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. 2024 Mar 27;16(1):e12569.
doi: 10.1002/dad2.12569. eCollection 2024 Jan-Mar.

Sex-specific blood biomarkers linked to memory changes in middle-aged adults: The Framingham Heart Study

Huitong Ding  1   2 , Chunyu Liu  2   3 , Yi Li  3 , Ting Fang Alvin Ang  1   2   4 , Sherral Devine  1   2 , Yulin Liu  1   2 , Rhoda Au  1   2   4   5   6 , P Murali Doraiswamy  7
Affiliations

Sex-specific blood biomarkers linked to memory changes in middle-aged adults: The Framingham Heart Study

Huitong Ding et al. Alzheimers Dement (Amst). .

Abstract

The relationship between sex-specific blood biomarkers and memory changes in middle-aged adults remains unclear. We aimed to investigate this relationship using the data from the Framingham Heart Study (FHS). We conducted association analysis, partial correlation analysis, and causal dose-response curves using blood biomarkers and other data from 793 middle-aged participants (≤ 60 years) from the FHS Offspring Cohort. The results revealed associations of adiponectin and fasting blood glucose with midlife memory change, along with a U-shaped relationship of high-density lipoprotein cholesterol with memory change. No significant associations were found for the other blood biomarkers (e.g., amyloid beta protein 42) with memory change. To our knowledge, this is the first sex-specific network analysis of blood biomarkers related to midlife memory change in a prospective cohort study. Our findings highlight the importance of targeting cardiometabolic risks and the need to validate midlife-specific biomarkers that can accelerate the development of primary preventive strategies.

Keywords: association; blood biomarkers; memory decline; middle‐aged adults; sex difference.

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Conflict of interest statement

PMD has received research grants, advisory/board fees, and/or stock from several companies and is a co‐inventor on several patents related to the diagnosis and treatment of dementia. Other authors declare that they have no conflict of interests. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Casual dose‐response curves of FBG, HDL, and adiponectin with annualized memory change. The x axis represents the values of biomarkers. The y axis represents the annualized memory change, where a higher value indicates a slower memory decline. FBG, fasting blood glucose; HDL, high‐density lipoprotein
FIGURE 2
FIGURE 2
Three key biomarkers that impact memory change in a sex‐specific way. FBG, fasting blood glucose; HDL, high‐density lipoprotein
FIGURE 3
FIGURE 3
Partial correlation network of all biomarkers and annualized memory change in pooled samples, men, and women. Each biomarker is represented as a node in the graph. Nodes with absolute partial correlation coefficients above 0.05 are connected by edges. Blue edges indicate negative partial correlation coefficients, while red edges indicate positive partial correlation coefficients. BMI, body mass index; CRP, C‐reactive protein; DBP, diastolic blood pressure; FBG, fasting blood glucose; HbA1c, hemoglobin A1c; HDL, high‐density lipoprotein; HR, ventricular heart rate; LDL, low‐density lipoprotein; SBP, systolic blood pressure; TC, total cholesterol; TNF‐ɑ, tumor necrosis factor alpha
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