Context (Background): Cognitive dysfunctions as the unexplored complications in diabetics need to be systematically studied. Aims: To assess the correlation between type 2 diabetes mellitus (DM) and associated cognitive dysfunctions with varying age groups and duration. Settings and Design: A hospital-based cross-sectional study was conducted in a tertiary care teaching institute in eastern India. Materials and Methods: In this study the participants were allocated into five groups according to duration of diabetes, for example, less than 3 months, 3 months-5 years, 6-10 years, 11-20 years, and more than 20 years. Each of these groups was then classified into following six subgroups according to age: group A (20 years or less), group B (21-30 years), group C (31-40 years), group D (41-50 years), group E (51-60 years), and group F (more than 60 years). A predesigned, pretested, semi-structured questionnaire was used to find the cognitive functions based on the Global Deterioration Scale (GDS) in diabetics and age-matched nondiabetic participants. Statistical Analysis Used: Statistical analysis using Statistical Package for the Social Sciences (SPSS) version 11.0 to calculate proportions and significance test were done in this study. Results: There was noticeable attenuation of cognitive functions in diabetics in all age groups irrespective of duration of the morbidity. Further, a distinct pattern of incremental cognitive dysfunctions was also noticed as the age progressed in diabetics and in healthy controls. Conclusion: Diabetics are more at risk of cognitive dysfunctions than age-matched controls, which needs more elaborative studies.
Keywords: Cognitive dysfunctions, duration of disease, type 2 diabetes mellitus (DM)
Diabetes mellitus (DM) affects all systems of the body and the cognitive dysfunctions resulting due to this is a global public health problem, particularly for the elderly population. Yet not many studies have been reported in the literature on the psychological effects of this morbid condition under varying state of affairs. 
Diabetes is a major and specific risk factor for cerebral microangiopathy with varying incidences as reported in several studies [between 5% and 25%] including subclinical cognitive impairment in middle-aged patients amidst well-known and widely accepted cerebrovascular complications along with risk correlates of arterial hypertension, smoking, and dyslipidemia. It is plausible that the main consequence of small cerebral vessels disease might be a cause of decrease in individual cognitive capability. ,,,
Numerous community-based sociodemographic studies have shown that diabetes is a specific risk factor intimately related to cognitive impairments particularly occurring in middle and elderly persons. , Other research groups have reported their analysis focussing the cognitive impairment of elderly age groups (above 60 years) and by now, this fact has been substantially a well-established matter of concern in the healthcare arena. ,,
Our study was conducted in a tertiary-care teaching institute in eastern India among participants presenting with diabetes, who were from all age groups and with varying durations of the disease, to find out the downstream effects of DM on cognitive impairment.
A hospital-based cross-sectional study was conducted in a tertiary-care teaching institute in eastern India to find correlation between DM and cognitive functions across varying age groups and durations of the disease.
The study was conducted from July 2010 to June 2013.
All the consecutive diabetic patients presenting at the outpatients departments of general medicine, pediatric, and diabetic clinic were included as participants in this study; consecutive nondiabetic subjects were considered as controls. The participants were divided into the following age groups for the purposes of comparison: Group A (aged up to 20 years), group B (aged 21-30 years), group C (aged 31-40 years), group D (aged 41-50 years), group E (aged 51-60 years), and group F (aged above 60 years). Further comparisons were made between controls and diabetic patients with different durations of the disease (less than 3 months, 3 months-5 years, 6-10 years, 11-20 years, and above 20 years).  In all these groups, factors such as restrictions on gender, ethnicity, literacy, occupation, addiction, dietary patterns, nonpsychiatric comorbidities, and medications were set aside for participation requisites of inclusion or exclusion.
Data collection procedure
Ethical clearance was obtained from Institutional Ethics Committee. The data-collection tool used for this study was an interview schedule that was developed at the institute with the assistance from the faculty members and a statistician. A predesigned, pretested, and semi-structured questionnaire was used to collect the data relating to cognitive function based on the Global Deterioration Scale (GDS). By initial translation, back-translation, retranslation followed by a pilot study, the data were collected, and this collection module was custom-made for the study. The pilot study was carried out at the outpatient department among comparable subjects, following which some of the questions from the interview schedule were modified. Informed consent was obtained from each of the participants and in the case of minor from his or her caregivers wherever necessary. Persons who were severely ill and those with known psychiatric morbidity, pregnant women, and nonconsenting individuals were excluded from the study.
Operational definitions used
GDS: The GDS was used for the evaluation of cognitive function in our study. Initially the participants were assessed on overall characteristics on the GDS for a preliminary diagnosis of mild cognitive impairment (MCI).  These characteristics were as follows: (a) mild decline in cognitive function reported by the patient or caregiver and confirmed objectively, which is more than typical for age, but less severe than dementia; (b) mild impairment, primarily involving memory; and (c) a subtle impairment in complex, instrumental activities of daily living (keeping the common activities of daily living intact). The GDS thus provided an overview of the stages of cognitive function that can be classified into seven different levels: levels 1-4 (predementia stages) and levels 5-7 (dementia stages where individual cannot survive without assistance) – each level was numbered (1-7) with short title (i.e., forgetfulness, early confusional, and others followed by a brief characteristics for that stage). The levels are as follows: 
Level 1: No cognitive disorder – clinically normal.
