Alzheimer's disease

What is Alzheimer’s disease?

Alzheimer’s disease, or AD, is a progressive, age-related form of dementia. Dementia is the loss of cognitive function such as memory, language skills, abstract thinking, and attention.

Alzheimer’s disease is a neurodegenerative dementia, meaning that the cognitive deficits result from degeneration and loss of neurons, which are the information-processing cells in the brain. Medical treatments can boost cognitive function for a time, but so far we have no effective treatments for stopping or preventing AD. 

The first signs of AD typically involve memory and word-finding difficulties. Symptoms include repeating the same questions minutes apart without remembering the previous question and answer, increasing forgetfulness with appointments or medications, or difficulty remembering the names of acquaintances and family members.

Long-term memories about the past remain intact as these symptoms appear and progress. AD progresses steadily, for up to a decade or longer, and eventually affects most aspects of cognitive function. As the condition progresses, symptoms often include

• Difficulty with directions and spatial navigation
• Depression
• Inability to complete everyday tasks
• Difficulty recognizing familiar people and places
• Difficulties maintaining a normal sleep-wake rhythm
• Susceptibility to experiencing disorientation and hallucinations when suffering from a medical illness or when put in an unfamiliar place 

Why does Alzheimer’s disease occur?

The exact cause of Alzheimer’s disease remains uncertain, but a great deal of research has identified variants in the genetic makeup between people that predispose to Alzheimer’s disease or protect against it. Some of these genetic variants involve the immune system, while others involve the brain’s production and metabolism of otherwise normal proteins.

One of these proteins, amyloid precursor protein, or APP, can form “mis-folded” clumps, known as A-beta plaques, in many brain regions. The presence of these A-beta plaques is one of two required criteria for the brain tissue diagnosis of AD. The other criterion involves a separate protein, tau, which is part of the normal support structure in neurons. When tau becomes “hyperphosphorylated” it is referred to as P-tau, and tangles of P-tau protein form inside neurons destined for degeneration and loss.

All patients with AD have the combination of A-beta plaques and P-tau tangles, but the link between these two proteins in the overall disease process is uncertain and remains the subject of intense scientific research. Despite our incomplete understanding of the full mechanism, these two protein abnormalities are useful diagnostically. We now can test their levels in cerebrospinal fluid, after a spinal tap, or use special brain imaging tests to measure their distribution throughout the brain. This information can be very helpful in diagnosing patients with cognitive deficits potentially caused by AD.

The most common genetic risk factors for AD is a gene called APOE. Everyone has two copies of this gene, which has three common variants: E2, E3, and E4. Most people have the E3 variant or “allele.” The minority of people with an E2 allele are largely protected from developing AD, while the somewhat larger minority with E4 are at increased risk of developing AD late in life or at a slightly younger age than other patients with AD.

Other, very rare genetic variants cause “early-onset” AD, which is when a person develops the disease in their 30s, 40s or 50s. This is very rare, and these genetic variants are typically inherited from other family members, who themselves may be affected by early-onset AD. One exception is Down’s syndrome, which is caused by an extra copy of part or all of chromosome 21, which carries an extra copy of the amyloid precursor protein. Many people with Down’s syndrome develop A-beta plaques and P-tau tangles by their 40s or 50s.

In the large majority of cases, AD symptoms first appear at age 65 or older. However, even in this more common form, known as late-onset Alzheimer’s disease, the A-beta plaques and P-tau tangles begin forming in the brain several years, possibly more than a decade, before symptoms appear.

Who’s at risk?

Being over the age of 65 means you are at risk and your risk increases significantly as you grow older. After age 65, the number of those suffering from the disease doubles every five years. There are no known causes of the disease, only potential risk factors.

The risk factors are largely genetic. If a family member had the disease, your chances of developing it are significantly higher. Women are more likely to get AD than men—this is partially due to the fact that women tend to live longer than men. 

There is growing evidence of a link between heart and blood disorders and dementia. Conditions that affect the quality of blood reaching the brain, such as smoking, high blood pressure, high cholesterol, and diabetes, greatly increase your chances of developing dementia. These risk factors cause microvascular ischemic disease (MVID), which is the accumulation of microscopic injuries deep inside the brain, across many years, injuring the wiring bundles that connect brain regions. MVID often causes cognitive deficits on its own, but in combination with AD there is much worse loss of cognitive function. Fortunately, many of the risk factors for cerebral MVID can be eliminated by not smoking, controlling blood pressure and blood sugar, and reducing cholesterol.

Additional risk factors are environmental. Some studies show a link between head injuries and the disease. Others show that your level of education could play a role in the development of AD. The more brain activity you have the less you may be at risk. People who get less sleep or have their sleep interrupted frequently by snoring may be at increased risk. Finally, people who get more exercise seem to be at a lower risk of developing AD or may develop the disease later and more slowly.

Maintaining your brain health

Doctors have developed recommendations for brain health.

