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  • Wiley  (3)
  • Chen, Jinluan  (3)
  • 1
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S11 ( 2022-12)
    Abstract: Conditions such as hyperglycemia and oxidative stress lead to the formation of advanced glycation end products (AGEs), which have also been implicated in neurodegeneration including dementia. Previous studies have shown a link between these AGEs and the occurrence of Alzheimer’s neuropathology and worse cognitive functioning. However, no study examined the association between AGE levels and the risk of dementia. Therefore, we used skin AGE levels, reflecting accumulation of AGEs in long‐lived tissues, to determine the association with the risk of dementia and brain MRI measures. Method Within the Rotterdam Study, we determined skin AGEs using skin autofluorescence (SAF [arbitrary units]) measured at the forearm, between 2013 and 2016 in 2938 participants without dementia. Of them, 1515 also underwent brain MRI. All participants were followed for the incidence of dementia until 2020. The associations of SAF with incident dementia and with brain MRI measures were assessed, adjusting for potential confounders, namely age, sex, education, APOE ε4 carriership, smoking, estimated glomerular filtration rate, fasting glucose level and use of antidiabetic medication. Result Of 2938 participants (mean age 72.6 years, 57% women), 124 developed dementia during a median follow‐up of 4.3 years. Higher SAF was associated with an increased risk of dementia (hazard ratio (HR) 1.22 per standard deviation increase of SAF [95% confidence interval 1.03‐1.45]) and of Alzheimer’s disease (HR 1.21 [1.00‐1.48] ). Stronger effects were seen in APOE ε4 carriers with HRs of 1.38 [1.03‐1.84] for all‐cause dementia and 1.51 [1.10‐2.09] for Alzheimer’s disease. Participants with higher SAF also had lower total brain volumes on MRI (difference per standard deviation increase: ‐2.71 mL [‐4.54; ‐0.89]), lower grey matter volumes (‐1.77 mL [‐3.45; ‐0.08] ) and lower hippocampus volumes (‐0.04 [‐0.07; ‐0.01]). In addition, they tended to more often have lacunar infarcts and microbleeds (odds ratios: 1.22 [0.99‐1.50] and 1.09 [0.96‐1.25]). Conclusion Higher levels of AGEs in the skin are associated with an increased risk of dementia, especially in APOE ε4 carriers, and with lower brain volumes. These results suggest that AGEs are involved in dementia pathophysiology and may provide potential for prevention.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2201940-6
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  • 2
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S4 ( 2020-12)
    Abstract: Advanced glycation end products (AGEs) and their receptor (RAGE) are implicated in the pathophysiology of dementia and potentially underlie the relation between diabetes and neurodegeneration. We determined the link between two proteins involved in the AGE‐RAGE system, namely Extracellular Newly identified RAGE binding protein (EN‐RAGE) and the soluble form of RAGE (sRAGE), and dementia prevalence and incidence. Additionally, we assessed the association between skin auto fluorescence (SAF), a proxy for AGEs tissue accumulation, and cognition. Method Within the prospective Rotterdam Study, plasma EN‐RAGE and sRAGE were measured in 1208 participants (mean age 74.1 (standard deviation (SD) 7.7); 57.5% women). Participants were categorized into tertiles, to compare participants with high, intermediate and low concentrations, with the lowest tertile as the reference. Associations of SAF, measured in 3009 participants (mean age 72.3 (SD 9.4); 56.4% women), and cognition were assessed using linear models. We adjusted for age, sex, diabetes, APOE ε4 carrier status and other potential confounders, including cardiovascular risk factors, and additionally stratified by sex and APOE ε4 status. Result Participants with higher EN‐RAGE and lower sRAGE levels were more likely to have dementia (adjusted odds ratio (OR); 3.64 [95% confidence interval 1.56‐8.50] and OR 0.39 [0.17‐0.83] , for high level compared to low level). During follow‐up (median 12.4 years), 161 participants developed dementia, of whom 130 Alzheimer’s disease (AD). Higher EN‐RAGE was non‐significantly associated with higher risk of dementia during the first years of follow‐up (adjusted hazard ratio (HR); 1.48 [0.52‐4.25] after 4 years of follow‐up), while a lower risk was found over the entire follow‐up duration (HR 0.65 [0.42‐1.01] ) (Figure 1). Higher SAF was associated with lower global cognitive function (adjusted difference in z score per SAF standard deviation (SD); 0.07 [0.04‐0.11]). This effect was stronger for carriers of the APOE ε4 allele (0.15 [0.07‐0.22]). Conclusion Our results indicate involvement of the AGE‐RAGE system in the pathophysiology of dementia, independent of the history of diabetes, showing involvement of EN‐RAGE and sRAGE, and of SAF in cognitive functioning. These associations were stronger for APOE ε4 carriers, suggesting a combined role of AGEs and APOE in neurodegeneration.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
    Location Call Number Limitation Availability
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  • 3
    In: Journal of Bone and Mineral Research, Wiley, Vol. 35, No. 10 ( 2020-10), p. 1904-1913
    Abstract: Advanced glycation end‐products (AGEs), which bind to type 1 collagen in bone and skin, have been implicated in reduced bone quality. The AGE reader™ measures skin autofluorescence (SAF), which might be regarded as a marker of long‐term accumulation of AGEs in tissues. We investigated the association of SAF with bone mineral density (BMD) and fractures in the general population. We studied 2853 individuals from the Rotterdam Study with available SAF measurements (median age, 74.1 years) and with data on prevalent major osteoporotic (MOFs: hip, humerus, wrist, clinical vertebral) and vertebral fractures (VFs: clinical + radiographic Genant’s grade 2 and 3). Radiographs were assessed 4 to 5 years before SAF. Multivariate regression models were performed adjusted for age, sex, BMI, creatinine, smoking status, and presence of diabetes and additionally for BMD with interaction terms to test for effect modification. Prevalence of MOFs was 8.5% and of VFs 7%. SAF had a curvilinear association with prevalent MOFs and VFs and therefore, age‐adjusted, sex stratified SAF quartiles were used. The odds ratio (OR) (95% confidence interval [CI]) of the second, third and fourth quartiles of SAF for MOFs were as follows: OR 1.60 (95% CI, 1.08–2.35; p = .02); OR 1.30 (95% CI, 0.89–1.97; p = .20), and OR 1.40 (95% CI, 0.95–2.10; p = .09), respectively, with first (lowest) quartile as reference. For VFs the ORs were as follows: OR 1.69 (95% CI, 1.08–2.64; p = .02), OR 1.74(95% CI, 1.11–2.71; p = .01), and OR 1.73 (95% CI, 1.12–2.73; p = .02) for second, third, and fourth quartiles, respectively. When comparing the top three quartiles combined with the first quartile, the OR (95% CI) for MOFs was 1.43 (95% CI, 1.04–2.00; p = .03) and for VFs was 1.72 (95% CI, 1.18–2.53; p = .005). Additional adjustment for BMD did not change the associations. In conclusion, there is evidence of presence of a threshold of skin AGEs below which there is distinctly lower prevalence of fractures. Longitudinal analyses are needed to confirm our cross‐sectional findings. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2008867-X
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