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Neuropathology of cognitively normal elderly
D S Knopman1, J E Parisi, A Salviati
1Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. knopman@mayo.edu
Journal of Neuropathology and Experimental Neurology
|December 6, 2003
Summary
Most cognitively normal elderly individuals show minimal Alzheimer disease (AD) pathology. Defining maximum limits for AD pathology in healthy brains helps identify when it becomes clinically significant.
Area of Science:
- Neuropathology
- Gerontology
- Neurodegenerative Diseases
Background:
- Alzheimer disease (AD) diagnosis relies on clinical symptoms and confirmed pathology.
- Establishing thresholds for AD-type pathology in cognitively normal individuals is crucial for clinical relevance.
Purpose of the Study:
- To quantify neuropathological changes in cognitively normal elderly individuals.
- To determine maximum limits of Alzheimer-type pathology in the absence of cognitive impairment.
Main Methods:
- Examined brains of 39 cognitively normal elderly individuals (age 74-95).
- Quantified neurofibrillary tangle (NFT) staging (Braak and Braak) and plaque burden (CERAD).
- Assessed vascular, Lewy body, and argyrophilic grain pathology.
Main Results:
- 87% had Braak stage
- None met high likelihood criteria for AD by NIA-Reagan Institute (NIA-RI) criteria; 4 met intermediate.
- Majority had minimal tau-positive neuritic pathology (Braak stage
Conclusions:
- Cognitively normal elderly individuals typically exhibit minimal Alzheimer-type neuropathology.
- Defining pathology limits in normal aging brain aids in understanding AD progression.
- Severe AD pathology in cognitively normal individuals is rare and aligns with incidence rates in the very elderly.