Type 2 diabetes is an independent risk factor for dementia conversion in patients with mild cognitive impairment

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Abstract

Aims

To explore whether type 2 diabetes (T2D) is a risk factor for dementia conversion in patients with mild cognitive impairment (MCI).

Methods

A longitudinal nested case–control study in which 101 T2D patients and 101 non-diabetic patients with MCI matched by age and gender were included.

Results

The dementia conversion rate was 57.4% in T2D patients vs. 42.6% in non-diabetic subjects (p = 0.02). T2D and APOE ε4 allele were independent risk factors for developing dementia.

Conclusion

T2D is an independent risk factor for dementia conversion in MCI patients. This finding has significant clinical implications.

Section snippets

Research design and methods

This was a retrospective nested case–control study in which 101 T2D patients with MCI and 101 non-diabetic controls with MCI, matched by age, and attending a memory clinic (Fundació ACE) over a 2-year period were included (NCT02501876). The mean follow-up was 28 ± 8 months. All subjects had at least one year of follow-up. The inclusion criteria were: a Clinical Dementia Rating Scale (CDR) of 0.5, > 60 years of age, functional literacy and no severe auditory or visual abnormalities.

All subjects were

Results

Apart from age, T2D diabetic patients and non-diabetic subjects were similar as to gender, cardiovascular risk factors, education level and APOEe4 genotype frequency (Table 1).

The dementia conversion rate was higher in T2D patients than in non-diabetic subjects (57.4% vs. 42.6%, p = 0.02) and the elapsed time (months) for conversion was significantly lower in T2D patients than in controls (22.3 ± 4 versus 26.2 ± 7, p = 0.041).

Most of the subjects converted to AD (23%), followed by vascular dementia

Discussion

In this case–control study we found that T2D was an independent risk factor for the conversion to dementia in a Caucasian population with MCI. In addition, the diagnoses of dementia comprised AD in most cases.

The impairment of insulin signaling, the presence of low-grade inflammation and the pathways directly related to chronic hyperglycemia such as the accumulation of advanced glycation end-products (AGEs) and the increase of oxidative stress play an essential role in the pathogenesis of AD.13.

Funding

This research was supported by the Agency for the Management of University and Research Grants (2014-SGR-270) and the Spanish Society of Diabetes.

Author contributions

AC, AE obtained study data, assisted in the study design and data analysis, and drafted the initial manuscript. OS, AR, MA and CH made substantial contributions to the acquisition, analysis and interpretation of data, and critically reviewed the manuscript. MB and RS designed the study, obtained funds and critically reviewed the manuscript. All authors approved the final manuscript as submitted. R.S. is the guarantor of this work and, as such, had full access to all the data in the study and

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Duality of interest: No potential conflicts of interest relevant to this article were reported.

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