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Stages

Although Alzheimer's disease (AD) is most commonly diagnosed after age 65, changes in the brain may begin 10 - 20 years before symptoms appear. The pathological changes in the Alzheimer's brain include a reduction of the neurotransmitters acetylcholine, dopamine, norepinephrine, glutamate and serotonin. There is an abnormal accumulation of proteins forming amyloid plaque on the neurons, which in turn leads to inflammation, cell death, and brain atrophy. While the plaque is causing cellular death outside the cell, the subsequent development of neurofibrillary tangles of Tau protein is occurring inside the cell body of the neuron. The combination of these events is what causes the loss of the ability of the neurons to communicate with each other and which compromises the functioning of whatever neurons that individual may have left.

When Alzheimer's disease is diagnosed in an individual before age 65 it is called Early Onset Alzheimer's disease. Early Onset AD is generally diagnosed when individuals are in their 40's and 50's. It is thought more often to be genetic as opposed the more common age-related AD, and it's progression can be more rapid.

The risk of Alzheimer's disease doubles every five years beyond age 65. The course of the disease varies from person to person. The entire disease course typically lasts from three to 12 years, although it can be as short as one or as long as 20 years. The stages vary too, with Stage I (Early Stage) typically lasting three to five years, Stage II (Middle Stage) two to three years, and Stage III (Late Stage) one to two years. Alzheimer's disease is a terminal illness.

The way an individual develops from infancy to adulthood, first sucking and then eating from a spoon, to walking, toileting, dressing, and developing a social personality is reversed in someone with Alzheimer's disease. This unraveling of competency and function is commonly referred to as "retrogenesis".

The Early Stage

Early stage Alzheimer's disease first affects memory, language, and reasoning. This stage of the disease is often quite insidious since there are still enough functioning neurons in the brain to compensate for the cellular losses that are beginning to take place. The disease is characterized by a decrease in many of the neurotransmitters that help regulate mood (serotonin), our sense of being grounded and connected to reality (dopamine), and the transmission of messages associated with memory formation and retention (acetylcholine). The Early Stage is typically marked by one of the following symptoms; short term memory loss, changes in mood, changes in personality, loss of initiative, depression, isolation, inability to learn new things, disorientation, difficulty with word finding, confusion, problems with abstract thinking, confabulation, poor judgment, altered sense of time, or visual spatial disturbances.

Most individuals are still capable of living alone with minimal supervision and are able to functionally manage their activities of daily living (ADL's). It is not uncommon for someone to consider the changes associated with early stage Alzheimer's disease to be normal age related problems. However, most individuals do not seek a medical diagnosis until they are well into the early stage of the disease unless prompted by a family member or if there have been mood changes and concerns about depression.

Usually a primary care physician (PCP) or a neurologist makes the initial diagnosis based on findings from memory testing, a mini-mental status exam, the results from neuro-imaging, and any behavioral information reported by the patient or family. If the patient is diagnosed with DAT (Dementia of the Alzheimer Type), the doctor will typically prescribe a cholinesterase inhibitor such as Aricept, Exelon, or Razadyne in the hope of improving the "memory signal" damaged by the decrease of the production of the neurotransmitter acetylcholine. If the individual is also experiencing changes in mood, an antidepressant might also be prescribed to help compensate for the decreased production of serotonin.

Some of the side effects of cholinesterase inhibitors are nausea, vomiting, and diarrhea. These may resolve in a few weeks, which is why the medication dosage is slowly increased to a therapeutic dosage. If the symptoms do not resolve, or if no significant improvement is seen in 6 - 12 months of drug therapy, the doctor may switch to a different cholinesterase inhibitor or discontinue the medication. Each person responds differently to drug therapy. If one cholinesterase drug fails to elicit a response, another may prove effective. Individuals are usually asked to follow up yearly on any testing and neuro-imaging for the sake of comparison to monitor the disease progression.

