Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia

Research output: Contribution to journalArticle

Alex E. Roher, Suzanne L. Tyas, Chera L. Maarouf, Ian D. Daugs, Tyler A. Kokjohn, Mark R. Emmerling, Zsolt Garami, Marek Belohlavek, Marwan N. Sabbagh, Lucia I. Sue, Thomas G. Beach

Background: A substantial body of evidence collected from epidemiologic, correlative, and experimental studies strongly associates atherosclerotic vascular disease (AVD) with Alzheimer's disease (AD). Depending on the precise interrelationship between AVD and AD, systematic application of interventions used to maintain vascular health and function as a component of standard AD therapy offers the prospect of mitigating the presently inexorable course of dementia. To assess this hypothesis, it is vital to rigorously establish the measures of AVD that are most strongly associated with an AD diagnosis. Methods: A precise neuropathological diagnosis was established for all subjects, using a battery of genetic, clinical, and histological methods. The severity of atherosclerosis in the circle of Willis was quantified by direct digitized measurement of arterial occlusion in postmortem specimens and was compared between AD and nondemented control groups by calculating a corresponding index of occlusion. Results: Atherosclerotic occlusion of the circle of Willis arteries was more extensive in the AD group than in the nondemented control group. Statistically significant differences were also observed between control and AD groups with regard to Braak stage, total plaque score, total neurofibrillary tangle score, total white matter rarefaction score, brain weight, Mini-Mental State Examination scores, and apolipoprotein E allelic frequencies. Conclusions: Our results, combined with a consideration of the multifaceted effects of impaired cerebral circulation, suggest an immediate need for prospective clinical trials to assess the efficacy of AD prevention using antiatherosclerotic agents.

Original languageEnglish
Pages (from-to)436-444
Number of pages9
JournalAlzheimer's and Dementia
Volume7
Issue number4
DOIs
StatePublished - Jul 1 2011

PMID: 21388893

PMCID: PMC3117084

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Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia. / Roher, Alex E.; Tyas, Suzanne L.; Maarouf, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Emmerling, Mark R.; Garami, Zsolt; Belohlavek, Marek; Sabbagh, Marwan N.; Sue, Lucia I.; Beach, Thomas G.

In: Alzheimer's and Dementia, Vol. 7, No. 4, 01.07.2011, p. 436-444.

Research output: Contribution to journalArticle

Harvard

Roher, AE, Tyas, SL, Maarouf, CL, Daugs, ID, Kokjohn, TA, Emmerling, MR, Garami, Z, Belohlavek, M, Sabbagh, MN, Sue, LI & Beach, TG 2011, 'Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia' Alzheimer's and Dementia, vol. 7, no. 4, pp. 436-444. https://doi.org/10.1016/j.jalz.2010.08.228

APA

Roher, A. E., Tyas, S. L., Maarouf, C. L., Daugs, I. D., Kokjohn, T. A., Emmerling, M. R., ... Beach, T. G. (2011). Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia. Alzheimer's and Dementia, 7(4), 436-444. https://doi.org/10.1016/j.jalz.2010.08.228

Vancouver

Roher AE, Tyas SL, Maarouf CL, Daugs ID, Kokjohn TA, Emmerling MR et al. Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia. Alzheimer's and Dementia. 2011 Jul 1;7(4):436-444. https://doi.org/10.1016/j.jalz.2010.08.228

Author

Roher, Alex E. ; Tyas, Suzanne L. ; Maarouf, Chera L. ; Daugs, Ian D. ; Kokjohn, Tyler A. ; Emmerling, Mark R. ; Garami, Zsolt ; Belohlavek, Marek ; Sabbagh, Marwan N. ; Sue, Lucia I. ; Beach, Thomas G. / Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia. In: Alzheimer's and Dementia. 2011 ; Vol. 7, No. 4. pp. 436-444.

