DIABETES/METABOLISM RESEARCH AND REVIEWS REVIEW Diabetes Metab Res Rev 2014; 30: 341–345. Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/dmrr.2507
ARTICLE
Proceedings of the Second International Conference of the Bildirici Diabetes Center, Laniado Hospital, Netanya, Israel, January 24–25, 2012. Part 2
Diabetes, dysglycemia and cognitive dysfunction
Tali Cukierman-Yaffe* Endocrinology Institute, Gertner Institute, Sheba Medical Center, Epidemiology Department, Tel-Aviv University, Tel Aviv, Israel *Correspondence to: Tali Cukierman-Yaffe, Endocrinology Institute, Gertner Institute, Sheba Medical Center, Epidemiology Department, Tel-Aviv University, Tel Aviv, Israel. E-mail: [email protected]
Summary Evidence from the last decade supports the hypothesis that diabetes may be viewed as a disease of accelerated cognitive ageing. It is a risk factor for the development of dementia, for an accelerated rate of cognitive decline and for cognitive dysfunction. Thus, ‘diabetes-related cognitive dysfunction’ may be viewed as another long-term complication of diabetes. This article will review the evidence supporting this hypothesis and will elaborate on the implications for patient care, as well as discuss potential treatment options and their limitation. The final section reviews possible mechanistic explanations. Copyright © 2013 John Wiley & Sons, Ltd. Keywords
diabetes; cognitive dysfunction; Dysglycemia
Introduction The population is ageing. Indeed, by the year 2050, individuals age 60 years or older will represent 25% of the world’s population [1]. Thus, successful/healthy ageing becomes a priority. Data from the US have shown that amongst those that were fully independent at the age of 60 years, less than 25% will reach the age of 80 years without some form of disability [2]. An important determinant of successful/healthy ageing is the preservation of cognitive function and the prevention of cognitive decline. Studies have shown that cognitive function generally declines with age [3,4]; however, the degree and the speed vary among individuals. Evidence from the last several years has conclusively demonstrated that people with diabetes are more likely to experience an accelerated rate of cognitive decline or cognitive dysfunction and are also more likely to progress to dementia [5–10]. This article reviews the evidence that ‘diabetes-related cognitive dysfunction’ is another complication of diabetes. We present the possible implications for patient care and touch on possible mechanistic explanations.
Diabetes-related Cognitive Dysfunction – an underinvestigated complication of diabetes: epidemiological evidence supporting a relationship between diabetes, cognitive dysfunction and dementia Received: 26 November 2013 Accepted: 26 November 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Type 2 diabetes is a metabolic disorder characterized by hyperglycaemia that is caused by a relative deficiency of insulin and insulin insensitivity. It is
342
associated with a high risk of serious chronic diseases. It is well established as an independent risk factor for eye, kidney and neurological diseases as well as for cardiovascular morbidity and mortality. In the last several years, many longitudinal studies and several reviews have demonstrated that type 2 diabetes is also a risk factor for cognitive dysfunction and dementia: a 1.4–1.8-fold greater risk for Minimal Cognitive Impairment, a 1.5–2-fold greater risk for Alzheimer’s disease (AD) and a 2–2.5-fold greater risk for vascular dementia have been reported [5,9–16]. There is also evidence that diabetes is a risk factor for an accelerated rate of cognitive decline [5,8,17–20]. The cognitive domains that are most affected are psychomotor efficiency, learning, memory and executive function [6,21,22]. Prospective studies with very long follow-up periods provide further evidence of a relationship. Thus, the Adult Health Study followed a cohort of atomic bomb survivors from Hiroshima and Nagasaki. After 34–39 years of follow-up, 1774 participants were screened for dementia. Compared with non-diabetic individuals, diabetes increased the risk of vascular dementia and Alzheimer’s dementia 1.3-fold and 4.4-fold, respectively [23]. The Israel Ischemic Heart Disease study showed that people with a diagnosis of diabetes in midlife had a 2.8 greater risk of developing dementia three decades later compared with individuals without diabetes [24].
