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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 20
| Issue : 1 | Page : 27-31 |
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Cognitive impairment in diabetic adults with and without hypertension
Gurinder Mohan, Jaskaran Vir Singh Sarao, Ranjeet Kaur, Manish Chandey
Department of Medicine, SGRD Institute of Medical Sciences and Research, Amritsar, Punjab, India
| Date of Submission | 09-Jun-2022 |
| Date of Decision | 02-Dec-2022 |
| Date of Acceptance | 12-Dec-2022 |
| Date of Web Publication | 19-Jan-2023 |
Correspondence Address:
Dr. Gurinder Mohan
Department of Medicine, SGRD Institute of Medical Sciences and Research, Amritsar, Punjab
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/am.am_89_22
Background: Diabetes is a heterogeneous disease that is modified by many risk factors, most notably hypertension. Although its negative effects on the retinal, renal, cardiovascular, and peripheral nervous systems are well known, its impact on cognitive performance has received less attention. It has been shown that diabetes is linked to mild cognitive impairment, a transitional stage between normal aging and dementia. Methods: In this case–control study, 150 patients, which were further divided into three groups of 50 patients each with 50 patients who fulfilled the American Diabetes Association's (ADA) Guidelines 2018 for diabetes were in Group A, 50 patients who fulfilled both ADA Guidelines 2018 for diabetes and Joint National Committee 7 (JNC 7) Guidelines for hypertension in Group B while 50 healthy subjects in Group C, were included after applying the exclusion criteria and were subjected to cognitive assessment by Montreal cognitive assessment (MoCA) test. Results: In the diabetic arm of the study (n = 100), 65% (n = 65) of the patients had cognitive impairment as compared to the control group (n = 50), where only 12% (n = 6) of the patients had cognitive decline (P < 0.001). The mean MoCA scores were lowest in patients who had concomitant diabetes and hypertension (23.86 ± 1.78) as compared to patients having diabetes alone (24.76 ± 1.38) while the control group had the highest mean MoCA score (27.46 ± 1.69) (P < 0.001). Age correlated negatively with MoCA while no correlation was observed with gender distribution and area of residence. Duration of diabetes correlated negatively with MoCA scores in Group A (−0.874) (P < 0.001) and Group B (−0.801) (P < 0.001). Duration of hypertension also showed a negative correlation with MoCA scores in Group B (−0.745) (P < 0.001). A negative correlation was also observed between glycated hemoglobin and MoCA scores in Group A (−0.665) (P = 0.001) and Group B (−0.567) (P = 0.034). Conclusions: In conclusion, the incidence and severity of cognitive impairment was more in patients having concomitant diabetes and hypertension as compared to patients having diabetes alone, thus signifying the additional burden and contribution of hypertension to the cognitive decline.
Keywords: Cognitive impairment, diabetes mellitus, hypertension, Montreal cognitive assessment score
How to cite this article:
Mohan G, Singh Sarao JV, Kaur R, Chandey M. Cognitive impairment in diabetic adults with and without hypertension. Apollo Med 2023;20:27-31 |
| Introduction | |  |
Around 171 million people worldwide have diabetes mellitus (DM), and this number is estimated to double by the year 2030. Diabetes is a heterogeneous disease that is associated with hypertension, dyslipidemia, and so on. It is considered to be a clinical condition that is modified by many factors.[1]
DM has been associated with reduced performance on numerous domains of cognitive function, a process often termed as diabetic encephalopathy. Major mechanisms considered for an association between diabetes and cognitive dysfunction are atherosclerosis, leading to brain infarcts; microvascular disease, resulting in insidious ischemia; and glucose toxicity resulting in advanced protein glycation and oxidative stress.[2]
It is now being increasingly recognized that a substantial number of cases with cognitive impairment may be attributable to vascular risk factors, most notably hypertension. Recent studies have revealed that diabetes and hypertension in midlife (rather than late life) may have a role in causing cognitive impairment.[3]
The objective of the study was to evaluate the interplay between diabetes, hypertension, and cognitive impairment and its association with glycemic control and the duration of diabetes and hypertension.
