Association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathology
Year: 2024
Type: article
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.
Source: Alzheimer s Research & Therapy
Institutions: Semmelweis University, University of Eastern Finland, Karolinska Institutet, Imperial College London, Poznan University of Medical Sciences, University of Szeged, University of Pecs, National Institute of Menthal Health, Neurology and Neurosurgery - Nyírő Gyula Hospital, Hungarian Research Network, HUN-REN Research Centre for Natural Sciences, Karolinska University Hospital
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,990
Awards: G2479307120, G3623051260, G4420182926
OpenAlex ID: W4403787051