Hyperglycaemia There is also evidence suggesting that hyperglycaemia per se has detrimental effects on cognitive function. In a crosssectional analysis of 378 high-functioning individuals with diabetes, higher A1C levels were consistently associated with lower scores on two cognitive tests [25]. Another cross-sectional analysis of approximately 3000 individuals with established type 2 diabetes (participating in the Action to Control Cardiovascular Risk in DiabetesMemory in Diabetes ACCORD-MIND sub-study) demonstrated an age-adjusted inverse relationship between cognitive function and the degree of chronic hyperglycaemia as measured by the A1C level [26]. A recent longitudinal study with a median follow-up of 6.8 years conducted amongst ~200 individuals with diabetes reported that higher glucose levels were related to an increased risk for incident dementia [27]. Glucose levels in the non-diabetic range. Data from people without diabetes demonstrate a similar relationship. For example, the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET/TRANSCEND) cognitive baseline analysis showed that in ~ 20 000 individuals without diabetes, there Copyright © 2013 John Wiley & Sons, Ltd.
T. Cukierman-Yaffe
was an inverse association between higher levels of fasting plasma glucose levels and cognitive function as assessed by the Mini-Mental State Examination (MMSE) [28]. There are several prospective studies that have compared different categories of dysglycemia: diabetes, as well as pre-diabetes states such as impaired fasting glucose or impaired glucose tolerance with relation to the level of cognitive decline experienced. These studies have shown that people with pre-diabetes when compared with those who were normoglycaemic were at increased risk of cognitive decline [8,9]. In a prospective study of ~5000 women who were followed for ~4 years, those with the metabolic syndrome had a ~1.7 greater risk for the development of cognitive dysfunction. Amongst the components of the metabolic syndrome, fasting plasma glucose was the strongest determinant [29]. Finally, in the same cohort described previously, (median follow-up of 6.8 years) amongst ~2000 individuals without diabetes with a mean age of 76 years, higher glucose levels not within the diabetic range were related to an increased risk for incident dementia [27].
Implications for patient care Diabetes is a disease that requires complex self-care capacity. A major determinant of this capacity is cognitive function. Several guidelines on treatment of diabetes in the elderly have been published in the last 2 years [30,31]. All these guidelines promote screening for cognitive dysfunction – the rationale being that cognitive dysfunction may impede self-care capacity [32,33].
Treating hypoglycaemia – preventing mild episodes from becoming episodes that require the aid of another One of the important aspects of diabetes self-care capacity is treatment of hypoglycaemic episodes in an adequate manner. This requires that the individual identifies the symptoms of hypoglycaemia, that he/she measures blood glucose levels and responds appropriately thus preventing these non-severe episodes from progressing to hypoglycaemic events requiring the aid of another individual. There is evidence that individuals with diabetes who have cognitive dysfunction have a higher risk of developing severe hypoglycaemia. In the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Controlled Evaluation (ADVANCE), study people with diabetes with severe cognitive impairment (MMSE < =23) had a statistically significant greater risk of developing severe hypoglycaemia [34]. In the Action Diabetes Metab Res Rev 2014; 30: 341–345. DOI: 10.1002/dmrr
343
Diabetes-related cognitive dysfunction
to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND), study people who scored in the lower DSS tertile had a 50% greater risk for the development of severe hypoglycaemia [35]. These data suggest that there is value to screening and maybe to surveillance of cognitive function, and these should be part of the routine care of older people with diabetes. Healthy ageing with diabetes In our Endocrinology institute, we have recently founded the ‘Center for successful ageing with diabetes’ where people over the age of 60 years with diabetes under-go cognitive, physical and functional periodic assessment creating a baseline measure for each individual (thus enabling the detection of an acceleration in decline during follow-up), enabling referral for further treatment and evaluation when needed and tailoring of diabetes treatment regimens.
total brain MRI volumes with the intensively treated group experiencing less of a reduction than the conventional group. Ongoing studies Some of the ongoing cardiovascular (CV) outcome studies of dysglycemia treatment regimens include cognitive assessment, and their results may shed light on the effect of these interventions on the rate of cognitive decline in people with diabetes.
Mechanistic explanations A number of possible mechanisms to explain the association between dysglycemia, hyperglycaemia and cognitive dysfunction have been suggested.