| Methods | | |
This study was a case–control study and was conducted in Medicine Department of SGRDIMSR, Amritsar. A total of 150 subjects in the age group of 18–65 years presenting in the IPD of SGRDIMSR for related or unrelated problems were selected for the current study and were included in the study group after applying inclusion and exclusion criteria and after taking written informed consent. The 2018 American Diabetes Association's (ADA) Guidelines for diabetes were taken to categorize the patients in whether they belonged to the diabetic arm of the study or were to be included among nondiabetic adults. The Montreal cognitive assessment (MoCA) test was adopted after validation from the committee. The patients were further divided into three groups, 50 subjects who fulfilled ADA Guidelines for diabetes [Table 1] were placed in Group A and 50 subjects who fulfilled both ADA Guidelines for diabetes and JNC 7 Guidelines for hypertension [Table 2] were placed in Group B while 50 healthy subjects were placed in Group C. | Table 1: American Diabetes Association guidelines 2018 for diabetes mellitus
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Cognitive score was assessed by MoCA test, a score of ≥26 points is considered normal cognitive function while a score of <26 points denote cognitive impairment. MoCA test is peculiar in identifying mild cognitive impairment and thus acts as a better screening test and provides a window of therapeutic intervention before the advent of dementia as evident in the study conducted by Eftekhari et al. where the prevalence of cognitive impairment was calculated to be 41.5% and between 47.7% and 60% by mini-mental state examination and MoCA, respectively.[4]
The following patients were excluded from the study: age <18 years and more than 65 years, history of psychiatric illness, diabetic ketoacidosis, intake of centrally active medications (sedatives, anticonvulsants), alcohol dependence, patients with obstructive sleep apnea, thyroid disorders, cerebrovascular accident, chronic kidney disease, and chronic liver disease.
A proper history was taken from the patients and other available sources. A thorough general physical and systemic examination was done and a final diagnosis was made after doing all the necessary investigations.
The study was approved by the Ethical Committee of the institute.
Data obtained were analyzed statistically. The data were expressed as mean with standard deviation for quantitative variables. Comparisons between groups were performed using Student's t-test and analysis of variance test for quantitative variables and Chi-square test for nominal/qualitative data. A value of P < 0.05 was taken as significant.
| Results | | |
A total of 150 patients were included in the study. Majority of the patients were women (52%) (n = 78) while men constituted 48% (n = 72) of the patients.
Most of the patients belonged to the 61–65 years' age group (n = 39) followed by 46–50 years' age group (n = 28). The mean age of the patients was 54.14 ± 7.78 years in Group A, 56.90 ± 6.31 years in Group B, and 50.62 ± 9.11 years in Group C.
Most of the patients had rural residence (61.3%) (n = 92) while 38.7% (n = 58) had urban residence.
Out of 150 patients, majority of the patients attained education till high school (45.3%) (n = 68) followed by 29.3% (n = 44) who received education till junior high school and 25.3% (n = 38) patients attended at least college/university.
The mean duration of diabetes in Group A was 13.50 ± 5.30 years and in Group B was 15.00 ± 4.74 years (P = 0.139).
The mean glycated hemoglobin (HbA1c) levels were 9.36 ± 2.39 in Group A and 8.94 ± 2.21 in Group B (P = 0.520).
In the study, out of 150 patients (Groups A, B, and C), cognitive impairment was seen in 47.33% (n = 71) patients while 52.67% (n = 79) patients had normal cognition as assessed by MoCA score. Among 100 patients who had DM (Group A and Group B), cognitive impairment (MoCA score <26) was seen in 65% (n = 65) of the patients and 35% (n = 35) of the patients had normal cognitive function (MoCA score ≥26). Among patients who had only DM (Group A), 54% (n = 27) of the patients had cognitive impairment while among patients who had concomitant diabetes and hypertension (Group B), cognitive impairment was seen in 76% (n = 38) of the patients and among controls who did not have diabetes or hypertension (Group C), only 12% (n = 6) of the patients had cognitive impairment (P < 0.001).
