As we age, memory slips—whether it’s misplacing your keys or forgetting the name of a person you just met. Often this is part of the normal aging process. But if those slips become worse, more frequent, and start to interfere with daily life, they could be the initial signs of Alzheimer’s disease, a progressive disease that causes memory loss, behavioral changes, and the decline of other mental abilities. Eventually, as the disease progresses, people with Alzheimer’s disease may no longer recognize their family and friends and will need help performing daily activities like dressing or using the bathroom.

Alzheimer’s disease is an emotional and difficult experience for those who live with it, as well as for their friends, family, and caregivers. It is more common than it used to be, in part, because the likelihood of getting Alzheimer’s rises with age, and people are living longer. In the U.S., it affects around 6 million people and leads to over 120,000 deaths every year. It’s estimated that by 2050, Alzheimer’s disease will affect nearly 14 million people in the U.S.

“A key part of the clinical care provided in the Yale Memory Disorders Clinic is to distinguish when cognitive difficulties exceed the normal aging process, and then to diagnosis the cause,” says Stephen Strittmatter, MD, PhD, director of the Yale Alzheimer’s Disease Research Center. “While the majority of dementia cases are due to Alzheimer’s, a third of cases are due to alternate conditions, and a number of these have specific and effective therapies to modify their course.”

Named after Alois Alzheimer, who first discovered it in 1906, Alzheimer’s disease is a progressive disorder that damages and destroys nerve cells in the brain. Over time, the disease leads to a gradual loss of cognitive functions, including the ability to remember, reason, use language, and recognize familiar places. It can also cause a range of behavioral changes.

Alzheimer’s typically affects adults over the age of 65. Though not the only type of dementia (a term used to describe diminished cognitive function that interferes with day-to-day living) it is the most common type in elderly people, accounting for 60 to 80% of all cases.

Alzheimer’s disease progresses gradually, with symptoms typically worsening over the course of up to ten years. It ultimately results in death, usually from illnesses such as pneumonia or heart failure. Alzheimer’s disease is the sixth leading cause of death in the U.S.

In your brain, billions of cells (called neurons) play a critical role in your ability to think, feel, remember, use language, and recognize familiar places. Your neurons communicate with each other by sending chemical signals across narrow spaces (called synapses) to create a neural network, similar to a supercomputer.

Alzheimer’s disease causes these synapses to degenerate so that they no longer function properly, limiting communication between cells and causing deterioration of brain function. Eventually, some of the neurons die off in moderate and severe disease. Ultimately, the brain atrophies, or shrinks.

Scientists do not know what causes these changes to occur, but have identified brain changes in people who have died of Alzheimer’s disease. Outside the neurons, a protein called “beta amyloid” accumulates and clumps together to form what are known as amyloid plaques. And inside the neurons, a protein called “tau” accumulates and clumps together to form what are known as neurofibrillary tangles.

Several risk factors have been associated with Alzheimer’s disease.

Non-Modifiable Risk Factors. Factors that influence risk but over which a person has no control include:

• Age, the most important risk factor for Alzheimer’s disease. The disease usually occurs in people over 65, and by age 85, it affects between 20 and 40% of people. In very rare cases, called early onset Alzheimer’s disease, symptoms can appear in people in their 30s.
• Family history and genetics. Though most cases of Alzheimer’s disease are not inherited, people who have a family history of dementia may be at increased risk—by 10 to 30%—for Alzheimer’s disease.
• Traumatic brain injury. Head injuries resulting from accidents and sports, like football, can increase the risk of developing Alzheimer’s.  

Modifiable Risk Factors. There are also risk factors that can be helped by lifestyle change or medication, reducing the likelihood Alzheimer’s will develop.  They include:

• High blood pressure
• High cholesterol
• Obesity
• Type 2 diabetes
• Physical inactivity
• Smoking tobacco

The symptoms of Alzheimer’s disease begin gradually and progressively worsen over time.

The progression is often divided into three stages, each with a characteristic set of symptoms:

Early (or mild) stage Alzheimer’s disease.

• Memory loss, such as forgetting recent events or conversations, misplacing items, repeating questions or stories, forgetting appointments
• Difficulty with performing complex tasks such as managing finances or following instructions
• Difficulty recalling the name of a person, object, or place
• Struggling to find the right word
• Mood and/or personality changes
• Anxiety
• Impaired judgment and reasoning ability
• Difficulty with performing math calculations
• Feeling disorientated or confused in familiar places

Middle (or moderate) stage Alzheimer’s disease.

People at this stage of the disease usually cannot work and may require daily assistance with getting dressed, bathing, and eating.

Symptoms include:

• Worsened memory impairment:
  • Difficulty with recognizing or recalling the names of familiar places, objects, and people, including friends and family
  • Increasingly difficult to remember past experiences and familiar facts, such as address and phone number
• Getting lost in familiar places; wandering aimlessly; confusion and disorientation
• Worsened mood and/or personality changes that may include anxiety, agitation, frustration, and aggression
• Difficulty with learning new things
• Language problems, including diminished writing, reading, and comprehension abilities
• Depression
• Hallucinations
• Delusions, often causing paranoia and mistrust of others
• Difficulty performing complex motor tasks such as using utensils while eating
• Problems with visual and spatial perception; unable to judge distances
• Difficulty concentrating
• Lack of interest in previous hobbies or pastimes
• Disrupted sleep

Late stage (or severe) Alzheimer’s disease.

People at this stage require full-time supervision and assistance with everyday activities such as eating, bathing, and using the bathroom.

