Type 2 Diabetes Cognition And Dementia In Older Adults: Toward A Precision Health Approach
Diabetes Spectr
Brenna Cholerton, Laura D. Baker, Thomas J. Montine, Suzanne Craft Type 2 Diabetes, Cognition, and Dementia in Older Adults: Toward a Precision Health Approach. Diabetes Spectr 1 November 2016 29 : 210219.
IN BRIEF There has been a concurrent dramatic rise in type 2 diabetes and dementia in the United States, and type 2 diabetes shares common genetic and environmental risk factors and underlying pathology with both vascular and Alzheimers dementias. Given the ability to identify this at-risk population and a variety of potential targeted treatments, type 2 diabetes represents a promising focus for a precision health approach to reduce the impact of cognitive decline and dementia in older adults.
A confluence of factors related to dietary changes, sedentary lifestyle, and an aging population in Western cultures has led to a rapid rise in the incidence of type 2 diabetes, a disease that carries enormous burden in terms of health and economic outcomes. Increasingly, type 2 diabetes is recognized as a major contributor to cognitive decline and dementia in older adults. As both type 2 diabetes and dementia reach epidemic proportions in the United States, the need to identify methods of prevention and treatment grows increasingly important.
Whats The Link Between Diabetes And Alzheimers
Although scientists have yet to discover the exact mechanism of how diabetes and Alzheimers is linked, they have confirmed that high blood glucose can harm the brain in the following ways:
#1 Uncontrolled blood sugar can affect the blood vessels in the brain which may be a contributing factor of Alzheimers.
#2 The unstable insulin and high blood sugar can cause an imbalance of chemicals in the brain.
#3 Hyperglycemia leads to inflammation in the body that may damage brain cells.
Strategies To Reduce Your Risk Of Alzheimers/ Dementia
Many risk factors that lead to the development of Alzheimers disease are related to controllable lifestyle factors these are things you DO, things you can control, such as diet and exercise.
Being proactive and taking control of your diabetes can help reduce your risk of many forms of cognitive impairment, including Alzheimers disease.
So heres what you can do:
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Amylin Dyshomeostasis: A Bridge Between Ad And Non
Amylin is a pancreatic -cell hormone co-secreted with insulin and plays a role in normal glucose homeostasis. Amylin from humans is amyloidogenic and aggregates quickly when overexpressed. The majority of individuals with T2DM have large deposits of aggregated amylin in the pancreatic islets, kidneys and heart. Aggregated amylin induces cell dysfunction and apoptosis. Accumulating data from several laboratories have confirmed that the brains of patients with T2DM and AD contain an abnormally increased level of aggregated amylin and mixed amylin-A plaques . A recent epidemiological study indicated also a genetic risk for developing mixed A-amylin plaques in the brain. The results indicate amylin dyshomeostasis as a possible new link between T2DM and increased risk of AD.
Pancreatic amylin forms amyloid and interacts with A in the brains of patients with T2DM Sections through the brains of patients with T2DM and AD showing amylin-positive vascular wall contours in capillaries , small arterioles , neurons and plaques . Vascular amylin deposits in shows apple-green birefringence in the Congo red stain . Same blood vessel shows no A immunoreactivity . Amylin interacts with A forming cerebral mixed amylin-A deposits . In J, vascular deposition of amylin and astroglial reaction are shown. A and J are from Ref., B,C, F, G, H and I are from Ref. , D and E are from Ref. .
Toward A Precision Medicine Model For Dementia: Type 2 Diabetes As A Target Risk Factor
Precision health uses emerging knowledge about specific diseases to identify optimal and targeted interventions based on individually determined risk factors. To effectively adapt the concept of precision health to cognitive impairment and dementia in older adults, it is imperative to first identify groups of differing risk.