Mean MoCA scores were lowest in patients who had concomitant diabetes and hypertension (23.86 ± 1.78) as compared to patients who had diabetes alone (24.76 ± 1.38) while patients who had neither diabetes nor hypertension had the highest mean MoCA score (27.46 ± 1.69) (P < 0.001).
A negative correlation was observed between age and MoCA scores in Group A (−0.712) (P = 0.001), Group B (−0.594) (P = 0.042), and Group C (−0.835) (P = 0.061)[Table 3]. | Table 3: Correlation of Montreal cognitive assessment score with various variables
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No statistically significant correlation was observed between gender distribution and cognitive impairment in Group A (P = 0.283), Group B (P = 0.730), and Group C (P = 0.279).
Urban or Rural residence showed no significant correlation with cognitive impairment in Group A (P = 0.465), Group B (P = 0.206), and Group C (P = 0.373).
Level of education showed a significant correlation with cognitive impairment with more incidence of decreased cognitive function observed in patients who received fewer years of education in Group A (P = 0.008) and Group B (P = 0.001) but not in Group C (P = 0.064).
Duration of diabetes correlates negatively with MoCA scores in Group A (−0.874) (P < 0.001) and Group B (−0.801) (P < 0.001). Duration of hypertension also showed a negative correlation with MoCA scores in Group B (−0.745) (P < 0.001) [Table 3].
A negative correlation was also observed between Hba1c and MoCA scores and a lower MoCA scores were observed with increasing Hba1c levels in Group A (−0.665) (P = 0.001) and Group B (−0.567) (P = 0.034) [Table 3].
The MoCA test evaluates several cognitive domains. On comparison of these domains among patients who had diabetes (Groups A and B) and those without diabetes (Group C), we found that diabetic patients presented with significantly lower scores compared to nondiabetic patients for the visuospatial domain in Groups A and B (3.36 ± 0.80, 3.28 ± 0.73) versus Group C (4.10 ± 0.81) (P < 0.001); for the attention domain in Groups A and B (4.18 ± 0.596, 3.90 ± 0.614) versus Group C (5.44 ± 0.760) (P < 0.001); for delayed recall domain in Groups A and B (3.46 ± 0.788, 3.22 ± 0.815) versus Group C (4.10 ± 0.886) (P < 0.001); However no statistically significant difference was obtained for the naming domain in Groups A and B (2.96 ± 0.198, 2.90 ± 0.303) versus Group C (2.96 ± 0.198) (P = 0.350); for the language domain in Groups A and B (2.90 ± 0.303, 2.78 ± 0.418) versus Group C (2.90 ± 0.303) (P = 0.138); for abstraction domain in Groups A and B (1.90 ± 0.303, 1.88 ± 0.328) versus Group C (1.98 ± 0.141) (P = 0.151); for orientation domain in Groups A and B (5.96 ± 0.198, 5.96 ± 0.198) versus Group C (5.98 ± 0.141) (P = 0.816) [Figure 1]. | Figure 1: Correlation between cognitive domains of MoCA. MoCA: Montreal cognitive assessment
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| Discussion | | |
This was a hospital-based study conducted in the Department of Medicine in SGRD Hospital, Amritsar. A total of 150 patients were studied.
The patients who fulfilled the ADA criteria 2018 for DM and JNC 7 Guidelines for hypertension were included in the study.
In our study, the age range of the patients was 36–65 years with a mean age of 54.14 ± 7.78 years in Group A, 56.90 ± 6.31 years in Group B, and 50.62 ± 9.11 years in Group C. This was consistent with the study conducted by Petrova et al. where the mean age was 53 ± 7.45 years in patients having DM only and 56 ± 7.4 years in patients having both diabetes and hypertension.[5] However, the mean age varied amongst various studies and no fixed pattern was observed in the studies conducted due to the varying population characteristics.
