Circulating non-esterified fatty acids, risk of dementia and cognitive decline: The cardiovascular health study and multi-ethnic study of atherosclerosis

Kristine F. Moseholm; Majken K. Jensen; Petra Buzkova; Sarah A. Aroner; Annette L. Fitzpatrick; W. T. Longstreth; Oscar Lopez; David S. Siscovick; Jorge R. Kizer; Joachim H. Ix; Timothy M. Hughes; Kathleen M. Hayden; Sarah Nomura; Michael Y. Tsai; Robyn McClelland; Luc Djoussé; Kenneth J. Mukamal

doi:10.1016/j.neurobiolaging.2025.01.009

Circulating non-esterified fatty acids, risk of dementia and cognitive decline: The cardiovascular health study and multi-ethnic study of atherosclerosis

Kristine F. Moseholm^*, Majken K. Jensen, Petra Buzkova, Sarah A. Aroner, Annette L. Fitzpatrick, W. T. Longstreth, Oscar Lopez, David S. Siscovick, Jorge R. Kizer, Joachim H. Ix, Timothy M. Hughes, Kathleen M. Hayden, Sarah Nomura, Michael Y. Tsai, Robyn McClelland, Luc Djoussé, Kenneth J. Mukamal

^*Corresponding author for this work

Section of Epidemiology

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Circulating non-esterified fatty acids (NEFAs) have toxic effects on a variety of organs central to cardiometabolic disease and can cross the blood-brain barrier. Whether NEFAs associate with cognitive decline or dementia remains unknown. Circulating total NEFA levels were measured in 3242 participants without dementia among older adults of the Cardiovascular Health Study (CHS) and related to adjudicated dementia over 6 years (n = 456 cases) and annually assessed cognitive decline. For confirmation, we related circulating NEFAs to cognition assessed 10 years later among 4361 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). In CHS participants, each SD higher NEFA levels were associated with a hazard ratio (HR) for all-cause dementia of 1.11 (95 % CI: 1.01; 1.22). Baseline NEFA levels were also associated with more rapid decline in cognition over 6 years of follow-up. In MESA, circulating NEFA measurements were associated with lower cognitive scores measured 10 years later.’

Original language	English
Journal	Neurobiology of Aging
Volume	148
Pages (from-to)	71-79
Number of pages	9
ISSN	0197-4580
DOIs	https://doi.org/10.1016/j.neurobiolaging.2025.01.009
Publication status	Published - 2025

Bibliographical note

Publisher Copyright:
© 2025 Elsevier Inc.

Keywords

Cognition
Dementia
Free fatty acids
Non-esterified fatty acids
Plasma biomarkers

Access to Document

10.1016/j.neurobiolaging.2025.01.009

Cite this

Moseholm, K. F., Jensen, M. K., Buzkova, P., Aroner, S. A., Fitzpatrick, A. L., Longstreth, W. T., Lopez, O., Siscovick, D. S., Kizer, J. R., Ix, J. H., Hughes, T. M., Hayden, K. M., Nomura, S., Tsai, M. Y., McClelland, R., Djoussé, L., & Mukamal, K. J. (2025). Circulating non-esterified fatty acids, risk of dementia and cognitive decline: The cardiovascular health study and multi-ethnic study of atherosclerosis. Neurobiology of Aging, 148, 71-79. https://doi.org/10.1016/j.neurobiolaging.2025.01.009

Moseholm, KF , Jensen, MK, Buzkova, P, Aroner, SA, Fitzpatrick, AL, Longstreth, WT, Lopez, O, Siscovick, DS, Kizer, JR, Ix, JH, Hughes, TM, Hayden, KM, Nomura, S, Tsai, MY, McClelland, R, Djoussé, L & Mukamal, KJ 2025, 'Circulating non-esterified fatty acids, risk of dementia and cognitive decline: The cardiovascular health study and multi-ethnic study of atherosclerosis', Neurobiology of Aging, vol. 148, pp. 71-79. https://doi.org/10.1016/j.neurobiolaging.2025.01.009

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abstract = "Circulating non-esterified fatty acids (NEFAs) have toxic effects on a variety of organs central to cardiometabolic disease and can cross the blood-brain barrier. Whether NEFAs associate with cognitive decline or dementia remains unknown. Circulating total NEFA levels were measured in 3242 participants without dementia among older adults of the Cardiovascular Health Study (CHS) and related to adjudicated dementia over 6 years (n = 456 cases) and annually assessed cognitive decline. For confirmation, we related circulating NEFAs to cognition assessed 10 years later among 4361 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). In CHS participants, each SD higher NEFA levels were associated with a hazard ratio (HR) for all-cause dementia of 1.11 (95 % CI: 1.01; 1.22). Baseline NEFA levels were also associated with more rapid decline in cognition over 6 years of follow-up. In MESA, circulating NEFA measurements were associated with lower cognitive scores measured 10 years later.{\textquoteright}",

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doi = "10.1016/j.neurobiolaging.2025.01.009",

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AU - Moseholm, Kristine F.

AU - Jensen, Majken K.

AU - Buzkova, Petra

AU - Aroner, Sarah A.

AU - Fitzpatrick, Annette L.

AU - Longstreth, W. T.

AU - Lopez, Oscar

AU - Siscovick, David S.

AU - Kizer, Jorge R.

AU - Ix, Joachim H.

AU - Hughes, Timothy M.

AU - Hayden, Kathleen M.

AU - Nomura, Sarah

AU - Tsai, Michael Y.

AU - McClelland, Robyn

AU - Djoussé, Luc

AU - Mukamal, Kenneth J.

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N2 - Circulating non-esterified fatty acids (NEFAs) have toxic effects on a variety of organs central to cardiometabolic disease and can cross the blood-brain barrier. Whether NEFAs associate with cognitive decline or dementia remains unknown. Circulating total NEFA levels were measured in 3242 participants without dementia among older adults of the Cardiovascular Health Study (CHS) and related to adjudicated dementia over 6 years (n = 456 cases) and annually assessed cognitive decline. For confirmation, we related circulating NEFAs to cognition assessed 10 years later among 4361 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). In CHS participants, each SD higher NEFA levels were associated with a hazard ratio (HR) for all-cause dementia of 1.11 (95 % CI: 1.01; 1.22). Baseline NEFA levels were also associated with more rapid decline in cognition over 6 years of follow-up. In MESA, circulating NEFA measurements were associated with lower cognitive scores measured 10 years later.’

AB - Circulating non-esterified fatty acids (NEFAs) have toxic effects on a variety of organs central to cardiometabolic disease and can cross the blood-brain barrier. Whether NEFAs associate with cognitive decline or dementia remains unknown. Circulating total NEFA levels were measured in 3242 participants without dementia among older adults of the Cardiovascular Health Study (CHS) and related to adjudicated dementia over 6 years (n = 456 cases) and annually assessed cognitive decline. For confirmation, we related circulating NEFAs to cognition assessed 10 years later among 4361 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). In CHS participants, each SD higher NEFA levels were associated with a hazard ratio (HR) for all-cause dementia of 1.11 (95 % CI: 1.01; 1.22). Baseline NEFA levels were also associated with more rapid decline in cognition over 6 years of follow-up. In MESA, circulating NEFA measurements were associated with lower cognitive scores measured 10 years later.’

KW - Cognition

KW - Dementia

KW - Free fatty acids

KW - Non-esterified fatty acids

KW - Plasma biomarkers

U2 - 10.1016/j.neurobiolaging.2025.01.009

DO - 10.1016/j.neurobiolaging.2025.01.009

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SN - 0197-4580

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