Deans' stroke musings: Aging and cognitive resilience: Molecular mechanisms as new potential therapeutic targets

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Thursday, July 25, 2024

Aging and cognitive resilience: Molecular mechanisms as new potential therapeutic targets

You'll want something like this to restore your cognitive abilities so go ask your competent? doctor for EXACT PROTOCOLS to accomplish that.

https://doi.org/10.1016/j.drudis.2024.104093

Get rights and content

Under a Creative Commons license

open access

Highlights

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Aging and cognitive resilience depend on genetic and epigenetic factors.
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Dendritic spines and microglia are at the forefront of aging and cognitive resilience.
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Dendritic spines and microglia improve cognitive resilience.
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Outcomes may be boosted if these approaches are combined.

As the global population ages, the need to prolong lifespan and healthspan becomes increasingly imperative. Understanding the molecular determinants underlying cognitive resilience, together with changes during aging and the (epi)genetic factors that predispose an individual to decreased cognitive resilience, open avenues for researching novel therapies. This review provides a critical and timely appraisal of the molecular mechanisms underlying cognitive resilience, framed within a critical analysis of emerging therapeutic strategies to mitigate age-related cognitive decline. Significant insights from both animals and human subjects are discussed herein, directed either toward active pharmaceutical ingredients (drug repositioning or macromolecules), or, alternatively, advanced cellular therapies.

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Keywords

Aging

Cognitive impairment

Cognitive reserve

Cognitive resilience

Neurodegenerative disease

Neuroinflammation

Neuroplasticity

Introduction

In recent years, aging rates have been increasing due to greater longevity combined with falling birth rates around the world.^(p1) The increase in human life expectancy over the last two centuries represents a remarkable achievement of modern civilization. However, it has also become a worldwide concern; in particular, there is a need to discover the mechanisms underlying cognitive aging given the increase in dementia cases in Portugal and worldwide.^(p2)

Aging, a complex, natural, and gradual process experienced by all living beings, is characterized by physical, psychological, and social changes that can affect the quality of life of individuals. It can represent both an opportunity for society (people gain increased experience) and a threat (due to the high costs to families associated with dementia, as well as limited medical resources).^(p1) The aging process is associated with decreased function of organs and systems, leading to various diseases and health problems.^(p3)^,^(p4)^,^(p5)

Brain aging is characterized by physiological, structural, and functional modifications, culminating in cognitive decline and a heightened susceptibility to develop neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD).^(p4) However, there are multiple factors during fetal development and childhood, and throughout the living adult lifespan, which promote, intensify, or even protect against the pathophysiologic processes that lead to neurodegeneration and its consequent clinical expression.^(p3)^,^(p4)^,^(p5) These factors, some of which are negative, may operate together, hampering their investigation on an individual basis.^(p4)^,^(p5)^,^(p6)^,^(p7)

The research on cognitive decline demonstrates how important cognition is. Cognition includes functions like memory, attention, perception, and language, among others,^(p1) and encompasses the acquisition, storage, manipulation, and use of information. With aging, cognition is commonly compromised. For instance, processing speed decreases, as well as working memory and the ability to multitask.^(p1) With the increasing number of elderly persons, it has become important to investigate the effects of the aging process on cognition to develop cognitive-behavioral interventions and public health policies, including preventive psychological therapeutic strategies.^(p6)^,^(p8) These strategies are expected to promote healthy aging, improve the quality of life of elderly people, and reduce the risk of dementia development.^(p8) However, for this emergent field to achieve maximum development and benefit, it is essential to address major unanswered questions.^(p9)

In this context, the current monography aimed to provide a comprehensive overview of existing conceptual models of cognitive reserve and resilience, along with their associated mechanisms. Additionally, it endeavors to investigate the pivotal determinants impacting cognitive resilience and clarify the mechanisms. In parallel, the molecular attributes responsible for preserving cognitive function are critically discussed herein to highlight their potential as therapeutic targets for both neurodegenerative disorders and healthy aging.