Risk factors for Alzheimer’s disease and cognitive function before middle age in a U.S. representative population-based studyResearch in context
Summary: Background: Alzheimer’s disease is a major health concern in the U.S., but most research has focused on older populations. We examined whether established risk factors and blood biomarkers are associated with cognition before midlife. Methods: Data from the National Longitudinal Study of A...
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Elsevier
2025-05-01
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| Series: | The Lancet Regional Health. Americas |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667193X25000973 |
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| author | Allison E. Aiello Jennifer Momkus Rebecca C. Stebbins Yuan S. Zhang Chantel L. Martin Y. Claire Yang Lauren Gaydosh Taylor Hargrove Adina Zeki Al Hazzouri Kathleen Mullan Harris |
| author_facet | Allison E. Aiello Jennifer Momkus Rebecca C. Stebbins Yuan S. Zhang Chantel L. Martin Y. Claire Yang Lauren Gaydosh Taylor Hargrove Adina Zeki Al Hazzouri Kathleen Mullan Harris |
| author_sort | Allison E. Aiello |
| collection | DOAJ |
| description | Summary: Background: Alzheimer’s disease is a major health concern in the U.S., but most research has focused on older populations. We examined whether established risk factors and blood biomarkers are associated with cognition before midlife. Methods: Data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were analyzed. Participants were enrolled in 1994–95 (grades 7–12) and followed through 2018. We cross-sectionally analyzed weighted survey and biomarker data from Waves IV and V. We measured the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score comprised of age, education, sex, systolic blood pressure, body mass index, cholesteroal, and physical activity and apolipoprotein E ε4 allele (APOE ε4) status. We also measured total Tau and Neurofilament light (NfL), high sensitivity C-reactive protein (hsCRP), Interleukin (IL)-1β, IL-6, IL-8, IL-10, and Tumor necrosis factor alpha (TNF-α). Outcomes included immediate word recall, delayed word recall, and backward digit span. Findings: Analytic sample sizes ranged from 4507 to 11,449 participants in Wave IV and from 529 to 1121 participants in Wave V. The survey-weighted median (IQR) age was 28 (26–29) years in Wave IV and 38 (36–29) years in Wave V. About half of the survey-weighted Wave IV participants were female (48.4–52.1% across analytic samples), 71.4–72.5% were White, 12.5–14.9% were Black, and 9.3–10.2% were Hispanic. In Wave V, 43.6–46.8% were female, 68.7–69.3% were White, 17.1%–20.0% were Black, and 7.3%–9.6% were Hispanic. The CAIDE score was associated with all cognition measures in Wave IV. For example, among adults aged 24–34, each 1-point increase in CAIDE was associated with a 0.03 standard deviation lower backward digit span score (95% CI: −0.04, −0.02). Total Tau was associated with immediate word recall in Wave V (β = −0.13, 95% CI: −0.23, −0.04). Wave IV hsCRP and IL-10 and Wave V IL-6, IL-1β, and IL-8 were also associated with lower cognitive scores. Interpretation: Key risk factors for Alzheimer’s Disease are linked to cognitive function as early as ages 24–44, highlighting the need for early prevention in the US. Funding: NIH P01HD31921, U01AG071448, U01AG071450, R01AG057800, P30AG066615, T32HD091058, P2CHD050924. |
| format | Article |
| id | doaj-art-c75c2c6bf0fb476cad235407f5c53b2b |
| institution | DOAJ |
| issn | 2667-193X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
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| series | The Lancet Regional Health. Americas |
| spelling | doaj-art-c75c2c6bf0fb476cad235407f5c53b2b2025-08-20T03:09:27ZengElsevierThe Lancet Regional Health. Americas2667-193X2025-05-014510108710.1016/j.lana.2025.101087Risk factors for Alzheimer’s disease and cognitive function before middle age in a U.S. representative population-based studyResearch in contextAllison E. Aiello0Jennifer Momkus1Rebecca C. Stebbins2Yuan S. Zhang3Chantel L. Martin4Y. Claire Yang5Lauren Gaydosh6Taylor Hargrove7Adina Zeki Al Hazzouri8Kathleen Mullan Harris9Robert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Corresponding author. Department of Epidemiology, Robert N Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, USA.Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USARobert N. Butler Columbia Aging Center, Columbia University, New York, NY, USARobert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA; Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, NY, USACarolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USACarolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USACarolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USACarolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USARobert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USACarolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USASummary: Background: Alzheimer’s disease is a major health concern in the U.S., but most research has focused on older populations. We examined whether established risk factors and blood biomarkers are associated with cognition before midlife. Methods: Data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were analyzed. Participants were enrolled in 1994–95 (grades 7–12) and followed through 2018. We cross-sectionally analyzed weighted survey and biomarker data from Waves IV and V. We measured the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score comprised of age, education, sex, systolic blood pressure, body mass index, cholesteroal, and physical activity and apolipoprotein E ε4 allele (APOE ε4) status. We also measured total Tau and Neurofilament light (NfL), high sensitivity C-reactive protein (hsCRP), Interleukin (IL)-1β, IL-6, IL-8, IL-10, and Tumor necrosis factor alpha (TNF-α). Outcomes included immediate word recall, delayed word recall, and backward digit span. Findings: Analytic sample sizes ranged from 4507 to 11,449 participants in Wave IV and from 529 to 1121 participants in Wave V. The survey-weighted median (IQR) age was 28 (26–29) years in Wave IV and 38 (36–29) years in Wave V. About half of the survey-weighted Wave IV participants were female (48.4–52.1% across analytic samples), 71.4–72.5% were White, 12.5–14.9% were Black, and 9.3–10.2% were Hispanic. In Wave V, 43.6–46.8% were female, 68.7–69.3% were White, 17.1%–20.0% were Black, and 7.3%–9.6% were Hispanic. The CAIDE score was associated with all cognition measures in Wave IV. For example, among adults aged 24–34, each 1-point increase in CAIDE was associated with a 0.03 standard deviation lower backward digit span score (95% CI: −0.04, −0.02). Total Tau was associated with immediate word recall in Wave V (β = −0.13, 95% CI: −0.23, −0.04). Wave IV hsCRP and IL-10 and Wave V IL-6, IL-1β, and IL-8 were also associated with lower cognitive scores. Interpretation: Key risk factors for Alzheimer’s Disease are linked to cognitive function as early as ages 24–44, highlighting the need for early prevention in the US. Funding: NIH P01HD31921, U01AG071448, U01AG071450, R01AG057800, P30AG066615, T32HD091058, P2CHD050924.http://www.sciencedirect.com/science/article/pii/S2667193X25000973Alzheimer’s diseaseDementia risk factorsCAIDE risk scoreDementia risk scoreAPOENeurofilament light chain |
| spellingShingle | Allison E. Aiello Jennifer Momkus Rebecca C. Stebbins Yuan S. Zhang Chantel L. Martin Y. Claire Yang Lauren Gaydosh Taylor Hargrove Adina Zeki Al Hazzouri Kathleen Mullan Harris Risk factors for Alzheimer’s disease and cognitive function before middle age in a U.S. representative population-based studyResearch in context The Lancet Regional Health. Americas Alzheimer’s disease Dementia risk factors CAIDE risk score Dementia risk score APOE Neurofilament light chain |
| title | Risk factors for Alzheimer’s disease and cognitive function before middle age in a U.S. representative population-based studyResearch in context |
| title_full | Risk factors for Alzheimer’s disease and cognitive function before middle age in a U.S. representative population-based studyResearch in context |
| title_fullStr | Risk factors for Alzheimer’s disease and cognitive function before middle age in a U.S. representative population-based studyResearch in context |
| title_full_unstemmed | Risk factors for Alzheimer’s disease and cognitive function before middle age in a U.S. representative population-based studyResearch in context |
| title_short | Risk factors for Alzheimer’s disease and cognitive function before middle age in a U.S. representative population-based studyResearch in context |
| title_sort | risk factors for alzheimer s disease and cognitive function before middle age in a u s representative population based studyresearch in context |
| topic | Alzheimer’s disease Dementia risk factors CAIDE risk score Dementia risk score APOE Neurofilament light chain |
| url | http://www.sciencedirect.com/science/article/pii/S2667193X25000973 |
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