide (Aβ), tau and neurofilament light chain (Nfl)) vascular markers, inflammatory markers, and neurotrophins were less conclusive, though physical exercise consistently appeared to impact several of these pathways. The findings of this review underscore the potential of lifestyle-based interventions in modulating several different types of pathophysiological pathways associated with dementia. As the number of dementia cases reach epidemic proportions, a multifaceted approach is needed. We propose that the next critical step in dementia prevention/risk reduction is to refine existing intervention tools and develop an adaptive platform that integrates different lifestyle interventions tailored to individual risk profiles and needs. Understanding the underlying mechanisms and biomarkers related to modifiable risk factors will be instrumental to optimising these interventions.
The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia, exploring preventative strategies is critical. Lifestyle-based interventions show promise in preventing or delaying dementia onset. However, understanding the complex and multifactorial mechanisms underlying dementia, and how interventions target these pathways, is essential for developing personalized and effective strategies. In this review, we examined the current evidence of the mediating pathways in dementia risk reduction. We focused on mechanisms investigated in single-domain interventions on physical exercise, cognitive training, diet, metabolic/cardiovascular or psycho-social risk factors in line with those combined in the landmark FINGER trial. Additionally, we synthesized existing literature on mechanisms of action in multimodal interventions combining multiple lifestyle changes. Most evidence was identified in relation to neuroimaging biomarkers with positive effects for all intervention components. The evidence among fluid biomarkers of Alzheimer’s disease and related disorders (ADRD) (amyloid-beta peptide (Aβ), tau and neurofilament light chain (Nfl)) vascular markers, inflammatory markers, and neurotrophins were less conclusive, though physical exercise consistently appeared to impact several of these pathways. The findings of this review underscore the potential of lifestyle-based interventions in modulating several different types of pathophysiological pathways associated with dementia. As the number of dementia cases reach epidemic proportions, a multifaceted approach is needed. We propose that the next critical step in dementia prevention/risk reduction is to refine existing intervention tools and develop an adaptive platform that integrates different lifestyle interventions tailored to individual risk profiles and needs. Understanding the underlying mechanisms and biomarkers related to modifiable risk factors will be instrumental to optimising these interventions.
The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia, exploring preventative strategies is critical. Lifestyle-based interventions show promise in preventing or delaying dementia onset. However, understanding the complex and multifactorial mechanisms underlying dementia, and how interventions target these pathways, is essential for developing personalized and effective strategies. In this review, we examined the current evidence of the mediating pathways in dementia risk reduction. We focused on mechanisms investigated in single-domain interventions on physical exercise, cognitive training, diet, metabolic/cardiovascular or psycho-social risk factors in line with those combined in the landmark FINGER trial. Additionally, we synthesized existing literature on mechanisms of action in multimodal interventions combining multiple lifestyle changes. Most evidence was identified in relation to neuroimaging biomarkers with positive effects for all intervention components. The evidence among fluid biomarkers of Alzheimer's disease and related disorders (ADRD) (amyloid-beta peptide (A beta), tau and neurofilament light chain (Nfl)) vascular markers, inflammatory markers, and neurotrophins were less conclusive, though physical exercise consistently appeared to impact several of these pathways. The findings of this review underscore the potential of lifestyle-based interventions in modulating several different types of pathophysiological pathways associated with dementia. As the number of dementia cases reach epidemic proportions, a multifaceted approach is needed. We propose that the next critical step in dementia prevention/risk reduction is to refine existing intervention tools and develop an adaptive platform that integrates different lifestyle interventions tailored to individual risk profiles and needs. Understanding the underlying mechanisms and biomarkers related to modifiable risk factors will be instrumental to optimising these interventions.
