Neuroscience of aging

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The neuroscience of aging is the study of the changes in the nervous system that occur with ageing. Aging is associated with many changes in the central nervous system, such as mild atrophy of the cortex that is considered non-pathological. Aging is also associated with many neurological and neurodegenerative disease such as amyotrophic lateral sclerosis, dementia, mild cognitive impairment, Parkinson's disease, and Creutzfeldt–Jakob disease. [1]

Contents

Normal structural and neural changes

Neurogenesis occurs very little in adults, only occurring in the hypothalamus and striatum to a small extent in a process called adult neurogenesis. The volume of the brain actually decrease roughly 5% per decade after forty. It is currently unclear why brain volume decreases with age, however, a few causes may include: cell death, decreased cell volume, and changes in synaptic structure. The changes in brain volume is heterogenous across regions with prefrontal cortex receiving the most significant reduction in volume followed in order by the striatum, the temporal lobe, cerebellar vermis, cerebellar hemispheres, and the hippocampus. [2] However, one review found that the amygdala and ventromedial prefrontal cortex remained relatively free of atrophy, which is consistent with the finding of emotional stability occurring with non-pathological aging. [3] Enlargement of the ventricles, sulci and fissures are also common in non-pathological aging. [4]

Changes may also be associated with neuroplasticity, synaptic functionality and voltage gated calcium channels. [5] Increased magnitude of hyperpolarization, possibly a result of dysfunctional calcium regulation, leads to decreased firing rate of neurons and decreased plasticity. This effect is particularly pronounced in the hippocampus of aged animals, and may be an important contributor to age-associated memory deficits. The hyperpolarization of a neuron can be divided into three stages: the fast, medium and slow hyperpolarization. In aged neurons, the medium and slow hyperpolarization phases involve the prolonged opening of calcium-dependent potassium channels. The prolonging of this phase has been hypothesized to be a result of deregulated calcium and hypoactivity of cholinergic, dopaminergic, serotonergic and glutaminergic pathways. [6]

Normal functional changes

Episodic memory starts to decline gradually from middle age, while semantic memory increases all the way into early old age and declines thereafter. [7] Older adults tend to engage their prefrontal cortex more often during working memory tasks, possibly to compensate with executive functions. Further impairments of cognitive function associated with aging include decrease in processing speed and inability to focus. A model proposed to account for altered activation posits that decreased neural efficiency driven by amyloid plaques and decreased dopamine functionality lead to compensatory activation. [8] Decreased processing of negative stimuli as opposed to positive stimuli appear in aging, become significant enough to detect even with autonomic nervous responses to emotionally charged stimuli. [9] Aging is also associated with decreased plantar reflex and achilles reflex response. Nerve conductance also decreases during normal aging. [10]

DNA damage

Certain genes of the human frontal cortex display reduced transcriptional expression after age 40, and especially after age 70. [11] In particular, genes that have central roles in synaptic plasticity display reduced expression with age. The promoters of genes with reduced expression in the cortex of older individuals have a marked increase in DNA damage, likely oxidative DNA damage. [11]

Pathological changes

Roughly 20% of persons greater than 60 years of age have a neurological disorder, with episodic disorders being the most common followed by extrapyramidal movement disorders, and nerve disorders. [12] Diseases commonly associated with old age include

The misfolding of proteins is a common component of the proposed pathophysiology of many diseases associated with aging, however there is insufficient evidence to prove this. For example, the tau hypothesis to Alzheimer's proposes that tau protein accumulation results in the breakdown neuron cytoskeletons leading to Alzheimer's. [22] Another proposed mechanism for Alzheimer's is related to the accumulation of amyloid beta,. [23] in a similar mechanism to the prion propagation of Creutzfeldt-Jakob disease. Similarly the protein alpha-synuclein is hypothesized to accumulate in Parkinson's and related diseases. [24]

Chemo brain

Treatments with anticancer chemotherapeutic agents often are toxic to the cells of the brain, leading to memory loss and cognitive dysfunction that can persist long after the period of exposure. This condition, termed chemo brain, appears to be due to DNA damages that cause epigenetic changes in the brain that accelerate the brain aging process. [25]

Management

Treatment of an age related neurological disease varies from disease to disease. Modifiable risk factors for dementia include diabetes, hypertension, smoking, hyperhomocysteinemia, hypercholesterolemia, and obesity (which is usually associated with many other risk factors for dementia). Paradoxically, smoking confers protection against Parkinson's disease. [26] Also conferring protective benefits to age related neurological disease in consumption of coffee or caffeine. [27] [28] [29] Consumption of fruits, fish and vegetables confer protection against dementia, as does a Mediterranean diet. [30] Physical exercise significantly lowers the risk of cognitive decline in old age, [31] and is an effective treatment for those with dementia [32] [33] and Parkinson's disease. [34] [35] [36] [37]

