Diabetes and cognitive impairment pdf

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diabetes and cognitive impairment pdf

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To investigate the risk factors for cognitive impairment in Chinese type 2 diabetes mellitus T2DM patients of advanced age and to identify effective biomarkers of mild cognitive impairment MCI in these patients.

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Relation of Diabetes to Mild Cognitive Impairment

There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications.

In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings.

Core tip: Diabetes mellitus increases the risk of cognitive impairment and dementia. Impairment of insulin signaling is a critically important factor and may be the cornerstone of the development of these cognitive sequences regardless of diabetic status.

Therefore, anti-diabetic medications especially insulin therapy may have a significant role in the management of various cognitive and mental dysfunctions. Type 2 diabetes mellitus T2DM is one of the most common diseases whose prevalence is on the rise. It is believed that within the next 30 years, the number of diabetic patients will double in comparison to the year [ 1 ].

On the other hand, diabetes is amongst the diseases with higher complications perhaps even the highest and these complications lower the quality of life in patients significantly [ 2 - 4 ]. Diabetes is a systemic disease as it affects various body systems to some extent. For instance, diabetes can disrupt proper function in cardiovascular, gastrointestinal, immune and nervous systems. The functional impairment of peripheral nervous system can lead to diabetic foot and in worst cases to amputation and hence physical disability.

Involvement of retina [diabetic retinopathy DR ] can lead to loss of vision and blindness. Adverse effects of diabetes on cognitive system and memory disorders have been noticed by researchers for a long time [ 2 - 4 ].

Equally, dementia is one of the most disabling public health problems. It affects the quality of life of demented patients and their caregivers. It also imposes a huge economic burden on countries. Therefore, identification of risk factors of dementia and the control of those factors is with utmost importance. This review discusses the association between diabetes and the risk of cognitive impairment with more clinical aspects. Therefore, possible underlying mechanisms of cognitive impairment in diabetic patients will be discussed, and the effect of various treatments on prophylaxis and improvement of mental dysfunction will be reviewed.

Memory is the retention, recording, and process of retrieving knowledge. All knowledge gained from experience such as known facts, remembered events, gained and applied skills would be considered as memory [ 6 ]. Memory can be categorized into declarative and non-declarative memory. Declarative memory mostly corresponds to the learning and recalling new facts, events, and materials.

Non-declarative memory refers to the many forms of memories that are reflective or incidental [ 6 ]. The majority of advanced cortical functions arise from association cortex. The main association areas are: 1 the parieto-occipitotemporal association area; 2 the prefrontal association area; and 3 the limbic association area [ 7 ]. Our knowledge about the mechanisms of thinking and remembering is little. It seems that each thought arises from simultaneous activation of many parts of the different areas in the brain such as cerebral cortex, limbic system, thalamus and reticular formation of the brainstem.

The memory is the result of some events in the synaptic transmission by changing its basic sensitivity [ 7 ]. The hippocampus and, to a lesser degree, the thalamus are responsible for deciding which thoughts are important enough to be saved as memories [ 7 ]. These data can be used in the diagnosis of cognitive disorders and for localization of the abnormality in the brain, as well as, the assessment of therapeutic effects of any treatment modality on the cognitive dysfunction.

Neurocognitive domains and some examples for their assessment are categorized in the Table 1 [ 8 , 9 ]. In addition, reliability, validity, sensitivity, and specificity of these tests are important aspects that should be considered.

Dementia and cognitive dysfunction have many causes. Additional disorders that can cause memory loss and other cognitive impairments are listed in the Table 2 [ 9 ]. Cognitive dysfunction with its wide range, from mild cognitive impairment MCI through dementia, is one of the chronic complications of diabetes mellitus [ 10 ]. Both diabetes and cognitive impairment occur more commonly at older age. There is strong evidence that T2D increases the risk of dementia in the form of multi-infarct dementia, AD and mixed type dementia.

The long-term risk of dementia increases in patients with diabetes by a factor of two [ 11 ]. T2D also increases the risk of progression of MCI to dementia [ 11 ]. Even in pre-diabetic state; there is an increased risk of AD and dementia which are not related to the future development of diabetes [ 10 ].

There is a faster deterioration of cognition in diabetic patients rather than non-diabetic elderly ones [ 13 ]. Diabetes is associated with 1. In recent years, the relation of diabetes to memory disorders has been well established. In , Wessels et al [ 16 ] published results of their comprehensive prospective study on a large sample size from to Patients in this cohort were examined at baseline and five follow-up assessments throughout the 15 years of study.

During each evaluation, participants were given the Community Screening Interview for Dementia as part of a home visit. They followed up subjects and showed that diabetes reduced their cognitive capabilities via cardiovascular disruption [ 16 ]. The results of the Edinburgh Type 2 Diabetes Study that was conducted for evaluation of this correlation were published in At baseline, any clinical and subclinical macrovascular diseases including cardiovascular event history, carotid intima-media thickness, ankle brachial index, and serum N-terminal probrain natriuretic peptide NT-proBNP were evaluated.

Seven neuropsychological tests were also done at baseline, and after 4 years. They found that stroke and subclinical markers of cardiovascular and atherosclerosis are associated with cognitive decline in older patients with type 2 diabetes T2D [ 17 ]. Recent research collaboration between Mayo Clinic and Shanghai was reported in In this study, involving a considerable number of patients, the effect of diabetes on the cognitive function of patients was strongly evident.

Diabetes was also associated with increased odds of cognitive decline as determined by MMSE scores [odds ratio OR , 1. In a different study that was carried out on subjects by Qiu et al [ 20 ] , they investigated whether and the extent to which vascular and degenerative lesions in the brain mediate the association of diabetes with poor cognitive performance.

