Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow CME: Take the course for this article:
 Volume 72, Number 16, April 21, 2009
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bohnen, N. I.
Right arrow Articles by Studenski, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bohnen, N. I.
Right arrow Articles by Studenski, S. A.
Related Collections
Right arrow MRI
Right arrow PET
Right arrow Other cerebrovascular disease/ Stroke
Right arrow Cognitive aging
NEUROLOGY 2009;72:1411-1416
© 2009 American Academy of Neurology

Age-associated leukoaraiosis and cortical cholinergic deafferentation

N. I. Bohnen, MD, PhD, M. L.T.M. Müller, PhD, H. Kuwabara, MD, PhD, G. M. Constantine, PhD and S. A. Studenski, MD, MPH

From VA Ann Arbor Healthcare System (N.I.B.), GRECC, MI; Functional Neuroimaging, Cognitive and Mobility Laboratory (N.I.B., M.L.T.M.M.), Departments of Radiology and Neurology, University of Michigan, Ann Arbor, MI; Department of Radiology (H.K.), Johns Hopkins University; Baltimore, MD; Department of Mathematics and Statistics (G.M.C.), University of Pittsburgh, PA; VA Pittsburgh Healthcare System (S.A.S.), GRECC, PA; and Department of Medicine (S.A.S.), Division of Geriatric Medicine, University of Pittsburgh Medical School, PA.

Address correspondence and reprint requests to Dr. Nicolaas I. Bohnen, Functional Neuroimaging, Cognitive and Mobility Laboratory, Departments of Radiology and Neurology, The University of Michigan, 24 Frank Lloyd Wright Dr., Box 362, Ann Arbor, MI 48105-9755 nbohnen{at}umich.edu

Objective: To investigate the relationship between age-associated MRI leukoaraiosis or white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity.

Background: One possible mechanism of cognitive decline in elderly individuals with leukoaraiosis is disruption of cholinergic fibers by strategically located white matter lesions. Periventricular lesions may have a higher chance of disrupting cholinergic projections compared with more superficial nonperiventricular white matter lesions because of anatomic proximity to the major cholinergic axonal projection bundles that originate from the basal forebrain.

Methods: Community-dwelling, middle-aged and elderly subjects without dementia (mean age 71.0 ± 9.2 years; 55–84 years; n = 18) underwent brain MRI and AChE PET imaging. The severity of periventricular and nonperiventricular WMH on fluid-attenuated inversion recovery MRI images was scored using the semiquantitative rating scale of Scheltens et al. [11C]methyl-4-piperidinyl propionate AChE PET imaging was used to assess cortical AChE activity. Age-corrected Spearman partial rank correlation coefficients were calculated.

Results: The severity of periventricular (R = –0.52, p = 0.04) but not nonperiventricular (R = –0.20, not significant) WMH was inversely related to global cortical AChE activity. Regional cortical cholinergic effects of periventricular WMH were most significant for the occipital lobe (R = –0.58, p = 0.02).

Conclusions: The presence of periventricular but not nonperiventricular white matter hyperintensities (WMH) is significantly associated with lower cortical cholinergic activity. These findings support a regionally specific disruption of cholinergic projection fibers by WMH.

Abbreviations: AChE = acetylcholinesterase; AD = Alzheimer disease; CADASIL = cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CPT-RT = Conners continuous performance test reaction time; CPT-SE = Conners continuous performance test standard error; FLAIR = fluid-attenuated inversion recovery; FWHM = full-width at half-maximum; MMSE = Mini-Mental State Examination; nbM = nucleus basalis of Meynert; NEX = number of excitations; NS = not significant; [11C]PMP = [11C]methyl-4-piperidinyl propionate; SPGR = spoiled gradient recall; TAC = time–radioactivity curve; TE = echo time; TMT-BA = Trail Making Test B minus A; TR = repetition time; VOI = volume of interest; WMH = white matter hyperintensities.

Supported by the Department of Veterans Affairs and National Institute on Aging grants AG023641 and AG024827.

Disclosure: The authors report no disclosures.

Received September 16, 2008. Accepted in final form January 5, 2009.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by AAN Enterprises, Inc.