• Kaushik Subramanian

Does age affect memory?

Human memory can be divided into hierarchical taxonomic models based on the duration of memory retention and the type of information being retrieved. Short-term memory or working memory is defined as the short-term store employed to perform certain cognitive tasks during memory retention. Long-term memory can be categorized into Declarative memory and Non-declarative memory.

Further, declarative memory is defined as the explicit recall of information and can be classified into semantic, episodic, and perceptual memory. On the contrary, non-declarative memory is the cognitive process that facilitates implicit recall of information and can be categorized into priming, procedural and conditioning modules. It is crucial to understand how normal cognitive ageing affects these different types of memory modules.

Memory is defined as the neural mechanism by which the brain stores, remembers and recalls information.

In recent times, cognitive decline and frailty as a result of normal ageing have emerged as one of the greatest health threats of old age. Ageing, which is a normal and complex biological process is characterized by a steady decline in various physiological functions that result in both physical and cognitive impairment. The elderly population of the world is growing at a faster rate than ever before. In order to better comprehend and develop therapeutic interventions for this cognitive decline, we need to arrive at a greater and much deeper understanding of the cognitive processes that underlie normal and pathological ageing.

In the United States, cognitive decline and dementia, usually in the form of Alzheimer’s disease, affects almost 50% of adults above the age of 85. The development of pathologies such as these in the brain, need to be understood in the context of the molecular biology and mechanisms of the ageing process. The rate of ageing in humans is not fixed, but rather a more plastic, variable and modulatory number depending upon a whole array of factors. These altered regulations of the fundamental mechanisms of ageing may contribute to the pathogenesis of neurodegenerative disorders.

Because the amount of col­lagen decreases with age, flexibility of ligaments, tendons, muscles and joints decline and this affects muscle function over time. This reduction in muscle tone is directly linked to reduced lung capacity and therefore reduced oxygen consumption. Ageing also causes thinning of arterial walls and increases fat deposi­tion within arteries. These cardiovascular problems, along with reduced lung capac­ity, render physical activity a difficult task. It is therefore no surprise that the elderly are susceptible to a range of medical complications over time.

Moreover, the skin undergoes changes in pigmentation, water content and elasticity via a decrease in elastin and collagen content which presents as wrinkles on the face and body. Hair loss, which is perhaps one of the most well known physical conse­quence of ageing, is dependent upon genetics and involves thinning and depigmentation of hair follicles perceived as greying of the hair. In addition, bone density decreases with age and this is threefold greater in women than men. Recent research suggests that decreased integrity of a portion of the corpus callosum during ageing leads to reduced perceptual speed and memory retrieval. Furthermore, functionality of posterior regions of the brain also decline with age, particularly the ventral visual cortex that exhibits less neural selectivity to inputs from the visual system.

It is important to note that the rate and degree of cognitive decline varies widely across individuals and there are various reasons to explain this, such as changes in diet and lifestyle, inflammation, genetics and the presence of confounding illness and comorbidities.

Microarray genetic analysis and functional image studies of the ageing human brain, has given us an unprecedented systems view of neural activity and its variability with ageing and cognitive decline. Age-dependent breakdown in higher-order brain systems may relate, in part, to disruption of myelinated fibres that connect neurons in different cortical regions. Although neuronal loss is minimal in most cortical regions of the normal ageing brain, changes in the synaptic physiology of ageing neurons may contribute to altered connectivity and higher-order integration. Functional MRI studies suggest that changes in the activity of the hippocampus and associated cortical regions can distinguish normal ageing from pathological ageing.

However, conserved mechanisms of stress resistance during ageing may also be used by the brain to protect against the pathology of neuro-degenerative disorders. To better understand the relationship between neurodegenerative diseases and normal brain ageing, we must first gain a greater understanding of the mechanistic basis of the ageing process itself. The identification of ageing pathways in model organisms is slowly beginning to shed light on this fundamental question. There is increasing evidence that the nervous system may act as a central regulator of ageing by coordinating the physiology of extraneural tissues. However, the role of the brain as a central integrator of physiological changes during ageing is just beginning to be explored. Recent findings suggest that higher-order brain systems become less efficient with age, with some degree of disconnection between brain areas that normally function together in young adults.

Age-dependent breakdown in higher-order brain systems may relate, in part, to disruption of myelinated fibres that connect neurons in different cortical regions.

This may contribute to increased neural activity in the prefrontal cortex of aged individuals, that may initially be compensatory but could predispose the individuals to brain toxicity and neurodegenerative pathology. Furthermore, reduced expression of genes involved in mitochondrial energy metabolism may become more pronounced in humans with cognitive decline and Alzheimer’s disease. Another feature of ageing is increased expression of genes involved in stress-response pathways. It is important to appreciate the evolution of these gene expression changes, as they may contribute to the apparent human specificity of neurodegenerative disorders.

The question then arises- How can we intervene to prevent Cognitive failure with age? As of today, there is a large number of different pharmacological and behavioural approaches that have been used in an attempt to enhance cognitive function with ageing. For instance, increased physical activity, social involvement and taking part in intellectually demanding activities such as computer use, reading and music have shown to increase cognitive performance in older adults. Alternatively, cognitive training has been shown to increase individuals’ performance in day to day activities. The advantage to this is that cognitive training is a method accessible to most of the population as it can be delivered within a clinical or home setting. These behavioural methods of either preserving, or enhancing, cognition with age may also be augmented through the use of targeted therapeutics.

Zinc is essential for the normal functioning of the brain and there is an increasing body of evidence to suggest that zinc plays an important role in Age related cognitive decline.

Recent advancements in the field have allowed for the identifica­tion of specific molecules and pathways that are dysfunctional or altered during ageing and which may represent tractable therapeutic targets. For example, recent evidence suggests that there may be a crucial link between zinc levels in the brain and cognitive function. Hence, several pharmacological strategies that target zinc have been assessed for their therapeutic efficacy in both cognitive ageing and a range of neurodegenerative diseases over the last decade.

Sadly, there is no current treatment available for age-related cognitive decline. This is due to the fact that our current knowledge on normal ageing is still relatively lim­ited. However, future research into the biological implications of ageing will help reveal what aberrant processes contribute to cognitive decline in both normal and pathological ageing. While the research is ongoing, immediate efforts should work to maximize and preserve cognitive function in order to improve the quality of life of those affected.

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