Dementia develops as a result of a complex interplay of clinical and biological factors and is beset by multiple underlying pathological features. People with type 2 diabetes represent an important risk group for cognitive impairment and dementia caused by both Alzheimers disease dementia and vascular brain injury. For example, a recent meta-analysis found that type 2 diabetes was associated with a 60% increase in risk for all-cause dementia , and a population-based longitudinal study found a 16% increased risk for dementia even among those in which type 2 diabetes onset was recent . Furthermore, type 2 diabetes increases the risk of mortality in patients who already have dementia, suggesting that targeted intervention at any point may improve health outcomes . Although many of these studies examined risk related to all-cause dementia, there is evidence that two specific subtypes, Alzheimers disease dementia and vascular dementia, are most strongly associated with type 2 diabetes.
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What Can I Do To Reduce The Risk Of Dementia
The most important thing to do is to control your blood sugar levels. This can be done by having a healthy diet, exercising regularly, taking your medications as prescribed, and to stay socially and mentally active.
Alzheimers disease and type 2 diabetes: A growing connection. Alzheimers Association. Accessed 5/9/2017. URL Link
Diabetes and dementia in older adults. BD. Accessed 5/9/2017. URL Link
Diabetes and dementia is there a connection. Alzheimer Society Canada. Accessed 5/9/2017. URL Link
Low Blood Sugar May Trigger Dementia In Those With Diabetes
Older adults with diabetes who experience severe episodes of low blood sugar, or hypoglycemia, are at increased risk of developing Alzheimers disease and other forms of dementia, a new study shows. And those with diabetes and dementia are more likely to experience hypoglycemia.
The results suggest that hypoglycemia and dementia can create a vicious cycle, in which low blood sugar damages the brain, which in turn makes people less able to manage their diabetes, leading in turn to more episodes of low blood sugar. Older patients with diabetes may be especially vulnerable to a vicious cycle in which poor diabetes management may lead to cognitive decline and then to even worse diabetes management, said Dr. Kristine Yaffe, the senior author.
The findings, which appeared in the journal JAMA Internal Medicine, add to a growing body of evidence linking Type 2 diabetes to Alzheimers and other forms of dementia. Studies suggest that having diabetes may increase the risk for developing serious memory and thinking problems, including dementia. And some research has suggested that careful control of diabetes can help to prevent memory decline. In addition, low levels of blood sugar in the brain can trigger thinking problems and damage nerves.
Hypoglycemia commonly occurs in patients with diabetes mellitus and may negatively influence cognitive performance. Cognitive impairment in turn can compromise diabetes management and lead to hypoglycemia, the authors wrote.
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Clinical Symptoms In Dementia Associated With Diabetes
Diabetic patients show impaired cognitive function, increased behavioral symptoms, and decreased activity of daily living . Diabetic patients show impairment of memory , attention , executive function , information processing , planning , visuospatial construction , and visual memory . Diabetic patients are reported to have impaired memory retrieval rather than encoding . Patients with higher HbA1c have increased behavioral and psychological symptoms such as apathy, overeating, and excessive daytime sleeping, and also have impaired activities of daily living . Therefore, the knowledge about brain alterations and clinical symptoms suggests that diabetes affects cognitive function through not only simply AD pathological feature-dependent mechanisms but also independent mechanisms .
Table 2. Comparison of cognitive and behavioral alterations in diabetes and Alzheimer disease.
Figure 1. Association of dementia with diabetes: A/tau-dependent and independent mechanisms. Diabetes modifies cognitive function through A/tau-dependent and independent mechanisms. Interaction between these two mechanisms forms a vicious cycle.
How Diabetes Relates To Memory Loss
Memory loss and general cognitive impairment, which are both symptoms of AD, may be connected to type 2 diabetes. Damage to the blood vessels is common in people with diabetes. This damage can lead to cognitive problems and vascular dementia. These are often seen with symptoms of AD.
The results of one study show that AD is closely connected to insulin signaling and glucose metabolism in the brain. The brain contains insulin receptors. These structures recognize insulin. Insulin affects cognition and memory. When the insulin in your body is imbalanced, it increases your risk for AD. This imbalance can occur in people with type 2 diabetes.
Scientists also looked at how symptoms of metabolic syndrome affect memory. Metabolic syndrome is a risk factor for type 2 diabetes. Symptoms of the syndrome can include:
- increased blood pressure
- abnormal cholesterol levels
- increased body fat especially around the waist
The study concluded that the connection between high levels of sugar and AD goes both ways. People with metabolic syndrome have a higher risk of developing AD. People with AD often develop hyperglycemia and insulin resistance.
