diabetes

Cognitive impairment associated with diabetes (CIAD)

Diabetes is a chronic condition that affects the way the body processes blood sugar (glucose) and with type 2 diabetes, the body either does not produce enough insulin, or is resistant to insulin.

Mounting evidence suggest both types of diabetes (Type 1 and Type 2) are associated with reduced performance in multiple types of cognitive function1,2,3. Research has shown the duration of disease and extent of glucose control in the blood can impact the type and severity of resulting cognitive impairment. However, many factors are known to play a role in the progression of disease making it difficult to predict the severity of impairment that a patient may ultimately develop.

While both forms of diabetes have been implicated, Type 2 has demonstrated a greater overall association with cognitive decline, with a 50% increased risk for dementia and associated impaired attention, processing and motor speed, executive functioning and verbal memory1,2,4,5. Diabetes confers a significant risk of Alzheimer’s disease and vascular dementia, with hyperglycemia having the strongest associated risk of development of cognitive impairment of any of the metabolic syndrome components6.

The progression of disease in CIAD may include defects in insulin signaling, autonomic function, neuroinflammatory pathways, mitochondrial (Mt) metabolism, Tau signaling, and other pathways12. Approximately 40 million people worldwide live with dementia at present, and this is expected to double every 20 years to over 110 million in 20507,8. Moreover, diabetes is increasing in prevalence worldwide with 463 million adults currently, and 700 million adults estimated to have the disease by 20459. Therefore, there is a compelling need for better understanding of the biology, targets, and therapies which will be effective against CIAD10.

Thus far, few studies have proposed the use of a drug specifically designed to treat CIAD. However, previous work with a drug with a similar mechanism of action to Xanamem™ showed cognitive improvement in otherwise healthy cognitively unimpaired elderly men with type 2 diabetes11.

Actinogen are currently evaluating the potential to study Xanamem™ in the treatment of cognitive impairment associated with diabetes.

1. Assessing Premorbid Cognitive Ability in Adults With Type 2 Diabetes Mellitus-a Review With Implications for Future Intervention Studies
Wong, R. H. X., Scholey, A. & Howe, P. R. C. 2014. Current Diabetes Reports, 14, 12.

2. Risk of dementia in diabetes mellitus: a systematic review
Biessels, G. J., Staekenborg, S., Brunner, E., Brayne, C. & Scheltens, P. 2006. Lancet Neurology, 5, 64-74.

3. The link between iron, metabolic syndrome, and Alzheimer’s disease
Grunblatt, E., Bartl, J. & Riederer, P. 2011. Journal of Neural Transmission, 118, 371-379.

4. A Meta-Analysis of Cognitive Functioning in Nondemented Adults with Type 2 Diabetes Mellitus
Monette, M. C. E., Baird, A. & Jackson, D. L. 2014. Canadian Journal of Diabetes, 38, 401-408.

5. Magnitude of Cognitive Dysfunction in Adults with Type 2 Diabetes: A Meta-analysis of Six Cognitive Domains and the Most Frequently Reported Neuropsychological Tests Within Domains
Palta, P., Schneider, A. L. C., Biessels, G. J., Touradji, P. & Hill-Briggs, F. 2014. Journal of the International Neuropsychological Society, 20, 278-291.

6. Contribution of metabolic syndrome components to cognition in older individuals
Dik, M. G., Jonker, C., Comijs, H. C., Deeg, D. J. H., Kok, A., Yaffe, K. & Penninx, B. W. 2007. Diabetes Care, 30, 2655-2660.

7. The global prevalence of dementia: A systematic review and meta-analysis
Prince, M., Bryce, R., Albanese, E., Wimo, A., Ribeiro, W. & Ferri, C. P. 2013. Alzheimers & Dementia, 9, 63-75.

8. Global Epidemiology of Dementia: Alzheimer’s and Vascular Types
Rizzi, L., Rosset, I. & Roriz-Cruz, M. 2014. Biomed Research International, 8.

9. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition
Saeedi, P., Petersohn, I., Salpea, P., Malanda, B., Karuranga, S., Unwin, N., Colagiuri, S., Guariguata, L., Motala, A. A., Ogurtsova, K., Shaw, J. E., Bright, D., Williams, R., Almutairi, R., Montoya, P. A., Basit, A., Besanccon, S., Bommer, C., Borgnakke, W., Boyko, E., Chan, J. L., Divakar, H., Esteghamati, A., Forouhi, N., Franco, L., Gregg, E., Hassanein, M., Ke, C., Levitt, D., Lim, L. L., Ogle, G. D., Owens, D., Pavkov, M., Pearson-Stuttard, J., Ramachandran, A., Rathmann, W., Riaz, M., Simmons, D., Sinclair, A., Sobngwi, E., Thomas, R., Ward, H., Wild, S., Yang, X. L., Yuen, L. L., Zhang, P. & Comm, I. D. F. D. A. 2019. Diabetes Research and Clinical Practice, 157, 10.

10. Diabetes in Midlife and Cognitive Change Over 20 Years A Cohort Study
Rawlings, A. M., Sharrett, A. R., Schneider, A. L. C., Coresh, J., Albert, M., Couper, D., Griswold, M., Gottesman, R. F., Wagenknecht, L. E., Windham, B. G. & Selvin, E. 2014. Annals of Internal Medicine, 161, 785-U68.

