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Neuropathology of cognitively normal elderly.
J Neuropathol Exp Neurol 2003; 62(11):1087-95JN

Abstract

Despite general agreement about the boundaries of Alzheimer disease (AD), establishing a maximum limit for Alzheimer-type pathology in cognitively intact individuals might aid in defining more precisely the point at which Alzheimer pathology becomes clinically relevant. In this study, we examined the neuropathological changes in the brains of 39 longitudinally followed. cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median 85 years). Neuropathological changes of the Alzheimer type were quantified by determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak and by quantification of the abundance of diffuse, cored, and neuritic plaque burden using the scheme developed by the Consortium to Establish a Registry for Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology were also assessed. We found 34 subjects (87%) with a Braak stage <IV; 32 subjects (82%) with less than moderate numbers of cored plaques and 37 subjects (95%) with less than moderate numbers of tau-positive neuritic plaques. Many subjects had moderate or frequent diffuse plaques (n = 19, 49%). By the National Institute on Aging-Reagan Institute (NIA-RI) criteria, none of our cases met criteria for high "likelihood" of AD. Four met NIA-RI criteria for intermediate "likelihood." Seven cases met CERAD criteria for possible AD. Nineteen met Khachaturian criteria for AD. Only 1 subject had neocortical Lewy bodies. Small, old infarcts were common, but no subjects had more than 2 of these and none had a single large infarction. Thus, the majority of individuals who are cognitively normal near the time of their death have minimal amounts of tau-positive neuritic pathology (Braak stage <IV and neuritic plaques <6 per x100 field in the most affected neocortical region). The few subjects with more severe AD pathology can be expected based on incidence rates of AD in the very elderly.

Authors+Show Affiliations

Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. knopman@mayo.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14656067

Citation

Knopman, D S., et al. "Neuropathology of Cognitively Normal Elderly." Journal of Neuropathology and Experimental Neurology, vol. 62, no. 11, 2003, pp. 1087-95.
Knopman DS, Parisi JE, Salviati A, et al. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003;62(11):1087-95.
Knopman, D. S., Parisi, J. E., Salviati, A., Floriach-Robert, M., Boeve, B. F., Ivnik, R. J., ... Petersen, R. C. (2003). Neuropathology of cognitively normal elderly. Journal of Neuropathology and Experimental Neurology, 62(11), pp. 1087-95.
Knopman DS, et al. Neuropathology of Cognitively Normal Elderly. J Neuropathol Exp Neurol. 2003;62(11):1087-95. PubMed PMID: 14656067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropathology of cognitively normal elderly. AU - Knopman,D S, AU - Parisi,J E, AU - Salviati,A, AU - Floriach-Robert,M, AU - Boeve,B F, AU - Ivnik,R J, AU - Smith,G E, AU - Dickson,D W, AU - Johnson,K A, AU - Petersen,L E, AU - McDonald,W C, AU - Braak,H, AU - Petersen,R C, PY - 2003/12/6/pubmed PY - 2004/1/6/medline PY - 2003/12/6/entrez SP - 1087 EP - 95 JF - Journal of neuropathology and experimental neurology JO - J. Neuropathol. Exp. Neurol. VL - 62 IS - 11 N2 - Despite general agreement about the boundaries of Alzheimer disease (AD), establishing a maximum limit for Alzheimer-type pathology in cognitively intact individuals might aid in defining more precisely the point at which Alzheimer pathology becomes clinically relevant. In this study, we examined the neuropathological changes in the brains of 39 longitudinally followed. cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median 85 years). Neuropathological changes of the Alzheimer type were quantified by determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak and by quantification of the abundance of diffuse, cored, and neuritic plaque burden using the scheme developed by the Consortium to Establish a Registry for Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology were also assessed. We found 34 subjects (87%) with a Braak stage <IV; 32 subjects (82%) with less than moderate numbers of cored plaques and 37 subjects (95%) with less than moderate numbers of tau-positive neuritic plaques. Many subjects had moderate or frequent diffuse plaques (n = 19, 49%). By the National Institute on Aging-Reagan Institute (NIA-RI) criteria, none of our cases met criteria for high "likelihood" of AD. Four met NIA-RI criteria for intermediate "likelihood." Seven cases met CERAD criteria for possible AD. Nineteen met Khachaturian criteria for AD. Only 1 subject had neocortical Lewy bodies. Small, old infarcts were common, but no subjects had more than 2 of these and none had a single large infarction. Thus, the majority of individuals who are cognitively normal near the time of their death have minimal amounts of tau-positive neuritic pathology (Braak stage <IV and neuritic plaques <6 per x100 field in the most affected neocortical region). The few subjects with more severe AD pathology can be expected based on incidence rates of AD in the very elderly. SN - 0022-3069 UR - https://www.unboundmedicine.com/medline/citation/14656067/Neuropathology_of_cognitively_normal_elderly_ L2 - https://academic.oup.com/jnen/article-lookup/doi/10.1093/jnen/62.11.1087 DB - PRIME DP - Unbound Medicine ER -