Cardiovascular disease Treatment options for diabetes-related cognitive dysfunction Designing studies One of the major obstacles in assessing treatment options for diabetes-related cognitive dysfunction is defining which outcomes we should be measuring. One possibility is to use dementia as a major outcome. The drawback is that the incidence of dementia is quite low in the younger age group and in the older age group might be too late in the process to discern the effect of an intervention. A second possibility is to test the effect of an intervention on cognitive decline or cognitive maintenance. It is unclear which measurements of cognition should be used. A third possibility is to use surrogates of cognitive reserve such as brain imaging (total brain volumes, hippocampus volumes or developing functional Magnetic Resonance Imaging (fMRI) techniques). This field would benefit substantially from research aimed at elucidating the optimal instruments and unifications of the different tools used so that meaningful comparisons may be made. The ACCORD-MIND trial The ACCORD trial included a cognitive sub-study. Unfortunately, the study was terminated early so that sample size assumptions were not met, meaning that there was a high chance of a beta type error, that is, that no difference was detected between the groups despite the existence of such a difference. An analysis including the 20 and 40 month data failed to show an effect on the change in the cognitive test scores utilized. However, in the sub-group that underwent brain MRI, a significant difference was noted in the change in Copyright © 2013 John Wiley & Sons, Ltd.
As higher glucose levels are associated with a higher prevalence of CV risk factors and CV disease, the relationship with cognitive dysfunction may be mediated through CV disease. However, in many of the studies after adjustment for CV disease and CV risk factors, the relationship remained.
Hyperglycaemia It is also possible that chronic exposure of the brain to high levels of glucose may accelerate cognitive decline. Indeed, post-mortem studies from the brains of people with AD demonstrate metabolic oxidation products associated with hyperglycaemia [36,37]. A recent study in older individuals demonstrated an inverse relationship between glucose levels and function of the dentate gyrus, an area of the brain thought to be important in age-related cognitive decline [38].
Impaired insulin activity There are many insulin receptors in the brain. Some have a role in glucose transport, but many are thought to have a function in cognitive processes [39]. Several observations suggest that cognitive decline is a consequence of insufficient insulin action in the brain, either due to insulin resistance, insulin deficiency or both. Thus, (a) in individuals without diabetes, worse glucoregulation (as measured by a glucose tolerance test) was associated with worse outcomes on cognitive assessment, especially in the elderly [40]; (b) individuals with AD have less efficient glucoregulation than unaffected individuals [41]; Diabetes Metab Res Rev 2014; 30: 341–345. DOI: 10.1002/dmrr
344
T. Cukierman-Yaffe
exposure of individuals with AD to a hyperinsulinemic euglycaemic clamp improved cognitive function, whereas exposure to an euinsulinemic hyperglycaemic clamp had no effect [40–43]. There have been several small scale, short duration studies looking at the effect of a form of insulin that enters the brain selectively – intra-nasal insulin. In a recent systematic review, these studies were summarized. All studies were of a very short duration (up to 8 weeks) and showed some effect [44]. The preliminary results of a 4-month randomized controlled trial of 104 participants with Minimal Cognitive Impairment/early AD have recently been published. The patients were randomized to placebo, 20U, 40 U of intra-nasal insulin. In the short follow-up, they demonstrated an improvement in delayed memory (p < 0.05) and in preservation of caregiver rated functional ability (p < 0.01) [45].
Microvascular disease Finally, microvascular disease may also be responsible for the deleterious effects of chronic hyperglycaemia on cognitive function. Microvascular disease has been demonstrated to be worsened by chronic hyperglycaemia [46,47]. In people with diabetes, it causes pathology in the retina and in the peripheral nervous system. Thus, it
may well be that microvascular disease occurs also in the brain resulting in cognitive dysfunction.
Conclusion Diabetes may be viewed as a disease of accelerated cognitive ageing. It is a risk factor for progression of cognitive impairment and for future dementia. Thus, diabetes-related cognitive dysfunction should be considered another complication of diabetes. Especially in the elderly, cognitive dysfunction should be screened for as it may affect self-care capacity of the individual and thereby increase the risk of hypoglycaemia. More studies aimed at finding the optimal way to screen and measure progression of cognitive dysfunction in people with diabetes are needed. This may be a first step in aiding people with diabetes to healthier cognitive ageing as well as to elucidating treatment options. More studies are needed to gain insight into the mechanisms and risk factors for diabetes-related cognitive dysfunction. Finally, ongoing intervention studies in people with diabetes should include measures of cognitive function.
Conflict of interest None declared.
