**2.3 Influence of age and cognitive impairment**

A prospective study is done to observe and determine the impact of DM on the cognitive function impairment in the oldest of the old participants. The study was conducted using prospective population method. They have chosen approximately 599 participants with the respond rate of 87% with the age ranges from 85 to 90 years old. The memory function test does not show any differences between both diabetic and nondiabetic participants. Cognitive function of diabetic participants is affected when the time and speed test has been conducted [29].

The results of another research show that diabetic patients more than 65 years old have higher chances to be associated with impaired cognitive function [24]. Besides that, one more study was conducted that is related to assessing the status of cognitive function in people that have DM. The chosen patients were assessed by using MMSE and 3MS (the modified mini-mental state examination). The scores for both assessments were 30 and 100, respectively. At the same time, the relationships of age, gender and duration of diabetes and HbA1c among the DM with 3MS will also be assessed. The results of this study were diabetic patients have lower

MMSE and 3MS than nondiabetic patients. This mean cognitive function will be reduced as the age increases and when having DM [30].

The uncontrolled DM which is one of the risk factors for cognitive impairment and dementia especially in Alzheimer patients. Therefore, controlling DM can reduce the possibility to get cognitive impairment and Alzheimer disease [5].

#### **2.4 Association between duration of DM and age towards cognitive impairment**

According to a homogenous cohort study on the community-dwelling women in 11 US states. This study focusses on women that live in the community which are on their own compared to living in nursing or old folk home. The result of this research was participants (women) with type 2 DM had lower mean score in all the tests conducted than women without DM. At the same time, when duration has been diagnosed with DM and insufficiency in pharmacological treatment, it can worsen or cause increment in cognitive impairment. One of the limitations for this research is self-reporting regarding diabetes diagnosis [31].

Meanwhile, another study was done regarding the cognitive impairment in diabetic patients with special references to age of onset, duration and also control of diabetes. The study was conducted in diabetic patients that came to the medicine inpatient and outpatient departments and diabetic clinic of SSKM Hospital, India. It is used to calculate the mean effect of sugar control after a 6-month period. The result of this study was cognitive impairment has a relationship with diabetes. The cognitive function that usually affected were recognition, fluency and immediate memory power of the patients. Control of DM can help in improving cognitive function of the patients. Other habits such as smoking, poor control of sugar intake as well as life style can enhance the effect of cognitive impairment [32].

A cross-sectional study was conducted which is related to prevalence and predictors of cognitive dysfunction in type 2 DM population of Punjab, India. The study involves 516 type 2 DM participants that attended the endocrinology outpatient department of the Government Medical College and Hospital, Patiala, Punjab, India. The result of this study shows that many of diabetic participants that are living in Punjab, India, remain undiagnosed with cognitive impairment during their life. Cognitive impairment in diabetic participants is independently influenced by duration of diabetes, age of the patients and other complications besides diabetes such as hypertension and others [33].

#### **2.5 HbA1c control and cognitive decline**

HbA1c is recommended to be used to identify the people at risk of developing diabetes as well as to diagnose diabetes. It is the most important biomarker for the management of blood glucose control in individuals with already diagnosed diabetes [34]. It is also a strong predictor for ensuing diabetes, because it incorporates the average blood glucose level over the last 2–3 months [35] and has better reliability than fasting or postprandial blood glucose test [36]. The cohort studies conducted in middle-aged populations show that the cognitive decline in people with diabetes is significantly faster than those with normal blood glucose levels [26, 37]. The study also reported that there is no significant difference in cognitive decline in people with prediabetes than in those with normal blood glucose levels [13]. On the contrary, the other study reported significantly faster cognitive decline among people with prediabetes than those with normal HbA1c levels [26]. The longitudinal study done reported significant longitudinal associations between HbA1c levels, diabetes status and long-term cognitive decline [38].

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**Table 2.**

*Cognitive Dysfunction in Diabetes Mellitus DOI: http://dx.doi.org/10.5772/intechopen.85940*

other pathways [61].

**3.2 Treatment strategy**

glycaemic control [67].

