Update on Treatment Options for Alzheimer’s

IN A WORLD in which many deadly diseases have been defeated by the advent of modern medicine, perhaps no diagnosis is still so frightening as Alzheimer’s disease.

A cancer diagnosis is certainly devastating, but many treatments offer realistic hope for beating the disease. Alzheimer’s, on the other hand, is incurable. The diagnosis is an inevitable death sentence, and the unknown compounds fear. While most lay people understand the basics of cancer, even physicians struggle to understand Alzheimer’s. We don’t know the cause, there is no cure and available treatment options often feel inadequate for the task.

Alzheimer’s inexorably steals that which most makes us who we are: our memory. It leaves families physically exhausted and emotionally hollowed. While a cure remains elusive for now, there are new drugs that can slow the progression of symptoms. In addition, researchers and caregivers learn more every day about how to provide care in ways that reduce stress for both patients and their families.

What Is Alzheimer’s?

While the ancients wrote about dementia in both classical-era Egypt and Greece, Alzheimer’s disease was first described in 1910 by German psychiatrist and neuropathologist Alois Alzheimer. One of Alzheimer’s colleagues, Emil Kraepelin, is credited with naming the condition after his friend.¹

During an autopsy of a woman who died of an unusual mental illness, Alzheimer noticed physical changes to her brain tissue, including clumps and bundles of fibers. More than a century later, researchers are still trying to determine exactly what causes the development of these clumps, now known as amyloid plaques, and fiber bundles, or tau tangles. We now know these result from abnormal concentrations of amyloid and tau proteins, but what is behind the abnormalities is not yet clear.² It is thought that the plaques and tangles cause neurons to lose connectivity with the rest of the brain, which leads to the observed memory and behavioral symptoms.³

Today, Alzheimer’s is responsible for about 80 percent of all cases of dementia. Approximately 90 percent of people who develop Alzheimer’s disease will first exhibit symptoms in their mid-60s or later, known as late-onset Alzheimer’s. The 10 percent diagnosed in their early 60s or younger have early-onset Alzheimer’s. The progression of the disease is the same for both populations.
Alzheimer’s disease is the seventh-leading cause of death in the United States, taking about 134,000 American lives each year. Approximately six million Americans are suffering from Alzheimer’s at any time.4 Ten percent of Americans older than age 65 and about one-third of Americans older than age 85 have Alzheimer’s. The life expectancy of someone diagnosed with Alzheimer’s ranges from three to 11 years, although some live two decades or longer with the disease.⁶

Diagnosing Alzheimer’s

Minor-to-moderate memory loss and decline in mental acuity is a normal part of aging. But Alzheimer’s disease is marked by a decline so significant that it impacts a person’s ability to function in everyday life.

Until recently, a definitive diagnosis could be made only after death when an autopsy could confirm the specific physical damage to the brain associated with Alzheimer’s. While there is still no single test to diagnose the disease, doctors now have tools to confidently make a diagnosis through a combination of patient evaluation, family history and eliminating other possible causes of the reported or observed symptoms, as well as use of new imaging technology and tests that can detect biomarkers specific to Alzheimer’s.

Memory loss is typically the first symptom patients and/or family members notice and report. In the earliest stages of Alzheimer’s, patients may forget a recent conversation, not recognize familiar surroundings or put possessions in odd locations. Other symptoms that may accompany memory loss are changes in personality: becoming more irritable or aggressive; withdrawal from social situations; depression; or increased distrust or suspicion.

During an initial consultation, physicians should collect a family history, since Alzheimer’s does seem to have a genetic component. A review of currently prescribed medications can identify other possible causes of memory loss. Physicians should also be sure to discuss patients’ current emotional health. Stress, anxiety, depression and loss of sleep can also lead to memory loss, confusion and difficulty concentrating.⁷

Tools used to help diagnose Alzheimer’s disease include:

• Blood and urine tests. These help identify other possible causes of the symptoms: vitamin B-12 deficiency, hypothyroidism and kidney or liver disease.
• Magnetic resonance imaging (MRI). MRI scans look for evidence of strokes, tumors, cranial fluid buildup or other conditions that can cause memory issues similar to those of Alzheimer’s disease.
• Mental tests. These help physicians identify any issues with problem-solving, memory, counting and language skills that are consistent with Alzheimer’s.

