Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer's Disease.

Type 2 diabetes mellitus (T2D) is a metabolic disease reaching pandemic levels worldwide. In parallel, Alzheimer's disease (AD) and vascular dementia (VaD) are the two leading causes of dementia in an increasingly long-living Western society. Numerous epidemiological studies support the role of T2D as a risk factor for the development of dementia. However, few basic science studies have focused on the possible mechanisms involved in this relationship. On the other hand, this review of the literature also aims to explore the relationship between T2D, AD and VaD. The data found show that there are several alterations in the central nervous system that may be promoting the development of T2D. In addition, there are some mechanisms by which T2D may contribute to the development of neurodegenerative diseases such as AD or VaD.

Amyotrophic Lateral Sclerosis and Serum Lipid Level Association: A Systematic Review and Meta-Analytic Study.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. Many metabolic alterations occur during ALS progress and can be used as a method of pre-diagnostic and early diagnosis. Dyslipidemia is one of the physiological changes observed in numerous ALS patients. The aim of this study is to analyze the possible relationship between the rate of disease progression (functional rating scale (ALS-FRS)) and the plasma lipid levels at the early stage of ALS. A systematic review was carried out in July 2022. The search equation was "Triglycerides AND amyotrophic lateral sclerosis" and its variants. Four meta-analyses were performed. Four studies were included in the meta-analysis. No significant differences were observed between the lipid levels (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol) and the ALS-FRS score at the onset of the disease. Although the number of studies included in this research was low, the results of this meta-analytic study suggest that there is no clear relationship between the symptoms observed in ALS patients and the plasma lipid levels. An increase in research, as well as an expansion of the geographical area, would be of interest.

Metabolic Disturbance of High-Saturated Fatty Acid Diet in Cognitive Preservation.

Aging continues to be the main cause of the development of Alzheimer's, although it has been described that certain chronic inflammatory pathologies can negatively influence the progress of dementia, including obesity and hyperlipidemia. In this sense, previous studies have shown a relationship between low-density lipoprotein receptor (LDLR) and the amyloid-beta (Aß) binding activity, one of the main neuropathological features of Alzheimer's disease (AD). LDLR is involved in several processes, including lipid transport, regulation of inflammatory response and lipid metabolism. From this perspective, LDLR-/- mice are a widely accepted animal model for the study of pathologies associated with alterations in lipid metabolism, such as familial hypercholesterolemia, cardiovascular diseases, metabolic syndrome, or early cognitive decline. In this context, we induced hyperlipidemia in LDLR-/- mice after feeding with a high-saturated fatty acid diet (HFD) for 44 weeks. LDLR-/--HFD mice exhibited obesity, hypertriglyceridemia, higher glucose levels, and early hepatic steatosis. In addition, HFD increased plasmatic APOE and ubiquitin 60S levels. These proteins are related to neuronal integrity and health maintenance. In agreement, we detected mild cognitive dysfunctions in mice fed with HFD, whereas LDLR-/--HFD mice showed a more severe and evident affectation. Our data suggest central nervous system dysfunction is associated with a well-established metabolic syndrome. As a late consequence, metabolic syndrome boots many behavioral and pathological alterations recognized in dementia, supporting that the control of metabolic parameters could improve cognitive preservation and prognosis.

Current Treatments and New, Tentative Therapies for Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative pathology, the origin of which is associated with the death of neuronal cells involved in the production of dopamine. The prevalence of PD has increased exponentially. The aim of this review was to describe the novel treatments for PD that are currently under investigation and study and the possible therapeutic targets. The pathophysiology of this disease is based on the formation of alpha-synuclein folds that generate Lewy bodies, which are cytotoxic and reduce dopamine levels. Most pharmacological treatments for PD target alpha-synuclein to reduce the symptoms. These include treatments aimed at reducing the accumulation of alpha-synuclein (epigallocatechin), reducing its clearance via immunotherapy, inhibiting LRRK2, and upregulating cerebrosidase (ambroxol). Parkinson's disease continues to be a pathology of unknown origin that generates a significant social cost for the patients who suffer from it. Although there is still no definitive cure for this disease at present, there are numerous treatments available aimed at reducing the symptomatology of PD in addition to other therapeutic alternatives that are still under investigation. However, the therapeutic approach to this pathology should include a combination of pharmacological and non-pharmacological strategies to maximise outcomes and improve symptomatological control in these patients. It is therefore necessary to delve deeper into the pathophysiology of the disease in order to improve these treatments and therefore the quality of life of the patients.

Poor Cognitive Agility Conservation in Obese Aging People.

Life expectancy has been boosted in recent decades at expenses of increasing the age-associated diseases. Dementia, for its incidence, stands out among the pathologies associated with aging. The exacerbated cognitive deterioration disables people from carrying out their daily lives autonomously and this incidence increases exponentially after 65 years of age. The etiology of dementia is a miscellaneous combination of risk factors that restrain the quality of life of our elderly. In this sense, it has been established that some metabolic pathologies such as obesity and diabetes act as a risk factor for dementia development. In contrast, a high educational level, as well as moderate physical activity, have been shown to be protective factors against cognitive impairment and the development of dementia. In the present study, we have evaluated the metabolic composition of a population between 60-90 years old, mentally healthy and with high academic degrees. After assessing agility in mental state, we have established relationships between their cognitive abilities and their body composition. Our data support that excess body fat is associated with poorer maintenance of cognition, while higher percentages of muscle mass are associated with the best results in the cognitive tests.