How Alzheimer’s Disease Progresses: From Diagnosis Through the 7 Stages

Alzheimer’s disease is a progressive neurological disorder commonly affecting older adults, characterized by memory loss, confusion, behavioral changes, and other distressing symptoms. It is the most prevalent form of dementia, with approximately 10.7% of Americans aged 65 and above living with the condition, with women accounting for nearly two-thirds of cases.1 As the baby boomer generation enters their senior years, the number of individuals with Alzheimer’s disease is projected to reach 7.16 million by 2025 and 13.9 million by 2060.

To aid in the diagnosis of Alzheimer’s disease, Dr. Barry Reisberg, a psychiatrist at New York University School of Medicine, developed the Global Deterioration Scale (GDS), which defines seven distinct clinical stages of the disease.3 These stages are often summarized into a three-stage classification system: early stage, middle stage, and late stage. The early stages encompass GDS stages one to three, the middle stages include stages four and five, and the late stages comprise stages six and seven.11

Medical examinations play a crucial role in determining the stage of Alzheimer’s disease. Physicians typically rely on clinical interviews and medical evaluations during the diagnostic process. The clinical interview involves discussing the person’s symptoms and feelings, as well as cognitive assessments like counting backward from 50. Depending on the stage of Alzheimer’s, these interviews may be conducted with or without a caregiver present.8

Furthermore, medical evaluations involve brain imaging techniques such as magnetic resonance imaging (MRI) or computed tomography (CT) scans. These scans help identify brain abnormalities like tumors, strokes, fluid accumulation, or other damage resulting from head trauma. Brain imaging is primarily used to rule out other neurological conditions and detect shrinkage of the hippocampus, the region responsible for memory and learning, which indicates signs of memory loss.

Stage 1: Preclinical Alzheimer’s disease, No Sign of Dementia

In the initial stage of the Global Deterioration Scale (GDS), individuals do not experience any memory or thinking issues. All individuals, including those who will not develop Alzheimer’s disease, start at stage one. These first three stages are referred to as the "preclinical stages" of the disease, and they cannot be detected through clinical interviews and medical evaluations.

An alternative examination method that may detect early signs of Alzheimer’s is the use of biomarkers. Biomarkers are biological indicators that measure the presence of a disease in the body. Examples of biomarkers include blood pressure, heart rate, and x-rays. Some biomarkers, such as levels of beta-amyloid proteins and tau proteins, were initially believed to be early warning signs of Alzheimer’s disease.

However, a study published in Science in July 2022 raised questions about the significance of beta-amyloid proteins as a primary predictor of Alzheimer’s disease. While scientists acknowledge that beta-amyloid proteins likely play a role in understanding the disease, further research may explore other protein theories. Currently, healthcare providers are more likely to use a comprehensive approach, including behavioral and cognitive tests, for an accurate diagnosis.

Stage 2: Very Mild Cognitive Decline, Age-Related

In the second stage of Alzheimer’s disease, symptoms may become noticeable. However, similar to the first stage, clinical interviews and evaluations may not provide significant evidence of dementia. During this stage, individuals may start experiencing growing memory problems, such as difficulty remembering familiar names or struggling to recall the location of items like keys or wallets. These issues are often attributed to normal age-related declines in cognitive function.

Stage 3: Mild Cognitive Impairment

In the third stage of Alzheimer’s disease, also known as mild cognitive impairment (MCI), there is clearer evidence of memory loss, lack of focus, and trouble thinking. According to the GDS, individuals experiencing two or more of the following symptoms are considered to be at stage 3:

• Getting lost when going to a new location
• Decline in work performance that is noticeable to coworkers
• Difficulty remembering names or finding the right words
• Retaining or remembering very little of what was just read
• Trouble remembering the names of newly-introduced people
• Losing valuable or cherished objects
• Worsening job performance
• Difficulty socializing with others
• Denial of memory problems or cognitive issues
• Anxiety related to memory difficulties

During this stage, clinical tests and evaluations can pick up signs of impairment, particularly issues related to concentration.

Stage 4: Mild Dementia, Moderate Cognitive Decline

In stage 4 of Alzheimer’s disease, clear signs of the condition can be detected in clinical interviews and through careful evaluation. Individuals in this stage may experience difficulty remembering aspects of their personal life experiences and have reduced comprehension of current events. Some of the defining signs of stage 4 include:

• Reduced understanding of current events or news
• Difficulty remembering aspects of personal history and life experiences
• Inability to perform subtraction by 7 starting from 100, as assessed through a cognitive test
• Inability to travel independently, handle finances, or perform complex tasks
• Denial of memory problems
• Lack of emotional expression (flat affect)
• Frequent withdrawal from challenging or stressful social situations

People in stage 4 of Alzheimer’s disease generally retain awareness of the time and day, their location, and the ability to recognize familiar faces.

Stage 5: Moderate Dementia, Moderately Severe Decline

In the fifth stage of Alzheimer’s disease, which is known as moderate dementia, memory and cognitive deficits are evident through clinical evaluation and interviews. Individuals in this stage may experience the following:

• Trouble remembering important aspects of their life, such as their address, names of close friends or family members, or their hometown and schools.
• Difficulty identifying the current date, day of the week, or season.
• Inability to count down from 20 by twos or fours.
• Difficulty getting dressed independently.
• Some individuals may still retain long-term memories of major life events or the names of their spouse and children.
• Motor tasks, such as using the restroom or eating, may still be performed independently.

