Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort

K M Hayden; M M Mielke; J K Evans; R Neiberg; D Molina-Henry; M Culkin; S Marcovina; K C Johnson; O T Carmichael; S R Rapp; B C Sachs; J Ding; H Shappell; L Wagenknecht; J A Luchsinger; M A Espeland

doi:10.14283/jarlife.2024.1

Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort

JAR Life. 2024 Jan 5:13:1-21. doi: 10.14283/jarlife.2024.1. eCollection 2024.

Authors

K M Hayden¹, M M Mielke², J K Evans³, R Neiberg³, D Molina-Henry^{4

5}, M Culkin¹, S Marcovina⁶, K C Johnson⁷, O T Carmichael⁸, S R Rapp^{1

9}, B C Sachs^{10

11}, J Ding¹¹, H Shappell³, L Wagenknecht², J A Luchsinger¹², M A Espeland^{3

11}

Affiliations

¹ Department of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
² Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
³ Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁴ Winston-Salem State University, Winston-Salem, NC, USA.
⁵ Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego, CA, USA.
⁶ Medpace Reference Laboratories, Cincinnati, OH, USA.
⁷ Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
⁸ Biomedical Imaging Center, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
⁹ Department of Psychiatry & Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
¹⁰ Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
¹¹ Sticht Division of Gerontology and Geriatric Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
¹² Departments of Medicine and Epidemiology, Columbia University Irving Medical Center, New York, NY, USA.

Abstract

Background: Emerging evidence suggests that a number of factors can influence blood-based biomarker levels for Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD). We examined the associations that demographic and clinical characteristics have with AD/ADRD blood-based biomarker levels in an observational continuation of a clinical trial cohort of older individuals with type 2 diabetes and overweight or obesity.

Methods: Participants aged 45-76 years were randomized to a 10-year Intensive Lifestyle Intervention (ILI) or a diabetes support and education (DSE) condition. Stored baseline and end of intervention (8-13 years later) plasma samples were analyzed with the Quanterix Simoa HD-X Analyzer. Changes in Aβ42, Aβ40, Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic, and clinical characteristics.

Results: In a sample of 779 participants from the Look AHEAD cohort, we found significant associations between blood-based biomarkers for AD/ADRD and 15 of 18 demographic (age, gender, race and ethnicity, education) and clinical characteristics (APOE, depression, alcohol use, smoking, body mass index, HbA1c, diabetes duration, diabetes treatment, estimated glomerular filtration rate, hypertension, and history of cardiovascular disease) .

Conclusions: Blood-based biomarkers of AD/ADRD are influenced by common demographic and clinical characteristics. These factors should be considered carefully when interpreting these AD/ADRD blood biomarker values for clinical or research purposes.

Keywords: Alzheimer’s disease; blood-based biomarkers of AD; comorbidities; diabetes; obesity.

Abstract

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