Incidence of Dementia is Increased in Type 2 Diabetes and Reduced by the Use of Sulfonylureas and Metformin

Article type: Research Article

Authors: Hsu, Chih-Cheng^{a; b; *} | Wahlqvist, Mark L.^{a; c} | Lee, Meei-Shyuan^c | Tsai, Hsin-Ni^a

Affiliations: [a] Division of Health Policy Research and Development, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan, ROC | [b] Department of Health Services Administration, China Medical University and Hospital, Taiwan, ROC | [c] School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC

Correspondence: [*] Correspondence to: Dr. Chih-Cheng Hsu, Division of Health Policy Research and Development, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, 35053 Taiwan, ROC. Tel.: +886 37 246 166 ext. 36336; Fax: +886 37 586 261; E-mail: cch@nhri.org.tw.

Abstract: To determine incidence of dementia in type 2 diabetic (T2DM) patients, and whether there are adverse or favorable effects of oral agents (OA) in DM, we obtained a representative cohort of 800,000 from Taiwan's National Health Insurance database. Those who, as of on January 1, 2000, were 50 years or older and dementia free (n = 127,209) were followed until December 31, 2007, in relation to absence (n = 101,816) or presence (n = 25,393) of T2DM, and whether any OA was used. Dementia was ascertained by ICD9-CM or A-code. Dementia incidence densities (DID) and fully adjusted Cox proportional hazard models were used to estimate association between dementia, DM, and OA. Notably, DID (per 10,000 person-years) was markedly increased with DM (without medication), compared to DM free subjects (119 versus 46). Using non-DM as reference, the adjusted hazard ratios (HRs) (95% confidence interval) for DM without and with OA were 2.41 (2.17–2.66) and 1.62 (1.49–1.77), respectively. For T2DM, compared with no medication, sulfonylureas alone reduced the HR from 1 to 0.85 (0.71–1.01), metformin alone to 0.76 (0.58–0.98), while with combined oral therapy the HR was 0.65 (0.56–0.74). Adjustments included cerebrovascular diseases so that non-stroke related dementias were found to be decreased in DM with sulfonylurea and metformin therapy. T2DM increases the risk of dementia more than 2-fold. On the other hand, sulfonylureas may decrease the risk of dementia, as does metformin; together, these 2 OAs decrease the risk of dementia in T2DM patients by 35% over 8 years.

Keywords: Alzheimer's disease, anti-diabetic medication, dementia, type 2 diabetes

DOI: 10.3233/JAD-2011-101524

Journal: Journal of Alzheimer's Disease, vol. 24, no. 3, pp. 485-493, 2011