Attention [42] Visuoconstruction [42]

Memory [44] Motor speed [41, 49–51] Vocabulary [44, 52–54] General intelligence [53, 54] Visual perception Motor strength [51] Executive function [49, 57]

**Table 1.**

Slowing of information processing [39–42] Psychomotor efficiency [39, 40, 44]

**3. Cognitive deficits in patients with type 1 and type 2 DM**

The cognitive domains that were negatively affected have been identified in

The cognitive domains that were negatively affected have been identified in

The link between diabetes and cognitive impairment was first reported in 1922 [58]. The exact physiologic pathways linking the two conditions remain unclear. The hypothetical mechanisms include which is related to cerebrovascular complications, neuronal glucose processing and frequent episodes of hypoglycaemia [3, 59, 60]. The diabetic patients are more prone to develop comorbid cardiovascular disease, which is itself predictive of cognitive decline through cerebrovascular events and

There are some complications of type 2 DM that affect the brain; it is believed that diabetes treatment may have beneficial effects on cognition. Three different trials reported that intensive glycaemic control alleviate microvascular complications but does not alleviate macrovascular complications in geriatric patients with long-duration of type 2 diabetes and high cardiovascular risk [62–64]. The intensive treatment of type 2 DM leads to hypoglycaemia which may contribute to cognitive decline and eliminate the benefits of intensive treatment [63, 65, 66]. Hypoglycaemia is more common in intensive glycaemic control than in standard

Psychomotor speed [43]

Working memory [45, 46] Verbal memory [47] Immediate recall Delayed recall [31]

Executive function [43, 45, 46]

Memory

Verbal fluency [43, 48] Complex motor function [43] Processing speed [47] Attention [55] Depression [45, 56]

patients with type 1 and type 2 DM with strong supporting data (**Table 1**).

patients with type 1 and type 2 DM with less supporting data (**Table 2**).

**3.1 Physiological pathways linking diabetes and cognition**

**Type 1 DM Type 2 DM**

*Cognitive domains affected by type 1 and type 2 DM (with strong supporting data).*

**Type 1 DM Type 2 DM**

*Cognitive domains affected by type 1 and type 2 DM (with less supporting data).*

*Type 2 Diabetes - From Pathophysiology to Modern Management*

reduced as the age increases and when having DM [30].

is self-reporting regarding diabetes diagnosis [31].

such as hypertension and others [33].

**2.5 HbA1c control and cognitive decline**

diabetes status and long-term cognitive decline [38].

MMSE and 3MS than nondiabetic patients. This mean cognitive function will be

The uncontrolled DM which is one of the risk factors for cognitive impairment and dementia especially in Alzheimer patients. Therefore, controlling DM can reduce the possibility to get cognitive impairment and Alzheimer disease [5].

**2.4 Association between duration of DM and age towards cognitive impairment**

According to a homogenous cohort study on the community-dwelling women in 11 US states. This study focusses on women that live in the community which are on their own compared to living in nursing or old folk home. The result of this research was participants (women) with type 2 DM had lower mean score in all the tests conducted than women without DM. At the same time, when duration has been diagnosed with DM and insufficiency in pharmacological treatment, it can worsen or cause increment in cognitive impairment. One of the limitations for this research

Meanwhile, another study was done regarding the cognitive impairment in diabetic patients with special references to age of onset, duration and also control of diabetes. The study was conducted in diabetic patients that came to the medicine inpatient and outpatient departments and diabetic clinic of SSKM Hospital, India. It is used to calculate the mean effect of sugar control after a 6-month period. The result of this study was cognitive impairment has a relationship with diabetes. The cognitive function that usually affected were recognition, fluency and immediate memory power of the patients. Control of DM can help in improving cognitive function of the patients. Other habits such as smoking, poor control of sugar intake as well as life style can enhance the effect of cognitive impairment [32]. A cross-sectional study was conducted which is related to prevalence and predictors of cognitive dysfunction in type 2 DM population of Punjab, India. The study involves 516 type 2 DM participants that attended the endocrinology outpatient department of the Government Medical College and Hospital, Patiala, Punjab, India. The result of this study shows that many of diabetic participants that are living in Punjab, India, remain undiagnosed with cognitive impairment during their life. Cognitive impairment in diabetic participants is independently influenced by duration of diabetes, age of the patients and other complications besides diabetes

HbA1c is recommended to be used to identify the people at risk of developing diabetes as well as to diagnose diabetes. It is the most important biomarker for the management of blood glucose control in individuals with already diagnosed diabetes [34]. It is also a strong predictor for ensuing diabetes, because it incorporates the average blood glucose level over the last 2–3 months [35] and has better reliability than fasting or postprandial blood glucose test [36]. The cohort studies conducted in middle-aged populations show that the cognitive decline in people with diabetes is significantly faster than those with normal blood glucose levels [26, 37]. The study also reported that there is no significant difference in cognitive decline in people with prediabetes than in those with normal blood glucose levels [13]. On the contrary, the other study reported significantly faster cognitive decline among people with prediabetes than those with normal HbA1c levels [26]. The longitudinal study done reported significant longitudinal associations between HbA1c levels,

**64**