The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia, exploring preventative strategies is critical. Lifestyle-based interventions show promise in preventing or delaying dementia onset. However, understanding the complex and multifactorial mechanisms underlying dementia, and how interventions target these pathways, is essential for developing personalized and effective strategies. In this review, we examined the current evidence of the mediating pathways in dementia risk reduction. We focused on mechanisms investigated in single-domain interventions on physical exercise, cognitive training, diet, metabolic/cardiovascular or psycho-social risk factors in line with those combined in the landmark FINGER trial. Additionally, we synthesized existing literature on mechanisms of action in multimodal interventions combining multiple lifestyle changes. Most evidence was identified in relation to neuroimaging biomarkers with positive effects for all intervention components. The evidence among fluid biomarkers of Alzheimer's disease and related disorders (ADRD) (amyloid-beta peptide (Aβ), tau and neurofilament light chain (Nfl)) vascular markers, inflammatory markers, and neurotrophins were less conclusive, though physical exercise consistently appeared to impact several of these pathways. The findings of this review underscore the potential of lifestyle-based interventions in modulating several different types of pathophysiological pathways associated with dementia. As the number of dementia cases reach epidemic proportions, a multifaceted approach is needed. We propose that the next critical step in dementia prevention/risk reduction is to refine existing intervention tools and develop an adaptive platform that integrates different lifestyle interventions tailored to individual risk profiles and needs. Understanding the underlying mechanisms and biomarkers related to modifiable risk factors will be instrumental to optimising these interventions.The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia, exploring preventative strategies is critical. Lifestyle-based interventions show promise in preventing or delaying dementia onset. However, understanding the complex and multifactorial mechanisms underlying dementia, and how interventions target these pathways, is essential for developing personalized and effective strategies. In this review, we examined the current evidence of the mediating pathways in dementia risk reduction. We focused on mechanisms investigated in single-domain interventions on physical exercise, cognitive training, diet, metabolic/cardiovascular or psycho-social risk factors in line with those combined in the landmark FINGER trial. Additionally, we synthesized existing literature on mechanisms of action in multimodal interventions combining multiple lifestyle changes. Most evidence was identified in relation to neuroimaging biomarkers with positive effects for all intervention components. The evidence among fluid biomarkers of Alzheimer's disease and related disorders (ADRD) (amyloid-beta peptide (Aβ), tau and neurofilament light chain (Nfl)) vascular markers, inflammatory markers, and neurotrophins were less conclusive, though physical exercise consistently appeared to impact several of these pathways. The findings of this review underscore the potential of lifestyle-based interventions in modulating several different types of pathophysiological pathways associated with dementia. As the number of dementia cases reach epidemic proportions, a multifaceted approach is needed. We propose that the next critical step in dementia prevention/risk reduction is to refine existing intervention tools and develop an adaptive platform that integrates different lifestyle interventions tailored to individual risk profiles and needs. Understanding the underlying mechanisms and biomarkers related to modifiable risk factors will be instrumental to optimising these interventions.
ArticleNumber 75
Audience Academic
Author Matton, Anna
Hemiö, Katri
Mangialasche, Francesca
Udeh-Momoh, Chinedu
Kivipelto, Miia
Solomon, Alina
Rosenberg, Anna
Rocha, Sabsil López
Ballin, Marcel
Lehtisalo, Jenni
Saadmaan, Gazi
Barbera, Mariagnese
Stephen, Ruth
Ngandu, Tiia
Alanko, Vilma
Uusimäki, Kerttu
Daniilidou, Makrina
Ford, Jamie
Author_xml – sequence: 1
  givenname: Anna
  orcidid: 0000-0002-7819-0495
  surname: Matton
  fullname: Matton, Anna
  email: anna.matton@ki.se
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Ageing Epidemiology (AGE) Research Unit, SchoolofPublicHealth, Imperial College London, FINGERs Brain Health Institute
– sequence: 2
  givenname: Ruth
  orcidid: 0000-0002-3380-9530
  surname: Stephen
  fullname: Stephen, Ruth
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, FINGERs Brain Health Institute
– sequence: 3
  givenname: Makrina
  orcidid: 0000-0002-5460-9802
  surname: Daniilidou
  fullname: Daniilidou, Makrina
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, FINGERs Brain Health Institute
– sequence: 4
  givenname: Mariagnese
  orcidid: 0000-0002-8983-1294
  surname: Barbera
  fullname: Barbera, Mariagnese
