Report On Diabetes And Cognitive Loss In Adults Above 65 years old

INTRODUCTION

Currently, most of the world’s population suffers from major chronic diseases like Myocardial Infarction, Hypertension, Obesity and last but not the least Diabetes Mellitus. The discussion is based on Diabetes Mellitus with its essential effects on cognition in the individuals of 65 years of age or older. Diabetes mellitus is a highly complex metabolic disorder which affects nearly all the organs and normal physiological functions of the human body. It is mainly divided into two categories named as Type 1 Diabetes and Type 2 Diabetes. Type 1 has an autoimmune aetiology, while Type 2 is due to insulin resistance due to various other causes. Insulin and glucagon are the hormones typically produced by the β cells of the pancreas. Insulin has a role of regulating the blood sugar levels by various means like increased glycolysis, increased conversion into the storage form of glucose, i.e. glycogen and formation of TGs for storage.

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BACKGROUND

It is known that elevated blood sugar levels can result in brain malfunction. The pathophysiology behind it is that it promotes the synthesis of sorbitol, which accumulates and damages the cerebral blood vessels and causes degeneration of the nerves, ultimately resulting in neuropathology which can then lead to dementia or cognitive impairment (Kodl, & Seaquist, 2008). Researching about the word ‘Cognition’ tells us that it is “the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses” (Oxford, n.d). Whereas memory is the name given to “process of retention, recording, and retrieving the stored knowledge”. It also includes the knowledge gathered from experiences and applied skills (Goetz, 2007).

On the other hand the ‘working memory of brain’ is defined as the ability to store bits of information and simultaneously to be able to recall this information at the time it is needed for thoughts processing (Hall, 2010). The importance of this working memory is that as soon as it is damaged, a spectrum of cognition impairments start to occur. Thus the patient becomes unable to use the stored information for the process of thinking appropriately and tackling in different situations. Diabetes has a spectrum of complications ranging from hypoglycemia, hyperglycemia, atherosclerosis, MI, stroke, weight loss, diabetic foot, nephropathy, neuropathy and the one under our discussion, i.e. Cognitive decline/loss. Association of Diabetes with cognition has been known for a while; however, it is not mentioned as frequently as other complications. However, recently the impact of hyperglycemia on the cognitive ability of individuals has been the topic of interest. Moreover, it has been estimated by Misiak et al. that the prevalence of cognitive decline is expected to see a rise due to increase in the world population and progressive ageing of the population (Misiak, Cialkowska-Kuzminska, Frydecka, Chladzinska-Kiejna, and Kiejna, 2013).

SIGNIFICANCE

This topic holds a significant clinical as well as therapeutic importance because cognitive disability can cause various other problems in such a vulnerable age group, i.e. 65 years and older. Along with cognitive impairment, depression and functional disability have also been observed in the studies on the older population. It has been found that issues and co-morbidities of Diabetes Mellitus are more frequent in old diabetics compared to the young ones. The most prevalent of these complications are related to the cardiovascular system due to precocious atherosclerosis, a phenomenon highly specific to DM. In contrast, the most bothersome complications are visual and cognitive impairments, especially Alzheimer disease and other kinds of dementia (Chentli, Azzoug, & Mahgoun, 2015). All these complications are an essential issue for older adults as well as health care providers. It can lead to frustration, depression, and can give way to other mental and personality problems in the affected individuals. Similarly, based on this concept, the Alzheimer’s Association has been able to recognize and establish Diabetes as an essential risk factor for cognitive dysfunction and decline (“Diabetes and Cognitive Decline”, 2015).

Hence many studies have shown that there exists an association between diabetes mellitus and increased risk of Cognitive Loss. The same will be the topic of discussion in the following sections.

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METHOD

Databases used – research articles relevant to the topic under discussion were searched to know, understand, present and reach a particular conclusion by considering all the published reports. For this purpose, the databases used to explore articles were – MEDLINE, PubMed, SCOPUS, Web of Science, Science Direct, CORE, Science Open, Public Library of Science and Google Scholar. Other related information was obtained through Google Search.

