In a recent study published in Npj Aging, researchers reviewed existing knowledge about age-related cognitive decline and changes in the brain based on studies from rodent models and humans, covering a wide range of cognitive assessments from pen and paper tests to behavior paradigms based on virtual reality.
Study: Assessing cognitive decline in the aging brain: lessons from rodent and human studies. Image Credit: Carlos_Pascual/Shutterstock.com
Background
While modern medicine and major improvements in the quality of life have increased longevity, the growing aging population also brings various health problems related to age-related decline.
Age also correlates with an increased incidence of cardiovascular disease, arthritis, cancers, and neurodegenerative diseases. Cognitive decline related to age is one of the major drivers of the increased prevalence of neurological disorders.
Furthermore, while age is a known risk factor for Alzheimer’s disease, the neurobiological changes resulting from cognitive deficits occur as a natural part of aging. They are substantially different from those observed in Alzheimer’s disease.
Studies have reported that mild cognitive impairment and dementia are present in about 16% and 14%, respectively, of adults above 70 years of age.
Research from human and animal models has also reported that age-associated cognitive decline is largely characterized by synaptic loss, while Alzheimer's disease also involves neuronal loss.
About the study
In the present study, the researchers examined human and animal model studies to understand the biological modifications associated with the cognitive decline that occurs with age and with no associations with specific diseases.
The review did not examine the modifications associated with synaptic and molecular plasticity and instead discussed the major types of memory and the changes in various regions of the brain that correlate to altered cognitive function with age. They also discussed the methodologies employed to conduct age-related clinical trials.
Research over the past few decades has shown that age-related cognitive dysfunction is similar across various animal models, such as rodents and primates, and given the various logistical and ethical challenges in designing and completing longitudinal aging studies in humans, these animal models provide a suitable system to study age-related cognitive decline over time.
Similar to humans, the decline in cognitive function associated with age in animal models such as canines, rodents, and non-human primates is seen largely in the hippocampal region, which is linked to memory impairments but not to neuronal loss.
Therefore, age-related cognitive changes in animal models are translatable to humans, providing a promising alternative for conducting longitudinal studies on aging and alterations in cognition.
Major findings
The review examined the major memory types affected during aging and found that intelligence is classified into two major categories — crystallized and fluid intelligence.
Crystalized intelligence, which includes knowledge/vocabulary acquisition and procedural memories, does not decline over time and often even increases with age.
Fluid intelligence, which includes reasoning and problem-solving abilities and the processing of new information, peak during the early adult stage and then decline with age.
Furthermore, while autobiographical memories from the past remain unaffected, the ability to form new memories declines with age. Studies in human and rodent models also found that aging was linked to altered brain activity in the hippocampus, cortex, cerebellum, and motor-associated brain regions.
Numerous cognitive tests have been employed to study cognitive decline with age in humans and animal models. The simplest of these include questionnaire-based methods such as the Mini-Mental State Examination and the Montreal Cognitive Assessment to assess cognitive impairments and dementia.
However, these methods are often subject to bias based on gender and education levels and are less sensitive to milder cognitive impairments.
Behavior paradigms based on factors such as Pavlovian conditioning and spatial navigation have also been widely used in animal models to understand age-related cognitive decline.
The Pavlovian conditioning studies include contextual and cue-based fear-conditioning and conditioning based on aversive stimuli. In contrast, the ones found on spatial navigation assessments use designs such as the Morris water and Barnes mazes.
Recent studies have also employed virtual-reality-based methods to assess cognitive abilities in humans and rodents.
The authors also discussed some of the shortcomings and potential strategies for improvement regarding cognitive tests used for screening older adults for clinical trials investigating age-related cognitive decline.
Conclusions
To summarize, the review presented a comprehensive assessment of the findings from human and animal model-based studies on cognitive decline related to aging.
The findings covered the major brain changes associated with aging and cognitive impairments and discussed the various assessments used in these studies to evaluate cognitive function.
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