Insulin Resistance and Mild Cognitive Impairment (IRMCI) Study

Summary

Dementia (Alzheimer's Disease) is sometimes called "Type 3 Diabetes" because of the strong connection between Type 2 diabetes (a function of insulin resistance) with Dementia. The investigators therefore hypothesize that Reducing Insulin Resistance using Intensive Lifestyle Intervention (Exercise and Weight loss) + Metformin Treatment in Prediabetic \& diet-control-only Diabetic overweight and mildly cognitively impaired individuals 55 years or older would lead to better Cognitive Function (compared to standard care) after 2 years. Subjects will be monitored and assessed using a battery of Cognitive and psychological tests and PET scans to demonstrate glucose utilization in the relevant areas of the brain. This 3-year open-label study aims to recruit 360 subjects with 50% (180 subjects) randomized to receiving Intensive lifestyle intervention with Metformin (if diabetic) vs the other 50% who would receive only the usual standard level of care in the primary care setting.

Timeline

Start

2015-03-11

Primary completion

2019-12-31

Completion

2019-12-31

Outcome

Outcome not reported

Stopped (Business): “1. Limits of grant funding reached 2. A/Prof Ng Tze Pin (P.I. \& holder of NMRC Grant (CIRG12may033) funding this study) retired in Aug 2022. 3. Resignations of staff and collaborators especially over the 1st 2 years of the COVID-19 pandemic”

Publications

• Background Pathan AR, Gaikwad AB, Viswanad B, Ramarao P. Rosiglitazone attenuates the cognitive deficits induced by high fat diet feeding in rats. Eur J Pharmacol. 2008 Jul 28;589(1-3):176-9. doi: 10.1016/j.ejphar.2008.06.016. Epub 2008 Jun 7.
• Background Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, Asthana S, Fishel MA, Kulstad JJ, Green PS, Cook DG, Kahn SE, Keeling ML, Craft S. Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am J Geriatr Psychiatry. 2005 Nov;13(11):950-8. doi: 10.1176/appi.ajgp.13.11.950.
• Background Risner ME, Saunders AM, Altman JF, Ormandy GC, Craft S, Foley IM, Zvartau-Hind ME, Hosford DA, Roses AD; Rosiglitazone in Alzheimer's Disease Study Group. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J. 2006 Jul-Aug;6(4):246-54. doi: 10.1038/sj.tpj.6500369. Epub 2006 Jan 31.
• Background Abbatecola AM, Lattanzio F, Molinari AM, Cioffi M, Mansi L, Rambaldi P, DiCioccio L, Cacciapuoti F, Canonico R, Paolisso G. Rosiglitazone and cognitive stability in older individuals with type 2 diabetes and mild cognitive impairment. Diabetes Care. 2010 Aug;33(8):1706-11. doi: 10.2337/dc09-2030. Epub 2010 Apr 30.
• Background Gold M, Alderton C, Zvartau-Hind M, Egginton S, Saunders AM, Irizarry M, Craft S, Landreth G, Linnamagi U, Sawchak S. Rosiglitazone monotherapy in mild-to-moderate Alzheimer's disease: results from a randomized, double-blind, placebo-controlled phase III study. Dement Geriatr Cogn Disord. 2010;30(2):131-46. doi: 10.1159/000318845. Epub 2010 Aug 21.
• Background Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, Irizarry M, Jeter B, Zvartau-Hind M, van Dyck CH, Gold M. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies. Curr Alzheimer Res. 2011 Aug;8(5):592-606. doi: 10.2174/156720511796391935.
• Background Ng TP, Feng L, Yap KB, Lee TS, Tan CH, Winblad B. Long-term metformin usage and cognitive function among older adults with diabetes. J Alzheimers Dis. 2014;41(1):61-8. doi: 10.3233/JAD-131901.
• Background Brackett CC. Clarifying metformin's role and risks in liver dysfunction. J Am Pharm Assoc (2003). 2010 May-Jun;50(3):407-10. doi: 10.1331/JAPhA.2010.08090.
• Background American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014. No abstract available.
• Background American Diabetes Association. (6) Glycemic targets. Diabetes Care. 2015 Jan;38 Suppl:S33-40. doi: 10.2337/dc15-S009. No abstract available.
• Background Standards of medical care in diabetes--2015: summary of revisions. Diabetes Care. 2015 Jan;38 Suppl:S4. doi: 10.2337/dc15-S003. No abstract available.

Drugs

Indications