Type 2 DM [formerly known as noninsulin-dependent DM (NIDDM) or adult-onset diabetes] is a metabolic disorder that is characterized by hyperglycemia (high blood sugar) in the context of insulin resistance and relative lack of insulin. 
Only those participants were included in the study who presented with DM with no accompanying disease or condition that requires certain medications that affects the mental status.
The collected data were thoroughly screened and entered into Excel spreadsheets and were analyzed for interpretation. Statistical Package for the Social Sciences (SPSS) version 11.0 (SPSS-Inc., Chicago, US) was used to calculate proportions. Significance test was also used in this study.
Overall minimum cognitive dysfunction was in 21.33% among those detected less than three months in less than 20 years age group. In this group, the cognitive dysfunction were noted highest in 60 years and above in control (27.27%) and in diabetic (46.96%) followed by 51-60 years age group controls (12.28%) and diabetics (41.93%), respectively [Table 1].
Minimum cognitive dysfunction was in 34.37% among diabetics detected between 3 months and 5 years in less than 20 years age group. In this group, cognitive dysfunction was maximum above 60 years of age in controls (34.16%) and in diabetics (51.61%) followed by controls (32.00%) and diabetics (48.48%) from the 31-40 years age group [Table 2].
Under 20 years of age, cognitive dysfunction were noted minimum (39.21%) among those cases who are suffering for the 6-10 years. Cognitive dysfunction were 56.31% in diabetics in more than 60 years age groups followed by 54.90% in 51 to 60 years age groups [Table 3].
Similarly, minimum cognitive dysfunction was noted in diabetic cases (48.57%) from the less than 20 years age groups for whom diabetes was detected within last 11-20 years of age. In this group, the maximum cognitive dysfunction was 67.34% in 51-60 years age groups followed by 59.45% in 41-50 years age groups [Table 4].
Again minimum cognitive dysfunction was noted in diabetic cases (42.85%) from less than 20 years age groups who were suffering from diabetes for more than 20 years. In this group, the maximum cognitive dysfunction was 70.58% in 51-60 years age groups followed by 66.66% in 41-50 years age groups [Table 5].
As per the overall data across all age groups irrespective of the duration of diabetes, normal cognitive function (level 1) was noted among 73.57% in the nondiabetic control groups and 53.55% in diabetic groups. Cognitive dysfunction in diabetic groups was 46.45% and it was only 26.43% in control groups [Table 6].
Cognitive dysfunctions in diabetics and age-matched nondiabetic participants were studied by using the GDS, and it was noted that there was noticeable diminution of cognitive functions in diabetics from all age groups irrespective of the duration of the morbidity that uniformly increased with age.
Life expectancy is increasing as a result of advances in medical science and the availability of better healthcare services. The proportion of elderly persons in the general population is therefore rising along with the spectrum of cognitive dysfunctions. As the risk of dementia increases with increasing age, the number of persons with dementia in the general population is also rising.  Related study in the United States demonstrated that the incidence of dementia increased among the elderly population over time. 
The prevalence of MCI was 5.3% in Japan; the yearly rate of progression of MCI to dementia was about 4%.  The rate of amnestic MCI in the USA, in a cohort of 1,248 individuals with the mean age of 74.6 (±5.3) years, was about 3-4%.  In a Swedish cohort, among those aged 75-95 years, the rates of amnestic MCI, single domain non-memory MCI, and multi-domain MCI were found to 2.1%, 7.2%, and 1.8%, respectively, using standard definitions; these rates were almost doubled when the criterion for normal cognitive functioning was removed in the modified definitions.  The rate of MCI in India among those aged 50 years or more was 14.9%; amnestic MCI accounted for 6.0% and multi-domain MCI accounted for 8.9%. 
Nowadays, diabetes is considered as an epidemic disease, with about 173 million diabetic people all over the world. Diabetes is a chronic disease that leads to long-term complications, which include the risk of cognitive changes. A preserved cognitive status is essential for the understanding of the outcome. ,
Cognitive performance of diabetic patients is lower compared to that of subjects that do not suffer from this kind of metabolic impairment. Considering the results, the “brain at risk” stage (risk of dementia) is not asymptomatic, manifests subclinically as cognitive impairment. 
Cognitive ability of diabetic patients was poor when compared to subjects with no metabolic impairment. Executive function was the most affected. The risk factors for cognitive impairment determine not only an increased risk for dementia in “late life” but also a cognitive ability impairment during “middle life”. 
Forty two percent cognitive dysfunction found in a study conducted by Priyam et al.  In a study conducted by Solanki et al., 48% of the diabetic patients below 60 years of age showed cognitive impairment.  Another study conducted by Shuba et al.  revealed that 63.33% of the diabetics had a decreased cognition.
