scholarly journals Necroptosis inhibition counteracts axonal degeneration, cognitive decline and key hallmarks of aging, promoting brain rejuvenation.

2021 ◽  
Author(s):  
Macarena S Arrázola ◽  
Matías Lira ◽  
Gabriel Quiroz ◽  
Somya Iqbal ◽  
Samantha L Eaton ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Axonal Degeneration ◽  
Brain Aging ◽  
Neuronal Connectivity ◽  
Main Risk Factor ◽  
Short Term ◽  
Memory Decline ◽  
Age Related ◽  
Pathological Event ◽  
Pharmacologic Inhibition

Age is the main risk factor for cognitive impairment and the development of neurodegenerative diseases. In the aged brain, axonal degeneration is an early pathological event, preceding neuronal dysfunction and brain disabilities in humans, primates, rodents, and invertebrates. Necroptosis activation mediates degeneration of mechanical and chemically injured axons, but whether this pathway triggers axonal degeneration and cognitive impairment during brain aging has not been studied. Here we show that necroptosis is activated in the hippocampus during aging, especially in axonal tracts. Loss of the main necroptotic effector, Mlkl, was sufficient to delay age-associated axonal degeneration. Accordingly, aged Mlkl-KO mice also displayed a youthful phenotype at the synaptic and functional level, protecting against decreased synaptic transmission and memory decline. Short-term pharmacologic inhibition of necroptosis by targeting RIPK3 in aged mice, proved to be extraordinarily effective at reverting axonal degeneration and hippocampal-dependent functional impairment at the electrophysiological and behavioral level. Remarkably, a comprehensive quantitative proteomic analysis uncovered a set of aging hallmarks that were recovered in both, the genetic and pharmacologic models of necroptosis inhibition, including molecular biofunctions associated with brain rejuvenation. Taken together, these findings demonstrate that necroptosis contributes to the age-associated deterioration of axonal integrity, affecting hippocampal neuronal connectivity and cognitive function in aged individuals. We therefore propose necroptosis as an attractive target for the future development of geroprotective tools to treat age-related disabilities.

scholarly journals Mild cognitive impairment (MCI) twenty years on

2011 ◽  
Vol 24 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Karen Ritchie ◽  
Craig W Ritchie
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Brain Aging ◽  
Cognitive Change ◽  
Cognitive Disorder ◽  
Everyday Functioning ◽  
Normal Limits ◽  
Age Related ◽  
The Usa

Cognitive decline has commonly been considered an inevitable result of brain aging and has been of clinical interest principally because of related difficulties with everyday functioning. Since the 1990s the “normality” of age-related cognitive decline has been called into question, being commonly attributed to a number of underlying disorders. Numerous concepts have been proposed which link subclinical cognitive change to pathological states (mild cognitive disorder, mild neurocognitive disorder, mild cognitive impairment). Of these, mild cognitive impairment (MCI) has become the most popular, driven on the one hand by industrial interests seeking to extend new dementia treatments for a more prevalent subclinical syndrome, and on the other by researchers attempting to identify at-risk populations. MCI has been both criticized for “medicalizing” behavior still within normal limits (Stephan et al., 2008; Moreira et al., 2008) and welcomed in that it suggests cognitive decline with aging may not be inevitable, but rather due to abnormalities which could ultimately be treated. Recently, in both Europe (DuBois et al., 2007) and the USA (Albert et al., 2011), panels of experts have scrutinized the concept of MCI and more broadly the pre-dementia stages of neurodegenerative diseases and offered new research diagnostic criteria. These proposed criteria have highlighted the (potential) value of biomarkers in assisting diagnosis, although some have considered the elevation of biomarkers to this level of importance in diagnosing disease before dementia develops to be premature given both the extent and quality of diagnostic biomarker data currently available (McShane et al., 2011a; 2011b).

scholarly journals Free Recall of Bound Information Held in Short-Term Memory is Unimpaired by Age and Education