Stage 6: Moderately Severe Dementia

In the sixth stage of Alzheimer’s disease, individuals experience noticeable difficulty with memory and thinking. The general characteristics of stage 6 include:

• Occasional inability to remember the names of a spouse, partner, or caregiver.
• Difficulty or inability to recall recent life experiences or events.
• Difficulty counting down from 10.
• Needing assistance for basic daily activities, such as bathing, using the bathroom, or getting dressed.
• Disrupted sleep/wake cycles, insomnia, or other sleep problems.

Furthermore, the sixth stage is marked by changes in personality and behavioral symptoms, such as:

• Delusional behaviors, such as the belief that spouses or caregivers are imposters or talking to imagined people or their image in the mirror.
• Obsessive symptoms, such as compulsively cleaning the same area.
• Feelings of anxiety, agitation, increased irritability, or violence.
• Cognitive abulia, which is the loss of desire or ability to carry out an action due to the inability to focus on a thought.

Stage 6 Substages

Stage 6 of Alzheimer’s disease can be further divided into five substages (6a to 6e) to better understand the progression of the disease. Here are some signs you may observe in a loved one with Alzheimer’s disease within each substage:

• Substage 6a: Difficulty dressing independently, such as struggling with shoelaces or distinguishing between left and right shoes.
• Substage 6b: Challenges with bathing and personal hygiene, including difficulties with filling a bath, adjusting water temperature, or drying off with a towel. Anxiety or fear about bathing may also be present.
• Substage 6c: Inability to use the toilet independently, forgetting to flush, wipe, or pull up underwear after using the toilet.
• Substage 6d: Loss of urinary control, leading to accidents or not recognizing the need to use the toilet, resulting in urination in their pants.
• Substage 6e: Difficulty with bowel control, causing fecal incontinence and an inability to recognize the need to use the toilet for bowel movements. Support will be necessary for bathroom use in this substage.

These substages help healthcare professionals and caregivers understand the specific challenges individuals with Alzheimer’s disease may face as the disease progresses.

Stage 7: Very Severe Dementia

Stage 7 of Alzheimer’s disease, also known as Very Severe Dementia, represents the final stage of the disease. In this stage, individuals experience a significant decline in cognitive function and physical abilities. Here are some common characteristics of stage 7:

• Loss of basic motor skills: Individuals may lose the ability to walk independently and have difficulty controlling their limbs.
• Dependence in daily activities: Assistance is required for essential tasks such as eating, bathing, and using the bathroom.
• Loss of verbal communication: Many individuals become nonverbal and have difficulty expressing themselves through speech.
• Full-time caregiver support: People in stage 7 typically require round-the-clock care and support from a caregiver.

It’s important to note that the progression of Alzheimer’s disease can vary from person to person, and individuals may experience different symptoms and progression rates. Caregivers and healthcare professionals play a crucial role in providing the necessary support and ensuring the comfort and well-being of individuals in stage 7.

Stage 7 substages

Within Stage 7 of Alzheimer’s disease, there are six distinct substages that reflect the progression of very severe dementia. These substages help healthcare providers and caregivers track the decline in cognitive and physical abilities. Here’s an overview of each substage:

• Substage 7a: Difficulty speaking in full sentences, limited to about six words at a time.
• Substage 7b: Increased trouble with words, limited to saying "yes" or "OK," which may eventually be replaced by vocalizations or grunts.
• Substage 7c: Gradual loss of the ability to walk independently, with shorter steps, difficulty climbing stairs, and a tendency to tilt forward or sideways when standing.
• Substage 7d: Difficulty sitting upright without assistance, but still able to smile, chew, vocalize, and grasp objects.
• Substage 7e: Loss of facial expressions and struggle to recognize familiar faces, but still able to move eyes, chew, swallow, and grasp objects.
• Substage 7f: Inability to hold up the head, requiring feeding tubes for nutrition, and limited responsiveness with soft grunts or vocalizations. Only a small number of people reach this final substage, and survival is rare.

It’s important to note that as individuals progress through these substages, their condition becomes increasingly dangerous and life-threatening, particularly when combined with other health issues. The survival rate at this stage is relatively low, with individuals typically living for six months to two years after reaching Stage 7. However, it’s worth mentioning that most individuals with Alzheimer’s disease do not reach the later substages of Stage 7.

Summary

Since its introduction in 1982, the Global Deterioration Scale has played a vital role in helping physicians and caregivers track the progression of Alzheimer’s disease through its seven stages. Living with Alzheimer’s disease is challenging, both for those diagnosed with the condition and their loved ones. If you notice signs of Alzheimer’s disease in a loved one, it’s important to encourage them to seek a proper diagnosis. While there is currently no cure for Alzheimer’s, medical interventions and therapies can help manage symptoms and slow the disease’s progression.

As a caregiver, it’s crucial to prioritize your own well-being as well. Look for programs that offer financial assistance to support both you and your loved one. Additionally, consider reaching out to a mental health professional to help navigate the emotional toll of caregiving. Remember that it’s okay to ask for help during this difficult time. By seeking support and accessing available resources, you can provide the best possible care for your loved one while taking care of yourself.