Association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathology

Abstract Background Dementia preventive interventions targeting multiple modifiable risk factors are a promising approach. However, the impact of modifiable risk factors in the presence of beta-amyloid or phosphorylated-tau (p-tau) pathology is unclear. Methods The objective of the study was to exam...

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Main Authors: Zsolt Huszár, Alina Solomon, Marie Anne Engh, Vanda Koszovácz, Tamás Terebessy, Zsolt Molnár, Péter Hegyi, András Horváth, Francesca Mangialasche, Miia Kivipelto, Gábor Csukly
Format: Article
Language:English
Published: BMC 2024-10-01
Series:Alzheimer’s Research & Therapy
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Online Access:https://doi.org/10.1186/s13195-024-01602-9
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author Zsolt Huszár
Alina Solomon
Marie Anne Engh
Vanda Koszovácz
Tamás Terebessy
Zsolt Molnár
Péter Hegyi
András Horváth
Francesca Mangialasche
Miia Kivipelto
Gábor Csukly
author_facet Zsolt Huszár
Alina Solomon
Marie Anne Engh
Vanda Koszovácz
Tamás Terebessy
Zsolt Molnár
Péter Hegyi
András Horváth
Francesca Mangialasche
Miia Kivipelto
Gábor Csukly
author_sort Zsolt Huszár
collection DOAJ
description Abstract Background Dementia preventive interventions targeting multiple modifiable risk factors are a promising approach. However, the impact of modifiable risk factors in the presence of beta-amyloid or phosphorylated-tau (p-tau) pathology is unclear. Methods The objective of the study was to examine the role of modifiable risk factors (vascular factors, depression, and smoking) in the progression to mild cognitive impairment (MCI) or dementia among 434 cognitively unimpaired (CU) and 611 individuals with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Vascular risk factors were summarized with the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score, dichotomized into higher versus lower risk. Depression and smoking (yes/no) were categorised according to medical history or current symptoms. Analyses were stratified by beta-amyloid negative (A-) and positive (A +), p-tau negative (T-) and positive (T +), or beta-amyloid and p-tau negative (A-T-) and positive (A + T +) biomarker status. Cox proportional hazard models were adjusted for age, sex, education, baseline MMSE score, baseline hippocampal volume and ApoE4 carrier status. Results Higher CAIDE score was associated with increased risk of progression to all-cause dementia in most MCI subgroups: adjusted hazard ratios (aHR) [95% CI] were 3.1 [1.43; 6.53] in the A- subgroup, 1.7 [1.20–2.27] in T + , 2.6 [1.06–6.59] in A-T-, and 1.6 [1.15–2.22] in the A + T + subgroup. Smoking (yes/no) was associated with increased dementia aHR in the A + MCI subgroup: 1.6 [1.07–2.34]. Depression increased dementia aHR in the T + MCI subgroup: 1.5 [1.06–2.02]. No significant associations were found in the CU biomarker subgroups. Conclusion Addressing modifiable risk factors carries an important potential for reducing the risk of dementia even after the onset of Alzheimer's pathology. Knowledge of biomarker status can further optimize prevention strategies.
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spelling doaj-art-c822ed57c83f49dc82d149b44050a63c2025-08-20T02:11:24ZengBMCAlzheimer’s Research & Therapy1758-91932024-10-0116111510.1186/s13195-024-01602-9Association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathologyZsolt Huszár0Alina Solomon1Marie Anne Engh2Vanda Koszovácz3Tamás Terebessy4Zsolt Molnár5Péter Hegyi6András Horváth7Francesca Mangialasche8Miia Kivipelto9Gábor Csukly10Centre for Translational Medicine, Semmelweis UniversityInstitute of Clinical Medicine/Neurology, University of Eastern FinlandCentre for Translational Medicine, Semmelweis UniversityDepartment of Psychiatry and Psychotherapy, Semmelweis UniversityCentre for Translational Medicine, Semmelweis UniversityCentre for Translational Medicine, Semmelweis UniversityCentre for Translational Medicine, Semmelweis UniversityCentre for Translational Medicine, Semmelweis UniversityInstitute of Public Health and Clinical Nutrition, University of Eastern FinlandDivision of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetCentre for Translational Medicine, Semmelweis UniversityAbstract Background Dementia preventive interventions targeting multiple modifiable risk factors are a promising approach. However, the impact of modifiable risk factors in the presence of beta-amyloid or phosphorylated-tau (p-tau) pathology is unclear. Methods The objective of the study was to examine the role of modifiable risk factors (vascular factors, depression, and smoking) in the progression to mild cognitive impairment (MCI) or dementia among 434 cognitively unimpaired (CU) and 611 individuals with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Vascular risk factors were summarized with the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score, dichotomized into higher versus lower risk. Depression and smoking (yes/no) were categorised according to medical history or current symptoms. Analyses were stratified by beta-amyloid negative (A-) and positive (A +), p-tau negative (T-) and positive (T +), or beta-amyloid and p-tau negative (A-T-) and positive (A + T +) biomarker status. Cox proportional hazard models were adjusted for age, sex, education, baseline MMSE score, baseline hippocampal volume and ApoE4 carrier status. Results Higher CAIDE score was associated with increased risk of progression to all-cause dementia in most MCI subgroups: adjusted hazard ratios (aHR) [95% CI] were 3.1 [1.43; 6.53] in the A- subgroup, 1.7 [1.20–2.27] in T + , 2.6 [1.06–6.59] in A-T-, and 1.6 [1.15–2.22] in the A + T + subgroup. Smoking (yes/no) was associated with increased dementia aHR in the A + MCI subgroup: 1.6 [1.07–2.34]. Depression increased dementia aHR in the T + MCI subgroup: 1.5 [1.06–2.02]. No significant associations were found in the CU biomarker subgroups. Conclusion Addressing modifiable risk factors carries an important potential for reducing the risk of dementia even after the onset of Alzheimer's pathology. Knowledge of biomarker status can further optimize prevention strategies.https://doi.org/10.1186/s13195-024-01602-9Modifiable risk factorsCAIDEDepressionSmokingAmyloidTau
spellingShingle Zsolt Huszár
Alina Solomon
Marie Anne Engh
Vanda Koszovácz
Tamás Terebessy
Zsolt Molnár
Péter Hegyi
András Horváth
Francesca Mangialasche
Miia Kivipelto
Gábor Csukly
Association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathology
Alzheimer’s Research & Therapy
Modifiable risk factors
CAIDE
Depression
Smoking
Amyloid
Tau
title Association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathology
title_full Association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathology
title_fullStr Association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathology
title_full_unstemmed Association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathology
title_short Association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathology
title_sort association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathology
topic Modifiable risk factors
CAIDE
Depression
Smoking
Amyloid
Tau
url https://doi.org/10.1186/s13195-024-01602-9
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