New research supports the classification system for preclinical Alzheimer’s proposed two years ago. The classification system divides preclinical Alzheimer's into three stages:
Stage 1: Levels of amyloid beta begin to decrease in the spinal fluid. This indicates that the substance is beginning to form plaques in the brain.
Stage 2: Levels of tau protein start to increase in the spinal fluid, indicating that brain cells are beginning to die. Amyloid beta levels are still abnormal and may continue to fall.
Stage 3: In the presence of abnormal amyloid and tau biomarker levels, subtle cognitive changes can be detected by neuropsychological testing.
Long-term evaluation of 311 cognitively healthy older adults (65+) found 31% with preclinical Alzheimer’s, of whom 15% were at stage 1, 12% at stage 2, and 4% at stage 3. This is consistent with autopsy studies, which have shown that around 30% of cognitively normal older adults die with some preclinical Alzheimer's pathology in their brain. Additionally, 23% were diagnosed with suspected non-Alzheimer pathophysiology (SNAP), 41% as cognitively normal, and 5% as unclassified.
Five years later, 2% of the cognitively normal, 5% of those with SNAP, 11% of the stage 1 group, 26% of the stage 2 group, and 56% of the stage 3 group had been diagnosed with symptomatic Alzheimer's.
(2013). Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study.
The Lancet Neurology. 12(10), 957 - 965.