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Neurology. 2012 Sep 25;79(13):1349-55. Epub 2012 Sep 12.

Vascular burden and Alzheimer disease pathologic progression.

Collaborators (225)

Weiner M, Aisen P, Petersen R, Jack CR Jr, Jagust W, Trojanowki JQ, Toga A, Beckett L, Green RC, Saykin AJ, Morris J, Liu E, Green RC, Montine T, Petersen R, Aisen P, Gamst A, Thomas RG, Donohue M, Walter S, Gessert D, Sather T, Beckett L, Harvey D, Gamst A, Donohue M, Kornak J, Jack CR Jr, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Jagust W, Bandy D, Koeppe RA, Foster N, Reiman EM, Chen K, Mathis C, Morris J, Cairns NJ, Taylor-Reinwald L, Trojanowki JQ, Shaw L, Lee VM, Korecka M, Toga AW, Crawford K, Neu S, Saykin AJ, Foroud TM, Potkin S, Shen L, Kachaturian Z, Frank R, Snyder PJ, Molchan S, Kaye J, Quinn J, Lind B, Schneider LS, Pawluczyk S, Spann BM, Brewer J, Vanderswag H, Heidebrink JL, Lord JL, Petersen R, Johnson K, Doody RS, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig LS, Bell KL, Morris JC, Ances B, Carroll M, Leon S, Marson D, Griffith R, Clark D, Grossman H, Mitsis E, Romirowsky A, deToledo-Morrell L, Shah RC, Duara R, Varon D, Roberts P, Albert M, Onyike C, Kielb S, Rusinek H, de Leon MJ, Glodzik L, Doraiswamy PM, Petrella JR, Coleman RE, Arnold SE, Karlawish JH, Wolk D, Smith CD, Jicha G, Hardy P, Lopez OL, Oakley M, Simpson DM, Porsteinsson AP, Goldstein BS, Martin K, Mulnard RA, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Swerdlow RH, Apostolova L, Lu PH, Graff-Radford N, Parfitt F, Johnson H, Farlow MR, Hake AM, Matthews BR, van Dyck CH, Carson RE, MacAvoy MG, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung GY, Feldman H, Mudge B, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Kerwin D, Mesulam MM, Lipowski K, Sadowsky C, Martinez W, Villena T, Turner RS, Johnson K, Reynolds B, Sperling RA, Johnson KA, Marshall G, Yesavage J, Taylor JL, Lane B, Sabbagh M, Belden C, Jacobson S, Kowall N, Killiany R, Budson AE, Obisesan TO, Wolday S, Lerner A, Hudson L, Ogrocki P, Fletcher E, Carmichael O, Olichney J, Kittur S, Borrie M, Lee TY, Bartha R, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre DW, Kataki M, Zimmerman EA, Celmins D, Pearlson GD, Blank K, Anderson K, Saykin AJ, Santulli RB, Schwartz ES, Sink KM, Williamson JD, Garg P, Ott BR, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Mintzer J, Longmire CF, Spicer K, Finger E, Rachinsky I, Rogers J, Drost D.

Author information

1
Division of Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. rayyenyu@hotmail.com

Abstract

OBJECTIVE:

To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers.

METHODS:

The Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden.

RESULTS:

Cardiovascular risk profiles were not predictive of progression in CSF β₄₂-amyloid, [¹⁸F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4.

CONCLUSION:

Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway.

PMID:
22972646
PMCID:
PMC3448744
DOI:
10.1212/WNL.0b013e31826c1b9d
[Indexed for MEDLINE]
Free PMC Article
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