There were 78 females (52%) and 72 males (48%) included in the study conducted by us. Similar pattern of gender distribution was seen in the study conducted by Singh et al. where 53% of the patients were females and 47% were males and in the study conducted by Yerrapragada et al. in which female participants (53.6%) outnumbered males (46.4%).[6],[7] However, in the study conducted by Kant et al. majority of the participants were males, constituting 66.2% of the subjects.[8] The gender distribution of the patients was a chance occurrence and was not prefixed in any of the studies including ours.
The mean duration of diabetes in Group A was 13.50 ± 5.30 years and in Group B was 15.00 ± 4.74 years. Similar pattern was seen in the study conducted by Lalithambika et al. in which the mean duration of diabetes was 12.04 ± 6.04 years.[9]
In our study, the mean Hba1c levels were 9.36 ± 2.39 in Group A and 8.94 ± 2.21 in Group B. This was consistent with the study conducted by Petrova et al. where the mean Hba1c in patients having diabetes alone was 9% while in patients having both diabetes and hypertension was 8.1%.[5]
Among 100 patients with DM (Group A and Group B), cognitive impairment (MoCA score <26) was seen in 65% of the patients and 35% of the patients had normal cognitive function (MoCA score ≥26). This was in accordance with the study conducted by Chen et al. where among patients having DM, 59.2% of the patients had cognitive impairment.[10] On the contrary, the study conducted by Kant et al. showed that the prevalence of cognitive impairment in diabetic patients was observed to be as high as 96.31% which can possibly be explained by the differences in the level of education and unawareness of diabetes and its complications amongst type 2 DM patients in remote areas of Eastern Uttar Pradesh.[8]
In our study, among patients who had only DM (Group A), 54% of the patients had cognitive impairment while among patients who had concomitant diabetes and hypertension (Group B), cognitive impairment was seen in 76% of the patients and among controls who did not have diabetes or hypertension (Group C), 12% of the patients had cognitive impairment (P < 0.001). These findings were in accordance with the studies conducted by Elias et al. which showed hypertension to be an independent risk factor for cognitive impairment and when present concomitantly with diabetes demonstrate greater cognitive changes as compared to normotensive diabetic patients.[11]
We compared the mean MoCA scores among the three groups which showed that patients who had concomitant diabetes and hypertension had lower mean MoCA score (23.86 ± 1.78) as compared to patients who had diabetes alone (24.76 ± 1.38) while patients who had neither diabetes nor hypertension had highest mean MoCA score (27.46 ± 1.69) (P < 0.001). Similar mean values were obtained in the study conducted by Abdel-Latif et al. where mean MoCA score in diabetic patients was 25.9 ± 2.5 and among nondiabetic patients were 27.4 ± 2.4.[12]
On comparing the age with the pattern of cognitive impairment, we found that age correlate negatively with MoCA scores in Group A (−0.712) (P = 0.001), Group B (−0.594) (P = 0.042), and Group C (−0.835) (P = 0.061) and a steady decline in cognitive performance was observed with advancing age. This was in accordance with the study conducted by Cernea et al. which also showed a negative correlation (−0.31) of age with MoCA score.[13]
Many previous studies showed that females were more susceptible to develop cognitive impairment. In our study, although 52.5% of the females had cognitive impairment as compared to 41.6% of males, this difference was not statistically significant in Group A (P = 0.283), Group B (P = 0.730), and Group C (P = 0.279). Similar observation was made in the study conducted by Kant et al. which also did not show statistical significance between susceptibility of gender and the occurrence of cognitive impairment.[8]
Our study also assessed the correlation between area of residence and cognitive impairment. Rural residence has been considered a risk factor for cognitive impairment. In our study, although 69% of the patients who had cognitive impairment resided in Rural areas while 31% of the patients had urban residence, this difference was not statistically significant in Group A (P = 0.465), Group B (P = 0.206), and Group C (P = 0.373). These findings were supported by the study conducted by Yarube and Gwarzo, which also showed that cognitive score was not influenced by the area of residence.[14]