These conclusions are reinforced by a review published in
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The Connection Between Uncontrolled Diabetes And Dementia
Diabetes mellitus is a group of diseases that influence your bodys utilization of blood sugar. Known to have two types 1 and 2 , both categories are characterized by excessive levels of blood sugar. People with uncontrolled diabetes usually suffer from a variety of complications, such as cardiovascular problems, nerve damage, kidney damage and eye damage, to name a few. Nowadays, it is has also been linked with higher risks of dementia, even Alzheimers disease.
The Possible Benefits Of Metformin For Type 2 Diabetes And Other Health Conditions
Meanwhile, its important for people who have type 2 diabetes, prediabetes, or a family history of diabetes to understand that they are not automatically destined to develop Alzheimers disease. Nor will consuming sugar in moderation necessarily lead one down that path, assuming that your blood glucose levels are under control. Actually, theres plenty people can do to decrease their risk.
My advice to somebody, whether they have or dont have diabetes, is that if they want to try to minimize their risk for Alzheimers disease, then try to do the things that guard against insulin resistance, such as staying lean and exercising, Kahn says.
Learn more about the relationship between these two conditions in Diabetes Daily’s article “Alzheimer’s Disease and Diabetes: What’s the Connection?“
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Diabetes And Dementia: Glycaemic Targets
Older people with dementia are likely to be frail with limited life expectancy and thus a target HbA1c of 6475mmol/mol is appropriate. Tight glycaemic control in this population may be harmful by inducing hypoglycaemia and reducing quality of life. Also higher HbA1c > 75mmol/mol has been shown to be associated with increased mortality.19 More importantly, targets in this population should focus on short term day-to-day blood glucose levels rather than a long term HbA1cdue to a limited life expectancy. This will avoid both hyperglycaemiawhich may lead to lethargy, dehydration, visual impairment and infections, and hypoglycaemiawhich may lead to falls and confusion. Short-term targets in a comfortable daily range of random blood glucose > 4 but < 15mmol/L is appropriate as blood glucose outside this range is likely to be symptomatic and results in cognitive changes.20
Patterns Of Brain Injury
There is an expanding literature on brain imaging studies in patients with diabetes,, although it should be noted that few studies included patients who were affected by MCI or dementia. As a framework for the interpretation of the findings, it is important to distinguish between imaging markers that primarily reflect brain injury, markers that reflect specific etiological processes, and markers that reflect both. Markers of injury include, for example, measures of atrophy and microstructural white matter integrity. Although patterns of injury may be suggestive of a particular etiology, they are by no means etiologically specific . Markers of etiological processes include for example amyloid PET and measures of cerebral blood flow, although the latter may also change as a consequence of brain injury.
It is clear from the literature that T2DM is associated with brain atrophy , although the regional pattern of brain volume changes varies between studies,. The magnitude of the volume reduction is modest, with effect sizes of 0.20.6 SD units, comparable with 35 years of normal aging. Another emerging marker of brain injury in T2DM is diffusion tensor imaging . This technique allows to explore microstructural integrity of the white matter and related changes in brain networks. DTI studies show widespread changes in white matter microstructure and connectivity in relation to T2DM, which are clearly related to cognitive dysfunction,.
Brain imaging findings in patients with T2DM
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Type 2 Diabetes And Alzheimers Disease Dementia
The importance of the connection between type 2 diabetes and Alzheimers disease dementia is perhaps best captured by the term type 3 diabetes, coined to describe a portion of patients who develop Alzheimers disease dementia presumably as a result of diabetes-related injury and degeneration . Meta-analytic data demonstrate a 56% increased risk for Alzheimers disease dementia among individuals with type 2 diabetes . Among the studies included in the meta-analysis was the prospective, community-based Rotterdam study, which found that type 2 diabetes significantly increased the risk of Alzheimers disease dementia, with greater risk apparent in people who were treated with insulin at baseline . A type 2 diabetes diagnosis appears to raise the risk for Alzheimers disease dementia independently from vascular or other dementias or from APOE E4 gene status . Among patients already diagnosed with Alzheimers disease dementia, an increased prevalence of type 2 diabetes and impaired glucose tolerance was reported .
