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Advanced Glycation End Products, Receptors Linked With Dementia

January 22, 2021

Advanced glycation end products (AGEs) and their receptor appear to be associated with cognitive decline and dementia for the short term, but their long-term role in the pathophysiological process needs further investigation, according to a study published online in JAMA Network Open. 

“AGEs are a group of molecules generated nonenzymatically by attaching sugars to proteins, lipids, or nucleic acids and lead to modification and cross-linking of proteins,” researchers explained in the study introduction. “Furthermore, activation of the AGE receptor (RAGE) by AGEs or by other RAGE ligands, including amyloid-β, results in an inflammatory response and subsequently to upregulation of the receptor.” 

The study involved 3889 adults from the general population in the Netherlands, 73 of whom had dementia at baseline and 161 of whom developed dementia over follow-up through 2016. Researchers measured markers of RAGE in plasma collected between 1997 and 1999 in 1021 participants.

RAGE markers in plasma were linked with prevalent dementia at baseline but not with the onset of dementia during follow-up, according to the study. Among 2890 participants without dementia, higher skin autofluorescence, a measurement of AGEs, was associated with worse cognitive function—notably in people who carried the APOE ε4 allele, according to the study.  

“These findings suggest that the AGE-RAGE system is associated with cognitive decline and dementia cross-sectionally but not longitudinally. This indicates either a short-term association or reverse causality,” researchers wrote. “Findings of cross-sectional associations between higher skin autofluorescence and lower cognitive function and an association with APOE status also warrant replication and prospective studies.” 

Jolynn Tumolo


Chen J, Mooldijk SS, Licher S, et al. Assessment of Advanced Glycation End Products and Receptors and the Risk of Dementia. JAMA Netw Open. 2021;4(1):e2033012. Published 2021 Jan 4. doi:10.1001/jamanetworkopen.2020.33012

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