Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies

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Abstract

Acetylcholinesterase inhibitors are commonly used to treat patients with dementia with Lewy bodies. Hippocampal atrophy on magnetic resonance imaging and amyloid-β load on positron emission tomography are associated with the Alzheimer's disease-related pathology in patients with dementia with Lewy bodies. To date, few studies have investigated imaging markers that predict treatment response in patients with dementia with Lewy bodies. Our objective was to determine whether imaging markers of Alzheimer's disease-related pathology such as hippocampal volume, brain amyloid-β load on 11C Pittsburgh compound B positron emission tomography predict treatment response to acetylcholinesterase inhibitors in patients with dementia with Lewy bodies. We performed a retrospective analysis on consecutive treatment-naive patients with dementia with Lewy bodies (n=54) from the Mayo Clinic Alzheimer's Disease Research Centre who subsequently received acetylcholinesterase inhibitors and underwent magnetic resonance imaging with hippocampal volumetry. Baseline and follow-up assessments were obtained with the Mattis Dementia Rating Scale. Subjects were divided into three groups (reliable improvement, stable or reliable decline) using Dementia Rating Scale reliable change indices determined previously. Associations between hippocampal volumes and treatment response were tested with analysis of covariance adjusting for baseline Dementia Rating Scale, age, gender, magnetic resonance field strength and Dementia Rating Scale interval. Seven subjects underwent 11C Pittsburgh compound B imaging within 12 weeks of magnetic resonance imaging. Global cortical 11C Pittsburgh compound B retention (scaled to cerebellar retention) was calculated in these patients. Using a conservative psychometric method of assessing treatment response, there were 12 patients with reliable decline, 29 stable cases and 13 patients with reliable improvement. The improvers had significantly larger hippocampi than those that declined (P=0.02) and the stable (P=0.04) group. An exploratory analysis demonstrated larger grey matter volumes in the temporal and parietal lobes in improvers compared with those who declined (P<0.05). The two patients who had a positive 11C Pittsburgh compound B positron emission tomography scan declined and those who had a negative 11C Pittsburgh compound B positron emission tomography scan improved or were stable after treatment. Patients with dementia with Lewy bodies who do not have the imaging features of coexistent Alzheimer's disease-related pathology are more likely to cognitively improve with acetylcholinesterase inhibitor treatment.

Original languageEnglish (US)
Pages (from-to)2470-2477
Number of pages8
JournalBrain
Volume135
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Lewy Body Disease
Cholinesterase Inhibitors
Positron-Emission Tomography
Dementia
Alzheimer Disease
Magnetic Resonance Imaging
Pathology
Amyloid
Therapeutics
Imaging
Parietal Lobe
Temporal Lobe
Magnetic Fields
Psychometrics
Atrophy
Hippocampus
Magnetic Resonance Spectroscopy
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Pittsburgh

Keywords

  • acetylcholinesterase inhibitors
  • amyloid
  • dementia with Lewy bodies
  • MRI
  • PET
  • PiB

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

@article{f5a070f6005f47fb83a4106a3d5437ac,
title = "Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies",
abstract = "Acetylcholinesterase inhibitors are commonly used to treat patients with dementia with Lewy bodies. Hippocampal atrophy on magnetic resonance imaging and amyloid-β load on positron emission tomography are associated with the Alzheimer's disease-related pathology in patients with dementia with Lewy bodies. To date, few studies have investigated imaging markers that predict treatment response in patients with dementia with Lewy bodies. Our objective was to determine whether imaging markers of Alzheimer's disease-related pathology such as hippocampal volume, brain amyloid-β load on 11C Pittsburgh compound B positron emission tomography predict treatment response to acetylcholinesterase inhibitors in patients with dementia with Lewy bodies. We performed a retrospective analysis on consecutive treatment-naive patients with dementia with Lewy bodies (n=54) from the Mayo Clinic Alzheimer's Disease Research Centre who subsequently received acetylcholinesterase inhibitors and underwent magnetic resonance imaging with hippocampal volumetry. Baseline and follow-up assessments were obtained with the Mattis Dementia Rating Scale. Subjects were divided into three groups (reliable improvement, stable or reliable decline) using Dementia Rating Scale reliable change indices determined previously. Associations between hippocampal volumes and treatment response were tested with analysis of covariance adjusting for baseline Dementia Rating Scale, age, gender, magnetic resonance field strength and Dementia Rating Scale interval. Seven subjects underwent 11C Pittsburgh compound B imaging within 12 weeks of magnetic resonance imaging. Global cortical 11C Pittsburgh compound B retention (scaled to cerebellar retention) was calculated in these patients. Using a conservative psychometric method of assessing treatment response, there were 12 patients with reliable decline, 29 stable cases and 13 patients with reliable improvement. The improvers had significantly larger hippocampi than those that declined (P=0.02) and the stable (P=0.04) group. An exploratory analysis demonstrated larger grey matter volumes in the temporal and parietal lobes in improvers compared with those who declined (P<0.05). The two patients who had a positive 11C Pittsburgh compound B positron emission tomography scan declined and those who had a negative 11C Pittsburgh compound B positron emission tomography scan improved or were stable after treatment. Patients with dementia with Lewy bodies who do not have the imaging features of coexistent Alzheimer's disease-related pathology are more likely to cognitively improve with acetylcholinesterase inhibitor treatment.",
keywords = "acetylcholinesterase inhibitors, amyloid, dementia with Lewy bodies, MRI, PET, PiB",
author = "Jonathan Graff-Radford and Boeve, {Bradley F} and Pedraza, {Otto D} and Ferman, {Tanis Jill} and Scott Przybelski and Lesnick, {Timothy G.} and Vemuri, {Prashanthi D} and Senjem, {Matthew L.} and Smith, {Glenn E.} and Knopman, {David S} and Val Lowe and Jack, {Clifford R Jr.} and Petersen, {Ronald Carl} and Kantarci, {Kejal M}",
year = "2012",
month = "8",
doi = "10.1093/brain/aws173",
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T1 - Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies

AU - Graff-Radford, Jonathan

AU - Boeve, Bradley F

AU - Pedraza, Otto D

AU - Ferman, Tanis Jill

AU - Przybelski, Scott

AU - Lesnick, Timothy G.

