Dietary Reduction of AGEs to Prevent Cognitive Decline in Elderly Diabetics

Dietary Reduction of Advanced Glycation End Products to Prevent Cognitive Decline in Elderly Diabetics - a Randomized Pilot Trial

Basic science and observational human studies suggest that high conentrations of circulating Advanced Glycation End-products (AGEs) may promote cognitive decline in older adults. The purpose of this pilot study is to test the methodology and feasibility of a dietary intervention to lower AGEs in elderly diabetics in order to lay the foundations for a future fully powered randomized clinical trial (RCT).To this end, the present study is focused on recruitment strategies, adherence to an innovative intervention in older adults and study methods. An exploratory aim will be the effect of the intervention on cognition and cerebral blood flow in order to obtain necessary data to estimate effect-size for a future fully-powered RCT.

The participants and study dietitian can not be blind to the assigned dietary intervention. However, the clinical testing and all data analysis are carried out blind to the intervention.

Participants randomized to this arm will receive active instruction on reducing dietary AGEs intake, in addition to standard of care dietary guidance for type 2 diabetes.

Participants randomized to this arm will only recieve standard of care dietary guidance for type 2 diabetes.

Oral and written instructions on how to reduce AGEs in diet, mainly by changing cooking methods in addition to standard of care dietary guidance for type 2 diabetes

Change from baseline in AGEs markers in serum (carboxymethyl lysine, CML and Methylglyoxal ,MG ) at 6 months

Changes in cognition using a Z score of global and domain specific (language, attention, memory ) cognition following 6 months of AGEs reduction compared to standard of care (this is an exploratory aim since this is a pilot study)

The influence of AGE reduction on cerebral blood flow-measured with arterial spin labeling MRI (ASL-MRI)

changes in cerebral blood flow measured with ASL MRI following 6 months of AGEs reduction compared to standard of care ( this is an exploratory aim since this is a pilot study)

microbiota composition will be analyzed (eg. the amount and relative proportions of major bacterial genus and species Bifidobacterium, Bacteroides, Lactobaillus, Enterobacteria, Eubacteria,etc. using 16S rRNA profiling ) before and after intervention of AGEs reduction and changes will compared to standard of care arm. This is a descriptive exploratory outcome.

Above the age 65 T2D diagnosis no dementia (i.e MCI or cognitively normal ) Not receiving cholinesterase inhibitors No other neurological (e.g. stroke, Parkinson's disease) or psychiatric conditions (e.g. schizophrenia, depression) that may affect cognition Dietary AGE levels > 13kU Not participating in another clinical trial An informant that is willing to actively support the participant throughout the study Exclusion Criteria: Dementia Stroke Other major neuropsychiatric condition that might affect cognition

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