Cognitive Decline: The Aging Human Brain

• What is Aging?• Alzheimer’s Disease• Parkinson’s Disease

What is Aging?

Denoted by the following: Declining ability to respond to stress. Increased homeostatic imbalance. Increased risk of aging-associated diseases.

Death is the ultimate consequence of aging. Gompertz-Makeham Law of Mortality-▪ Mortality rate rises rapidly with age.

What is Aging?

Organismal Senescence: Process in which normal diploid cells loose

their ability to divide. Shortened telomeres (ends of chromosomes). Causes cellular apoptosis .

Hayflick Limit: Human- 50 cell divisions in vitro Lobster- unlimited Each mitosis shortens the telomeres on the DNA of the cell. Telomere shortening in humans eventually blocks cell division

and correlates with aging. This mechanism prevents genomic instability and the

development of cancer. (Carnosine can increase the Hayflick limit in humans.)

What is Aging?

Why do our cells do this? Prevents tumor cell proliferation.

Fountain of Youth: Why is the cure for cancer much more

important than treating cancer? Polyploidy cells allow for cellular

immortality.

What is Aging?

What is Aging?

Henrietta Lacks (HELA)

The Aging Brain

Changes: Brain and spinal cord lose nerve cells and weight. Nerve cells transmit messages more slowly. Waste products collect in brain tissue as nerve cells

break down creating abnormal structures called plaques and tangles.

Reduced or even lost reflexes and sensation. Slowing of thought, memory. Senility is not a factor in aging,

it is a factor caused by illness of the brain.

Alzheimer’s Disease

Form of dementia that gradually gets worse over time.

Affects memory, thinking, and behavior. Includes problems with language, decision-

making, judgment, and personality.

Alzheimer’s Disease

Risk Factors: Age (not a part of normal aging). Close blood relatives. Certain combination of genes for proteins that

appear to be abnormal in Alzheimer's. Longstanding high blood

pressure. History of head trauma. Female gender.

Alzheimer’s Disease

Two Types: Early Onset-Symptoms before age 60 and much less

common. Late Onset-Symptoms after age 60 and much more common.

Diagnosis: The only way to know for certain that someone has AD is to

examine a sample of their brain tissue after death. Neurofibrillary tangles-twisted fragments of protein within

nerve cells that clog up the cell. Neuritic plaques-abnormal clusters of dead and dying nerve

cells. Senile plaques-areas where products of dying nerve cells

have accumulated around protein.

Alzheimer’s Disease

Alzheimer’s Disease

When nerve cells (neurons) are destroyed, there is a decrease in the chemicals that help nerve cells send messages to one another (called neurotransmitters).

As a result, areas of the brain that normally work together become disconnected.

Alzheimer’s Disease

Treatment: There is no cure for AD. The goals in treating :▪ Slow the progression of the disease▪ Manage behavior problems, confusion, sleep

problems, and agitation ▪ Modify the home environment

Medication: Donepezil (Aricept), rivastigmine (Exelon), and

galantamine (Razadyne, formerly called Reminyl) affect the level of a chemical in the brain called acetylcholine.

Parkinson’s Disease

Part of the brain that controls muscle movement (midbrain and substantia nigra involved).

Dopamine producing neurons. Characterized by the accumulation of alpha-synuclein

protein forming inclusions called Lewy bodies. This can only be demonstrated in autopsy.

Parkinson’s Disease

Symptoms: Trembling of hands, arms, legs, jaw and face Stiffness of the arms, legs and trunk Slowness of movement Poor balance and coordination Symptoms will continue to

get much worse.

Parkinson’s Disease

Begins around age 60. More common in men than in women. There is no cure for Parkinson's disease. Increased risk of PD in those living in rural

environments and those exposed to pesticides. Reduced risk in smokers.

Parkinson’s Disease

Treatment: Levodopa, dopamine agonists, and MAO-B

Inhibitors (reduce symptoms). As the disease advances the use of medication

produces motor symptoms known as dyskinesias.

Questions?