Ageing and the Brain

Original Editor - Created as part of the AGILE Project

Top Contributors - Alex Benham, Simisola Ajeyalemi, Kim Jackson, Lucinda hampton, Tolulope Adeniji, Rubi, Rishika Babburu, Claire Knott, Sai Kripa, Ewa Jaraczewska, Dinu Dixon and Janine van Dyk  

Introduction

Brain function varies normally as people pass from childhood through adulthood to living with frailty age.

• During childhood, cognitive abilities typically increase, enabling acquisition of progressively complex skills.
• During most of adulthood, brain function is relatively stable.
• Later in life, aspects of brain structure and function may decline, with substantial inter-individual variability.

As we age, brain size/volume, vasculature, and cognition change. Brain volume generally declines (especially in frontal/temporal regions), white-matter hyperintensities become more common, and the risks of stroke and dementia rise. Neurotransmitter and hormone levels also change. Although some slowing of processing speed and aspects of memory is common, healthy lifestyle factors, regular aerobic and resistance exercise, cognitive training/engagement, and social participation, support neuroplasticity and may mitigate risk.

Common Age Changes

Some brain regions show measurable volume loss (rates vary by region and decade), which may occur without overt functional impairment in many individuals.

• Age-related changes in brain structure do not always result in loss of brain function.
• A decrease in brain function with ageing may be the result of numerous factors that include changes in neurotransmitters, neurones, toxic substances that accumulate in the brain over time, and inherited changes.
• Brain shrinkage: Brain volume decreases, particularly in the frontal cortex.
• Nerve cell loss: The brain and spinal cord lose nerve cells and weigh
• Short-term memory and the ability to learn new material tend to be affected relatively early.
• Verbal abilities, including vocabulary and word usage, may begin to decline later.
• Intellectual performance (the ability to process information, regardless of speed) is usually maintained if no underlying neurologic or vascular disorders are present.

Morphological changes to the brain with ageing

• The volume of the brain, due to neuronal loss, occurs at an approximate reduction of 5% of brain weight, per decade, after the age of 40 , making some structures more pronounced: eg sulci of the cortex become deeper; ventricles becoming more pronounced
• Deposition of Brown (Lipofuscin) or black (Neuromelanin) pigments in the brain results in small discoloured areas due to normal ageing (these are noted more in age-related brain pathologies such as Alzheimer's). .

Physiological changes to the brain with ageing

• Cerebral blood flow has been shown to decrease by 27% decline over 70 years of age through direct changes in the cardiovascular system and may be exacerbated through blood vessel pathology .
• The effectiveness of the blood-brain barrier is found to be reduced with age and this leads to the increased opportunity for the pathogens and toxic materials crossing into the brain and the neural structures. Recent work has shown that this is often weakened in the hippocampus first which leads to damage to the area and can result in a cognitive decline to the function of the brain region.
• Ageing is also associated with declining production of some neurotransmitters, including noradrenaline, glutamate, dopamine and serotonin. Dopamine modulates motor function and the acquisition of new skills and is also one of the brain’s reward chemicals. The number of dopamine-producing neurons decreases as part of the normal ageing process, and this can adversely affect the ability to learn from past experiences .

The Brains Resilience

The brain has certain characteristics that help compensate for these losses.

1. Redundancy: The brain has more cells than it needs to function normally. Redundancy may help compensate for the loss of nerve cells that occurs with aging and disease.
2. Formation of new connections: The brain actively compensates for the age-related decrease in nerve cells by making new connections between the remaining nerve cells (experience-dependent synaptic/dendritic change supports compensation).
3. Production of new nerve cells: Some areas of the brain may produce new nerve cells, especially after a brain injury or a stroke. These areas include the hippocampus (involved in the formation and retrieval of memories) and the basal ganglia (coordinates and smooth out movements). N.B: Adult neurogenesis is reported only in restricted regions (e.g., hippocampus); its extent/functional impact in humans remains under active investigation

• People who have had a eg brain injury or stroke, can learn new skills, as occurs during physiotherapy treatment.
• People can influence how quickly brain function declines. eg. physical exercise seems to slow the loss of nerve cells in areas of the brain involved in memory. Such exercise also helps keep the remaining nerve cells functioning. On the other hand, consuming two or more drinks of alcohol a day can speed the decline in brain function.

Brain Workouts

Aging brains remain somewhat malleable and plastic. Plasticity refers to the ability to flexibly recruit different areas of the brain to do different jobs.

• In contrast to the earlier, largely pessimistic view of ageing, neuroimaging studies suggest ageing brains can reorganize and change, and not necessarily for the worse.
• Older brains’ plasticity suggests they could benefit from training programs and engaging, immersive experiences eg learning new skills, physical exercise, cognitive regimens and engaged, social lifestyles.
• Emerging evidence suggests that combined physical and cognitive training—such as practicing balance exercises while reciting lists or solving puzzles while walking—may yield greater improvements in executive functions than either modality alone

Neuroinflammation

Research within the past 30 years has identified that ageing affects the immune function within the central nervous system (CNS). Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty.

The ageing brain is vulnerable to inflammation, as demonstrated by the high prevalence of eg age-associated cognitive decline.

• Systemically, circulating pro-inflammatory factors can promote cognitive decline, and in the brain, microglia lose the ability to clear misfolded proteins that are associated with neurodegeneration
• Aging brains also have an increased number of activated microglia, a sign of activated immune system response, Microglia act as the brain's resident cleanup squad by phagocytosing apoptotic cells, plaques, and pathogens
• Immune cells called macrophages have been found to shut down major metabolic pathways during ageing. Restoring metabolism in these cells is sufficient to alleviate age-associated cognitive decline in mice. It is hoped these findings will help develop new ways of restoring migroglial function in humans.
• Research has shown that a healthy but ageing brain has chronically increased levels of pro-inflammatory cytokines and reduced levels of anti-inflammatory cytokines.

Diet, Exercise and Neuroinflammation: Anti-inflammatory dietary patterns eg Mediterranean diet and dietary approaches to stop hypertension (DASH) may be neuroprotective.

• Several dietary components consumed in the MD and DASH (omega-3 fatty acids, antioxidants and polyphenols) can inhibit neuroinflammation associated with AD.
• Anti-inflammatory diets may also attenuate neuroinflammation via indirect immune pathways from the gut microbiome and systemic circulation.
• Diet may influence cognitive ageing via several inflammatory pathways
• Physical activity also exerts anti‑inflammatory effects by reducing systemic pro‑inflammatory cytokines, complementing dietary approaches such as the Mediterranean diet. Together, exercise and anti‑inflammatory diets may attenuate neuroinflammation and cognitive decline.