  organization: Ageing Epidemiology (AGE) Research Unit, SchoolofPublicHealth, Imperial College London, Institute of Clinical Medicine/Neurology, University of Eastern Finland
– sequence: 5
  givenname: Vilma
  orcidid: 0000-0001-9918-9429
  surname: Alanko
  fullname: Alanko, Vilma
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, FINGERs Brain Health Institute
– sequence: 6
  givenname: Marcel
  orcidid: 0000-0002-9638-7208
  surname: Ballin
  fullname: Ballin, Marcel
  organization: Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University
– sequence: 7
  givenname: Jamie
  surname: Ford
  fullname: Ford, Jamie
  organization: Ageing Epidemiology (AGE) Research Unit, SchoolofPublicHealth, Imperial College London
– sequence: 8
  givenname: Katri
  surname: Hemiö
  fullname: Hemiö, Katri
  organization: Department of Public Health, The Lifestyles and Living Environments Unit, Finnish Institute for Health and Welfare
– sequence: 9
  givenname: Jenni
  orcidid: 0000-0002-8818-0848
  surname: Lehtisalo
  fullname: Lehtisalo, Jenni
  organization: Department of Public Health, The Lifestyles and Living Environments Unit, Finnish Institute for Health and Welfare, Institute of Public Health and Clinical Nutrition, University of Eastern Finland
– sequence: 10
  givenname: Sabsil López
  orcidid: 0009-0007-5435-6773
  surname: Rocha
  fullname: Rocha, Sabsil López
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet
– sequence: 11
  givenname: Francesca
  orcidid: 0000-0002-2686-3926
  surname: Mangialasche
  fullname: Mangialasche, Francesca
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, FINGERs Brain Health Institute, Theme Inflammation and Aging, Karolinska University Hospital
– sequence: 12
  givenname: Tiia
  orcidid: 0000-0002-3698-2021
  surname: Ngandu
  fullname: Ngandu, Tiia
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Department of Public Health, The Lifestyles and Living Environments Unit, Finnish Institute for Health and Welfare, Institute of Public Health and Clinical Nutrition, University of Eastern Finland
– sequence: 13
  givenname: Anna
  orcidid: 0000-0003-1456-7991
  surname: Rosenberg
  fullname: Rosenberg, Anna
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Institute of Clinical Medicine/Neurology, University of Eastern Finland, Department of Public Health, The Lifestyles and Living Environments Unit, Finnish Institute for Health and Welfare
– sequence: 14
  givenname: Gazi
  orcidid: 0000-0002-0925-7609
  surname: Saadmaan
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  organization: Institute of Clinical Medicine/Neurology, University of Eastern Finland
– sequence: 15
  givenname: Chinedu
  orcidid: 0000-0002-7357-4692
  surname: Udeh-Momoh
  fullname: Udeh-Momoh, Chinedu
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, School of Public Health Sciences, Wake Forest University School of Medicine, Brain and Mind Institute, Aga Khan University, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield
– sequence: 16
  givenname: Kerttu
  orcidid: 0000-0002-2090-5291
  surname: Uusimäki
  fullname: Uusimäki, Kerttu
  organization: Department of Public Health, The Lifestyles and Living Environments Unit, Finnish Institute for Health and Welfare, Institute of Public Health and Clinical Nutrition, University of Eastern Finland
– sequence: 17
  givenname: Alina
  orcidid: 0000-0002-7166-9903
  surname: Solomon
  fullname: Solomon, Alina
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Ageing Epidemiology (AGE) Research Unit, SchoolofPublicHealth, Imperial College London, FINGERs Brain Health Institute, Institute of Clinical Medicine/Neurology, University of Eastern Finland
– sequence: 18
  givenname: Miia
  orcidid: 0000-0003-0992-3875
  surname: Kivipelto
  fullname: Kivipelto, Miia
  email: miia.kivipelto@ki.se
  organization: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Ageing Epidemiology (AGE) Research Unit, SchoolofPublicHealth, Imperial College London, FINGERs Brain Health Institute, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Theme Inflammation and Aging, Karolinska University Hospital
BackLink https://www.ncbi.nlm.nih.gov/pubmed/40551205$$D View this record in MEDLINE/PubMed
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-563488$$DView record from Swedish Publication Index (Uppsala universitet)
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Snippet The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia, exploring...
Abstract The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia,...
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SubjectTerms Alzheimer's disease
Biomarkers - metabolism
Biomedical and Life Sciences
Biomedicine
Dementia - prevention & control
Development and progression
Exercise - physiology
Humans
Life Style
Molecular Medicine
Neurology
Neurosciences
Review
Risk Factors
Risk Reduction Behavior
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Title Mechanisms of interventions targeting modifiable factors for dementia risk reduction
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