Cognitive Decline In Type Research Articles

Hippocampal asymmetry is associated with cognitive decline in Type 2 diabetes

Hippocampal asymmetry is associated with cognitive decline in Type 2 diabetes

Diabetes and periodontal disease: What should we learn next?

Diabetes and periodontal disease: What should we learn next?

Multi-scale glycemic variability: a link to gray matter atrophy and cognitive decline in type 2 diabetes.

ObjectiveType 2 diabetes mellitus (DM) accelerates brain aging and cognitive decline. Complex interactions between hyperglycemia, glycemic variability and brain aging remain unresolved. This study investigated the relationship between glycemic variability at multiple time scales, brain volumes and cognition in type 2 DM.Research Design and MethodsForty-three older adults with and 26 without type 2 DM completed 72-hour continuous glucose monitoring, cognitive tests and anatomical MRI. We described a new analysis of continuous glucose monitoring, termed Multi-Scale glycemic variability (Multi-Scale GV), to examine glycemic variability at multiple time scales. Specifically, Ensemble Empirical Mode Decomposition was used to identify five unique ultradian glycemic variability cycles (GVC1–5) that modulate serum glucose with periods ranging from 0.5–12 hrs.ResultsType 2 DM subjects demonstrated greater variability in GVC3–5 (period 2.0–12 hrs) than controls (P<0.0001), during the day as well as during the night. Multi-Scale GV was related to conventional markers of glycemic variability (e.g. standard deviation and mean glycemic excursions), but demonstrated greater sensitivity and specificity to conventional markers, and was associated with worse long-term glycemic control (e.g. fasting glucose and HbA1c). Across all subjects, those with greater glycemic variability within higher frequency cycles (GVC1–3; 0.5–2.0 hrs) had less gray matter within the limbic system and temporo-parietal lobes (e.g. cingulum, insular, hippocampus), and exhibited worse cognitive performance. Specifically within those with type 2 DM, greater glycemic variability in GVC2–3 was associated with worse learning and memory scores. Greater variability in GVC5 was associated with longer DM duration and more depression. These relationships were independent of HbA1c and hypoglycemic episodes.ConclusionsType 2 DM is associated with dysregulation of glycemic variability over multiple scales of time. These time-scale-dependent glycemic fluctuations might contribute to brain atrophy and cognitive outcomes within this vulnerable population.

Severe Hypoglycemia and Cognitive Decline in Older People With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study

People with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Hypoglycemia is a candidate risk factor, but the direction of association between episodes of severe hypoglycemia and cognitive decline in type 2 diabetes remains uncertain. In the Edinburgh Type 2 Diabetes Study, cognitive function was assessed in 831 adults with type 2 diabetes (aged 60-75 years) at baseline and after 4 years. Scores on seven neuropsychological tests were combined into a standardized general ability factor g. Self-reported history of severe hypoglycemia at baseline (history of hypoglycemia) and at follow-up (incident hypoglycemia) was recorded. A history of hypoglycemia was reported by 9.3% of subjects, and 10.2% reported incident hypoglycemia. Incident hypoglycemia was associated with poorer cognitive ability at baseline (age- and sex-adjusted odds ratio for lowest tertile of g 2.04 [95% CI 1.25-3.31], P = 0.004). Both history of hypoglycemia and incident hypoglycemia were also associated with greater cognitive decline during follow-up (mean follow-up g adjusted for age, sex, and baseline g -0.25 vs. 0.03 [P = 0.02] and -0.28 vs. 0.04 [P = 0.01], respectively), including after addition of vascular risk factors and cardiovascular and microvascular disease to the models (-0.23 vs. 0.03 [P = 0.04] and -0.21 vs. 0.05 [P = 0.03], respectively). The relationship between cognitive impairment and hypoglycemia appeared complex, with severe hypoglycemia associated with both poorer initial cognitive ability and accelerated cognitive decline.

Changes in MEG resting-state networks are related to cognitive decline in type 1 diabetes mellitus patients.

ObjectiveIntegrity of resting-state functional brain networks (RSNs) is important for proper cognitive functioning. In type 1 diabetes mellitus (T1DM) cognitive decrements are commonly observed, possibly due to alterations in RSNs, which may vary according to microvascular complication status. Thus, we tested the hypothesis that functional connectivity in RSNs differs according to clinical status and correlates with cognition in T1DM patients, using an unbiased approach with high spatio-temporal resolution functional network.MethodsResting-state magnetoencephalographic (MEG) data for T1DM patients with (n = 42) and without (n = 41) microvascular complications and 33 healthy participants were recorded. MEG time-series at source level were reconstructed using a recently developed atlas-based beamformer. Functional connectivity within classical frequency bands, estimated by the phase lag index (PLI), was calculated within eight commonly found RSNs. Neuropsychological tests were used to assess cognitive performance, and the relation with RSNs was evaluated.ResultsSignificant differences in terms of RSN functional connectivity between the three groups were observed in the lower alpha band, in the default-mode (DMN), executive control (ECN) and sensorimotor (SMN) RSNs. T1DM patients with microvascular complications showed the weakest functional connectivity in these networks relative to the other groups. For DMN, functional connectivity was higher in patients without microangiopathy relative to controls (all p < 0.05). General cognitive performance for both patient groups was worse compared with healthy controls. Lower DMN alpha band functional connectivity correlated with poorer general cognitive ability in patients with microvascular complications.DiscussionAltered RSN functional connectivity was found in T1DM patients depending on clinical status. Lower DMN functional connectivity was related to poorer cognitive functioning. These results indicate that functional connectivity may play a key role in T1DM-related cognitive dysfunction.

