Effect of Advanced Glycation End Products on Cognition in Older Adults with Type 2 Diabetes: Results from a Pilot Clinical Trial

Article type: Research Article

Authors: Lotan, Roni^{a; b; *} | Ganmore, Ithamar^{b; c; d; e} | Livny, Abigail^{b; e; f} | Itzhaki, Nofar^f | Waserman, Mark^f | Shelly, Shahar^{b; g} | Zacharia, Moran^b | Moshier, Erin^h | Uribarri, Jaime^h | Beisswenger, Paulⁱ | Cai, Weijing^h | Troen, Aron M.^a | Beeri, Michal Schnaider^{b; j}

Affiliations: [a] The Nutrition and Brain Health Laboratory, The Institute of Biochemistry, Food and Nutrition Science, The Robert H. Smith Faculty of Agriculture Food and the Environment, The Hebrew University of Jerusalem, Rehovot, Israel | [b] The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer, Israel | [c] Memory Clinic, Sheba Medical Center, Tel Hashomer, Israel | [d] Neurology department, Sheba Medical Center, Tel Hashomer, Israel | [e] Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel | [f] Division of Diagnostic Imaging, Sheba Medical Center, Tel-Hashomer, Israel | [g] Department of Neurology, Mayo Clinic, Rochester, MN, USA | [h] Icahn School of Medicine at Mount Sinai, New York, NY, USA | [i] PreventAGE Healthcare, Lebanon, NH, USA | [j] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Correspondence: [*] Correspondence to: Roni Lotan, The Nutrition and Brain Health Laboratory, The Institute of Biochemistry, Food and Nutrition Science, The Robert H. Smith Faculty of Agriculture Food and the Environment, The Hebrew University of Jerusalem, Rehovot, Israel. E-mail: [email protected].

Abstract: Background:Dietary advanced glycation end-products (AGEs) are linked to cognitive decline. However, clinical trials have not tested the effect of AGEs on cognition in older adults. Objective:The aim of the current pilot trial was to examine the feasibility of an intervention to reduce dietary AGEs on cognition and on cerebral blood flow (CBF). Methods:The design is a pilot randomized controlled trial of dietary AGEs reduction in older adults with type 2 diabetes. Seventy-five participants were randomized to two arms. The control arm received standard of care (SOC) guidelines for good glycemic control; the intervention arm, in addition to SOC guidelines, were instructed to reduce their dietary AGEs intake. Global cognition and CBF were assessed at baseline and after 6 months of intervention. Results:At baseline, we found a reverse association between AGEs and cognitive functioning, possibly reflecting the long-term toxicity of AGEs on the brain. There was a significant improvement in global cognition at 6 months in both the intervention and SOC groups which was more prominent in participants with mild cognitive impairment. We also found that at baseline, higher AGEs were associated with increased CBF in the left inferior parietal cortex; however, 6 months of the AGEs lowering intervention did not affect CBF levels, despite lowering AGEs exposure in blood. Conclusion:The current pilot trial focused on the feasibility and methodology of intervening through diet to reduce AGEs in older adults with type 2 diabetes. Our results suggest that participants with mild cognitive impairment may benefit from an intensive dietary intervention.

Keywords: Advanced glycation end products, diet, feasibility, mild cognitive impairment, randomized controlled trial, pilot, type 2 diabetes

DOI: 10.3233/JAD-210131

Journal: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1785-1795, 2021