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Introduction
Progressive decline in cognitive function leading to dementia is common in older people with diabetes. Dementia affects up to 16% of patients with diabetes aged >=65years and 24% of those aged >=75years (Feil et al., 2011; Thorpe et al., 2012 ). The relative risk (RR) of Alzheimer's disease is 1.56 {95% confidence interval (CI) 1.41 to 1.73), that of vascular dementia is 2.27 (1.94 to 2.66) and that of all types of dementia is 1.73 (1.65 to 1.82) compared to those without diabetes (Gudala, Bansal, Schifano, & Bhansali, 2013 ). Persistent hyperglycemia on one hand increases the risk of cerebrovascular disease by inducing inflammation, endothelial dysfunction, oxidative stress and insulin resistance leading to an increased incidence of vascular dementia (Middleton & Yaffe, 2009 ). Accelerated brain aging from altered amyloid metabolism, increased protein glycation and direct cerebral glucotoxicity may explain the increased risk of Alzheimer's dementia (Biessels, Staekenborg, Brunner, Brayne, & Scheltens, 2006 ). On the other hand, repeated episodes of severe hypoglycemia may be implicated in inducing cognitive impairment and dementia; however, this issue remains controversial. Frailty is an emerging complication of diabetes related to diabetes-associated decline in physical and cognitive function. It is associated with weight loss and malnutrition which may increase the likelihood of hypoglycemia (Hubbard, Lang, Llewellyn, & Rockwood, 2010 ). The rate of progression of frailty increases with aging likely due to diminishing physiologic reserve and is accelerated by the presence of brain pathologies such as Alzheimer's diseases (Buchman, Yu, Wilson, Schneider, & Bennett, 2013 ). Therefore, frailty appears to be associated with both hypoglycemia and dementia. In this review we have explored the relationships between hypoglycemia, frailty and dementia and its implications in clinical practice.
Methods
We have performed a search of Medline and Embase from 1996 to present using keywords relating to hypoglycemia, frailty, dementia, older people, diabetes mellitus and management. Only English language articles were selected. Articles were reviewed for relevance by abstract. A manual review of citations in retrieved articles was performed in addition to the electronic literature search. The final list of cited references was chosen on the basis relevance to the topic of review.
Hypoglycemia in old age
The real incidence of hypoglycemia in older people with...