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Association cortex hypoperfusion in mild dementia with Lewy bodies: a potential indicator of cholinergic dysfunction?

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Abstract

Dementia with Lewy bodies (DLB) is often associated with occipital hypometabolism or hypoperfusion, as well as deficits in cholinergic neurotransmission. In this study, 11 mild DLB, 16 mild AD and 16 age-matched controls underwent arterial spin-labeled perfusion MRI (ASL-pMRI) and neuropsychological testing. Patterns of cerebral blood flow (CBF) and cognitive performance were compared. In addition, combined ASL-pMRI and ChEI drug challenge (pharmacologic MRI) was tested as a probe of cholinergic function in 4 of the DLB participants. Frontal and parieto-occipital hypoperfusion was observed in both DLB and AD but was more pronounced in DLB. Following ChEI treatment, perfusion increased in temporal and parieto-occipital cortex, and cognitive performance improved on a verbal fluency task. If confirmed in a larger study, these results provide further evidence for brain cholinergic dysfunction in DLB pathophysiology, and use of pharmacologic MRI as an in vivo measure of cholinergic function.

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The authors report no conflicts of interest.

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Authors and Affiliations

  1. Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA, 02131, USA

    Tamara G. Fong & Sharon K. Inouye

  2. Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Tamara G. Fong & Daniel Z. Press

  3. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Sharon K. Inouye

  4. Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Weiying Dai & David C. Alsop

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  1. Tamara G. Fong
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  2. Sharon K. Inouye
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  3. Weiying Dai
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  4. Daniel Z. Press
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  5. David C. Alsop
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Correspondence to Tamara G. Fong.

Additional information

Supported in part by F32NS047431(Fong) from the National Institute of Neurological Disorders and Stroke, K23AG031320 (Fong), K24AG000949 (Inouye) and RO1AG19599 (Alsop) from the National Institute on Aging, IIRG-08-88737 (Inouye) from the Alzheimer’s Association, and the Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife. Support provided to Dr. Fong, Department of Neurology, Beth Israel Deaconess Medical Center and the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center - Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Co., and in part by the John A. Hartford Harvard Center of Excellence. Dr. Inouye holds the Milton and Shirley F. Levy Family Chair. Study medications (donepezil and placebo) were provided by a grant from Pfizer/Eisai, Inc.

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Fong, T.G., Inouye, S.K., Dai, W. et al. Association cortex hypoperfusion in mild dementia with Lewy bodies: a potential indicator of cholinergic dysfunction?. Brain Imaging and Behavior 5, 25–35 (2011). https://doi.org/10.1007/s11682-010-9108-x

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