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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.

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  • Authors+Show Affiliations

    ,

    The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, AZ, USA. alex.roher@bannerhealth.com

    , , , , , , , , ,

    Source

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Apolipoprotein E4
    Circle of Willis
    Disease Progression
    Female
    Humans
    Intracranial Arteriosclerosis
    Male
    Neurofibrillary Tangles
    Plaque, Amyloid
    Postmortem Changes
    Psychiatric Status Rating Scales
    Risk Factors
    Vascular Diseases

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    21388893

    Citation

    Roher, Alex E., et al. "Intracranial Atherosclerosis as a Contributing Factor to Alzheimer's Disease Dementia." Alzheimer's & Dementia : the Journal of the Alzheimer's Association, vol. 7, no. 4, 2011, pp. 436-44.
    Roher AE, Tyas SL, Maarouf CL, et al. Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia. Alzheimers Dement. 2011;7(4):436-44.
    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 & Dementia : the Journal of the Alzheimer's Association, 7(4), pp. 436-44. doi:10.1016/j.jalz.2010.08.228.
    Roher AE, et al. Intracranial Atherosclerosis as a Contributing Factor to Alzheimer's Disease Dementia. Alzheimers Dement. 2011;7(4):436-44. PubMed PMID: 21388893.
    * Article titles in AMA citation format should be in sentence-case
    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, Y1 - 2011/03/09/ PY - 2010/01/22/received PY - 2010/06/30/revised PY - 2010/08/06/accepted PY - 2011/3/11/entrez PY - 2011/3/11/pubmed PY - 2011/12/13/medline SP - 436 EP - 44 JF - Alzheimer's & dementia : the journal of the Alzheimer's Association JO - Alzheimers Dement VL - 7 IS - 4 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. SN - 1552-5279 UR - https://www.unboundmedicine.com/medline/citation/21388893/Intracranial_atherosclerosis_as_a_contributing_factor_to_Alzheimer's_disease_dementia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1552-5260(10)02421-0 DB - PRIME DP - Unbound Medicine ER -