If a physician decides that the reported and/or observed decline in memory and other functioning is more severe than normal for a patient’s age range, and no other potential cause is identified, then the following tests can be ordered to help confirm an Alzheimer’s diagnosis:

• Elecsys Amyloid Plasma Panel. This newly approved blood scan tests for the presence of both tau proteins and the apolipoprotein E (APOE) genetic risk factor. A positive test will not be considered conclusive evidence of Alzheimer’s but a trigger for further testing. (A negative result will indicate that symptoms are likely due to another cause.⁸) The panel was called a “breakthrough device” by the U.S. Food and Drug Administration (FDA) in July 2022, a designation that is speeding its progress toward release.
• Spinal tap. A spinal tap can detect abnormal levels of amyloid and tau proteins.
• Computed tomography (CT) scan. A CT scan can look for structural changes in the brain consistent with Alzheimer’s.
• Positron emission tomography (PET) scan. A PET scan of the brain can detect accumulations of amyloid proteins, as well as locations where brain cells are inefficient in processing glucose, which is an important indication of Alzheimer’s.9

Once other likely causes of the symptoms are eliminated and a diagnosis is made, it is important to begin treatment quickly.

Treating Alzheimer’s

While a “whole patient” approach benefits prognosis in many cases, Alzheimer’s treatment will generally require a “whole family” approach. Caring for a loved one with Alzheimer’s takes both medical and emotional preparation and support.

Treatment specifics will depend on what stage of disease progression the patient is in at diagnosis: early-stage, middle-stage or late-stage. While there is no cure for Alzheimer’s, it is possible to slow the progression of symptoms and help preserve a higher quality of life.

During early- and middle-stage Alzheimer’s, cholinesterase inhibitors can help slow progression of both memory loss and mood changes. These drugs work by helping to increase levels of acetylcholine, a chemical needed for neurons to communicate with one another that is typically decreased in Alzheimer’s patients.⁹ Popular drugs in this class include donepezil (Aricept), galantamine (Razadyne ER) and rivastigmine (Exelon). During middle- and late-stage Alzheimer’s, memantine can be used to inhibit the effects of glutamate, which can overly excite neurons in Alzheimer’s patients.¹⁰ While both of these types of drugs can provide temporary relief from worsening symptoms for weeks — maybe even months — they eventually lose their efficacy.

Another option is aducanumab (Aduhelm), a recently approved drug found to help reduce amyloid plaque in Alzheimer’s patients. FDA granted accelerated approval for aducanumab in June 2021, and it is still undergoing study, so approval could be rescinded if significant side effects are discovered.¹¹

Antidepressants may also be used, by themselves or in conjunction with drugs listed above, to help treat behavioral issues associated with Alzheimer’s.

There are currently no direct medical interventions available for treating Alzheimer’s. Additional treatment options focus on keeping patients comfortable, doing as much as possible to lower stress-inducing events and ensuring patients’ physical well-being.

In early-stage Alzheimer’s, depending on the severity of the symptoms, patients often will be able to continue living at home as long as they have a strong support system. Modifications to living quarters and daily routines can help minimize stress.¹²

Modifications to living quarters include:

• Reducing clutter
• Removing throw rugs and other tripping hazards
• Keeping everyday items in the same place
• Removing as many mirrors as possible (Mirrors can confuse a patient with Alzheimer’s.)
• Displaying photographs of loved ones and familiar keepsakes in visible areas
• Installing sturdy handrails on staircases and in bathrooms

Modifications to daily routines include:

• Making appointments consistent (scheduling them at the same time and on the same day of the week as much as possible)
• Using a large calendar or bulletin board to outline daily tasks and schedules and checking off items as completed
• Giving patients a mobile phone with the location finder enabled, and preprogramming family members’ and other important phone numbers in the directory
• Ensuring patients carry their personal identification or wear a medical alert bracelet at all times
• Providing comfortable footwear that has good traction

While every case is unique, Alzheimer’s generally progresses from mild symptoms (for instance, trouble completing familiar tasks such as operating a microwave or writing a list) to the point of severe mood swings and increasing confusion about basic information such as where they are or what day it is. Patients may be unable to decide on what clothes to wear or have a tendency to wander off. Another unfortunate side effect of middle- to late-stage Alzheimer’s is incontinence.