The association between education and cognitive impairment has long been known and our study has also shown that patients who received education at least till college/university had fewer incidence of cognitive impairment as compared to patients who received education till Junior High school or less which is statistically significant in Group A (P = 0.008) and Group B (P = 0.001) but not in Group C (P = 0.064). These findings were supported by the study conducted by Cernea et al. which showed a statistically significant difference between level of education and cognitive impairment among patients having diabetes but the difference was insignificant among healthy controls.[13]
The duration of diabetes correlates negatively with MoCA scores as evident in Group A (−0.874) (P < 0.001) and Group B (−0.801) (P < 0.001) and there was a steady decline in cognitive performance with advancing duration of diabetes. These findings in accordance with the study conducted by Chen et al. where a negative correlation was seen between MoCA scores and duration of DM (−0.161) (P = 0.044).[10] Similar to diabetic duration, duration of hypertension also showed a negative correlation with MoCA scores in Group B (−0.745) (P < 0.001). The study conducted by Liu et al. also showed a negative correlation between MoCA scores and duration of hypertension (−0.242) (P = 0.006).[15]
Our study also showed a negative correlation between Hba1c and MoCA scores and a continuous decline in cognitive performance is observed with increasing Hba1c levels in Group A (−0.665) (P = 0.001) and Group B (−0.567) (P = 0.034). A study conducted by Lalithambika et al. also showed a negative correlation between Hba1c and MoCA score (−0.287) (P = 0.016).[9]
On comparison of cognitive domains of MoCA test, we found that diabetic patients presented with significantly lower scores compared to nondiabetic patients for the visuospatial domain in Groups A and B (3.36 ± 0.80, 3.28 ± 0.73) versus Group C (4.10 ± 0.81) (P < 0.001); for the attention domain in Groups A and B (4.18 ± 0.596, 3.90 ± 0.614) versus Group C (5.44 ± 0.760) (P < 0.001); for delayed recall domain in Groups A and B (3.46 ± 0.788, 3.22 ± 0.815) versus Group C (4.10 ± 0.886) (P < 0.001); however, no statistically significant difference was obtained for the naming domain in Groups A and B (2.96 ± 0.198, 2.90 ± 0.303) versus Group C (2.96 ± 0.198) (P = 0.350); for the language domain in Groups A and B (2.90 ± 0.303, 2.78 ± 0.418) versus Group C (2.90 ± 0.303) (P = 0.138); for abstraction domain in Groups A and B (1.90 ± 0.303, 1.88 ± 0.328) versus Group C (1.98 ± 0.141) (P = 0.151); and for orientation domain in Groups A and B (5.96 ± 0.198, 5.96 ± 0.198) versus Group C (5.98 ± 0.141) (P = 0.816). The study conducted by Cernea et al. showed that diabetic patients when compared with healthy controls, had lower scores for visuospatial domain (P = 0.04) and for delayed recall domain (P = 0.03) and the study conducted by Abdel-Latif et al. showed that diabetic patients scored poorly for abstraction domain and delayed recall domain when compared with nondiabetic patients.[12],[13]
However, there were a few limitations of our study. The hypertensive cases included in the study were all having concomitant diabetes and thus the isolated impact of hypertension on cognition was not assessed. The study measured the correlation between cognitive impairment in diabetics and compared them with patients having concomitant hypertension and with healthy controls at a single time rather than recording long-term repeated observations. The relatively small sample size might prevent us from extrapolating our results to the whole population.
| Conclusions | | |
Our study provides an understanding on how DM aids to the development of cognitive decline and the interplay between diabetes, hypertension, and cognitive impairment. Studies on the benefits of improved glycemic control on cognitive function would need to be performed in the future to help us understand the significance of our finding in the long-term management of these patients.
Acknowledgment
I would like to extend my deepest regards and heartfelt thanks to Dr. Ranjeet Kaur, Associate Professor, Department of Medicine, Sri Guru Ram Das Institute of Medical Sciences and Research, Sri Amritsar. I am also indebted to Dr. Manish Chandey, Professor, Department of Medicine, SGRD Institute of Medical Sciences and Research, Amritsar, and Dr. Jaskaran Vir Singh Sarao, Junior Resident, Department of Medicine, SGRD Institute of Medical Sciences and Research, Amritsar.
Conflicts of interest
There are no conflicts of interest.