  • Search terms

    applied were “Diabetes Mellitus in older adults”, “Hyperglycemia”, “Cognition”, “Cognitive Loss”, “Cognitive Loss in older adults”, “Diabetes Mellitus and Cognitive Impairment”. No filters of years of publication were applied. However, the main aim was to include all the recent articles. Filters of Comparative Study, Controlled Clinical Trials, Classical Articles, Observational Study, Multicenter Study, Introductory Journal Article and Journal Article etc. were mainly applied in the Article Type. There was no filter for Sex. Age parameter was chosen to be 65 years of age as it was relevant to our topic of study.

  • Inclusion criteria

    – All the articles which were Open Access, Full Articles and Full free text articles were included. All the chosen materials were in the English language. The main focus was to include credible studies conducted recently.

  • Exclusion criteria

    – Older studies and paid articles were excluded from the study. Along with those articles in the language other than English were also excluded.

RESULTS

Upon thorough research of the published articles, it was seen there has not been a definite result or outcome related to the topic under discussion. Hence the different effects which were obtained through the extensive literature search are summarized as follows:

DIABETES MELLITUS CAUSES COGNITIVE IMPAIRMENT

A cohort study was conducted on around 5653 participants in 1997. The participants enrolled in the study had a median age of about 55 years at the time of first cognitive assessment. The participants were followed up for ten years (1997-99 to 2007-09). During this period tests of memory, tests of reasoning, and a few other relevant tests were done three times. Moreover, a combined score for all the cognitive tests was also assessed. The results obtained from this extensive study showed that compared with the non-diabetic participants, the diabetic individuals with had a 45% faster decrease in the memory function (statistical results = ten-year difference in decline −0·13 SD, for 95% Confidence Interval −0·26 to −0·00; p-value obtained was p=0·046), people with Diabetes also had declined in reasoning at a rate of 29% faster (statistical results showed −0·10 SD, −0·19 to −0·01; and a p-value of 0·026), and in the overall cognitive score a decline of 24% was seen (statistical results showed −0·11 SD, −0·21 to −0·02; and a  p-value of 0·014).

Moreover, participants who were prediabetics or had recent onset of Diabetes depicted similar rates of decline to those with normoglycemic individuals. Similarly more inadequate glycemic control in the known diabetic participants was associated with a significantly faster regress in the memory at a considerably faster rate (p-value of 0·034) with a decrease in reasoning that was also significant (p-value of 0·052). Hence this study clearly shows a positive correlation of Diabetes with cognitive impairment with essential emphasis on the duration of Diabetes because the duration of this disease contributes to faster cognitive dysfunction. At the same time, an excellent glycemic control could reduce this risk (Tuligenga, Dugravot, Tabák, Elbaz, Brunner, Kivimäki, & Singh-Manoux, 2014).

In another community based prospective study, 13351 participants were enrolled belonging to black and white ethnic groups. They were representatives of mid-adults to older age groups at baseline time (1990-1992) were followed for 20 years. The results showed that Diabetes was linked with a significantly higher rate of 19% cognitive decline than those without Diabetes, over 20 years (statistical analysis showed adjusted Z-score difference of -0.15, with 95% Confidence Interval -0.22,-0.08). Cognitive decline was also seen to be significantly higher among pre-diabetes than those without Diabetes. Moreover, participants with poorly controlled Diabetes, i.e. HbA1c ≥7.0% had a more significant decline as compared to individuals who had controlled Diabetes (statistical analysis showed adjusted Z-score difference of -0.16, and p-value = 0.071). Similar to the study discussed above, this one also recognized the longer duration of disease to be associated with considerable late-life cognitive dysfunction (p-value for trend = <0.001). However, there was no significant difference in the rates of declines in white individuals as compared to blacks (Rawlings, Sharrett, Schneider, Coresh, Albert, Couper et al., 2014).

The American Diabetes Association (ADA) discusses and closely monitors all the ongoing issues and researches. The article published by this significant association also states the same thing that cognitive loss appears to be a consequence as well as a risk factor for poor diabetes self-management and associated glycemic levels. This article has discussed various other studies which were done to find out the relationship of cognitive impairment with the variable of age. Hence it only includes the data of the older individuals but also about the impact on the cognitive ability of the children and middle-aged diabetics. Moreover, it states that some treatment strategies such as cognitive compensatory strategies, assistive technology, and other simplified regimens may curb the effect of cognitive dysfunction on self-management in older adults having Diabetes (Chaytor, 2016).