11. Plasma and cerebrospinal fluid amyloid beta for the diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI)
Ritchie, C., Smailagic, N., Noel-Storr, A. H., Takwoingi, Y., Flicker, L., Mason, S. E. & Mcshane, R. 2014. Cochrane Database of Systematic Reviews, 91.

12. Diabetes and Cognitive Impairment
Zilliox, L. A., Chadrasekaran, K., Kwan, J. Y. & Russell, J. W. 2016. Current Diabetes Reports, 16, 11.

Diabetes is a chronic condition

Diabetes is increasing in prevalence worldwide

Diabetes is increasing in prevalence worldwide

Type 2 associated with cognitive decline

Type 2 diabetes has demonstrated a greater overall association with cognitive decline

External Links

International Diabetes Federation
https://idf.org/ 

Diabetes Australia
https://www.diabetesaustralia.com.au/

Australasian Diabetes Society
https://diabetessociety.com.au/

American Diabetes Association (ADA)
https://www.diabetes.org/

Diabetes UK
https://www.diabetes.org.uk/

PUBLICATIONS

Publications
Assessing Premorbid Cognitive Ability in Adults With Type 2 Diabetes Mellitus-a Review With Implications for Future Intervention Studies

Wong, R. H. X., Scholey, A. & Howe, P. R. C. 2014. Current Diabetes Reports, 14, 12.

Risk of dementia in diabetes mellitus: a systematic review

Biessels, G. J., Staekenborg, S., Brunner, E., Brayne, C. & Scheltens, P. 2006. Lancet Neurology, 5, 64-74.

The link between iron, metabolic syndrome, and Alzheimer’s disease

Grunblatt, E., Bartl, J. & Riederer, P. 2011. Journal of Neural Transmission, 118, 371-379.

A Meta-Analysis of Cognitive Functioning in Nondemented Adults with Type 2 Diabetes Mellitus

Monette, M. C. E., Baird, A. & Jackson, D. L. 2014. Canadian Journal of Diabetes, 38, 401-408.

Magnitude of Cognitive Dysfunction in Adults with Type 2 Diabetes: A Meta-analysis of Six Cognitive Domains and the Most Frequently Reported Neuropsychological Tests Within Domains

Palta, P., Schneider, A. L. C., Biessels, G. J., Touradji, P. & Hill-Briggs, F. 2014. Journal of the International Neuropsychological Society, 20, 278-291.

Contribution of metabolic syndrome components to cognition in older individuals

Dik, M. G., Jonker, C., Comijs, H. C., Deeg, D. J. H., Kok, A., Yaffe, K. & Penninx, B. W. 2007. Diabetes Care, 30, 2655-2660.

The global prevalence of dementia: A systematic review and meta-analysis

Prince, M., Bryce, R., Albanese, E., Wimo, A., Ribeiro, W. & Ferri, C. P. 2013. Alzheimers & Dementia, 9, 63-75.

Global Epidemiology of Dementia: Alzheimer’s and Vascular Types

Rizzi, L., Rosset, I. & Roriz-Cruz, M. 2014. Biomed Research International, 8.

Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition

Saeedi, P., Petersohn, I., Salpea, P., Malanda, B., Karuranga, S., Unwin, N., Colagiuri, S., Guariguata, L., Motala, A. A., Ogurtsova, K., Shaw, J. E., Bright, D., Williams, R., Almutairi, R., Montoya, P. A., Basit, A., Besanccon, S., Bommer, C., Borgnakke, W., Boyko, E., Chan, J. L., Divakar, H., Esteghamati, A., Forouhi, N., Franco, L., Gregg, E., Hassanein, M., Ke, C., Levitt, D., Lim, L. L., Ogle, G. D., Owens, D., Pavkov, M., Pearson-Stuttard, J., Ramachandran, A., Rathmann, W., Riaz, M., Simmons, D., Sinclair, A., Sobngwi, E., Thomas, R., Ward, H., Wild, S., Yang, X. L., Yuen, L. L., Zhang, P. & Comm, I. D. F. D. A. 2019. Diabetes Research and Clinical Practice, 157, 10.

Diabetes in Midlife and Cognitive Change Over 20 Years A Cohort Study

Rawlings, A. M., Sharrett, A. R., Schneider, A. L. C., Coresh, J., Albert, M., Couper, D., Griswold, M., Gottesman, R. F., Wagenknecht, L. E., Windham, B. G. & Selvin, E. 2014. Annals of Internal Medicine, 161, 785-U68.

Plasma and cerebrospinal fluid amyloid beta for the diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI)

Ritchie, C., Smailagic, N., Noel-Storr, A. H., Takwoingi, Y., Flicker, L., Mason, S. E. & Mcshane, R. 2014. Cochrane Database of Systematic Reviews, 91.

Diabetes and Cognitive Impairment

Zilliox, L. A., Chadrasekaran, K., Kwan, J. Y. & Russell, J. W. 2016. Current Diabetes Reports, 16, 11.