Patients with type 2 DM are at higher risk of developing dementia  for reasons of neurodegeneration and/ or microvascular changes,  where both conditions may lower the threshold for more severe cognitive impairment. Diabetes substantially accelerates progression from MCI to dementia in older patients. Earlier onset, longer duration, and poor glycemia control are all associated with cognitive dysfunction in diabetics. ,
In our study, the GDS was used to find cognitive dysfunction in diabetics.  Other research groups had used the GDS with stage 3 to define MCI. 
Both type 2 DM and dementia that are common in elderly individuals are often progressive and disabling conditions. Ten percent of people over the age of 65 years develop dementia, rising to more than 50% of people over the age of 85 years. ,
More than 10% of the elderly population in the United States suffer from type 2 DM, the prevalence of which rises with the increase of age, and a global pandemic of this condition is evident. ,
Cognitive function (particularly of memory) declines with age, although the rate of decline is not distributed uniformly within the population. For a minority, this progress in severity to cause disability until dementia is diagnosed. A possible relationship between cognitive decline and diabetes has been hypothesized since the discovery of insulin by Miles and Root. 
Type 2 DM increases the risk of cognitive dysfunction,  with resultant worse performance on neuropsychological screening tests, irrespective of the patient’s age and the DM type. ,,
The underlying mechanisms of cognitive impairment in patients with DM remain under investigation, but it seems clear that vascular endothelial disease, glucose and insulin abnormalities, dyslipidemia, metabolic syndrome, hypertension, and obesity and amyloid metabolism are all involved, both separately and in association. 
Microscopically, cognitive dysfunction may be the result of hippocampal injury, reduction in gray matter density, or microvascular changes in white matter. 
Several research groups had reported that type 2 DM was associated with cognitive impairment. ,,
The association between DM and cognitive performance is difficult to understand due to the fact that other complications typically observed with type 2 DM including cardiovascular disease; hypertension, and depression are also associated with cognitive deficit. Yet, the specific mechanism linking type 2 DM with cognitive deficits has yet to be clearly identified. However, extraneuronal hyperglycemia, disturbed brain glucose metabolism, and altered brain insulin signaling have been hypothesized. 
Identification and effective treatment of comorbid depression is increasingly considered as an essential component of the high-quality clinical care of patients with chronic illness, especially the geriatric population, in special medical settings. Diabetes is considered as one of the most psychological and behaviorally demanding chronic illness. Because 95% of diabetic management is conducted by patient; comorbid depression in diabetes that may lead to poorer outcomes and increased risk of complication by lowering adherence to glucose monitoring, exercise, diet, and medication regimens. 
Type 2 DM has been related to an accelerated cognitive decline in elderly people, the development of MCI and an increased risk of dementia, which include both Alzheimer’s disease and vascular dementia. 
Even a modest effect of diabetes on the cognitive function has significant public health implications. 
Ruis et al. had shown that diabetes duration was associated with the effect size (cognitive decline) of the study: The longer the duration of known diabetes, the bigger the effect size was substantiated by other studies that clearly showed that the age of diabetes onset was inversely related with performance of tasks for memory and information-processing speed in diabetic patients. Abovementioned findings were in concurrence with the findings of the present study.
In the study of osteoporotic fractures by Gregg et al.,  there was a trend of increasing risk of cognitive decline with increasing duration of diabetes, and in the Framingham study, Elias et al.,  each 5-year increment between diabetes diagnosis and cognitive assessment was associated with lower scores on tests of logical memory, word fluency, and similarities. Grodstein et al. showed beneficial effect of sugar control on cognitive dysfunction. But more study is needed to find adequate data demonstrating the same.
Strength of the study
Our study comprised a heterogeneous group of participants. Number of study participants was 1,629 and in control groups there were 1,650 patients from different age groups (from less than 20 years to 60 years and above) with varying duration of diabetes. Similar types of other studies had taken older age groups like around 50 years. The GDS was used in this study to assess cognitive function of diabetic patients but in similar type of other studies the mini-mental state examination (MMSE) was used.
Limitations of the study
Fewer studies were available using the GDS for comparison. Further, due to the resource-poor settings of diabetic care other variables like gender, literacy, and occupation could not be taken into account in our study.
Future directions of the study
In the next phase of our cognitive dysfunction study with other variable like demographic information such as age, sex, literacy level, years of schooling, occupation held during their work life, and addictions especially tobacco use will be included. Further, we wish to extend our study to find relation between cognitive dysfunction and other comorbidities like hypertension, dyslipidemia, obesity, type of antidiabetic medications, hemoglobin A 1 C (HbA 1 C) levels.
Diabetics suffer from more cognitive dysfunctions compared to nondiabetics that increases with the increase of age. There is also a significantly higher incidence of cognitive dysfunction in newly developed diabetics than age-matched controls, showing that cognitive dysfunction may not altogether be a result of long-standing diabetes but may also be a cause of comorbidity for which more elaborative studies are needed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]