Clinical Stages and Progression

The clinical presentation and progression of Alzheimer’s disease and other dementias can be conceptualized as a continuum, from preclinical stages through mild cognitive impairment to dementia of increasing severity.

Preclinical Alzheimer’s Disease

In the preclinical stage, individuals have evidence of Alzheimer’s disease pathology (as measured by biomarkers) but no detectable cognitive impairment. This stage may begin 20 years or more before symptoms become apparent and represents a critical period for potential intervention (Jack et al. 539).

Research is ongoing to identify individuals in this stage through biomarker testing, including measurements of amyloid-β and tau in cerebrospinal fluid or through specialized brain imaging techniques such as positron emission tomography (PET).

Mild Cognitive Impairment due to Alzheimer’s Disease

Mild cognitive impairment (MCI) represents a transitional state between normal cognition and dementia, characterized by objective cognitive decline that does not significantly interfere with daily functioning. When MCI is suspected to be due to Alzheimer’s disease based on clinical presentation and biomarker evidence, it is referred to as MCI due to AD.

Individuals with MCI due to AD typically present with:

• Memory complaints, often corroborated by an informant
• Objective memory impairment for age and education
• Preserved general cognitive function
• Intact activities of daily living
• Absence of dementia

Not all individuals with MCI progress to dementia; some remain stable or even revert to normal cognition. However, those with biomarker evidence of Alzheimer’s disease pathology have a higher risk of progression, with annual conversion rates of 10-15% compared to 1-2% in the general elderly population (Dubois et al. 486).

Mild Alzheimer’s Disease Dementia

In mild Alzheimer’s disease dementia, cognitive impairment extends beyond memory to other domains and begins to interfere with daily functioning. Common symptoms include:

• Increased forgetfulness, especially for recent events
• Difficulty learning and retaining new information
• Word-finding difficulties
• Getting lost in familiar places
• Difficulty managing finances or following complex instructions
• Changes in personality or judgment
• Increased anxiety, irritability, or apathy

At this stage, individuals may still be able to function independently in many areas but typically require some assistance with complex activities, such as managing finances or medications.

Moderate Alzheimer’s Disease Dementia

As Alzheimer’s disease progresses to the moderate stage, cognitive impairment becomes more pronounced, significantly impacting daily functioning. Symptoms include:

• Severe memory loss, including forgetting significant personal history
• Increased confusion about time, place, and people
• Significant language difficulties, including reduced vocabulary and comprehension
• Difficulty with simple tasks, such as dressing appropriately
• Restlessness, agitation, or wandering
• Changes in sleep patterns
• Delusions or hallucinations in some cases

At this stage, individuals typically require substantial assistance with daily activities and may need supervision to ensure safety.

Severe Alzheimer’s Disease Dementia

In the severe stage of Alzheimer’s disease dementia, individuals become completely dependent on others for care. Symptoms include:

• Inability to recognize family members or close friends
• Inability to communicate verbally
• Loss of basic psychomotor skills, including the ability to walk
• Incontinence
• Difficulty swallowing
• Increased vulnerability to infections, particularly pneumonia

The duration of each stage varies considerably among individuals, with the overall course from diagnosis to death typically ranging from 4 to 8 years, though some individuals may live up to 20 years or more with the disease (Alzheimer’s Association 351).