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AlzRisk Risk Factor Literature Search Strategy and Results

Risk Factor: Diabetes Mellitus
Risk Factor Type: Chronic disease, Metabolic
Current Understanding:
The tables below summarize results from observational studies of the relationship between diabetes mellitus and measures of pre-clinical diabetes with AD and total dementia. Overall, the evidence is consistent with an association between diabetes diagnosis and increased risk of AD, suggesting that measures to prevent diabetes -- such as exercise, weight reduction and diet control -- will likely provide some protective benefit. Preliminary studies examining the risk of AD in association with measures of pre-clinical diabetes seem to specifically link impaired glucose tolerance with increased AD risk, but further research is needed to better characterize the relationship between these measures and AD. While standard glucose control is critical to prevent microvascular and macrovascular complications of diabetes, and may also be beneficial for cognitive outcomes, the effects of tighter glucose control regimens on AD require further study. For a review of the putative mechanisms by which diabetes may influence AD risk and detailed commentary on interpreting the findings below in a broader context, please view the Discussion.
Last Search Completed: 26 June 2012 - Last content update released on 1 Nov 2012

Risk Factor Overview


PubMed and EMBASE were searched for peer-reviewed articles examining the association between diabetes mellitus and incidence of Alzheimer disease (AD) in cohort or nested case-control studies. Using the search strategy detailed below, 3198 unique citations were found. After review of article titles and abstracts against our inclusion criteria, 98 citations were identified for full-text review. Two non-English language articles were set aside for future translation, screening and review. Of the remaining English language articles, 13 met criteria for inclusion in our summary tables. We excluded two additional articles that duplicated analyses from cohorts that contributed data to other included articles. Additionally, one more article meeting our inclusion criteria was identified through a previous literature search. Overall, 14 articles were included in our final summary table and meta-analysis. Please see our methods section for more details on our general systematic review methods.

Search & Review Flowchart
Search Strategy
Selection of Papers Reporting on Data from the Same Cohort

Search Strategy Flowchart

Using our systematic review methods, we developed similar search strategies (table below) for PubMed and EMBASE.

Search Strategy Table

Washington-Heights Inwood Columbia Aging Project (WHICAP)

Luchsinger et al. (2001) and Cheng et al. (2011) were included, while Muller et al. (2007) was excluded. The study population in Luchsinger et al. was obtained entirely from the first wave of participant enrollment and data collection in the WHICAP, which took place in 1992-1996, while the study population in Cheng et al. is obtained entirely from the second enrollment wave, which took place in 1999-2001. In Muller et al., the study population was a sample of some study participants from both waves. This paper was therefore excluded as all its participants were already included either in Luchsinger et al., or in Cheng et al.

Honolulu-Asia Aging Study (HAAS)

Peila et al. (2002) and Curb et al. (1999) both reported on diabetes and Alzheimer disease (AD) in the HAAS. Curb et al. reported on the occurrence of dementia at the fourth (1991-1993) examination of this cohort, classifying study participants’ diabetic status based on data from mid-life glucose examinations conducted in 1965, 1967 and 1971. In Peila et al., the investigators also identified participants who had developed diabetes in the ensuing two decades on the basis of fasting and post-load glucose tests of participants who reported being non-diabetic at the fourth examination, and used all of this data on diabetes status to evaluated the association with documented dementia incidence at the fifth examination (1994-1996).

Although both of these studies were based in the HAAS cohort, they focused on the risk of AD associated with having a diabetes diagnosis at different periods of life – i.e., specifically “during mid-life” in Curb et al., versus “at any time in life” in Peila et al. Therefore, we included both Curb et al., and Peila et al. in Table 1. However, the exposure definition used in Peila et al. more closely corresponds to that used in the other studies listed in Table 1, and therefore, to reduce between-study heterogeneity and maintain independence between our included studies, we included only Peila et al. in our meta-analysis.


Cheng, D., et al., Type 2 diabetes and late-onset Alzheimer's disease. Dement Geriatr Cogn Disord, 2011. 31(6): p. 424-30.

Curb, J.D., et al., Longitudinal association of vascular and Alzheimer's dementias, diabetes, and glucose tolerance. Neurology, 1999. 52(5): p. 971-5.

Luchsinger, J.A., et al., Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol, 2001. 154(7): p. 635-41.

Muller, M., et al., Metabolic syndrome and dementia risk in a multiethnic elderly cohort. Dement Geriatr Cogn Disord, 2007. 24(3): p. 185-92.

Peila, R., et al., Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes, 2002. 51(4): p. 1256-62.