Elevated occipital β-amyloid deposition is associated with widespread cognitive impairment in logopenic progressive aphasia

Jennifer Lynn Whitwell, Val Lowe, Joseph R. Duffy, Edythe A. Strand, Mary Margaret Machulda, Kejal M Kantarci, Samantha M. Wille, Matthew L. Senjem, Matthew Murphy, Jeffrey L. Gunter, Clifford R Jr. Jack, Keith Anthony Josephs

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Abstract

Background: Most subjects with logopenic variant of primary progressive aphasia (lvPPA) have β-amyloid (Aβ) deposition on Pittsburgh Compound B positron emission tomography (PiB-PET), usually affecting prefrontal and temporoparietal cortices, with less occipital involvement. Objectives: To assess clinical and imaging features in lvPPA subjects with unusual topographic patterns of Aβ deposition with highest uptake in occipital lobe. Methods: Thirty-three lvPPA subjects with Aβ deposition on PiB-PET were included in this case-control study. Line plots of regional PiB uptake were created, including frontal, temporal, parietal and occipital regions, for each subject. Subjects in which the line sloped downwards in occipital lobe (lvPPA-low), representing low uptake, were separated from those where the line sloped upwards in occipital lobe (lvPPA-high), representing unusually high occipital uptake compared to other regions. Clinical variables, atrophy on MRI, hypometabolism on 18-Ffluorodeoxyglucose positron emission tomography (FDG-PET), and presence and distribution of microbleeds and white matter hyperintensities (WMHs) were assessed. Results: Seventeen subjects (52%) were classified as lvPPA-high. Mean occipital PiB uptake in lvPPA-high was higher than all other regions and higher than all regions in lvPPA-low. The lvPPA-high subjects performed more poorly on cognitive testing, including executive and visuospatial testing, but the two groups did not differ in aphasia severity. Proportion of microbleeds and WMH was higher in lvPPA-high than lvPPA-low. Parietal hypometabolism was greater in lvPPA-high than lvPPA-low. Conclusions: Unusually high occipital Aβ deposition is associated with widespread cognitive impairment and different imaging findings in lvPPA. These findings help explain clinical heterogeneity in lvPPA and suggest that Aβ influences severity of overall cognitive impairment but not aphasia.

Original languageEnglish (US)
Pages (from-to)1357-1364
Number of pages8
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume84
Issue number12
DOIs
StatePublished - Dec 2013

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Primary Progressive Aphasia
Aphasia
Amyloid
Occipital Lobe
Positron-Emission Tomography
Cognitive Dysfunction
Deposition
Cognitive Impairment
Progressive Aphasia
Parietal Lobe

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery
  • Arts and Humanities (miscellaneous)

Cite this

@article{747fa695d67746b28bf720497c15d1a3,
title = "Elevated occipital β-amyloid deposition is associated with widespread cognitive impairment in logopenic progressive aphasia",
abstract = "Background: Most subjects with logopenic variant of primary progressive aphasia (lvPPA) have β-amyloid (Aβ) deposition on Pittsburgh Compound B positron emission tomography (PiB-PET), usually affecting prefrontal and temporoparietal cortices, with less occipital involvement. Objectives: To assess clinical and imaging features in lvPPA subjects with unusual topographic patterns of Aβ deposition with highest uptake in occipital lobe. Methods: Thirty-three lvPPA subjects with Aβ deposition on PiB-PET were included in this case-control study. Line plots of regional PiB uptake were created, including frontal, temporal, parietal and occipital regions, for each subject. Subjects in which the line sloped downwards in occipital lobe (lvPPA-low), representing low uptake, were separated from those where the line sloped upwards in occipital lobe (lvPPA-high), representing unusually high occipital uptake compared to other regions. Clinical variables, atrophy on MRI, hypometabolism on 18-Ffluorodeoxyglucose positron emission tomography (FDG-PET), and presence and distribution of microbleeds and white matter hyperintensities (WMHs) were assessed. Results: Seventeen subjects (52{\%}) were classified as lvPPA-high. Mean occipital PiB uptake in lvPPA-high was higher than all other regions and higher than all regions in lvPPA-low. The lvPPA-high subjects performed more poorly on cognitive testing, including executive and visuospatial testing, but the two groups did not differ in aphasia severity. Proportion of microbleeds and WMH was higher in lvPPA-high than lvPPA-low. Parietal hypometabolism was greater in lvPPA-high than lvPPA-low. Conclusions: Unusually high occipital Aβ deposition is associated with widespread cognitive impairment and different imaging findings in lvPPA. These findings help explain clinical heterogeneity in lvPPA and suggest that Aβ influences severity of overall cognitive impairment but not aphasia.",
author = "Whitwell, {Jennifer Lynn} and Val Lowe and Duffy, {Joseph R.} and Strand, {Edythe A.} and Machulda, {Mary Margaret} and Kantarci, {Kejal M} and Wille, {Samantha M.} and Senjem, {Matthew L.} and Matthew Murphy and Gunter, {Jeffrey L.} and Jack, {Clifford R Jr.} and Josephs, {Keith Anthony}",
year = "2013",
month = "12",
doi = "10.1136/jnnp-2013-305628",
language = "English (US)",
volume = "84",
pages = "1357--1364",
journal = "Journal of Neurology, Neurosurgery and Psychiatry",
issn = "0022-3050",
publisher = "BMJ Publishing Group",
number = "12",