2019 ◽  
Vol 35 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Mônica Sanches Yassuda ◽  
Maria Teresa Carthery-Goulart ◽  
Mario Amore Cecchini ◽  
Luciana Cassimiro ◽  
Katarina Duarte Fernandes ◽  
...  
Keyword(s):  
Free Recall ◽  
Short Term Memory ◽  
Brain Aging ◽  
Short Term ◽  
Or Education ◽  
Experimental Conditions ◽  
Binding Condition ◽  
Term Memory ◽  
Age Related ◽  
Recall Paradigm

Abstract Objectives It has been challenging to identify cognitive markers to differentiate healthy brain aging from neurodegeneration due to Alzheimer’s disease (AD) that are not affected by age and education. The Short-Term Memory Binding (STMB) showed not to be affected by age or education when using the change detection paradigm. However, no previous study has tested the effect of age and education using the free recall paradigm of the STMB. Therefore, the objective of this study was to investigate age and education effects on the free recall version of the STMB test under different memory loads. Methods 126 healthy volunteers completed the free recall STMB test. The sample was divided into five age bands and into five education bands for comparisons. The STMB test assessed free recall of two (or three) common objects and two (or three) primary colors presented as individual features (unbound) or integrated into unified objects (bound). Results The binding condition and the larger set size generated lower free recall scores. Performance was lower in older and less educated participants. Critically, neither age nor education modified these effects when compared across experimental conditions (unbound v. bound features). Conclusions Binding in short-term memory carries a cost in performance. Age and education do not affect such a binding cost within a memory recall paradigm. These findings suggest that this paradigm is a suitable cognitive marker to differentiate healthy brain aging from age-related disease such as AD.

The Great Pond Snail (Lymnaea stagnalis) as a Model of Aging and Age-Related Memory Impairment: An Overview

2021 ◽  
Author(s):  
István Fodor ◽  
Réka Svigruha ◽  
György Kemenes ◽  
Ildikó Kemenes ◽  
Zsolt Pirger
Keyword(s):  
Nervous System ◽  
Life Span ◽  
Memory Impairment ◽  
Lymnaea Stagnalis ◽  
Brain Aging ◽  
Model Organism ◽  
Pond Snail ◽  
Memory Decline ◽  
Age Related ◽  
Behavioral Mechanisms

Abstract With the increase of life span, normal aging and age-related memory decline are affecting an increasing number of people; however, many aspects of these processes are still not fully understood. Although vertebrate models have provided considerable insights into the molecular and electrophysiological changes associated with brain aging, invertebrates, including the widely recognized molluscan model organism, the great pond snail (Lymnaea stagnalis), have proven to be extremely useful for studying mechanisms of aging at the level of identified individual neurons and well-defined circuits. Its numerically simpler nervous system, well-characterized life cycle, and relatively long life span make it an ideal organism to study age-related changes in the nervous system. Here, we provide an overview of age-related studies on L. stagnalis and showcase this species as a contemporary choice for modeling the molecular, cellular, circuit, and behavioral mechanisms of aging and age-related memory impairment.

scholarly journals Gut Microbiota: Critical Controller and Intervention Target in Brain Aging and Cognitive Impairment

2021 ◽  
Vol 13 ◽  
Author(s):  
Hui Li ◽  
Junjun Ni ◽  
Hong Qing
Keyword(s):  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Healthy Aging ◽  
Brain Aging ◽  
Current Trend ◽  
The Body ◽  
Dietary Interventions ◽  
Age Related ◽  
Functional Features ◽  
The Brain

The current trend for the rapid growth of the global aging population poses substantial challenges for society. The human aging process has been demonstrated to be closely associated with changes in gut microbiota composition, diversity, and functional features. During the first 2 years of life, the gut microbiota undergoes dramatic changes in composition and metabolic functions as it colonizes and develops in the body. Although the gut microbiota is nearly established by the age of three, it continues to mature until adulthood, when it comprises more stable and diverse microbial species. Meanwhile, as the physiological functions of the human body deteriorated with age, which may be a result of immunosenescence and “inflammaging,” the guts of elderly people are generally characterized by an enrichment of pro-inflammatory microbes and a reduced abundance of beneficial species. The gut microbiota affects the development of the brain through a bidirectional communication system, called the brain-gut-microbiota (BGM) axis, and dysregulation of this communication is pivotal in aging-related cognitive impairment. Microbiota-targeted dietary interventions and the intake of probiotics/prebiotics can increase the abundance of beneficial species, boost host immunity, and prevent gut-related diseases. This review summarizes the age-related changes in the human gut microbiota based on recent research developments. Understanding these changes will likely facilitate the design of novel therapeutic strategies to achieve healthy aging.

