The Aging Brain

The Aging Brain

Changing Attitudes

• Belief that mental decline is inevitable was and still is popular

• Now believe that while some changes do occur with age, they are not as severe as once thought.

• The brain can remain relatively healthy and fully functioning as it ages

• Disease is the cause of most severe decline in memory, intelligence, verbal fluency, etc.

Changing Demographics• Aging population has spurred research• Until 20th century, few people lived to old age. • 1900:

– life expectancy was about 47 years– 3 million people or 4.1 % of the population were

older than age 65– typically they were ill.

• 1990:– life expectancy was more than 75 years– 30 million people, or 12 % of the population, were

older than age 65

Increase in Elderly Population• Over the last 100 years

there has been a dramatic increase in persons age 65 years and older.

• As shown in the graph, elderly people in the US made up only 4.1% of the population in 1900, but 8.1% in 1950 and 12.8% in 1995.

• By 2050, it is estimated that 20% of the population will be 65 years old or older.

Varied Outcomes• Increase in the elderly population and the high incidence

of age-related neurological disorders focus research on the aging brain.

• The effects of age on brain function vary widely• Most people experience a slight decline in some

functions, particularly in forming memories of recent events

• The dementias - Alzheimer's disease, some cerebrovascular diseases, and others - affect about 11 percent of people older than age 65

• In a small number of individuals mental functioning seems unaffected by age.

What Causes Aging?• Many theories• One says that specific "aging" genes are switched

on at a certain time of life. • Another points to genetic mutations or deletions.• Other theories implicate hormonal influences or an

immune system gone awry • The accumulation of damage caused by cell

byproducts that destroy fats and proteins vital to normal cell function (“free radicals”)

Specific Anatomical Changes

• Brain weight and volume decrease. – The brain loses 5-10 % of weight between age 20

and 90. – these changes are probably caused by the loss of

neurons.

• Enlargement of the ventricles – It is thought that this enlargement occurs because

cells surrounding the ventricles are lost.

• Widening of sulci on the surface of the brain.

Anatomical Changes (Continued)

• Reductions in the size of many areas of the cerebral cortex have been reported.

• The volume the hippocampus, which is crucial to memory, shrinks about 7% per decade after age 45.

• "Senile plaques" (hard clusters of damaged or dying neurons) and "neurofibriallary tangles" (decayed portions of branch-like dentricles from the neurons) form.

Enlarged Ventricles in an Aging Brain

MRI of coronal section through an aging brain

Aging Neurons

• Brain weight is at maximum near age 20 • The brain loses about 10 % of weight over a

lifetime.• Number of brain cells does not increase

with age• Neurons in the brain do undergo change. • The brain loses some neurons & others

become damaged.

Dealing With Cell Loss• Brain tissue can respond by

expanding dendrites and refining connections between neurons.

• Damaged neuron can adjust only if its cell body is intact.

• Re-growth can occur in dendrites and axons.

• When neurons are destroyed, nearby surviving neurons can compensate by growing new dendrites and connections.

Orange dots represent the multiple synapses on a single neuron,

Intellectual Capacity

• Researchers have found declines in some mental functions and improvements in others.

• Capacity for processing information declines from age 20 through 80. – varies greatly from person to person

• Knowledge and understanding of words steadily increases up to age of 70.

• Several studies have found less severe declines in the type of intelligence relying on learned or stored information, compared with the type that uses the ability to deal with new information.

Evidence From PET Scans• PET scans reveal brain activity when subjects think • When a young person focuses on a verbal puzzle, the left

& right hemispheres both show activity, but only for a moment.

• A young person will quickly focus thought in the left brain.

• An older test-taker continues using more than one portion of the brain.

• The fastest older people show the strongest activity in the extra hemisphere.

• Suggests that many older people have developed means for calling in additional resources

Facial Recognition - An Example

• When elders are called on to match faces, they often go to the region of the brain that processes emotions.

• The older person may use the emotional content of the face, the expression, in the identification.