The Middle Stage

As the disease progresses, more amyloid plaque builds up on the neurons causing increased atrophy of the cerebral cortex. Additionally, the decrease in the production of the neurotransmitters necessary to transmit the messages of mood and memory continues. As the production of dopamine decreases, behavioral problems begin to manifest. The ability to have fluid muscle movement also declines as the loss of both gross motor and fine motor movement becomes noticeable. In addition, the deterioration and tangling of the neurons make it more difficult for any messages to be transmitted and received.

The hallmark of the Middle-Stage of the disease is therefore marked functional loss in the individual. Increasing memory loss causes problems with the sequencing of ADL's along with perceptual-motor problems exhibited with the decline of both gross motor and fine motor skills. With the decrease of available dopamine, serotonin, and acetylcholine in the brain, behavior problems (often called "positive symptoms") begin to erupt such as wandering, agitation, vocal outbursts, and sleep disturbances which require more intensive supervision and care. Delusions (often paranoid) and hallucinations may also occur.

Although medications are available to treat these disorders, antidepressants, antipsychotics, and sedatives all have side effects and can interact with other medications. Thus non-drug interventions should be attempted before resorting to medications. If the decision is made to treat pharmacologically, some physicians may order what is known as a "typical" neuroleptic, such as Haldol, though the atypical antipsychotics which include risperidone (Risperidol), quetiapine (Seroquel), olanzepine (Zyprexa), aripiprazole (Abilify), and ziprasidone (Geodon) may be better tolerated than the more traditional agents. They also tend to have fewer extrapyramidal symptoms which can cause a cumulative effect in the individual over time.

Benzodiazepines typically used to modify and treat anxiety are known to impair memory function. Their pharmacological effect is quite similar to alcohol since they are known to alter the GABAergic receptors in the brain. Individuals with Alzheimer's disease often become more confused when taking benzodiazepines, and are at an increased risk of falling. Often the antipsychotics are much better at treating anxiety since the behavior is usually related to a sense of fear or lack of control that the individual is experiencing secondary to the decreased dopamine production in the brain.

Since functional losses and behavioral issues occur in the Middle Stage of the disease, this is the most common time when families begin to seek medical intervention or assistance with their loved one. At this stage the person may become incontinent and their sleep cycle may be disturbed (up at night, sleeping during the day). Personality and emotional changes become more pronounced and the caregiver simply becomes overwhelmed.

The Late Stage

The downward spiral of disease progression continues as the individual enters the Late Stage of Alzheimer's disease. Comparison of either an MRI or CT scan would show global (all areas) atrophy of the cerebral cortex. When compared to previous images there would be a noted enlargement of the ventricles. (Note: the degree of atrophy is usually determined by viewing images of the size of an individual's ventricles. It is not that the ventricles actually are enlarged; they just appear larger because the cerebral cortex has atrophied significantly.)

At this point, patients with AD often cannot recognize family members or express themselves verbally. They are completely dependent on others for care and at times seem to have lost all sense of self. Common symptoms can include: weight loss, seizures, skin infections, difficulty swallowing, increased sleep, incontinence of both bowel and bladder, and loss of verbal skills.

Nonverbal communication, especially touch, between the caregiver and the patient is very important. Individuals who are unable to respond verbally will often respond to a smile, kind gesture, or a caring touch. Careful observation of the patient's facial expressions, eye contact or lack of it, and body language can help the caregiver assess comfort or pain, anger, hostility, and misunderstanding. As caregivers develop experience with the disease they will gain more skill in interpreting these nonverbal signals. We do not know to what degree the person is able to understand at any stage of this disease; therefore, the care of a person with AD demands ongoing assessment, planning, intervention, and evaluation throughout the course of the disease.

People with Alzheimer's disease often have other health problems common to older adults such as CHF (congestive heart failure), hypertension, diabetes, and genitourinary conditions. At the end of life individuals are partly or completely bedbound. Death comes most often in the form of a secondary infection which the body is unable to fight or from aspiration pneumonia caused by the individual's inability to swallow causing them to inhale food or liquid into their lungs.

Download a PDF document of the stages of Alzheimer's disease.

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