How Can I Reduce My Risk Of Alzheimers
Some of the preventative measures are similar to the lifestyle guidelines given to people with diabetes, namely:
- Stopping smoking
- Eat a healthy balanced diet
- Take some exercise each day
In addition, its recommended to keep your mind active and engaged by maintaining a social life, reading, writing, playing games or taking part in a course.
Reading, writing and being social can all be done on our very own Diabetes Forum
Keeping in good control of diabetes is also likely to reduce the extent of risk for Alzheimers.
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Hypoglycemia: Another Risk For Dementia
While spiked levels of blood glucose a hallmark of diabetes put a person at risk of developing dementia, further studies show that too low levels can have the same effect as well.
Researchers believe that this condition known as hypoglycemia deprives the brain of energy thus leading to damages that might cause dementia. Rallying this claim is a 2009 study printed in the Journal of the American Medical Association. The research featured more than 16,000 patients listed in a Californian diabetes registry. When these subjects enrolled in the study in 2003, none was diagnosed with dementia. Four years after, however, roughly 1,800 participants or 11% of the population have been diagnosed with dementia.
According to the statistics, those who were treated in the hospital once for hypoglycemia have a 26% risk of developing dementia, while those treated three or more times have double the risk compared to those with untreated hypoglycemia. While these researchers are lobbying for a less-aggressive approach on diabetic treatment, many physicians are calling for more studies before the revision of current therapeutic protocols.
Cognitive Dysfunction And Diabetes: Scope Of The Problem
There is strong epidemiological evidence for links between diabetes and cognitive dysfunction . Importantly, cognitive dysfunction in relation to diabetes should not be regarded as a unitary construct. Manifestations and prognosis of diabetes-associated cognitive dysfunction vary depending on diabetes type and age.
In children with T1DM, for example, there may be subtle changes in cognitive development, particularly in those with an onset of diabetes before the age of 7. Adults with T1DM also present subtle decrements in cognitive performance relative to age-matched controls, particularly affecting the domains intelligence , psychomotor efficiency , and cognitive flexibility . These decrements generally remain quite stable over time , although there may be subgroups of patients, particularly those with advanced microvascular complications, in whom the severity of cognitive impairment may worsen substantially over time,.
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What Is Diabetic Rage
What’s sometimes called “diabetic rage” can be dangerous, because it may involve behaviors a person isn’t consciously aware of. Physiologically, when someone’s blood sugar fluctuates, spikes, or drops, it can produce feelings of anger, anxiety, or depression that are out of the control of the person experiencing them.
Type 2 Diabetes And Vascular Dementia
Vascular disease represents a principle factor in accelerated brain aging, and vascular brain injury is an important contributor to cognitive dysfunction in older adults . Type 2 diabetes is a known risk factor for cardiovascular and cerebrovascular disease and may increase susceptibility to large and small caliber vesselmediated injury to the brain, including hypoxic events, ischemia, and blood-brain barrier leakage. Dysfunction of vascular endothelial cells secondary to insulin resistance and inflammation is a characteristic consequence of type 2 diabetes, and disruption of white matter networks is seen on neuroimaging in patients with type 2 diabetes . Furthermore, white matter dysfunction is associated with poorer cognitive performance in patients with type 2 diabetes .
Type 2 diabetes is frequently reported to be more strongly correlated with vascular dementia than with other types, including Alzheimers disease dementia. Indeed, a recent meta-analysis of prospective studies that examined the risk of dementia in patients with type 2 diabetes reported a pooled relative risk of 2.27 for vascular dementia . Interestingly, new evidence suggests the increased risk for vascular dementia may be especially prominent in women women with type 2 diabetes had a 19% greater chance of vascular dementia than men . In addition, those with longer duration and earlier age of onset of type 2 diabetes were more likely to develop vascular dementia.
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