What are the stages of Alzheimer's disease?

Stages of Alzheimer's Disease

Alzheimer's disease progresses through seven distinct clinical stages (0-6) according to the most recent 2025 Alzheimer's Association guidelines, ranging from asymptomatic individuals with genetic risk to severe dementia requiring complete care. 1

Clinical Staging Framework

The contemporary staging system recognizes that Alzheimer's disease exists on a continuum, beginning with pathological changes years before symptoms appear:

Stage 0: Asymptomatic with Genetic Risk

• Individuals carry deterministic genetic abnormalities (such as autosomal dominant mutations) but have no biomarker abnormalities and no symptoms 1
• This represents the earliest identifiable at-risk population, though pathological processes have not yet begun 1

Stage 1: Preclinical Alzheimer's Disease

• Asymptomatic individuals with biomarker evidence of Alzheimer's pathology 1
• Amyloid-beta accumulation detectable by PET imaging, CSF analysis, or plasma biomarkers 1
• Pathological changes begin 15-25 years before clinical symptoms emerge 1
• No clinical treatment is indicated at this stage, though it represents a critical window for future disease-modifying interventions 2
• Not all individuals with biomarker positivity will progress to symptomatic disease 1

Stage 2: Transitional Cognitive/Behavioral Decline

• Includes subjective cognitive decline where patients report cognitive changes but objective testing remains normal or shows only subtle decline 1
• Represents the earliest symptomatic phase where individuals notice changes from their own baseline that exceed normal aging 1
• Functional independence is preserved 1

Stage 3: Mild Cognitive Impairment (MCI)

• Objective evidence of impairment in one or more cognitive domains on formal testing 1
• Memory impairment is typically prominent, though other domains may be affected 1, 3
• Preservation of independence in functional abilities is the key distinguishing feature from dementia 1
• Patients manage to live alone but may need assistance with complex tasks 2, 3
• Depressive symptoms are not infrequent at this stage 3

Stage 4: Mild Dementia

• Cognitive impairment is severe enough to compromise activities of daily living 3
• Difficulties with declarative memory are usually prominent 3
• Patients can still participate in decision-making and advance care planning 2
• Cholinesterase inhibitors are most effective when initiated at this stage, providing modest symptom improvement or slowing cognitive decline in 20-35% of patients 2

Stage 5: Moderate Dementia

• Supervision is needed as multiple cognitive domains are affected in an obvious manner 3
• Non-cognitive disturbances of thought, perception, affect, and behavior emerge, placing increasing stress on caregivers 3
• Psychotic symptoms (hallucinations, delusions) increase in frequency 4
• Agitation and behavioral disturbances become more common 4
• Memantine is recommended at this stage according to the American Academy of Family Physicians 2

Stage 6: Severe Dementia

• Complete dependence on caregivers for all activities 3
• Neurological disturbances frequently develop 3
• Loss of ability to communicate verbally 5
• Requires total care for basic functions 5
• Cholinesterase inhibitors can be continued if tolerated and beneficial 2

Biological Staging (Alternative Framework)

The 2025 guidelines also describe a parallel biological staging system based on PET imaging that tracks pathological progression 1:

• Stage A: Amyloid-positive only
• Stage B: Amyloid-positive with tau in medial temporal lobe
• Stage C: Amyloid-positive with moderate neocortical tau
• Stage D: Amyloid-positive with high neocortical tau

This biological staging correlates with but does not perfectly align with clinical stages, as some individuals with advanced pathology remain cognitively normal 1, 6

Critical Clinical Considerations

The most common pitfall is delaying diagnosis and treatment initiation. Early intervention is more effective, yet symptoms are often dismissed as normal aging by both patients and providers 2, 7. The preclinical stage can last 15-25 years, during which pathological changes accumulate silently 1.

Recognizing transitions between stages is essential for adjusting treatment plans. Behavioral symptoms should be reassessed at least every six months as the disease progresses, since new symptoms emerge and treatment approaches must be modified accordingly 4.

Mixed etiology dementia is common in older adults, where vascular disease, Lewy body pathology, or other conditions contribute alongside Alzheimer's pathology 1. This is more likely when patients present with atypical or non-amnestic symptoms 1.

The life expectancy after clinical diagnosis is significantly reduced, though modern symptomatic treatments can prolong the period of relative well-being 3. The goal of staging is not merely prognostication but enabling appropriate interventions, advance care planning, and caregiver support at each phase of the disease continuum 2, 7.