BibTeX

@article{09d3762d7df144df816e8b5e8368e49a,
title = "Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia",
abstract = "Background: A substantial body of evidence collected from epidemiologic, correlative, and experimental studies strongly associates atherosclerotic vascular disease (AVD) with Alzheimer's disease (AD). Depending on the precise interrelationship between AVD and AD, systematic application of interventions used to maintain vascular health and function as a component of standard AD therapy offers the prospect of mitigating the presently inexorable course of dementia. To assess this hypothesis, it is vital to rigorously establish the measures of AVD that are most strongly associated with an AD diagnosis. Methods: A precise neuropathological diagnosis was established for all subjects, using a battery of genetic, clinical, and histological methods. The severity of atherosclerosis in the circle of Willis was quantified by direct digitized measurement of arterial occlusion in postmortem specimens and was compared between AD and nondemented control groups by calculating a corresponding index of occlusion. Results: Atherosclerotic occlusion of the circle of Willis arteries was more extensive in the AD group than in the nondemented control group. Statistically significant differences were also observed between control and AD groups with regard to Braak stage, total plaque score, total neurofibrillary tangle score, total white matter rarefaction score, brain weight, Mini-Mental State Examination scores, and apolipoprotein E allelic frequencies. Conclusions: Our results, combined with a consideration of the multifaceted effects of impaired cerebral circulation, suggest an immediate need for prospective clinical trials to assess the efficacy of AD prevention using antiatherosclerotic agents.",
keywords = "Alzheimer's disease, Brain hypoperfusion, Circle of Willis, Intracranial atherosclerosis, Vascular dementia",
author = "Roher, {Alex E.} and Tyas, {Suzanne L.} and Maarouf, {Chera L.} and Daugs, {Ian D.} and Kokjohn, {Tyler A.} and Emmerling, {Mark R.} and Zsolt Garami and Marek Belohlavek and Sabbagh, {Marwan N.} and Sue, {Lucia I.} and Beach, {Thomas G.}",
year = "2011",
month = "7",
day = "1",
doi = "10.1016/j.jalz.2010.08.228",
language = "English",
volume = "7",
pages = "436--444",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia

AU - Roher, Alex E.

AU - Tyas, Suzanne L.

AU - Maarouf, Chera L.

AU - Daugs, Ian D.

AU - Kokjohn, Tyler A.

AU - Emmerling, Mark R.

AU - Garami, Zsolt

AU - Belohlavek, Marek

AU - Sabbagh, Marwan N.

AU - Sue, Lucia I.

AU - Beach, Thomas G.

PY - 2011/7/1

Y1 - 2011/7/1

N2 - Background: A substantial body of evidence collected from epidemiologic, correlative, and experimental studies strongly associates atherosclerotic vascular disease (AVD) with Alzheimer's disease (AD). Depending on the precise interrelationship between AVD and AD, systematic application of interventions used to maintain vascular health and function as a component of standard AD therapy offers the prospect of mitigating the presently inexorable course of dementia. To assess this hypothesis, it is vital to rigorously establish the measures of AVD that are most strongly associated with an AD diagnosis. Methods: A precise neuropathological diagnosis was established for all subjects, using a battery of genetic, clinical, and histological methods. The severity of atherosclerosis in the circle of Willis was quantified by direct digitized measurement of arterial occlusion in postmortem specimens and was compared between AD and nondemented control groups by calculating a corresponding index of occlusion. Results: Atherosclerotic occlusion of the circle of Willis arteries was more extensive in the AD group than in the nondemented control group. Statistically significant differences were also observed between control and AD groups with regard to Braak stage, total plaque score, total neurofibrillary tangle score, total white matter rarefaction score, brain weight, Mini-Mental State Examination scores, and apolipoprotein E allelic frequencies. Conclusions: Our results, combined with a consideration of the multifaceted effects of impaired cerebral circulation, suggest an immediate need for prospective clinical trials to assess the efficacy of AD prevention using antiatherosclerotic agents.

AB - Background: A substantial body of evidence collected from epidemiologic, correlative, and experimental studies strongly associates atherosclerotic vascular disease (AVD) with Alzheimer's disease (AD). Depending on the precise interrelationship between AVD and AD, systematic application of interventions used to maintain vascular health and function as a component of standard AD therapy offers the prospect of mitigating the presently inexorable course of dementia. To assess this hypothesis, it is vital to rigorously establish the measures of AVD that are most strongly associated with an AD diagnosis. Methods: A precise neuropathological diagnosis was established for all subjects, using a battery of genetic, clinical, and histological methods. The severity of atherosclerosis in the circle of Willis was quantified by direct digitized measurement of arterial occlusion in postmortem specimens and was compared between AD and nondemented control groups by calculating a corresponding index of occlusion. Results: Atherosclerotic occlusion of the circle of Willis arteries was more extensive in the AD group than in the nondemented control group. Statistically significant differences were also observed between control and AD groups with regard to Braak stage, total plaque score, total neurofibrillary tangle score, total white matter rarefaction score, brain weight, Mini-Mental State Examination scores, and apolipoprotein E allelic frequencies. Conclusions: Our results, combined with a consideration of the multifaceted effects of impaired cerebral circulation, suggest an immediate need for prospective clinical trials to assess the efficacy of AD prevention using antiatherosclerotic agents.

KW - Alzheimer's disease

KW - Brain hypoperfusion

KW - Circle of Willis

KW - Intracranial atherosclerosis

KW - Vascular dementia

UR - http://www.scopus.com/inward/record.url?scp=79960838099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960838099&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2010.08.228

DO - 10.1016/j.jalz.2010.08.228

M3 - Article

VL - 7

SP - 436

EP - 444

JO - Alzheimer's and Dementia

T2 - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

IS - 4

ER -

ID: 2790439