DIABETES MELLITUS CAUSES A DECLINE IN COGNITIVE IMPAIRMENT

There are various epidemiological studies on the positive association of Diabetes with Cognitive Loss. Still, another exciting aspect of it can be seen by the studies which show the opposite of what has already been mentioned. In this regard, a cohort study, including 608 patients having Alzheimer’s disease, were enrolled. Mini-Mental State Examination (MMSE) score of these patients was somewhere between 10 and 26. It was a prospective and a multicenter study in which the participants were followed up to around 50 months. Diabetes Mellitus was evaluated at baseline via the history of the disease or use of medication) and cognitive function of the patients was evaluated after every two years with the MMSE. The results of this study show that considering a mixed model adjusted for age, gender, dementia severity, and vascular factors such as hypertension, coronary artery disease, and hyperlipidemia there were no differences found between the groups considering their MMSE scores (-0.75, p-value = 0.20), but the cognitive loss was found to be slower in the group of diabetic individuals (0.38, p-value = 0.01). Thus this shows that the existence of Diabetes mellitus in the individuals was in fact associated with a lower rate of cognitive loss contrary to the popular concept of positive association (Sanz, Andrieu, Sinclair, Hanaire, Vellas & REAL.FR Study Group, 2009).

Another study was done to assess and evaluate the role of Diabetes on the cognitive function loss in the old participants, i.e. with the range of age between 85 to 90 years old. This study was done using prospective population method, and a total of 599 participants were enrolled with the response rate of 87%. The results of the study show that there is no difference between the memory function test of both the diabetics and non-diabetics (Shaikh, Bhuvan, Htar, Gupta, & Kumari, 2019).

Similarly, a study was performed, which analyzed the results from 2 longitudinal and one cross-sectional study. Since it is known that Diabetes is connected both with cognitive loss and depressive symptoms while depression itself has been linked with cognitive loss directly. Hence, the aim of this study was to analyze the possible impact of depressive symptoms on the relation between Diabetes Mellitus and cognitive functions of the brain. The results that were obtained showed that Diabetes was not the cause of accelerated cognitive decline over the course of three years of follow-up in people with Diabetes relative to the control group (Koekkoek, Rutten, Ruis, Reijmer, van den Berg et al., 2013).

These two different sets of results can be described by several factors like dissimilarities in the method of study and design of the study, demographic features of the participants, i.e. age of participants, level of education etc., presence of Diabetes, and prevalence of risk factors. Thus it is unclear whether the likelihood of cognitive impairment is uniformly linked with Diabetes throughout the world or not. Similarly, it is also unclear whether this association is related to subgroups that are marked by varying levels of disease and the presence of co-morbidities. On the other hand, there is a possibility that differences observed in the association between cognitive loss and Diabetes are actually due to the diagnostic criteria which were adopted to define cognitive impairment and dementia etc.

Hence the strong evidence given by epidemiological studies in support to the common idea that recognizes the link between the two, i.e. Diabetes and Cognitive Impairment holds a greater value because the studies performed to determine the relationship were based on hundreds and thousands of participants and were multicenter studies. They were also followed up for as long as 10 20 years which clearly shows the importance of the research along with its validity, reliability and clinical implications. Therefore the final result which this article supports is the one which establishes the idea of the positive impact of Diabetes in declining the cognitive functions of the human brain.

DISCUSSION

Things which are known about the topic –

After being able to draw conclusions by doing a comprehensive analysis of various significant and large scale studies now we can discuss the possible causes or mechanisms which govern cognitive impairment in older diabetic individuals. The underlying pathophysiology involved in the development of cognitive dysfunction in diabetics has not been completely elucidated. However, many hypotheses do exist along with the supporting evidence like potential roles of hyperglycemia, vascular disease, hypoglycemia, insulin resistance, and amyloid deposition in causing the cognitive impairment. Further elaboration of the causative factors leads us to believe in the roles of hyperglycemia-induced end-organ damage, i.e. Microvascular disease, Macrovascular or cerebrovascular accidents, Insulin resistance, absence of C-peptide, absence of apoƐ4 allele and repeated episodes of hypoglycemia (Kodl, & Seaquist, 2008).

