The Diabetic Brain and Dementia

Abstract

Alzheimer's Disease (AD) and Diabetes Mellitus (DM) are the two most common and devastating health problems in the elderly. They share a number of common features among which are important impact on quality of life and substantial health care costs. Epidemiological and biological evidence support a pathophysiological link between Type 2 Diabetes Mellitus (DMT2) and cognitive impairment [1][2][3]. A causative association between DM and Alzheimer's disease has been suggested on the basis of clinical, epidemiological, genetic and experimental studies [2,[4][5][6][7][8][9]. Persons with DM have a higher incidence of cognitive decline and an increased risk of developing AD and other types of dementia, and comorbidity increases the risk [10,11]. Insulin resistance predicts medial temporal hypermetabolism in Mild Cognitive Impairment (MCI) conversion to AD [12] and glucose uptake changes in AD in medial temporal regions predicting worse memory performance [13]. DM has been shown to influence the rate of functional decline among patients with mild AD dementia than in those without comorbid DM [14]. However, the precise mechanisms involved in the development of AD in diabetics are not yet fully understood, and several pathogenic pathways have been discussed [3,4,[15][16][17][18][19][20].Autopsy studies stated that diabetic patients show significantly less AD pathology (senile plaques, neurofibrillary tangles, cerebral amyloid angiopathy, etc.) but more cerebrovascular lesions including microvascular lesions and white matter changes than subjects without DM [5,[21][22][23][24][25][26][27]. Vasculo-neural dysfunction has been suggested to represent a potential etiological linkage between DMT2 and AD [6,28], while others suggested that the association between DM and dementia is only partially mediated through cerebrovascular disease and that DM is associated independently with overal dementia among elderly, but not with AD or vascular dementia [29].Positive DMT2 status appears to exacerbate AD pathology in the presence of ApoE ε4 [30]. Although insulin mitigates Aβ deposition and hyperphosphorylation of tau [17,31], DM in combination with ApoE ε4 may lead to excessive phosphorylation of tau [32], but only in subjects with late stage AD [21]. DM modifies metabolism of Aβ and tau causing Aβ/tau-dependent pathological changes, although there is evidence that suggests an interaction of Aβ/tau-dependent and -independent mechanisms [31]. Evidence supports insulin's role in cognition, synaptic remodelling and facilitation of memory [33]. On the other hand, insulin has been shown to modulate the level of Aβ, to protect neurons against detrimental effects of Aβ on synapses [33]. It further facilitates reduction of amyloid plaques, downregulation of Aβ-derived diffusible ligand-binding sites and also to promote tau hypophosphorylation, which stabilizes microtubules. These data and the observation that the combination of insulin and other antidiabetic medication is associated with lower neuritic plaque density [23,34] are providing a...

Dynamics of diabetes and obesity: Epidemiological perspective

“…Because of brain dysfunction, cognitive impairment, oxidative stress and effects of glucose metabolism by IR on mitochondria leading to the “type 3 diabetes” which is classified as another form Alzheimer’s Disease (AD) [40–44]. Diabetics with this type of diabetes are at higher risk of cognitive decline when the age advances [45–48]. The mechanistic link between AD and diabetes is still unknown and recent literature suggesting inflammatory response, IR insulin growth factor (IGF) signaling, ApoEε4 allele on synaptic plasticity, acetylcholine esterase activity and vascular dysregulation of brain capillaries would play crucial role in forming pathophysiologic changes relating diabetes to dementia, including white matter disease, breakdown of the blood brain barrier, inflammation, and others [49–58].…”

Experience of actovegin use in a patient with cognitive impairment in diabetes mellitus (clinical case)

“…Диабетическая энцефалопатия занимает важное место в структуре сосудистых и смешанных форм когнитивных расстройств и деменции [3][4][5], увеличивая их риск по сравнению с лицами без СД на 19 % [6]. Тяжесть течения СД рассматривается как неблагоприятный прогностический фактор риска деменции [7].…”

The diabetic brain and cognition

“…In fact, recent studies demonstrate a pathophysiological link between diabetes mellitus type II (T2DM) and cognitive decline (Jellinger 2015b). This is demonstrated in persons with DM showing that a higher risk of developing Alzheimer's disease (AD), vascular dementia (VaD) and mixed-type dementia (AD plus cerebrovascular disease), and comorbidity, in particular cerebrovascular disease, hypertension, hypercholesterolemia, etc.…”

“…This is demonstrated in persons with DM showing that a higher risk of developing Alzheimer's disease (AD), vascular dementia (VaD) and mixed-type dementia (AD plus cerebrovascular disease), and comorbidity, in particular cerebrovascular disease, hypertension, hypercholesterolemia, etc. increases this risk (Jellinger 2015b;Haroon et al 2015;Kuo et al 2015). Insulin resistance predicts medial temporal hypermetabolism in Mild Cognitive Impairment (MCI) conversion to AD (Willette et al 2015b).…”