AU - Vemuri, Prashanthi D

AU - Senjem, Matthew L.

AU - Smith, Glenn E.

AU - Knopman, David S

AU - Lowe, Val

AU - Jack, Clifford R Jr.

AU - Petersen, Ronald Carl

AU - Kantarci, Kejal M

PY - 2012/8

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N2 - Acetylcholinesterase inhibitors are commonly used to treat patients with dementia with Lewy bodies. Hippocampal atrophy on magnetic resonance imaging and amyloid-β load on positron emission tomography are associated with the Alzheimer's disease-related pathology in patients with dementia with Lewy bodies. To date, few studies have investigated imaging markers that predict treatment response in patients with dementia with Lewy bodies. Our objective was to determine whether imaging markers of Alzheimer's disease-related pathology such as hippocampal volume, brain amyloid-β load on 11C Pittsburgh compound B positron emission tomography predict treatment response to acetylcholinesterase inhibitors in patients with dementia with Lewy bodies. We performed a retrospective analysis on consecutive treatment-naive patients with dementia with Lewy bodies (n=54) from the Mayo Clinic Alzheimer's Disease Research Centre who subsequently received acetylcholinesterase inhibitors and underwent magnetic resonance imaging with hippocampal volumetry. Baseline and follow-up assessments were obtained with the Mattis Dementia Rating Scale. Subjects were divided into three groups (reliable improvement, stable or reliable decline) using Dementia Rating Scale reliable change indices determined previously. Associations between hippocampal volumes and treatment response were tested with analysis of covariance adjusting for baseline Dementia Rating Scale, age, gender, magnetic resonance field strength and Dementia Rating Scale interval. Seven subjects underwent 11C Pittsburgh compound B imaging within 12 weeks of magnetic resonance imaging. Global cortical 11C Pittsburgh compound B retention (scaled to cerebellar retention) was calculated in these patients. Using a conservative psychometric method of assessing treatment response, there were 12 patients with reliable decline, 29 stable cases and 13 patients with reliable improvement. The improvers had significantly larger hippocampi than those that declined (P=0.02) and the stable (P=0.04) group. An exploratory analysis demonstrated larger grey matter volumes in the temporal and parietal lobes in improvers compared with those who declined (P<0.05). The two patients who had a positive 11C Pittsburgh compound B positron emission tomography scan declined and those who had a negative 11C Pittsburgh compound B positron emission tomography scan improved or were stable after treatment. Patients with dementia with Lewy bodies who do not have the imaging features of coexistent Alzheimer's disease-related pathology are more likely to cognitively improve with acetylcholinesterase inhibitor treatment.

AB - Acetylcholinesterase inhibitors are commonly used to treat patients with dementia with Lewy bodies. Hippocampal atrophy on magnetic resonance imaging and amyloid-β load on positron emission tomography are associated with the Alzheimer's disease-related pathology in patients with dementia with Lewy bodies. To date, few studies have investigated imaging markers that predict treatment response in patients with dementia with Lewy bodies. Our objective was to determine whether imaging markers of Alzheimer's disease-related pathology such as hippocampal volume, brain amyloid-β load on 11C Pittsburgh compound B positron emission tomography predict treatment response to acetylcholinesterase inhibitors in patients with dementia with Lewy bodies. We performed a retrospective analysis on consecutive treatment-naive patients with dementia with Lewy bodies (n=54) from the Mayo Clinic Alzheimer's Disease Research Centre who subsequently received acetylcholinesterase inhibitors and underwent magnetic resonance imaging with hippocampal volumetry. Baseline and follow-up assessments were obtained with the Mattis Dementia Rating Scale. Subjects were divided into three groups (reliable improvement, stable or reliable decline) using Dementia Rating Scale reliable change indices determined previously. Associations between hippocampal volumes and treatment response were tested with analysis of covariance adjusting for baseline Dementia Rating Scale, age, gender, magnetic resonance field strength and Dementia Rating Scale interval. Seven subjects underwent 11C Pittsburgh compound B imaging within 12 weeks of magnetic resonance imaging. Global cortical 11C Pittsburgh compound B retention (scaled to cerebellar retention) was calculated in these patients. Using a conservative psychometric method of assessing treatment response, there were 12 patients with reliable decline, 29 stable cases and 13 patients with reliable improvement. The improvers had significantly larger hippocampi than those that declined (P=0.02) and the stable (P=0.04) group. An exploratory analysis demonstrated larger grey matter volumes in the temporal and parietal lobes in improvers compared with those who declined (P<0.05). The two patients who had a positive 11C Pittsburgh compound B positron emission tomography scan declined and those who had a negative 11C Pittsburgh compound B positron emission tomography scan improved or were stable after treatment. Patients with dementia with Lewy bodies who do not have the imaging features of coexistent Alzheimer's disease-related pathology are more likely to cognitively improve with acetylcholinesterase inhibitor treatment.

KW - acetylcholinesterase inhibitors

KW - amyloid

KW - dementia with Lewy bodies

KW - MRI

KW - PET

KW - PiB

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