Even in the middle stage, many normal life activities can still be enjoyed with help from caregivers. The middle stage is usually the longest stage, often lasting years. However, noticeable declines are still likely to be apparent, and caregivers will likely need assistance, especially as the disease progresses.

During late-stage Alzheimer’s, patients’ ability to communicate becomes severely degraded. They may no longer be aware of their surroundings or be able to respond to normal stimuli. At some point, round-the-clock care will become necessary either at home or at a dedicated care facility. Many hospice programs will have an Alzheimer’s care plan already in place to assist families in the final weeks or months.

The Other Patients

Caregivers need to be taken care of, too. Primary at-home caregivers — usually family members or close friends — benefit from routine medical care. They need to eat a healthy diet, get a good night’s sleep, exercise regularly and find time to relax away from their caregiving duties. It is just as important for caregivers to receive care as it is for them to provide it.

Overwhelmed or depressed caregivers are not as effective as those who are taking care of their own health as well. Taking care of someone with Alzheimer’s is emotionally taxing. Referring caregivers to a trusted therapist or suggesting a local support group can help ensure they have resources available to help them feel less isolated. Also, the Alzheimer’s Association has a series of tools to help caregivers manage their own stress and understand when to seek help and how to process the grief that accompanies the progression of Alzheimer’s disease. (See www.alz.org/help-support/caregiving/caregiver-health for details.)

Looking Ahead

One of the more intriguing areas of research lately has focused on prevention.

While the specific triggers that lead to Alzheimer’s are unknown, there is quite a bit of evidence showing general rules of healthy living can significantly lower the risk of developing the disease. While no definitive link has been established (although active research continues), the National Institutes of Health suggests that individuals who control their blood pressure and weight; eat a healthy, balanced diet; and are physically active and socially engaged may be at a lower risk of developing Alzheimer’s.

Given both the severity of the disease and the number of people it affects, research into Alzheimer’s is a high priority. The government-run ClinicalTrials.gov site lists nearly 3,000 open or recent studies investigating the disease. Many of them are researching new methods of detecting Alzheimer’s biomarkers or improving upon existing methods to allow for a quicker, more definitive diagnosis.

But other studies are searching for an actual cure for Alzheimer’s. For instance, the University of Miami is studying patients who receive an injection of mesenchymal stem cells every 13 weeks for one year. Follow-up studies of cognitive function are due to be completed later this year, with results to follow.¹³

Other studies are researching both new and existing drugs, with many of them targeting the high concentrations of the amyloid and tau proteins causing the brain degeneration that leads to Alzheimer’s.
Another noninvasive treatment is being studied at the Massachusetts Institute of Technology. This treatment uses a device that exposes patients to controlled, calibrated light and sound to stimulate the brain — hopefully countering the degenerative effects of Alzheimer’s.¹⁴

Finally, a recent study looking at preventive measures found a strong correlation between those who receive an influenza vaccine and avoiding Alzheimer’s later in life. Authors of the study completed at the University of Texas, Houston were unable to attribute the lower incidence of Alzheimer’s to the vaccine itself, but noted that simply avoiding repeated influenza infections may have an impact. Other vaccinations have also shown a correlation with lower incidences of Alzheimer’s.¹⁵

While progress continues to be made, both in our understanding of the under-lying causes that lead to Alzheimer’s and ways of treating it, a major breakthrough does not seem imminent. For the foreseeable future, gains in treatment are likely to be incremental, with families and physicians joining forces to provide as high a quality of life for patients as possible.