• Be physically active. Live an energetic lifestyle to preserve cardiovascular health and in turn brain health. Exercise vigorously for at least 15-30 minutes, at least three times per week or every day, if possible.
• Be socially active. Interpersonal connections and relationships can stimulate brain function.
• Practice healthy eating for the heart and brain. Diets full of healthy fats and low cholesterol best support cardiovascular and cognitive health.
• Follow your physician’s advice to maintain a healthy blood pressure, blood sugar, and cholesterol.
• Avoid all tobacco products, especially cigarettes. Avoid alcohol, or consume no more than 0-1 drinks per day.
• Sleep with a regular schedule every day of the week, for 7-8 hours per night. If you have trouble sleeping, consider medical evaluation for conditions like obstructive sleep apnea or restless leg syndrome, which are common and when left untreated impair brain function.
• Be mentally active. Continually stimulate your brain through reading, learning, and challenging games.

The stages of Alzheimer’s disease

Three stages of AD are used to classify the progression of the disease.

1. Preclinical

• In this stage the brain is changing at a cellular level (A-beta plaques and P-tau tangles appear), but symptoms are not yet evident.

2. Mild cognitive impairment

• This classifies memory problems that are not yet severe enough to interfere with everyday function and independence. 

3. Alzheimer dementia

• The designation “dementia” is used when independent daily function is no longer possible. The dementia progresses gradually over months and years, from mild to severe—this classifies the final stage of the disease.

Symptoms

You may be unaware you are developing AD. Oftentimes symptoms can be confused with natural aging. However, cognitive changes that disrupt normal life are not typical signs of aging. One of the symptoms of AD is that sufferers are often unaware that their memory is slipping, so friends and family members are often the first or only people to notice a change.

Watch for signs of AD

• Forgetfulness, specifically of recent events or information, or repeatedly asking for the same information
• Difficulty completing common tasks
• Confusion about time or place, this includes failure to recognize familiar neighborhoods or losing track of months
• Getting lost when out driving or walking, having difficulty finding your way home on a previously familiar route
• Language complications, especially a persistent failure to recall names of objects or people, or a worsening tendency to use the wrong words for things
• Withdrawal from familiar hobbies or interests

Diagnosis

There is currently no definite method to diagnose AD in living persons, and the only way to diagnose or exclude it with 100 percent certainty is to examine brain tissue for A-beta plaques and P-tau tangles. This diagnostic certainty can only come from an autopsy of the brain following death, which our hospital offers free of charge to all patients and families who are interested. However, neurologists and other physicians now are able to identify or exclude an AD diagnosis with high probability using a variety of diagnostic tests.

Tests include

• Laboratory tests for biomarkers - This method measures proteins in the cerebrospinal fluid (CSF) to help predict diagnosis of the disease in its early stages. CSF is collected via lumbar puncture.
• Laboratory genetic tests - Testing blood cells for APOE and other genetic risk factors can help determine the genetic risk component for AD in an individual patient.
• Cognitive tests - These test a broad range of cognitive functions including attention, memory, language, mood, visuospatial abilities, and skilled movements. Basic tests may be administered by a physician, particularly a cognitive neurologist, while more in-depth testing is done by neuropsychologists, who are specialized in testing cognitive function.
• Structural brain-imaging scans - CT and MRI scans reveal the structure of the brain, which helps physicians determine the pattern and extent of neuron loss. AD and other neurodegenerative diseases cause different, specific patterns of brain tissue loss, known as atrophy. These studies are also the best way to evaluate and exclude other potential causes of cognitive loss such as tumors and other processes that distend brain tissue, or stroke and other problems with cerebral blood flow.
• Functional brain-imaging PET scans – FDG-PET scans reveal regions of the brain with normal and sub-normal metabolic activity. AD and other brain diseases typically show abnormal patterns on FDG-PET years before brain tissue atrophy is evident on CT or MRI.
• Biomarker brain-imaging PET scans – specialized PET scans available now can identify the brain tissue concentration of A-beta plaques and soon, the location and amount of P-tau tangles, which are the two essential elements for diagnosing AD. 

Many conditions and diseases have symptoms that are similar to AD.

These include:

• Vascular dementia
• Severe depression
• Obstructive sleep apnea
• Sedating medications
• Alcohol abuse
• Parkinson’s disease dementia
• Dementia with Lewy bodies
• Brain tumors
• Blood clots in the brain
• Thyroid disease

Treatment

No cure is currently available for AD. The pros and cons of treatment options should be considered by a patient’s doctors and caregivers on an individual basis. 

Medications are available to improve cognition in patients with AD for a time, but their effectiveness is mild, and short-term. Available medications may have side effects and they do not extend the amount of time a patient can live, or live independently.  

Certain symptoms of AD can be treated. Medication can be used to improve depression, sleep quality, and aggressive behavior. These medications, like those that treat the disease as a whole, also may have unpleasant to potentially severe side effects.

Caregiving 

Due to the personality changes of patients with AD, caregivers face several challenges. Many patients become fearful in new environments. Most AD patients become confused easily and may develop mood swings or violent outbursts.  

Recommendations for caregivers include the following:

• Follow a daily routine to increase comfort. Familiarity and habit are important.
• Speak calmly, in short sentences with simple words.
• While interacting, maintain a natural attitude.
• Find activities that can calm outbursts.

Eventually, all AD patients need round-the-clock care. This commitment is extremely stressful on loved ones and caregivers. As the disease progresses, the amount of care needed does as well. AD creates difficulties for the patient and everyone in their life. Loved ones and caregivers are encouraged to seek support, whether it be from friends, family, or AD support groups.