Cognitive decline in type 2 diabetes

Cognitive decline in type 2 diabetes

Possible synergistic effect of direct angiotensin II type 2 receptor stimulation by compound 21 with memantine on prevention of cognitive decline in type 2 diabetic mice

Type 2 diabetes mellitus (T2DM) is known to be associated with increased risk of cognitive impairment including Alzheimer disease. Recent studies have suggested an interaction between angiotensin II and N-methyl-d-aspartic acid (NMDA) glutamate receptors. We previously reported that stimulation of the angiotensin II type 2 (AT2) receptor exerts brain protective effects. A newly developed AT2 receptor agonist, compound 21 (C21), has enabled examination of the direct effect of AT2 receptor stimulation in vivo. Accordingly, we examined the possible synergistic effect of C21 and memantine on cognitive impairment in T2DM mice, KKAy. KKAy were divided into four groups; (1) control, (2) treatment with C21 (10μg/kg/day), (3) treatment with memantine (20mg/kg/day), and (4) treatment with both for 4 weeks, and subjected to Morris water maze tasks. Treatment with C21 or memantine alone at these doses tended to shorten escape latency compared to that in the control group. C21 treatment increased cerebral blood flow (CBF), but memantine did not influence CBF. Treatment with C21 or C21 plus memantine increased hippocampal field-excitatory postsynaptic potential (f-EPSP). Moreover, treatment with memantine or C21 increased acetylcholine level, which was lower in KKAy than in wild-type mice, and C21 plus memantine treatment enhanced memantine or C21-induced acetylcholine secretion. This study provides an insight into new approaches to understand the interaction of angiotensin II and neurotransmitters. We can anticipate a new therapeutic approach against cognitive decline using C21 and memantine.

P4‐206: Co‐treatment with memantine and compound 21, an angiotensin II type 2 receptor agonist, prevents cognitive decline in type 2 diabetic mice

P4‐206: Co‐treatment with memantine and compound 21, an angiotensin II type 2 receptor agonist, prevents cognitive decline in type 2 diabetic mice

Integrity of cerebral white matter in type 1 diabetes

To the Editor: In a recent issue of Diabetologia, Weinger et al. [1] report evidence of only mild white matter hyperintensities (WMHs) in a sample of adults with type 1 diabetes. These WMHs were comparable to those seen in a demographically similar sample of non-diabetic adults, and no association between diabetes characteristics and WMHs was found. As stated by the authors and from what is known from the literature, there is no clear understanding of the clinical relevance of WMHs. However there is evidence to suggest that whole grey and white matter volume, as compared with lesion burden, is more closely related to neuropsychological performance and neuropsychiatric symptoms [2, 3]. Our investigations of total white and grey matter volume in patients with type 1 diabetes revealed a relationship between cerebral white matter volume and cognitive performance [4]. Patients with diabetes demonstrated several subtle neuropsychological deficits, and patients with a microvascular complication (defined as proliferative retinopathy) showed a decreased white matter volume that was associated with worse cognitive performance. This suggests that cognitive decline is at least partly mediated by microvascular disease. Despite the fact that these studies differ methodologically and focus on different aspects of the brain (i.e. WMHs vs white matter volume), both aimed to elucidate the underlying mechanism of cognitive decline in type 1 diabetes. It is therefore unfortunate that Weinger et al. did not include this specific consideration in their paper. Whether WMHs are associated with white matter volume is still under debate. The results of a study by Wen et al. [5] suggest that WMHs are associated with loss of brain volume, which could presumably be the result of white matter pathology [6]. In contrast, Smith at al. [7] reported that decreased white matter volume measured from magnetic resonance imaging was associated with dementia and with lower cognitive test scores, whereas no such association was found with periventricular WMHs identified on the same images. WMHs were not related to white matter volume, stroke or dementia. Nonetheless, low white matter volume was strongly related to dementia and poor cognitive performance in this sample. In the elderly, the periventricular WMHs have been shown to be unrelated to total white matter volume loss [8]. Additional data from diffusion-weighted and magnetisation transfer (MT) imaging studies [9, 10] reveal that fractional anisotropy and the magnetisation ratio (a measure of the integrity of the microstructure) in white matter significantly decrease with age. These decreases suggest that white matter volume loss may result from these microscopic structural changes, which include myelin and axonal loss, dilatation of perivascular spaces and gliosis. To understand the mechanisms by which diabetes might affect the brain, it is important to consider the apparent Diabetologia (2008) 51:1554–1555 DOI 10.1007/s00125-008-1011-2

Cognition and Dementia in Type 2 Diabetes: Brain Imaging Correlates and Metabolic and Vascular Risk Factors

This review addresses the impact of Type 2 diabetes mellitus on the brain. We show that there is convincing evidence that Type 2 diabetes mellitus is associated with accelerated cognitive decline and dementia. The structural basis for these cognitive deficits includes both vascular lesions and global cerebral atrophy. Cerebral changes may already develop in prediabetes mellitus stages. Several areas of uncertainty need to be resolved in order to develop effective preventive strategies. Information on the risk factors for accelerated cognitive decline in patients with Type 2 diabetes mellitus is still scarce. Identification of these factors might help to identify individuals who are at risk for clinically relevant impairments and to develop specific interventions. Further studies on the course of development of cognitive decline in Type 2 diabetes mellitus may help to decide at what stage these interventions should be initiated.