Institutional ethical committee approval
The study was approved by the Institutional Ethics Committee.
Funding
Nil.
Author's contribution
Dr. Ranjeet Kaur: Critical revision of the article and final approval of the version to be published. Dr. Manish Chandey: conception of the idea, drafting the article, and critical revision of the article.
| References | | |
| 1. | Kloppenborg RP, van den Berg E, Kappelle LJ, Biessels GJ. Diabetes and other vascular risk factors for dementia: Which factor matters most? A systematic review. Eur J Pharmacol 2008;585:97-108.  |
| 2. | Etgen T, Sander D, Bickel H, Förstl H. Mild cognitive impairment and dementia: The importance of modifiable risk factors. Dtsch Arztebl Int 2011;108:743-50. |
| 3. | Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 2005;64:277-81. |
| 4. | Eftekhari SS, Hejazi SA, Sharifipour E, Hejazi SF, Talebizadeh M, Mostafavi H, et al. Cognitive impairment in patients with coronary artery disease; comparison of Montreal cognitive assessment (MoCA) and mini mental state examination (MMSE). J Adv Med Biomed Res 2018;26:12-6. |
| 5. | Petrova M, Prokopenko S, Pronina E, Mozheyko E. Diabetes type 2, hypertension and cognitive dysfunction in middle age women. J Neurol Sci 2010;299:39-41. |
| 6. | Singh K, Singh VB, Meena BL, Beniwal S, Gaur S, Ujwal V, Kumar H. Association of mild cognitive impairment with serum Vitamin D level in type 2 diabetes mellitus. Indian J Health Sci Biomed Res (KLEU) 2015;8:120. |
| 7. | Yerrapragada DB, Rao CR, Karunakaran K, Lee HS. Cognitive dysfunction among adults with type 2 diabetes mellitus in Karnataka, India. Ochsner J 2019;19:227-34. |
| 8. | Kant S, Poddar K, Kamle M, Patil C. Assessment of cognitive impairment by using Addenbrooke's cognitive examination (ACE) and Montreal cognitive assessment (MoCA) amongst type 2 diabetes mellitus patients in Eastern Uttar Pradesh, India. IP Indian J Neurosci 2020;4:185-90. |
| 9. | Lalithambika CV, Arun CS, Saraswathy LA, Bhaskaran R. Cognitive impairment and its association with glycemic control in type 2 diabetes mellitus patients. Indian J Endocrinol Metab 2019;23:353-6. |
| 10. | Chen RH, Jiang XZ, Zhao XH, Qin YL, Gu Z, Gu PL, et al. Risk factors of mild cognitive impairment in middle aged patients with type 2 diabetes: A cross-section study. Ann Endocrinol (Paris) 2012;73:208-12. |
| 11. | Elias PK, Elias MF, D'Agostino RB, Cupples LA, Wilson PW, Silbershatz H, et al. NIDDM and blood pressure as risk factors for poor cognitive performance. The Framingham study. Diabetes Care 1997;20:1388-95. |
| 12. | Abdel-Latif GA, Hassan AM, Gabal MS, Hemeda SA, El-Chami NH, Salama II. Mild cognitive impairment among type II diabetes mellitus patients attending university teaching hospital. Open Access Maced J Med Sci 2020 Mar 25;8:105-11. |
| 13. | Cernea S, Şular FL, Huţanu A, Voidăzan S. Markers of cognitive impairment in patients with type 2 diabetes. Rev Rom Med Lab 2016;24:256-9. |
| 14. | Yarube IU, Gwarzo IM. Cognitive impairment and reduced antioxidant capacity in patients with type 2 diabetes. Sahel Med J 2019;22:171. [Full text] |
| 15. | Liu ZQ, Zhang MX, Wang J, Ding N. Analysis of correlation between the mild cognitive impairment (MCI) and level of adiponectin in elderly patients with type 2 diabetes mellitus (T2DM). Eur Rev Med Pharmacol Sci 2017;21:5471-7. |
[Figure 1]
[Table 1], [Table 2], [Table 3]
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