The Spectrum of Alzheimer-Type Pathology in Cognitively Normal Individuals

Area of Science:

• Neuropathology
• Neuroscience
• Gerontology

Background:

• Age is the primary risk factor for Alzheimer's disease (AD).
• Previous studies documented age-related progression of Braak stage and Thal phase but lacked cognitive status data.
• Understanding normal aging brain pathology is crucial for identifying AD predictors.

Purpose of the Study:

• To establish normative values for Alzheimer-type pathological changes in cognitively normal individuals.
• To define thresholds for resilience or resistance to Alzheimer's pathology.
• To correlate specific pathological markers with cognitive status in aging.

Main Methods:

• Utilized neuropathology data from the National Alzheimer's Coordinating Center (NACC) for 542 cognitively normal individuals (CDR=0).
• Analyzed age-related progression of Alzheimer-type pathological changes, including Braak stage, Thal phase, neuritic plaque score, and AD neuropathologic change.
• Developed standard lines to measure individual pathology against estimated normal ranges.

Main Results:

• Braak stage and Thal phase progressively increased with age in cognitively normal individuals.
• Neuritic plaque score and overall Alzheimer's disease neuropathologic change remained low in this cohort.
• Established normative data for age-related neuropathology in the absence of cognitive decline.

Conclusions:

• Increasing neuritic plaques strongly predict cognitive decline.
• Neurofibrillary degeneration and diffuse amyloid-beta plaque deposition are normal aging processes, occurring in most individuals regardless of cognition.
• Defined criteria for 'resilient' (above-normal pathology, normal cognition) and 'resistant' (below-normal pathology, normal cognition) individuals.