Microinfarcts, brain atrophy, and cognitive function: The Honolulu Asia Aging Study Autopsy Study
Objective: This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association. Methods: Subjects we...
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| Published in: | Annals of neurology Vol. 70; no. 5; pp. 774 - 780 |
|---|---|
| Main Authors: | , , |
| Format: | Journal Article |
| Language: | English |
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Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.11.2011
Wiley-Liss Wiley Subscription Services, Inc |
| Subjects: | |
| ISSN: | 0364-5134, 1531-8249, 1531-8249 |
| Online Access: | Get full text |
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| Abstract | Objective:
This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association.
Methods:
Subjects were 436 well‐characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument, and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on antemortem diagnoses, demented and nondemented subjects were examined together and separately.
Results:
In those with no dementia, MBIs were strongly associated with the last antemortem CF score; this was significantly mediated by BW, and not NFTs or NPs. In contrast, among those with an antemortem diagnosis of dementia, NFTs had the strongest associations with BW and with CF, and MBIs were modestly associated with CF.
Interpretation:
This suggests that microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory toward dementia the lesions develop. ANN NEUROL 2011 |
|---|---|
| AbstractList | This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association.OBJECTIVEThis study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association.Subjects were 436 well-characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument, and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on antemortem diagnoses, demented and nondemented subjects were examined together and separately.METHODSSubjects were 436 well-characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument, and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on antemortem diagnoses, demented and nondemented subjects were examined together and separately.In those with no dementia, MBIs were strongly associated with the last antemortem CF score; this was significantly mediated by BW, and not NFTs or NPs. In contrast, among those with an antemortem diagnosis of dementia, NFTs had the strongest associations with BW and with CF, and MBIs were modestly associated with CF.RESULTSIn those with no dementia, MBIs were strongly associated with the last antemortem CF score; this was significantly mediated by BW, and not NFTs or NPs. In contrast, among those with an antemortem diagnosis of dementia, NFTs had the strongest associations with BW and with CF, and MBIs were modestly associated with CF.This suggests that microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory toward dementia the lesions develop.INTERPRETATIONThis suggests that microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory toward dementia the lesions develop. Objective: This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association. Methods: Subjects were 436 well‐characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument, and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on antemortem diagnoses, demented and nondemented subjects were examined together and separately. Results: In those with no dementia, MBIs were strongly associated with the last antemortem CF score; this was significantly mediated by BW, and not NFTs or NPs. In contrast, among those with an antemortem diagnosis of dementia, NFTs had the strongest associations with BW and with CF, and MBIs were modestly associated with CF. Interpretation: This suggests that microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory toward dementia the lesions develop. ANN NEUROL 2011 This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association. Subjects were 436 well-characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument, and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on antemortem diagnoses, demented and nondemented subjects were examined together and separately. In those with no dementia, MBIs were strongly associated with the last antemortem CF score; this was significantly mediated by BW, and not NFTs or NPs. In contrast, among those with an antemortem diagnosis of dementia, NFTs had the strongest associations with BW and with CF, and MBIs were modestly associated with CF. This suggests that microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory toward dementia the lesions develop. Objective: This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association. Methods: Subjects were 436 well-characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument, and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on antemortem diagnoses, demented and nondemented subjects were examined together and separately. Results: In those with no dementia, MBIs were strongly associated with the last antemortem CF score; this was significantly mediated by BW, and not NFTs or NPs. In contrast, among those with an antemortem diagnosis of dementia, NFTs had the strongest associations with BW and with CF, and MBIs were modestly associated with CF. Interpretation: This suggests that microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory toward dementia the lesions develop. ANN NEUROL 2011 [PUBLICATION ABSTRACT] Objective: This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association. Methods: Subjects were 436 well-characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument, and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on antemortem diagnoses, demented and nondemented subjects were examined together and separately. Results: In those with no dementia, MBIs were strongly associated with the last antemortem CF score; this was significantly mediated by BW, and not NFTs or NPs. In contrast, among those with an antemortem diagnosis of dementia, NFTs had the strongest associations with BW and with CF, and MBIs were modestly associated with CF. Interpretation: This suggests that microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory toward dementia the lesions develop. ANN NEUROL 2011 |
| Author | Hughes, Timothy M. Launer, Lenore J. White, Lon R. |
| Author_xml | – sequence: 1 givenname: Lenore J. surname: Launer fullname: Launer, Lenore J. email: launerl@nia.nih.gov organization: Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD – sequence: 2 givenname: Timothy M. surname: Hughes fullname: Hughes, Timothy M. organization: Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD – sequence: 3 givenname: Lon R. surname: White fullname: White, Lon R. organization: Department of Geriatric Medicine, University of Hawaii John A. Burns School of Medicine and Honolulu-Asia Aging Study, Kuakini Medical Center, Honolulu, HI |
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| Copyright | Copyright © 2011 American Neurological Association 2015 INIST-CNRS Copyright © 2011 American Neurological Association. |
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| Keywords | Atrophy Nervous system diseases Senescence Autopsy Central nervous system Encephalon |
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| References | Hoyer S. Is sporadic Alzheimer's disease the brain type of non- insulin dependent diabetes mellitus? A challenging hypothesis. J Neural Transm 1998; 105: 415-422. Longstreth WT Jr, Sonnen JA, Koepsell TD, et al. Associations between microinfarcts and other macroscopic vascular findings on neuropathologic examination in 2 databases. Alzheimer Dis Assoc Disord 2009; 23: 291-294. Preacher KJ, Hayes AF. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods 2008; 40: 879-891. R Development Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, 2008. White L, Petrovitch H, Ross GW, et al. Prevalence of dementia in older Japanese-American men living in Hawaii: the Honolulu-Asia Aging Study. JAMA 1996; 276: 955-960. Jack CR Jr, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010; 9: 119-128. Braak H, Braak E. Neuropathologic staging of Alzheimer-related changes. Acta Neuropathol 1991; 82: 239-259. Hardy J. The amyloid hypothesis for Alzheimer's disease: a critical reappraisal. J Neurochem 2009; 110: 1129-1134. Martins IJ, Hone E, Foster JK, et al. Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease. Mol Psychiatry 2006; 11: 721-736. SAS Institute Inc. SAS v 9.0. Cary, NC: SAS Institute Inc, 2004. Schneider JA, Aggarwal NT, Barnes LL, et al. The neuropathology of older persons with and without dementia from community vs. clinic cohorts. J Alzheimer Dis 2009; 18: 691-701. Teng EL, Hasegawa K, Homma A, et al. The Cognitive Abilities Screening Instrument (CASI): a practical test for cross-cultural epidemiological studies of dementia. Int Psychogeriatr 1994; 6: 45-58. Hartley SW, Scher AI, Korf ES, et al. Analysis and validation of automated skull stripping tools: a validation study based on 296 MR images from the Honolulu Asia aging study. Neuroimage 2006; 30: 1179-1186. Fernando MS, Ince PC. MRC Cognitive Function and Ageing Neuropathology Study Group. Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 2004; 235 226: 13-17. Gold G. Defining the neuropathological background of vascular and mixed dementia and comparison with magnetic resonance imaging findings. Front Neurol Neurosci 2009; 24: 86-94. Petrovitch H, Ross GW, Steinhorn SC, et al. AD lesions and infarcts in demented and non-demented Japanese-American men. Ann Neurol 2005; 57: 98-103. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed rev. Washington, DC: American Psychiatric Association, 1987. White L. Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia Aging Study. J Alzheimer Dis 2009; 18: 713-725. 2009; 23 2009; 24 2006; 30 2000 2006; 11 1987 2009; 110 1991; 82 2008 1996; 276 1994 2004 1998; 105 2008; 40 2009; 18 2005; 57 2010; 9 1994; 6 American Psychiatric Association (e_1_2_8_11_2) 1987 e_1_2_8_17_2 e_1_2_8_18_2 e_1_2_8_19_2 White L (e_1_2_8_9_2) 1996; 276 e_1_2_8_12_2 e_1_2_8_13_2 e_1_2_8_14_2 e_1_2_8_2_2 e_1_2_8_4_2 e_1_2_8_3_2 e_1_2_8_6_2 e_1_2_8_5_2 e_1_2_8_8_2 R Development Core Team (e_1_2_8_16_2) 2008 e_1_2_8_7_2 e_1_2_8_20_2 e_1_2_8_10_2 e_1_2_8_21_2 SAS Institute Inc (e_1_2_8_15_2) 2004 |
| References_xml | – reference: Braak H, Braak E. Neuropathologic staging of Alzheimer-related changes. Acta Neuropathol 1991; 82: 239-259. – reference: Gold G. Defining the neuropathological background of vascular and mixed dementia and comparison with magnetic resonance imaging findings. Front Neurol Neurosci 2009; 24: 86-94. – reference: White L. Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia Aging Study. J Alzheimer Dis 2009; 18: 713-725. – reference: White L, Petrovitch H, Ross GW, et al. Prevalence of dementia in older Japanese-American men living in Hawaii: the Honolulu-Asia Aging Study. JAMA 1996; 276: 955-960. – reference: Longstreth WT Jr, Sonnen JA, Koepsell TD, et al. Associations between microinfarcts and other macroscopic vascular findings on neuropathologic examination in 2 databases. Alzheimer Dis Assoc Disord 2009; 23: 291-294. – reference: Petrovitch H, Ross GW, Steinhorn SC, et al. AD lesions and infarcts in demented and non-demented Japanese-American men. Ann Neurol 2005; 57: 98-103. – reference: Fernando MS, Ince PC. MRC Cognitive Function and Ageing Neuropathology Study Group. Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 2004; 235 226: 13-17. – reference: Jack CR Jr, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010; 9: 119-128. – reference: Hoyer S. Is sporadic Alzheimer's disease the brain type of non- insulin dependent diabetes mellitus? A challenging hypothesis. J Neural Transm 1998; 105: 415-422. – reference: Schneider JA, Aggarwal NT, Barnes LL, et al. The neuropathology of older persons with and without dementia from community vs. clinic cohorts. J Alzheimer Dis 2009; 18: 691-701. – reference: SAS Institute Inc. SAS v 9.0. Cary, NC: SAS Institute Inc, 2004. – reference: American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed rev. Washington, DC: American Psychiatric Association, 1987. – reference: Teng EL, Hasegawa K, Homma A, et al. The Cognitive Abilities Screening Instrument (CASI): a practical test for cross-cultural epidemiological studies of dementia. Int Psychogeriatr 1994; 6: 45-58. – reference: Preacher KJ, Hayes AF. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods 2008; 40: 879-891. – reference: R Development Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, 2008. – reference: Hardy J. The amyloid hypothesis for Alzheimer's disease: a critical reappraisal. J Neurochem 2009; 110: 1129-1134. – reference: Hartley SW, Scher AI, Korf ES, et al. Analysis and validation of automated skull stripping tools: a validation study based on 296 MR images from the Honolulu Asia aging study. Neuroimage 2006; 30: 1179-1186. – reference: Martins IJ, Hone E, Foster JK, et al. Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease. Mol Psychiatry 2006; 11: 721-736. – volume: 24 start-page: 86 year: 2009 end-page: 94 article-title: Defining the neuropathological background of vascular and mixed dementia and comparison with magnetic resonance imaging findings publication-title: Front Neurol Neurosci – start-page: 13 year: 2004 end-page: 17 article-title: MRC Cognitive Function and Ageing Neuropathology Study Group. Vascular pathologies and cognition in a population‐based cohort of elderly people publication-title: J Neurol Sci – volume: 9 start-page: 119 year: 2010 end-page: 128 article-title: Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade publication-title: Lancet Neurol – volume: 105 start-page: 415 year: 1998 end-page: 422 article-title: Is sporadic Alzheimer's disease the brain type of non‐ insulin dependent diabetes mellitus? A challenging hypothesis publication-title: J Neural Transm – volume: 110 start-page: 1129 year: 2009 end-page: 1134 article-title: The amyloid hypothesis for Alzheimer's disease: a critical reappraisal publication-title: J Neurochem – volume: 276 start-page: 955 year: 1996 end-page: 960 article-title: Prevalence of dementia in older Japanese‐American men living in Hawaii: the Honolulu‐Asia Aging Study publication-title: JAMA – volume: 11 start-page: 721 year: 2006 end-page: 736 article-title: Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease publication-title: Mol Psychiatry – volume: 57 start-page: 98 year: 2005 end-page: 103 article-title: AD lesions and infarcts in demented and non‐demented Japanese‐American men publication-title: Ann Neurol – year: 1987 – year: 2008 – volume: 18 start-page: 713 year: 2009 end-page: 725 article-title: Brain lesions at autopsy in older Japanese‐American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu‐Asia Aging Study publication-title: J Alzheimer Dis – year: 2004 – volume: 30 start-page: 1179 year: 2006 end-page: 1186 article-title: Analysis and validation of automated skull stripping tools: a validation study based on 296 MR images from the Honolulu Asia aging study publication-title: Neuroimage – year: 2000 – volume: 23 start-page: 291 year: 2009 end-page: 294 article-title: Associations between microinfarcts and other macroscopic vascular findings on neuropathologic examination in 2 databases publication-title: Alzheimer Dis Assoc Disord – volume: 6 start-page: 45 year: 1994 end-page: 58 article-title: The Cognitive Abilities Screening Instrument (CASI): a practical test for cross‐cultural epidemiological studies of dementia publication-title: Int Psychogeriatr – volume: 18 start-page: 691 year: 2009 end-page: 701 article-title: The neuropathology of older persons with and without dementia from community vs. clinic cohorts publication-title: J Alzheimer Dis – volume: 82 start-page: 239 year: 1991 end-page: 259 article-title: Neuropathologic staging of Alzheimer‐related changes publication-title: Acta Neuropathol – start-page: 421 year: 1994 end-page: 431 – volume: 40 start-page: 879 year: 2008 end-page: 891 article-title: Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models publication-title: Behav Res Methods – volume-title: Diagnostic and statistical manual of mental disorders year: 1987 ident: e_1_2_8_11_2 – ident: e_1_2_8_18_2 doi: 10.1007/s007020050067 – ident: e_1_2_8_19_2 doi: 10.1007/978-1-4612-0303-2_33 – ident: e_1_2_8_10_2 doi: 10.1017/S1041610294001602 – ident: e_1_2_8_4_2 doi: 10.1016/j.jns.2004.09.004 – ident: e_1_2_8_7_2 doi: 10.3233/JAD-2009-1227 – ident: e_1_2_8_3_2 doi: 10.1159/000197887 – ident: e_1_2_8_14_2 – ident: e_1_2_8_6_2 doi: 10.1097/WAD.0b013e318199fc7a – ident: e_1_2_8_13_2 doi: 10.3758/BRM.40.3.879 – ident: e_1_2_8_5_2 doi: 10.3233/JAD-2009-1178 – ident: e_1_2_8_17_2 doi: 10.1016/S1474-4422(09)70299-6 – ident: e_1_2_8_12_2 doi: 10.1016/j.neuroimage.2005.10.043 – ident: e_1_2_8_21_2 doi: 10.1111/j.1471-4159.2009.06181.x – ident: e_1_2_8_2_2 doi: 10.1007/BF00308809 – ident: e_1_2_8_8_2 doi: 10.1002/ana.20318 – volume-title: R: a language and environment for statistical computing year: 2008 ident: e_1_2_8_16_2 – ident: e_1_2_8_20_2 doi: 10.1038/sj.mp.4001854 – volume: 276 start-page: 955 year: 1996 ident: e_1_2_8_9_2 article-title: Prevalence of dementia in older Japanese‐American men living in Hawaii: the Honolulu‐Asia Aging Study publication-title: JAMA doi: 10.1001/jama.1996.03540120033030 – volume-title: SAS v 9.0 year: 2004 ident: e_1_2_8_15_2 |
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| SubjectTerms | Aged Aged, 80 and over Aging - ethnology Aging - pathology Aging - psychology Alzheimer's disease Asian Atrophy Autopsy Biological and medical sciences Brain Brain - pathology Brain Infarction - ethnology Brain Infarction - pathology Brain Infarction - psychology Cognition Cognitive ability Cohort Studies Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Hawaii Humans Male Medical sciences Neurofibrillary Tangles - pathology Neurology Organ Size Plaque, Amyloid - ethnology Plaque, Amyloid - pathology |
| Title | Microinfarcts, brain atrophy, and cognitive function: The Honolulu Asia Aging Study Autopsy Study |
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