In another critical study, there has been documented that abnormal insulin signalling has a crucial role in triggering and initiating the phenomenon of neurodegeneration which can ultimately lead to cognitive impairment. Insulin affects the brain by downregulating the insulin receptors in the brain due to prolonged hyperinsulinemia, by causing an increase in Aβ as well as other inflammatory substances in the brain resulting in more neurofibrillary tangles and senile plaques, thus possibly causing an impaired cognitive state.

In a different cross-sectional study, the role of Diabetes in neurodegeneration has been confirmed by various neuroimaging techniques and neuropathological studies. MRI studies have been able to prove the fact that Diabetes is strongly associated with brain atrophy (Moran, Phan, Chen, Blizzard, Beare et al., 2013). In fact, the rate of global brain atrophy is up to 3 times faster in people with Diabetes than in normal ageing (van Elderen, de Roos, de Craen, Westendorp, Blauw et al., 2010).

Other mechanisms of cognitive impairment include chronic inflammation and genetic predisposition. Elevated levels of inflammatory cytokines are associated with the worsening of the cognition while genetic basis can be traced to the individuals possessing Apo E epsilon four allele (Saedi, Gheini, Faiz, & Arami, 2016).

The idea that links the incidence of Alzheimer’s disease with Diabetes Mellitus can be supported by a study which was conducted on around 800 older adults and women. The results of which showed that chronic and uncontrolled hyperglycemia could result in slowly progressive functional and structural abnormalities in the brain, along with a risk of about 65% occurrence of Alzheimer’s disease in Diabetics (Arvanitakis, Wilson, Bienias, Evans, and Bennett, 2004).

Gaps in the knowledge –

Now, after many critical and large scale studies, the fact that Diabetes and cognitive loss are related is well established. However, there is a lack of awareness regarding cognitive dysfunction, depression, and other physical disabilities. Cognitive dysfunction has been the topic of discussion because it holds a significant impact on the quality of life and self-care of the patients. Doctors follow a patient-centric management strategy for diabetics which are universal. But some age-related conditions are not well understood, and their impact on the management of Diabetes in the ageing population is still evolving. According to a study, presently, it is unclear whether improving glycemic control can improve the risk of cognitive decline. The studies performed to evaluate the impact of glycemic control on the progression of cognitive impairment in diabetics have shown conflicting results; therefore, nothing can be said with certainty (Munshi, 2017). Hence the gaps which currently exist must be filled up by research being focused on other possible strategies to Manage Diabetes in the presence of cognitive dysfunction and to decline it. A randomized controlled trial was done in this regard to assess and determine the role of intervention to induce and maintain weight loss in improving cognitive function, but the results of that study were failed to record any cognitive benefit (Rapp, Luchsinger, Baker, Blackburn, Hazuda et al., 2017).

CONCLUSION

Older adults are an essential part of our society, and as the population curve is on the rise, so is the proportion of older individuals in the world. Chronic disease is almost always are painful to bear for the patient and challenging for the health care workers to treat. Diabetes is a multiplex disease with a vast set of complications, and currently, the prevalence of the disease is on the higher end due to sedentary lifestyle and poor dietary habits. Cognitive impairment has now been a well-recognized complication of Diabetes, and all age groups are being affected with it. However, older adults seem to suffer more from it, which not only impairs their capabilities and mental capacity but also leave them hopeless and helpless. In order to find an effective solution to this problem, more studies are required which should explore various ways to decline and slow down the rate of progression of cognitive dysfunction in an older population. Moreover, proper awareness programs must be run to spread enough knowledge about the disease and its fearsome complications so that they can be avoided to some extent in the later ages. Clinicians must also play their roles at every possible level in order to save the individuals from brutal complications and consequences of the Diabetes Mellitus.

References

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