The Stages of Alzheimer's Disease

Though the time from diagnosis to death differs among people with Alzheimer's disease, the disease generally progresses through the same stages.

Dr. Ron Petersen was the first to define a condition called mild cognitive impairment (MCI) to describe early changes in memory. Dr. Petersen defined MCI as a condition in which a person has memory problems greater than expected for a person that age, but who does not have the other cognitive or personality changes that typically accompany AD. People with MCI are an important group for researchers to understand because about 80 percent of people with MCI characterized by memory loss go on to develop AD within seven years. (In contrast, only from 1 to 3 percent of people older than sixty-five with healthy cognitive abilities will develop AD in any given year.)

The definition and description of MCI has been a big advance because it provides a framework in which experienced clinicians, using sophisticated neuroimaging techniques and sensitive memory and cognitive tests, can monitor a person's cognitive changes over time. Being able to characterize and track cognitive changes is critical to determining whether a person has AD and when treatment may be most effective.

Over time, as the plaques and tangles continue to proliferate, an individual with MCI may progress to a clinical diagnosis of Alzheimer's disease. This stage is called mild, or early, Alzheimer's disease. More of the cerebral cortex will be affected so memory loss will increase, and other cognitive abilities will diminish. An individual with mild AD may get lost in familiar places or fail to recognize his surroundings. He may take longer to accomplish the daily tasks of living like washing, dressing, and eating. He may have trouble handling money or paying bills or exercise poor judgment. Mood and personality changes can also occur; he may lose spontaneity or drive, or show increased anxiety or aggression. Although a person with mild AD may still seem healthy, it will be harder for him to make sense of his world. Although the individual and his family members and friends may have been aware of troubling changes for some time, AD is often diagnosed during this phase. The diagnosis often helps families make sense of their loved one's behaviors.

As Alzheimer's disease progresses and the damage spreads further in the brain, the person enters a stage referred to as moderate Alzheimer's disease. The brain continues to shrink and symptoms become more pronounced as the disease reaches the areas of the cerebral cortex that control language, reasoning, sensory processing, and conscious thought. A person with moderate AD may wander or become confused, anxious or agitated, engaging in angry outbursts, tearfulness, irritability or restlessness. His attention span may shorten. He may have problems recognizing family and friends, and difficulty with language, reading, writing, and arithmetic, and with the logical organization of thoughts. He may be unable to learn new things and consequently be unable to cope with new situations. At this stage, a person with AD might also experience hallucinations and paranoid delusions, and lose impulse control, leading to things like inappropriate undressing or the use of vulgar language. It is helpful for caregivers to understand the disease and to be more prepared for these sorts of behaviors before they happen, and to know that it is the disease that is causing them.

A person with moderate AD may be unable to carry out activities that require him to follow a sequence, like getting dressed or setting the table. Anger may mask anxiety and confusion. According to the National Institute on Aging, a person at the moderate stage of AD "may angrily refuse to take a bath or get dressed because he does not understand what his caregiver has asked him to do. If he does understand, he may not remember how to do it."

At the last stage of this illness, severe Alzheimer's disease, plaques and tangles are found throughout the brain. Most areas have shrunken further, leaving only a thin ribbon of gray matter and even larger fluid-filled ventricles. An individual at this final stage cannot communicate in any way except moaning and grunting. He doesn't recognize loved ones and is completely dependent on others for care. He may experience weight loss and difficulty swallowing, seizures, skin infections, lack of bladder and bowel control, and increased sleeping. If bedridden, he is likely to die from pneumonia as a result of having inhaled food or drink because of difficulty swallowing.

Previous: What Happens in the Brain in Alzheimer's Disease

Next: Defining Early Changes

Excerpted from THE ALZHEIMER'S PROJECT: MOMENTUM IN SCIENCE, published by Public Affairs, www.publicaffairsbooks.com.

Alzheimer's Disease (AD)

A progressive degenerative disease of the brain that causes impairment of memory and other cognitive abilities.

Amyloid Precursor Protein (APP)

The larger protein from which beta-amyloid is formed.

ApoE Gene

A gene that codes for a protein that carries cholesterol to and within cells; different forms of the ApoE gene are associated with differing risks for late-onset Alzheimer's disease. This gene may be referred to as a risk factor gene or a "susceptibility gene" because one form of the gene, called APOE4, is associated with the risk of developing late onset AD.

Beta-Amyloid

Derived from the amyloid precursor protein and found in plaques, the insoluble deposits outside neurons. May also be called A-beta.

Beta-Amyloid Plaque

A largely insoluble deposit found in the space between nerve cells in the brain. The plaques in Alzheimer's disease are made of beta-amyloid and other molecules, surrounded by non-nerve cells (glia) and damaged axons and dendrites from nearby neurons.

Cognitive Reserve

The brain's ability to operate effectively even when some damage to cells or brain cell communications has occurred.

Dementia

A broad term referring to a decline in cognitive function that interferes with daily life and activities. Alzheimer's disease is one form of dementia.

Functional MRI (fMRI)

An adaptation of an MRI (see magnetic resonance imaging) technique that measures brain activity during a mental task, such as one involving memory, language, or attention.

Hippocampal Formation

A structure in the brain that plays a major role in learning and memory and is involved in converting short-term to long-term memory. Also called the hippocampus.

Inflammation

The process by which the body responds to cellular injury by attempting to eliminate foreign matter and damaged tissue.

Insulin Resistance

A condition in which the pancreas makes enough insulin, but the cells do not respond properly to it; characterizes and precedes type 2 diabetes.

Magnetic Resonance Imaging (MRI)

A diagnostic and research technique that uses magnetic fields to generate a computer image of internal structures in the body.

Mild Cognitive Impairment (MCI)

A condition in which a person has cognitive problems greater than those expected for his or her age. Amnestic MCI includes memory problems, but not the personality or other cognitive problems that characterize AD.

Neurodegenerative Disease

A disease characterized by a progressive decline in the structure and function of brain tissue. These diseases include AD, Parkinson's disease, frontotemporal lobar degeneration, and dementia with Lewy bodies. They are usually more common in older people.

Oligomers

Clusters of a small number of beta-amyloid peptides.

Oxidative Damage

Damage that can occur to cells when they are exposed to too many free radicals.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Synapse

The tiny gap between nerve cells across which neurotransmitters and nerve signals pass.

Tau

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Tangles

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Memory

Normal Aging

Genetic Risk Factor

Dominant and Recessive Genes

Genes and Proteins

Protein-Misfolding Disease

Cholesterol

Biomarkers

Disease-Modifying Drug

Transgenic Mice

An animal that has had a gene (such as the human APP gene) inserted into its chromosomes for the purpose of research. Mice carrying a mutated human APP gene often develop plaques in their brains as they age.

Pathology

Microglia

Insulin & Insulin Resistance

Susceptibility Gene

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Susceptibility Genes

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Genome-Wide Association Study

Vascular Disease

Genetics

Genetics

Normal Aging