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Diabetes Metab Res Rev 2014; 30: 341–345. DOI: 10.1002/dmrr
ARTICLE
Proceedings of the Second International Conference of the Bildirici Diabetes Center, Laniado Hospital, Netanya, Israel, January 24–25, 2012. Part 2
Diabetes, dysglycemia and cognitive dysfunction
Tali Cukierman-Yaffe* Endocrinology Institute, Gertner Institute, Sheba Medical Center, Epidemiology Department, Tel-Aviv University, Tel Aviv, Israel *Correspondence to: Tali Cukierman-Yaffe, Endocrinology Institute, Gertner Institute, Sheba Medical Center, Epidemiology Department, Tel-Aviv University, Tel Aviv, Israel. E-mail: [email protected]
Summary Evidence from the last decade supports the hypothesis that diabetes may be viewed as a disease of accelerated cognitive ageing. It is a risk factor for the development of dementia, for an accelerated rate of cognitive decline and for cognitive dysfunction. Thus, ‘diabetes-related cognitive dysfunction’ may be viewed as another long-term complication of diabetes. This article will review the evidence supporting this hypothesis and will elaborate on the implications for patient care, as well as discuss potential treatment options and their limitation. The final section reviews possible mechanistic explanations. Copyright © 2013 John Wiley & Sons, Ltd. Keywords
diabetes; cognitive dysfunction; Dysglycemia
Introduction The population is ageing. Indeed, by the year 2050, individuals age 60 years or older will represent 25% of the world’s population [1]. Thus, successful/healthy ageing becomes a priority. Data from the US have shown that amongst those that were fully independent at the age of 60 years, less than 25% will reach the age of 80 years without some form of disability [2]. An important determinant of successful/healthy ageing is the preservation of cognitive function and the prevention of cognitive decline. Studies have shown that cognitive function generally declines with age [3,4]; however, the degree and the speed vary among individuals. Evidence from the last several years has conclusively demonstrated that people with diabetes are more likely to experience an accelerated rate of cognitive decline or cognitive dysfunction and are also more likely to progress to dementia [5–10]. This article reviews the evidence that ‘diabetes-related cognitive dysfunction’ is another complication of diabetes. We present the possible implications for patient care and touch on possible mechanistic explanations.
Diabetes-related Cognitive Dysfunction – an underinvestigated complication of diabetes: epidemiological evidence supporting a relationship between diabetes, cognitive dysfunction and dementia Received: 26 November 2013 Accepted: 26 November 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Type 2 diabetes is a metabolic disorder characterized by hyperglycaemia that is caused by a relative deficiency of insulin and insulin insensitivity. It is
342
associated with a high risk of serious chronic diseases. It is well established as an independent risk factor for eye, kidney and neurological diseases as well as for cardiovascular morbidity and mortality. In the last several years, many longitudinal studies and several reviews have demonstrated that type 2 diabetes is also a risk factor for cognitive dysfunction and dementia: a 1.4–1.8-fold greater risk for Minimal Cognitive Impairment, a 1.5–2-fold greater risk for Alzheimer’s disease (AD) and a 2–2.5-fold greater risk for vascular dementia have been reported [5,9–16]. There is also evidence that diabetes is a risk factor for an accelerated rate of cognitive decline [5,8,17–20]. The cognitive domains that are most affected are psychomotor efficiency, learning, memory and executive function [6,21,22]. Prospective studies with very long follow-up periods provide further evidence of a relationship. Thus, the Adult Health Study followed a cohort of atomic bomb survivors from Hiroshima and Nagasaki. After 34–39 years of follow-up, 1774 participants were screened for dementia. Compared with non-diabetic individuals, diabetes increased the risk of vascular dementia and Alzheimer’s dementia 1.3-fold and 4.4-fold, respectively [23]. The Israel Ischemic Heart Disease study showed that people with a diagnosis of diabetes in midlife had a 2.8 greater risk of developing dementia three decades later compared with individuals without diabetes [24].
