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Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions.

Abstract

OBJECTIVES

To examine the extent to which persons with mild cognitive impairment have intermediate levels of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body disease.

METHODS

A total of 180 Catholic clergy participating in the Religious Orders Study underwent annual detailed evaluation and brain autopsy. Blocks of midfrontal, superior temporal, medial temporal lobe, inferior parietal, entorhinal cortex, hippocampus, and substantia nigra were paraffin embedded, and sectioned at 6 mum. Cortical neuritic plaques, diffuse plaques, and neurofibrillary tangles were visualized with Bielschowsky silver stain, and counted and summarized to yield a Braak stage, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) diagnosis, National Institute on Aging (NIA)-Reagan diagnosis, and composite measure of AD pathology. The authors recorded the number and location of all gross chronic cerebral infarctions. Lewy bodies were identified with antibodies to alpha-synuclein. Multiple regression analyses were used to examine the relation of AD pathology and cerebral infarctions to clinical diagnosis proximate to death, controlling for age, sex, and education.

RESULTS

A total of 37 had mild cognitive impairment, 60 did not have cognitive impairment, and 83 had dementia proximate to death. Nearly all persons had at least some AD pathology. Cerebral infarctions were present in 35.2%, and 15.6% had Lewy body disease. Persons with mild cognitive impairment were intermediate in terms of Braak stage and CERAD and NIA-Reagan neuropathologic criteria for AD compared to the other two groups. In multiple regression analyses, persons with mild cognitive impairment had intermediate levels of AD pathology from those without cognitive impairment and those with dementia (test for trend, F = 45.2, p < 0.001). Further, the relation between cognition and AD pathology in persons with mild cognitive impairment did not differ significantly from the relation between cognition and AD pathology in persons with dementia or those without cognitive impairment. Persons with mild cognitive impairment also had intermediate levels of cerebral infarctions (test for trend, p = 0.04). Only 3 (8.1%) persons with mild cognitive impairment had Lewy body disease.

CONCLUSION

These data suggest that mild cognitive impairment may be the earliest clinical manifestation of common age-related neurologic diseases.

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  • Authors+Show Affiliations

    ,

    Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. dbennett@rush.edu

    , , ,

    Source

    Neurology 64:5 2005 Mar 08 pg 834-41

    MeSH

    Age Factors
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Brain
    Cerebral Infarction
    Cognition Disorders
    Comorbidity
    Disease Progression
    Educational Status
    Female
    Humans
    Lewy Bodies
    Lewy Body Disease
    Male
    Neurofibrillary Tangles
    Neuropsychological Tests
    Plaque, Amyloid
    Sex Factors
    Statistics as Topic

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15753419

    Citation

    Bennett, D A., et al. "Mild Cognitive Impairment Is Related to Alzheimer Disease Pathology and Cerebral Infarctions." Neurology, vol. 64, no. 5, 2005, pp. 834-41.
    Bennett DA, Schneider JA, Bienias JL, et al. Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology. 2005;64(5):834-41.
    Bennett, D. A., Schneider, J. A., Bienias, J. L., Evans, D. A., & Wilson, R. S. (2005). Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology, 64(5), pp. 834-41.
    Bennett DA, et al. Mild Cognitive Impairment Is Related to Alzheimer Disease Pathology and Cerebral Infarctions. Neurology. 2005 Mar 8;64(5):834-41. PubMed PMID: 15753419.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. AU - Bennett,D A, AU - Schneider,J A, AU - Bienias,J L, AU - Evans,D A, AU - Wilson,R S, PY - 2005/3/9/pubmed PY - 2006/2/10/medline PY - 2005/3/9/entrez SP - 834 EP - 41 JF - Neurology JO - Neurology VL - 64 IS - 5 N2 - OBJECTIVES: To examine the extent to which persons with mild cognitive impairment have intermediate levels of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body disease. METHODS: A total of 180 Catholic clergy participating in the Religious Orders Study underwent annual detailed evaluation and brain autopsy. Blocks of midfrontal, superior temporal, medial temporal lobe, inferior parietal, entorhinal cortex, hippocampus, and substantia nigra were paraffin embedded, and sectioned at 6 mum. Cortical neuritic plaques, diffuse plaques, and neurofibrillary tangles were visualized with Bielschowsky silver stain, and counted and summarized to yield a Braak stage, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) diagnosis, National Institute on Aging (NIA)-Reagan diagnosis, and composite measure of AD pathology. The authors recorded the number and location of all gross chronic cerebral infarctions. Lewy bodies were identified with antibodies to alpha-synuclein. Multiple regression analyses were used to examine the relation of AD pathology and cerebral infarctions to clinical diagnosis proximate to death, controlling for age, sex, and education. RESULTS: A total of 37 had mild cognitive impairment, 60 did not have cognitive impairment, and 83 had dementia proximate to death. Nearly all persons had at least some AD pathology. Cerebral infarctions were present in 35.2%, and 15.6% had Lewy body disease. Persons with mild cognitive impairment were intermediate in terms of Braak stage and CERAD and NIA-Reagan neuropathologic criteria for AD compared to the other two groups. In multiple regression analyses, persons with mild cognitive impairment had intermediate levels of AD pathology from those without cognitive impairment and those with dementia (test for trend, F = 45.2, p < 0.001). Further, the relation between cognition and AD pathology in persons with mild cognitive impairment did not differ significantly from the relation between cognition and AD pathology in persons with dementia or those without cognitive impairment. Persons with mild cognitive impairment also had intermediate levels of cerebral infarctions (test for trend, p = 0.04). Only 3 (8.1%) persons with mild cognitive impairment had Lewy body disease. CONCLUSION: These data suggest that mild cognitive impairment may be the earliest clinical manifestation of common age-related neurologic diseases. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/15753419/Mild_cognitive_impairment_is_related_to_Alzheimer_disease_pathology_and_cerebral_infarctions_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&amp;pmid=15753419 DB - PRIME DP - Unbound Medicine ER -