Alzheimer's Disease Staging: Six Stages from Silent Biomarkers to Dementia

The series was sponsored independently by Eli Lilly.

Welcome back to another AJMC Insights series. In "Alzheimer's Disease Staging: Six Stages From Silent Biomarkers to Dementia," David Reuben, MD, Archstone Professor of Geriatrics at the David Geffen School of Medicine at UCLA, shares what drew him to dementia care and how the field now stages Alzheimer's disease.

Dr. Reuben has cared for people with dementia as a geriatrician for roughly 40 years. His interest did not come from family history, because his relatives died too young to develop dementia. Quality improvement work around the turn of the millennium showed him that care for people living with dementia and their caregivers was poor, and that it could improve.

He found that pressing physicians to do better had a ceiling. His team therefore developed comprehensive dementia care management approaches that address both the person with dementia and the caregiver. Dr. Reuben calls this work incredibly meaningful, because it improves care for thousands of patients, very few of whom were his own.

He then explains why staging matters. Alzheimer's disease once meant a clinical diagnosis, made when memory, personality, and language problems were obvious and dementia was already advanced. Over the past two decades, that picture has been revolutionized. Most research now centers on Alzheimer's disease because it is the most common dementia and has the best biomarkers.

Current thinking classifies the disease in two ways, clinical and biological. The biological definition rests on biomarkers that show what is happening in the brain long before symptoms begin. Some studies detect changes about 20 years before a diagnosis of dementia.

Combining the two approaches produces six stages. The first two are cognitively unimpaired. Stage one shows biological markers without symptoms, and stage two adds very minor cognitive issues that remain within the normal range. Stage three is mild cognitive impairment, followed by three categories of dementia.

Dr. Reuben stresses that function separates mild cognitive impairment from dementia. People with mild cognitive impairment make mistakes on testing, but those deficits do not interfere much with daily life. Once dementia develops, the deficits get in the way and functional impairment must be present.

Our next segment, "Preclinical Alzheimer's Disease: Intervention Timing and Blood Biomarker Limits," features Dr. Reuben comparing the long biomarker window to heart disease prevention and weighing what blood tests can and cannot tell patients today.