Hyperglycaemia There is also evidence suggesting that hyperglycaemia per se has detrimental effects on cognitive function. In a crosssectional analysis of 378 high-functioning individuals with diabetes, higher A1C levels were consistently associated with lower scores on two cognitive tests [25]. Another cross-sectional analysis of approximately 3000 individuals with established type 2 diabetes (participating in the Action to Control Cardiovascular Risk in DiabetesMemory in Diabetes ACCORD-MIND sub-study) demonstrated an age-adjusted inverse relationship between cognitive function and the degree of chronic hyperglycaemia as measured by the A1C level [26]. A recent longitudinal study with a median follow-up of 6.8 years conducted amongst ~200 individuals with diabetes reported that higher glucose levels were related to an increased risk for incident dementia [27]. Glucose levels in the non-diabetic range. Data from people without diabetes demonstrate a similar relationship. For example, the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET/TRANSCEND) cognitive baseline analysis showed that in ~ 20 000 individuals without diabetes, there Copyright © 2013 John Wiley & Sons, Ltd.
T. Cukierman-Yaffe
was an inverse association between higher levels of fasting plasma glucose levels and cognitive function as assessed by the Mini-Mental State Examination (MMSE) [28]. There are several prospective studies that have compared different categories of dysglycemia: diabetes, as well as pre-diabetes states such as impaired fasting glucose or impaired glucose tolerance with relation to the level of cognitive decline experienced. These studies have shown that people with pre-diabetes when compared with those who were normoglycaemic were at increased risk of cognitive decline [8,9]. In a prospective study of ~5000 women who were followed for ~4 years, those with the metabolic syndrome had a ~1.7 greater risk for the development of cognitive dysfunction. Amongst the components of the metabolic syndrome, fasting plasma glucose was the strongest determinant [29]. Finally, in the same cohort described previously, (median follow-up of 6.8 years) amongst ~2000 individuals without diabetes with a mean age of 76 years, higher glucose levels not within the diabetic range were related to an increased risk for incident dementia [27].
Implications for patient care Diabetes is a disease that requires complex self-care capacity. A major determinant of this capacity is cognitive function. Several guidelines on treatment of diabetes in the elderly have been published in the last 2 years [30,31]. All these guidelines promote screening for cognitive dysfunction – the rationale being that cognitive dysfunction may impede self-care capacity [32,33].
Treating hypoglycaemia – preventing mild episodes from becoming episodes that require the aid of another One of the important aspects of diabetes self-care capacity is treatment of hypoglycaemic episodes in an adequate manner. This requires that the individual identifies the symptoms of hypoglycaemia, that he/she measures blood glucose levels and responds appropriately thus preventing these non-severe episodes from progressing to hypoglycaemic events requiring the aid of another individual. There is evidence that individuals with diabetes who have cognitive dysfunction have a higher risk of developing severe hypoglycaemia. In the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Controlled Evaluation (ADVANCE), study people with diabetes with severe cognitive impairment (MMSE < =23) had a statistically significant greater risk of developing severe hypoglycaemia [34]. In the Action Diabetes Metab Res Rev 2014; 30: 341–345. DOI: 10.1002/dmrr
343
Diabetes-related cognitive dysfunction
to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND), study people who scored in the lower DSS tertile had a 50% greater risk for the development of severe hypoglycaemia [35]. These data suggest that there is value to screening and maybe to surveillance of cognitive function, and these should be part of the routine care of older people with diabetes. Healthy ageing with diabetes In our Endocrinology institute, we have recently founded the ‘Center for successful ageing with diabetes’ where people over the age of 60 years with diabetes under-go cognitive, physical and functional periodic assessment creating a baseline measure for each individual (thus enabling the detection of an acceleration in decline during follow-up), enabling referral for further treatment and evaluation when needed and tailoring of diabetes treatment regimens.
total brain MRI volumes with the intensively treated group experiencing less of a reduction than the conventional group. Ongoing studies Some of the ongoing cardiovascular (CV) outcome studies of dysglycemia treatment regimens include cognitive assessment, and their results may shed light on the effect of these interventions on the rate of cognitive decline in people with diabetes.
Mechanistic explanations A number of possible mechanisms to explain the association between dysglycemia, hyperglycaemia and cognitive dysfunction have been suggested.