Symptoms include:

• Frequent delusions
• Wandering and restlessness at night
• Gait impairment; shuffling gait
• Increased risk of falling
• Inability to speak
• Unable to recognize friends and family
• Difficulty swallowing and eating
• Loss of ability to walk
• Unable to control bladder and bowels
• Loss of awareness of time and place
• Increasing frailness and weight loss

To diagnose Alzheimer’s disease, doctors will need to collect a medical history, perform a physical exam, assess a series of cognitive tests, and order one or more diagnostic tests.

In a medical history, doctors ask about what symptoms are present, when they began, and whether they are worsening. Because of the memory loss associated with Alzheimer’s, doctors often discuss the patient’s symptoms with a family member, caregiver, or friend.

The patient’s overall health will also be assessed during a physical exam with a focus on neurological function. This may include an evaluation of balance, reflexes, gait, sensory function, and muscle strength.

Patients will also be asked to complete cognitive tests designed to assess memory, language and math skills, ability to follow instructions, and other mental functions.

Imaging tests such as a computed tomography (CT) scan or magnetic resonance imaging (MRI) study allow doctors to see changes in the brain, such as signs of atrophy (shrinking). These scans also rule out alternate causes of cognitive decline, such as vascular disease and malignancy. Another such test is positive emission tomography (PET), a type of imaging study in which a radioactive tracer is injected into the patient’s vein, allowing doctors to see amyloid plaques, glucose metabolism, or tau accumulation in the brain.

There is no cure for Alzheimer’s disease, though treatments can slow cognitive decline, help manage symptoms, and improve quality of life. Treatment also aims to support caregivers and family members.

Treatments for Alzheimer’s disease include:

Medication. Three classes of medications are used to treat Alzheimer’s disease.

• Anti-amyloid antibodies. These drugs work by clearing amyloid plaques from the brains of people with Alzheimer’s disease.
  • Lecanemab. Lecanemab (brand name Leqembi®) is a monoclonal antibody, a type of medication that contains laboratory-produced antibodies. The antibodies target and bind to amyloid plaques, signaling the immune system to clear them from the brain. In clinical trials, lecanemab was found to slow the rate of cognitive and functional decline in people with early Alzheimer’s disease compared to a placebo over 18 months. Lecanemab is administered via intravenous (IV) infusion every two weeks. It received full approval from the FDA in July 2023 for the treatment of people with early-stage Alzheimer’s disease.
  • Aducanumab. This monoclonal antibody, sold under the brand name Aduhelm®, received accelerated FDA approval in June 2021 for the treatment of people with Alzheimer’s disease who have mild cognitive impairment or mild dementia. Like lecanemab, the antibodies in aducanumab attach to amyloid plaques, triggering the patient’s immune system to remove them from the brain. It is administered every four weeks as an IV infusion. Evidence of slowing progression of the disease in clinical trials was inconsistent; thus, additional trials are needed to confirm its clinical benefit.
    
    In late January 2024, Biogen, the maker of Aduhelm, announced that they will stop selling the drug. The company is also ending the ENVISION clinical trial, a study aimed at determining the clinical benefit of Aduhelm. However, Biogen will continue to provide the drug to people enrolled in the study until May 2024, and Aduhelm will continue to be available for commercial use until November 1, 2024. In a press release, Biogen noted that the decision to stop selling Aduhelm “is not related to any safety or efficacy concerns.”
• Cholinesterase inhibitors. In people with Alzheimer’s disease, a chemical called acetylcholine (it helps neurons communicate with one another) is found in lower levels than in healthy people. This impairs cognitive functions such as memory and reasoning. Cholinesterase inhibitors boost levels of acetylcholine in the brain. In patients with mild-to-moderate Alzheimer’s disease, a dose of cholinesterase inhibitor may improve cognition mildly, such that function resembles what it was 6 to 12 months earlier.
• Memantine. Glutamate, another chemical that helps neurons communicate with one another, is overactive in the brains of people with Alzheimer’s disease. High levels of glutamate activity can impair neuronal function and damage neurons; memantine can reduce the harmful effects of excessive glutamate activity. Memantine is used to treat people with moderate-to-severe Alzheimer’s disease and, in the short term, can mildly reduce the degree of impaired cognitive function.

A combination of cholinesterase inhibitors, memantine, and anti-amyloid antibodies are sometimes used simultaneously.

Treating behavioral symptoms. People who have Alzheimer’s disease may develop depression, anxiety, mood and personality changes, and sleep disorders, along with other behavioral issues. Medications can sometimes help with these problems. In some cases, physicians will recommend behavioral therapies such as counseling and support groups for these patients.

Other treatments.

• Behavioral therapy. An Alzheimer’s disease diagnosis may make people feel sad, angry, and/or anxious. Counseling and support groups can help patients learn strategies for coping with these feelings.
• Cognitive therapies. A physician might recommend that patients undertake cognitive stimulation therapy and participate in activities that stimulate mental skills such as reasoning, thinking, and memory. These may involve activities that center on art, music, cooking, and other topics. People may also engage in memory games, solve puzzles, and share memories from their lives.
• Exercise. Exercise can improve cardiovascular and physical health, may reduce behavioral symptoms associated with Alzheimer’s disease, and can help mitigate some of the associated sleep problems.
• Environmental interventions. People with Alzheimer’s disease and their caregivers should modify their homes and activities to ensure safety and comfort. This may involve making arrangements for managing finances, and using calendars and journals to assist with remembering appointments, medication schedules, and setting up daily routines.

“Yale Medicine has a comprehensive and stepwise multidisciplinary approach to Alzheimer’s disease,” says Dr. Strittmatter. “This starts with a detailed assessment of the cause of cognitive difficulties using multiple modern diagnostic technologies, and is followed by the deployment of diverse pharmacological, behavioral, and lifestyle interventions to limit symptoms and their impact on patients and families.”