Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients

https://doi.org/10.1016/j.diabres.2012.05.013Get rights and content

Abstract

Aim

To evaluate the cognitive performance of a homogeneous population of Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a progressive dementia disorder characterized clinically by impairment of memory, cognition and behavior. Recently, a major research interest in AD has been placed on early evaluation. Diabetes is one of the clinical conditions that represent the greatest risk of developing oxidative stress and dementia. Glucose overload, leading to the development of impaired-induced insulin secretion in DIAB and has been suggested to slow or deter AD pathogenesis.

Methods

The degree of cognitive impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the Hamilton test was employed to evaluate depressive conditions; the final population studied was 101 subjects.

Results

The cognitive deterioration is statistically significantly lower (p < 0.05) in AD+DIAB patients as compared with AD patients.

Conclusions

In this longitudinal study the superimposed diabetic condition was associated with a lower rate of cognitive decline, while diabetic non-demented patients and controls present normal scores.

Introduction

Alzheimer's disease (AD) is the most common dementing disorder of late life characterized by progressive loss of cholinergic neurons and a devastating cognitive decline [1]. Currently there are no drugs that significantly improve the deteriorated cognitive conditions and/or stop the progression of the disease.

Diabetes Mellitus Type 2 (DIAB) is common in the elderly and in Alzheimer's patients as a concomitant pathology. DIAB is recognized as a risk factor for the development of probable AD [2], [3], [4]. Both entities share metabolic disorders associated with different pathological developments.

The study of peripheral markers in probable AD patients and AD with concomitant DIAB (AD+DIAB) has shown significant differences in biochemical variables: (i) reduced changes in the oxidative metabolism related with the damage stress and oxidative stress in AD+DIAB patients; (ii) similar reduction in the variables related with the methionine cycle (homocysteine, folic acid and vitamin B12), and; (iii) opposite signs in the correlation of insulin/glucose and insulin/glycated hemoglobin. Paradoxically, patients with both diseases – dementia plus diabetes – present significantly lower or attenuated metabolic disorders than the pure forms of dementia, e.g. Alzheimer's and vascular [5], [6], [7], [8].

Some recent works report that the presence of DIAB in conjunction with the AD, results in a better cognitive performance of patients suffering of both diseases [9], [10], [11].

Accordingly with these relatively new findings the presence of DIAB tends to decrease the alterations observed in biochemical variables when it is superimposed with the AD. However, current knowledge does not allow concluding that cognitive performance, as quantified by the tests applied with consensum scholarum, also could be improved in AD+DIAB patients.

The purpose of the present pilot study was to assess cognitive performance in a sample of a homogeneous population of probable AD with and without superimposed DIAB, non demented DIAB patients and a control group of healthy subjects. Cognitive and functional performances were assessed with the Alzheimer's Disease Assessment Scale (ADAS-Cog) [12], [13], the Folstein's Mini Mental State Examination (MMSE) [14], and the Clinical Dementia Rating (CDR) [15].

Two hypotheses were tested in this pilot study: (i) whether the degree of cognitive deterioration in AD+DIAB patients is lower than the decline observed in non-diabetic AD patients; (ii) whether there exists differences in the cognitive status of DIAB patients and healthy controls.

Section snippets

Patients and controls

The total population of one hundred and ten subjects consisted of non-demented Type 2 Diabetes Mellitus patients (DIAB), demented patients of the probable Alzheimer's disease with and without concomitant diabetes (AD+DIAB and AD, respectively) and healthy controls (C); all subjects were from Caucasian origin. This sample was studied at the Neurological Service of the Sirio-Libanés Hospital, in Buenos Aires. Control subjects were selected by age and sex to reflect the general gender and age

Materials and methods

Cognitive evaluation of the one hundred and ten subjects was studied with the Folstein's MMSE and the ADAS-Cog scale. Functional assessment of all patients and control subjects was conducted using the CDR. Depression was measured in all population with the Hamilton test [19].

All subjects had brain images with a 64-channel MDCT scanner GE Healthcare, Milwaukee (CT), or MR imaging of the brain at field strengths of 1.5 T, Signa, GE Medical Systems (MRI). The interpretation of the results was

Results

Table 1 summarizes the demographical and experimental data of the one hundred and one subjects studied in this protocol.

Arterial controlled hypertension was almost similar between groups: seven patients in the AD group (27%), six patients in the AD+DIAB group (23%), seven patients in the DIAB group (28%) and eight subjects in the C group (33%). The MRI shows that all patients and controls present a state of unspecific cerebral atrophy in accordance with their age.

The groups resulted homogenous

Discussion

Little is known about the effect of DIAB on the rate of cognitive decline in established probable AD [9]. This prospective and longitudinal study by Sanz et al. presented the usual problems in the following up of elderly populations. Starting with six hundred AD patients, sixty of them with concomitant DIAB, by death or other reasons less than half of them were included in the study.

Forgetfulness, distractibility and impaired executive function are manifestations of the normal aging process in

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgements

This study has been partially supported by a grant from the National Council of Scientific and Technical Research (CONICET), the Hospital Sirio-Libanés (School of Medicine, University of Buenos Aires, UBA) and the Institute of Biochemistry and Molecular Medicine (IBIMOL, CONICET-UBA), School of Pharmacy and Biochemistry, UBA) of Argentina. We thank Marcela Arata and Liliana Oudkerk (Psychology Graduates) for the evaluation of the cognitive tests and Eduardo Bartolomé (Medical Degree) by the

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