Causes of Intellectual Decline

• Cognitive decline (like age-related memory loss) is not due to neuron loss, as previously thought.

• Scientists now believe these changes have more to do with chemical interactions in the brain that occur over time

• One line of evidence that brain aging is related to chemical changes comes from studies showing that age-related loss of dopamine slows metabolism in regions of the brain related to cognition.

Animal Studies

• Similar changes have been found in animals

• In rodents and primates in which no disease can be found, certain spatial tasks - such as navigating to find food - tend to become more difficult with age.

The Role of Environment• Environment may influence brain cell fate. • Middle-aged rats in stimulating environments,

developed dendrites in the cerebral cortex with more and longer branches compared to rats housed in isolated conditions.

• Rats reared in a stimulating environment made significantly fewer errors on a maze test than did similar rats kept in an isolated environment– the stimulated rats showed an increase in brain weight

and cortical thickness compared to control animals.

The Role of Physical Activity

• Brain cells in rats given acrobatic training had greater numbers of synapses per cell than rats given only physical exercise or inactive rats.

• Older rats tend to form new dendrites and synapses, as do younger animals in response to enriched environments, but are restricted in their ability to grow new blood vessels which nourish neurons.

• Scientists concluded that motor learning generates new synapses.

Environmental Factors & Human Aging

• Walking rapidly for as little as 45 minutes three times a week significantly improves age-related declines in cognitive abilities.

• A regular pattern of eight hours of sleep per night helps protect against age-related chronic illnesses including memory loss.

• Hypertension speeds up normal brain shrinkage and loss of mental abilities.

• Stress causes production of cortisol. – In small amounts, it can improve memory.

– In larger amounts it destroys neurons in the hippocampus.

Education and Brain Health

• Evidence suggests that mental exercise can keep the brain fit - Use it or lose it!

• Researchers compared brain function in adults who attended college and those who did not– Brain function in age correlates with education

• One recent study showed that cognitive challenge actually created new neurons in adult rodents

Caloric Restriction & Brain Aging

• Maintaining lower weight may affect brain aging.• Experiments with mice found that those on restricted

diets had lower rates of brain aging disease • How cutting back food intake in rodents slows the

inflammatory process is not known– One possibility is that it lowers blood glucose levels.

– Blood glucose is very reactive and can cause damage to proteins.

– Diabetics have elevated blood sugar

– Diabetics typically show more signs of brain aging than non-diabetic individuals.

Changes in Alzheimer’s Disease• New research suggests Alzheimer's may be connected to

inflammatory processes associated with aging.• Amyloid deposits in the brain are characteristic of Alzheimer’s

disease• Amyloid is a hard deposit that results from tissue degeneration

– Forms in the presence of inflammatory proteins in the brain. – The inflammatory proteins occur in all maturing adults.

• Soluble amyloid aggregates form in the parts of the brain affected by Alzheimer's (including the hippocampus, the area responsible for forming new memory).

• Once there, they appear to interfere with the brain's basic mechanism of long-term memory

Potential Therapies• Attempt to prevent or slow cell loss with compounds that

promote cell growth, such as nerve growth factor (NGF).• Tested the effect of NGF on the survival of purposely

damaged brain neurons that make acetylcholine, which is important for learning and memory.

• Found that NGF prevented death of neurons and helped maintain the function of these cells in rats and monkeys.

• NGF may produce similar results when administered for long periods

• Researchers are considering human trials of NGF for Alzheimer's and other disorders involving these neurons.

Some Unanswered Questions• Does production of proteins decline with age in all brain

neurons? • In a given neuron, does atrophy cause a higher likelihood

of death? • How does aging affect gene expression in the brain-the

organ with the greatest number of active genes?• Neuroscientists speculate that certain genes may be

linked to events leading to death in the nervous system. • By understanding the biology of the proteins produced

by genes they hope to be able to influence survival and degeneration of nerve cells.

Closing Thoughts

The wiser mindMourns less for what age takes awayThan what it leaves behind

And often, glad no more, We wear a face of joy becauseWe have been glad of yore.

William Wordsworth