Related Research Articles

Dementia long-term brain disorders causing impaired memory, reasoning, and normal function together with personality changes

Dementia manifests as a set of related symptoms, which usually surface when the brain is damaged by injury or disease. The symptoms involve progressive impairments to memory, thinking, and behavior, which negatively impact a person's ability to function and carry out everyday activities. Aside from memory impairment and a disruption in thought patterns, the most common symptoms include emotional problems, difficulties with language, and decreased motivation. Dementia is not a disorder of consciousness, and consciousness is not usually affected.

Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive decline that occurs step by step. The term refers to a syndrome consisting of a complex interaction of cerebrovascular disease and risk factors that lead to changes in the brain structures due to strokes and lesions, and resulting changes in cognition. The temporal relationship between a stroke and cognitive deficits is needed to make the diagnosis.

Frontotemporal dementia Types of dementia involving the frontal or temporal lobes

Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the frontal and temporal lobes. FTDs are broadly presented as behavioral or language disorders. The three main subtypes or variant syndromes are a behavioral variant (bvFTD) previously known as Pick's disease, and two variants of primary progressive aphasia – semantic variant (svPPA), and nonfluent variant (nfvPPA). Two rare distinct subtypes of FTD are neuronal intermediate filament inclusion disease (NIFID), and basophilic inclusion body disease. Other related disorders include corticobasal syndrome and FTD with amyotrophic lateral sclerosis (ALS) FTD-ALS also called FTD-MND.

Aging is a major risk factor for most common neurodegenerative diseases, including mild cognitive impairment, dementias including Alzheimer's disease, cerebrovascular disease, Parkinson's disease, and Lou Gehrig's disease. While much research has focused on diseases of aging, there are few informative studies on the molecular biology of the aging brain in the absence of neurodegenerative disease or the neuropsychological profile of healthy older adults. However, research suggests that the aging process is associated with several structural, chemical, and functional changes in the brain as well as a host of neurocognitive changes. Recent reports in model organisms suggest that as organisms age, there are distinct changes in the expression of genes at the single neuron level. This page is devoted to reviewing the changes associated with healthy aging.

Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and cognitive impairment. PSP may be mistaken for other neurodegenerative diseases such as Parkinson's, frontotemporal dementia and Alzheimer's. The cause of the condition is uncertain, but involves accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases.

Cerebral atrophy is a common feature of many of the diseases that affect the brain. Atrophy of any tissue means a decrement in the size of the cell, which can be due to progressive loss of cytoplasmic proteins. In brain tissue, atrophy describes a loss of neurons and the connections between them. Atrophy can be generalized, which means that all of the brain has shrunk; or it can be focal, affecting only a limited area of the brain and resulting in a decrease of the functions that area of the brain controls. If the cerebral hemispheres are affected, conscious thought and voluntary processes may be impaired.

Neurofibrillary tangle

Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. Their presence is also found in numerous other diseases known as tauopathies. Little is known about their exact relationship to the different pathologies.

Corticobasal degeneration (CBD) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia. CBD symptoms typically begin in people from 50 to 70 years of age, and the average disease duration is six years. It is characterized by marked disorders in movement and cognition, and is classified as one of the Parkinson plus syndromes. Diagnosis is difficult, as symptoms are often similar to those of other disorders, such as Parkinson's disease, progressive supranuclear palsy, and dementia with Lewy bodies, and a definitive diagnosis of CBD can only be made upon neuropathologic examination.

Memory disorders are the result of damage to neuroanatomical structures that hinders the storage, retention and recollection of memories. Memory disorders can be progressive, including Alzheimer's disease, or they can be immediate including disorders resulting from head injury.

Basal forebrain

The basal forebrain structures are located in the forebrain to the front of and below the striatum. They include the ventral basal ganglia, nucleus basalis, diagonal band of Broca, substantia innominata, and the medial septal nucleus. These structures are important in the production of acetylcholine, which is then distributed widely throughout the brain. The basal forebrain is considered to be the major cholinergic output of the central nervous system (CNS) centred on the output of the nucleus basalis. The presence of non-cholinergic neurons projecting to the cortex have been found to act with the cholinergic neurons to dynamically modulate activity in the cortex.

