Diabetes and hypertension are related to amyloid-beta burden in the population-based Rotterdam Study

Joyce van Arendonk, Julia Neitzel, Rebecca Steketee, Danielle van Assema, Henri Vrooman, Marcel Segbers, Arfan Ikram, Meike Vernooij*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)
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Abstract

Higher vascular disease burden increases the likelihood of developing dementia, including Alzheimer’s disease. Better understanding the association between vascular risk factors and Alzheimer’s disease pathology at the predementia stage is critical for developing effective strategies to delay cognitive decline. In this work, we estimated the impact of six vascular risk factors on the presence and severity of in vivo measured brain amyloid-beta (Aβ) plaques in participants from the population-based Rotterdam Study. Vascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, physical inactivity and smoking) were assessed 13 (2004–2008) and 7 years (2009–2014) prior to 18F-florbetaben PET (2018–2021) in 635 dementia-free participants. Vascular risk factors were associated with binary amyloid PET status or continuous PET readouts (standard uptake value ratios, SUVrs) using logistic and linear regression models, respectively, adjusted for age, sex, education, APOE4 risk allele count and time between vascular risk and PET assessment. Participants’ mean age at time of amyloid PET was 69 years (range: 60–90), 325 (51.2%) were women and 190 (29.9%) carried at least one APOE4 risk allele. The adjusted prevalence estimates of an amyloid-positive PET status markedly increased with age [12.8% (95% CI 11.6; 14) in 60–69 years versus 35% (36; 40.8) in 80–89 years age groups] and APOE4 allele count [9.7% (8.8; 10.6) in non-carriers versus 38.4% (36; 40.8) to 60.4% (54; 66.8) in carriers of one or two risk allele(s)]. Diabetes 7 years prior to PET assessment was associated with a higher risk of a positive amyloid status [odds ratio (95% CI) = 3.68 (1.76; 7.61), P < 0.001] and higher standard uptake value ratios, indicating more severe Aβ pathology [standardized beta = 0.40 (0.17; 0.64), P = 0.001]. Hypertension was associated with higher SUVr values in APOE4 carriers (mean SUVr difference of 0.09), but not in non-carriers (mean SUVr difference 0.02; P = 0.005). In contrast, hypercholesterolaemia was related to lower SUVr values in APOE4 carriers (mean SUVr difference −0.06), but not in non-carriers (mean SUVr difference 0.02). Obesity, physical inactivity and smoking were not related to amyloid PET measures. The current findings suggest a contribution of diabetes, hypertension and hypercholesterolaemia to the pathophysiology of Alzheimer’s disease in a general population of older non-demented adults. As these conditions respond well to lifestyle modification and drug treatment, further research should focus on the preventative effect of early risk management on the development of Alzheimer’s disease neuropathology.
Original languageEnglish
Pages (from-to)337-348
Number of pages12
JournalBrain
Volume146
Issue number1
Early online date12 Nov 2022
DOIs
Publication statusPublished - 1 Jan 2023

Bibliographical note

Funding Information:
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 101032288 (MSCA-IF-GF to J.N.) and no. 667375 (CoSTREAM to M.W.V.), Alzheimer’s Association Research Grant (no. AARG-22-972229 to M.W.V. and J.N.) and ZonMw Memorabel grant (no. 733050817 to M.W.V.). PET tracer supply was supported by Life Molecular Imaging GmbH, Berlin (Germany). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. None of the funding organizations or sponsors were involved in study design, in collection, analysis, and interpretation of data, in writing of the report, or in the decision to submit the article for publication.

Funding Information:
We are thankful to Dr Roelf Valkema, for his help in initiating this study and providing clinical expertise and assistance. Moreover, we would like to thank the entire staff of the Nuclear Medicine department for their help in acquiring the amyloid PET data, including but not limited to Dennis Kuijper, Annelies Schipper, Pieter Meppelink and Jean-Baptiste Aarssen for their coordinating roles. We would also like to acknowledge the immense contribution of the data management team of the Rotterdam Study, with Jolande Verkroost-van Heemst in particular, and of the Imaging Trialbureau. Lastly, we would like to thank our study participants for their contribution. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 101032288 (MSCA-IF-GF to J.N.) and no. 667375 (CoSTREAM to M.W.V.), Alzheimer’s Association Research Grant (no. AARG-22-972229 to M.W.V. and J.N.) and ZonMw Memorabel grant (no. 733050817 to M.W.V.). PET tracer supply was supported by Life Molecular Imaging GmbH, Berlin (Germany). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. None of the funding organizations or sponsors were involved in study design, in collection, analysis, and interpretation of data, in writing of the report, or in the decision to submit the article for publication.

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.

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