They assessed cortical and subcortical infarcts and higher white matter lesion volume. They also evaluated neurodegenerative processes on magnetic resonance images.

However, their memory function score was not any better either [ 20 ]. The role of diabetes in neurodegeneration has been confirmed by neuroimaging and neuropathological studies. MRI studies have shown that T2D is strongly associated with brain atrophy [ 21 ].

The rate of global brain atrophy in T2D is up to 3 times faster than in normal aging [ 22 , 23 ]. This is especially true when diabetes starts before the age of 65, or when the disease is more than 10 years. Treatment with insulin and the presence of diabetes complications such as retinopathy are other risk factors [ 25 , 26 ]. In children, the relationship between T1D and cognitive disorders is also reported [ 27 ].

Cognitive flexibility, visual perception, psychomotor speed, and attention are the main domains which are mostly affected early on within 2 years in T1D , among which the mental slowing is the principal deficiency.

Learning and memory function seem to be intact even in a prolonged hyperglycemia in T1D [ 25 ]. Young age is an important risk factor in developing cognitive deficits in T1D. It seems that children whose disease is diagnosed under the age of 7 are at a greater risk for more severe cognitive dysfunction [ 28 ].

Single-photon emission tomography in diabetic patients shows an abnormality in many brain regions, which correlate especially with diabetic microvascular complications and poor glycemic control in T1D. However, there is no strong evidence to support the importance of brain perfusion abnormalities in the development of cognitive dysfunction in T1D [ 29 ].

In both types of diabetes, neural slowing, cortical atrophy and microstructural abnormalities in white matter are prominent [ 24 ]. In a recent article by Ho et al [ 30 ] , they have pointed out the effects of diabetes on hippocampus neurogenesis and depression and the resulting cognitive.

It has been shown that there is an association between DR and cognitive impairment. According to some studies, the vascular complications of diabetes such as retinopathy are the most important predictors for the cognitive decline. Based on the similarity in anatomy, physiology, and embryology of cerebral and retinal small vessels, this association is particularly interesting [ 31 ].

In a systematic review which analyzed three studies, it has been proven a near three fold increased risk of cognitive impairment in patients with DR. However; the association between the severity of DR and cognitive decline was not clearly demonstrated. Only one study showed that the men with more severe cognitive impairment had greater degree of retinal involvement. The recent memory and the verbal learning were the most defective cognitive domains in these studies [ 32 ].

Some studies have reported an association between cognitive impairment and general not diabetic retinopathy independent of other cardiovascular risk factors but underlying etiology has not been clearly identified [ 33 , 34 ]. The higher prevalence of cognitive impairment even in those with non-DR provides some clues to investigate the underlying mechanism for this association in wider metabolic abnormalities hypertension, dyslipidemia, and inflammatory stress rather than a pure glucotoxic effect [ 32 ].

This study showed that cognitive dysfunction was a predictable consequence of DR. In one cohort study by Crosby-Nwaobi et al [ 36 ] , they compared patients with Proliferative Diabetic Retinopathy with patients with Non Proliferative Diabetic Retinopathy or no retinopathy.

However; their study showed that cognitive impairment was more prominent in those with mild retinopathy than those without retinopathy [ 36 ]. Brain imaging can be an important tool to clarify the underlying pathogenesis for cognitive impairments in diabetic patients. Some researchers have been reported both focal and global cerebral changes [ 37 ]. Slight brain structural abnormalities have been reported in T1D [ 25 , 38 ]. A study showed that the gray matter density of patients with T1D was less than the control group and this finding correlated with severe hypoglycemic attacks and higher HbA1c levels.

This assessment was performed with voxel-based morphometry - a well-known quantitative MRI technique [ 25 , 38 ]. The direction of water diffusion in tissues is measured by using diffusion tensor imaging DTI that is an index for the integrity of white matter [ 25 ]. DT1 shows microstructural abnormalities particularly in the optic radiations and posterior corona radiata in T1D patients.

These findings correlate with longstanding diabetes and high concentrations of HbA1c [ 39 ]. These abnormalities may be the underlying pathogenesis in the mental slowing that is the main cognitive problem in T1D [ 40 ].

DT1 Technique will be a good research tool for future studies in this setting. This association between T2D and white matter lesions is less clear [ 37 ]. It was reported that hippocampal atrophy is a consistent neuroimaging finding in patients with T2D [ 41 ] , but a relatively recent study that evaluated the data from one cohort study and two case control studies, concluded that these patients did not have any specific vulnerability to hippocampal atrophy.

Risk Factors for Cognitive Impairment in Patients with Type 2 Diabetes

Metrics details. Diabetes is a risk factor for cognitive impairment, but whether there is also a link between pre-diabetes and cognitive dysfunction is not yet fully established. Regression analyses were performed to investigate associations between: a categories of normal or impaired glucose metabolism, and b OGTT measurements, respectively, as exposure variables and cognitive test results as outcomes. Adjustments were made for demographics, lifestyle factors and cardiovascular risk factors. Participants with pre-diabetes and diabetes scored slightly worse cognitive test results compared to the control group. Associations were stronger for older or less physically active individuals.

Relation of Diabetes to Mild Cognitive Impairment

Relation of Diabetes to Mild Cognitive Impairment. Arch Neurol. Of participants with a complete neuropsychological evaluation, Diabetes was related to a significantly higher risk of all-cause MCI and amnestic MCI after adjustment for all covariates. Diabetes was also related to a higher risk of nonamnestic MCI, but this association was appreciably attenuated after adjustment for socioeconomic variables and vascular risk factors.

Cognitive dysfunction in diabetes: how to implement emerging guidelines