Tauopathy Medical condition

Tauopathy belongs to a class of neurodegenerative diseases involving the aggregation of tau protein into neurofibrillary or gliofibrillary tangles (NFTs) in the human brain. Tangles are formed by hyperphosphorylation of the microtubule protein known as tau, causing the protein to dissociate from microtubules and form insoluble aggregates. The mechanism of tangle formation is not well understood, and whether tangles are a primary cause of Alzheimer's disease or play a peripheral role is unknown.

Neurodegeneration Central nervous system disease

Neurodegeneration is the progressive loss of structure or function of neurons, which may ultimately involve cell death. Many neurodegenerative diseases—such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, and prion diseases—occur as a result of neurodegenerative processes. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable. Biomedical research has revealed many similarities between these diseases at the sub-cellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

The prevention of dementia involves reducing the number of risk factors for the development of dementia, and is a global health priority needing a global response. Initiatives include the establishment of the International Research Network on Dementia Prevention (IRNDP) which aims to link researchers in this field globally, and the establishment of the Global Dementia Observatory a web-based data knowledge and exchange platform, which will collate and disseminate key dementia data from members states. Although there is no cure for dementia, it is well established that modifiable risk factors influence both the likelihood of developing dementia and the age at which it is developed. Dementia can be prevented by reducing the risk factors for vascular disease such as diabetes, high blood pressure, obesity, smoking, physical inactivity and depression. A study concluded that more than a third of dementia cases are theoretically preventable. Among older adults both an unfavorable lifestyle and high genetic risk are independently associated with higher dementia risk. A favorable lifestyle is associated with a lower dementia risk, regardless of genetic risk.In 2020 a study identified 12 modifiable lifestyle factors, and the early treatment of acquired hearing loss was estimated as the most significant of these factors, potentially preventing up to 9% of dementia cases.

Posterior cortical atrophy Medical condition

Posterior cortical atrophy (PCA), also called Benson's syndrome, is a rare form of dementia which is considered a visual variant or an atypical variant of Alzheimer's disease (AD). The disease causes atrophy of the posterior part of the cerebral cortex, resulting in the progressive disruption of complex visual processing. PCA was first described by D. Frank Benson in 1988.

Alzheimers disease Progressive, neurodegenerative disease characterized by memory loss

Alzheimer's disease (AD), also referred to simply as Alzheimer's, is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation, mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years.

Parkinsons disease Long-term degenerative neurological disorder

Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, nonmotor symptoms become more common. The most obvious early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking. Cognitive and behavioral problems may also occur with depression, anxiety, and apathy occurring in many people with PD. Parkinson's disease dementia becomes common in the advanced stages of the disease. Those with Parkinson's can also have problems with their sleep and sensory systems. The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to a dopamine deficit. The cause of this cell death is poorly understood, but involves the build-up of misfolded proteins into Lewy bodies in the neurons. Collectively, the main motor symptoms are also known as "parkinsonism" or a "parkinsonian syndrome".

Nucleus basalis

The nucleus basalis, also known as the nucleus basalis of Meynert or nucleus basalis magnocellularis, is a group of neurons located mainly in the substantia innominata of the basal forebrain. Most neurons of the nucleus basalis are rich in the neurotransmitter acetylcholine, and they have widespread projections to the neocortex and other brain structures.

Neurobiological effects of physical exercise Neural, cognitive, and behavioral effects of physical exercise

The neurobiological effects of physical exercise are numerous and involve a wide range of interrelated effects on brain structure, brain function, and cognition. A large body of research in humans has demonstrated that consistent aerobic exercise induces persistent improvements in certain cognitive functions, healthy alterations in gene expression in the brain, and beneficial forms of neuroplasticity and behavioral plasticity; some of these long-term effects include: increased neuron growth, increased neurological activity, improved stress coping, enhanced cognitive control of behavior, improved declarative, spatial, and working memory, and structural and functional improvements in brain structures and pathways associated with cognitive control and memory. The effects of exercise on cognition have important implications for improving academic performance in children and college students, improving adult productivity, preserving cognitive function in old age, preventing or treating certain neurological disorders, and improving overall quality of life.

The temporal dynamics of music and language describes how the brain coordinates its different regions to process musical and vocal sounds. Both music and language feature rhythmic and melodic structure. Both employ a finite set of basic elements that are combined in ordered ways to create complete musical or lingual ideas.

Corticobasal syndrome (CBS) is a rare, progressive atypical Parkinsonism syndrome and is a tauopathy related to frontotemporal dementia. CBS is typically caused by the deposit of tau proteins forming in different areas of the brain.

References

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