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Background Type 2 diabetes (T2D) is associated with increased risk of dementia. The prospective longitudinal Israel Diabetes and Cognitive Decline study aims at identifying T2D-related characteristics associated with cognitive decline. Methods Subjects are population-based T2D 65+, initially cognitively intact. Medical conditions, blood examinations, and medication use data are since 1998; cognitive, functional, demographic, psychiatric, DNA, and inflammatory marker study assessments were conducted every 18 months. Because the duration of T2D reflects its chronicity and implications, we compared short (0–4.99 years), moderate (5–9.99), and long (10+) duration for the first 897 subjects. Results The long duration group used more T2D medications, had higher glucose, lower glomerular filtration rate, slower walking speed, and poorer cognitive functioning. Duration was not associated with most medical, blood, urine, and vital characteristics. Conclusions Tracking cognition, with face-to-face evaluations, exploiting 15 years of historical detailed computerized, easily accessible, and validated T2D-related characteristics may provide novel insights into T2D-related dementia.

SummaryThere is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42, AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD‐like model mice on high‐AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood–brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle‐linked disease epidemic.

Risk of schizophrenia may increase when people with a genetic liability to the disorder, expressed as poor social and cognitive functioning, need to cope with city life.