Cardiovascular disease Treatment options for diabetes-related cognitive dysfunction Designing studies One of the major obstacles in assessing treatment options for diabetes-related cognitive dysfunction is defining which outcomes we should be measuring. One possibility is to use dementia as a major outcome. The drawback is that the incidence of dementia is quite low in the younger age group and in the older age group might be too late in the process to discern the effect of an intervention. A second possibility is to test the effect of an intervention on cognitive decline or cognitive maintenance. It is unclear which measurements of cognition should be used. A third possibility is to use surrogates of cognitive reserve such as brain imaging (total brain volumes, hippocampus volumes or developing functional Magnetic Resonance Imaging (fMRI) techniques). This field would benefit substantially from research aimed at elucidating the optimal instruments and unifications of the different tools used so that meaningful comparisons may be made. The ACCORD-MIND trial The ACCORD trial included a cognitive sub-study. Unfortunately, the study was terminated early so that sample size assumptions were not met, meaning that there was a high chance of a beta type error, that is, that no difference was detected between the groups despite the existence of such a difference. An analysis including the 20 and 40 month data failed to show an effect on the change in the cognitive test scores utilized. However, in the sub-group that underwent brain MRI, a significant difference was noted in the change in Copyright © 2013 John Wiley & Sons, Ltd.
As higher glucose levels are associated with a higher prevalence of CV risk factors and CV disease, the relationship with cognitive dysfunction may be mediated through CV disease. However, in many of the studies after adjustment for CV disease and CV risk factors, the relationship remained.
Hyperglycaemia It is also possible that chronic exposure of the brain to high levels of glucose may accelerate cognitive decline. Indeed, post-mortem studies from the brains of people with AD demonstrate metabolic oxidation products associated with hyperglycaemia [36,37]. A recent study in older individuals demonstrated an inverse relationship between glucose levels and function of the dentate gyrus, an area of the brain thought to be important in age-related cognitive decline [38].
Impaired insulin activity There are many insulin receptors in the brain. Some have a role in glucose transport, but many are thought to have a function in cognitive processes [39]. Several observations suggest that cognitive decline is a consequence of insufficient insulin action in the brain, either due to insulin resistance, insulin deficiency or both. Thus, (a) in individuals without diabetes, worse glucoregulation (as measured by a glucose tolerance test) was associated with worse outcomes on cognitive assessment, especially in the elderly [40]; (b) individuals with AD have less efficient glucoregulation than unaffected individuals [41]; Diabetes Metab Res Rev 2014; 30: 341–345. DOI: 10.1002/dmrr
344
T. Cukierman-Yaffe
exposure of individuals with AD to a hyperinsulinemic euglycaemic clamp improved cognitive function, whereas exposure to an euinsulinemic hyperglycaemic clamp had no effect [40–43]. There have been several small scale, short duration studies looking at the effect of a form of insulin that enters the brain selectively – intra-nasal insulin. In a recent systematic review, these studies were summarized. All studies were of a very short duration (up to 8 weeks) and showed some effect [44]. The preliminary results of a 4-month randomized controlled trial of 104 participants with Minimal Cognitive Impairment/early AD have recently been published. The patients were randomized to placebo, 20U, 40 U of intra-nasal insulin. In the short follow-up, they demonstrated an improvement in delayed memory (p < 0.05) and in preservation of caregiver rated functional ability (p < 0.01) [45].
Microvascular disease Finally, microvascular disease may also be responsible for the deleterious effects of chronic hyperglycaemia on cognitive function. Microvascular disease has been demonstrated to be worsened by chronic hyperglycaemia [46,47]. In people with diabetes, it causes pathology in the retina and in the peripheral nervous system. Thus, it
may well be that microvascular disease occurs also in the brain resulting in cognitive dysfunction.
Conclusion Diabetes may be viewed as a disease of accelerated cognitive ageing. It is a risk factor for progression of cognitive impairment and for future dementia. Thus, diabetes-related cognitive dysfunction should be considered another complication of diabetes. Especially in the elderly, cognitive dysfunction should be screened for as it may affect self-care capacity of the individual and thereby increase the risk of hypoglycaemia. More studies aimed at finding the optimal way to screen and measure progression of cognitive dysfunction in people with diabetes are needed. This may be a first step in aiding people with diabetes to healthier cognitive ageing as well as to elucidating treatment options. More studies are needed to gain insight into the mechanisms and risk factors for diabetes-related cognitive dysfunction. Finally, ongoing intervention studies in people with diabetes should include measures of cognitive function.
Conflict of interest None declared.
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Diabetes Metab Res Rev 2014; 30: 341–345. DOI: 10.1002/dmrr