Brain Ageing and Cognitive Impairment

2018 ◽  
pp. 152-173
Author(s):  
Rajpal Kaushik ◽  
Pratima Kaushik
Keyword(s):  
Cognitive Impairment ◽  
Brain Aging ◽  
Brain Size ◽  
Cognitive Effort ◽  
Regular Exercise ◽  
Healthy Life ◽  
Age Related ◽  
Brain Ageing ◽  
Moderate Alcohol Intake ◽  
Ageing Brain

This chapter describes how an individual progresses towards aging, several age-related cognitive declines are becoming an ever-increasing problem. Ageing causes changes to brain size, vasculature, and cognition. Protective factors that reduce cardiovascular risk, namely regular exercise, a healthy diet, and low to moderate alcohol intake, seem to aid the ageing brain as does increase cognitive effort in the form of education or occupational attainment. A healthy life both physically and mentally may be the best defense against the changes of an ageing brain. This chapter aims to characterize changes in brain structure with aging, and to investigate relationships between brain aging and cognitive decline. Along with these it will make and attempt to identify possible management, treatment and preventive measures for managing cognitive impairment in brain ageing and promoting cognitive reserve for healthy brain ageing.

Brain Structural Substrates of Semantic Memory Decline in Mild Cognitive Impairment

2013 ◽  
Vol 10 (4) ◽  
pp. 373-389 ◽  
Author(s):  
Simona Gardini ◽  
Fernando Cuetos ◽  
Fabrizio Fasano ◽  
Francesca Ferrari Pellegrini ◽  
Massimo Marchi ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Semantic Memory ◽  
Memory Decline

The Oxford Handbook of Adult Cognitive Disorders

2019 ◽  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Neurodevelopmental Disorders ◽  
Brain Aging ◽  
Cognitive Disorders ◽  
Diverse Range ◽  
Medical Specialties ◽  
Psychiatric Illnesses ◽  
Medical Disorders ◽  
The Impact

The prevalence of cognitive impairment caused by neurodegenerative diseases and other neurologic disorders associated with aging is expected to rise dramatically between now and year 2050, when the population of Americans aged 65 or older will nearly double. Cognitive impairment also commonly occurs in other neurologic conditions, as well as in non-neurologic medical disorders (and their treatments), idiopathic psychiatric illnesses, and adult neurodevelopmental disorders. Cognitive impairment can thus infiltrate all aspects of healthcare, making it necessary for clinicians and clinical researchers to have an integrated knowledge of the spectrum of adult cognitive disorders. The Oxford Handbook of Adult Cognitive Disorders is meant to serve as an up-to-date, scholarly, and comprehensive volume covering most diseases, conditions, and injuries resulting in impairments in cognitive function in adults. Topics covered include normal cognitive and brain aging, the impact of medical disorders (e.g., cardiovascular, liver, pulmonary) and psychiatric illnesses (e.g., depression and bipolar disorder) on cognitive function, adult neurodevelopmental disorders (e.g., Down Syndrome, Attention Deficit/Hyperactivity Disorder), as well as the various neurological conditions (e.g., Alzheimer’s disease, chronic traumatic encephalopathy, concussion). A section of the Handbook is also dedicated to unique perspectives and special considerations for the clinicians and clinical researchers, covering topics such as cognitive reserve, genetics, diversity, and neuroethics. The target audience of this Handbook includes: (1) clinicians, particularly psychologists, neuropsychologists, neurologists (including behavioral and cognitive neurologists), geriatricians, and psychiatrists (including neuropsychiatrists), who provide clinical care and management for adults with a diverse range of cognitive disorders; (2) clinical researchers who investigate cognitive outcomes and functioning in adult populations; and (3) graduate level students and post-doctoral trainees studying psychology, clinical neuroscience, and various medical specialties.

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