}

TY - JOUR

T1 - Elevated occipital β-amyloid deposition is associated with widespread cognitive impairment in logopenic progressive aphasia

AU - Whitwell, Jennifer Lynn

AU - Lowe, Val

AU - Duffy, Joseph R.

AU - Strand, Edythe A.

AU - Machulda, Mary Margaret

AU - Kantarci, Kejal M

AU - Wille, Samantha M.

AU - Senjem, Matthew L.

AU - Murphy, Matthew

AU - Gunter, Jeffrey L.

AU - Jack, Clifford R Jr.

AU - Josephs, Keith Anthony

PY - 2013/12

Y1 - 2013/12

N2 - Background: Most subjects with logopenic variant of primary progressive aphasia (lvPPA) have β-amyloid (Aβ) deposition on Pittsburgh Compound B positron emission tomography (PiB-PET), usually affecting prefrontal and temporoparietal cortices, with less occipital involvement. Objectives: To assess clinical and imaging features in lvPPA subjects with unusual topographic patterns of Aβ deposition with highest uptake in occipital lobe. Methods: Thirty-three lvPPA subjects with Aβ deposition on PiB-PET were included in this case-control study. Line plots of regional PiB uptake were created, including frontal, temporal, parietal and occipital regions, for each subject. Subjects in which the line sloped downwards in occipital lobe (lvPPA-low), representing low uptake, were separated from those where the line sloped upwards in occipital lobe (lvPPA-high), representing unusually high occipital uptake compared to other regions. Clinical variables, atrophy on MRI, hypometabolism on 18-Ffluorodeoxyglucose positron emission tomography (FDG-PET), and presence and distribution of microbleeds and white matter hyperintensities (WMHs) were assessed. Results: Seventeen subjects (52%) were classified as lvPPA-high. Mean occipital PiB uptake in lvPPA-high was higher than all other regions and higher than all regions in lvPPA-low. The lvPPA-high subjects performed more poorly on cognitive testing, including executive and visuospatial testing, but the two groups did not differ in aphasia severity. Proportion of microbleeds and WMH was higher in lvPPA-high than lvPPA-low. Parietal hypometabolism was greater in lvPPA-high than lvPPA-low. Conclusions: Unusually high occipital Aβ deposition is associated with widespread cognitive impairment and different imaging findings in lvPPA. These findings help explain clinical heterogeneity in lvPPA and suggest that Aβ influences severity of overall cognitive impairment but not aphasia.

AB - Background: Most subjects with logopenic variant of primary progressive aphasia (lvPPA) have β-amyloid (Aβ) deposition on Pittsburgh Compound B positron emission tomography (PiB-PET), usually affecting prefrontal and temporoparietal cortices, with less occipital involvement. Objectives: To assess clinical and imaging features in lvPPA subjects with unusual topographic patterns of Aβ deposition with highest uptake in occipital lobe. Methods: Thirty-three lvPPA subjects with Aβ deposition on PiB-PET were included in this case-control study. Line plots of regional PiB uptake were created, including frontal, temporal, parietal and occipital regions, for each subject. Subjects in which the line sloped downwards in occipital lobe (lvPPA-low), representing low uptake, were separated from those where the line sloped upwards in occipital lobe (lvPPA-high), representing unusually high occipital uptake compared to other regions. Clinical variables, atrophy on MRI, hypometabolism on 18-Ffluorodeoxyglucose positron emission tomography (FDG-PET), and presence and distribution of microbleeds and white matter hyperintensities (WMHs) were assessed. Results: Seventeen subjects (52%) were classified as lvPPA-high. Mean occipital PiB uptake in lvPPA-high was higher than all other regions and higher than all regions in lvPPA-low. The lvPPA-high subjects performed more poorly on cognitive testing, including executive and visuospatial testing, but the two groups did not differ in aphasia severity. Proportion of microbleeds and WMH was higher in lvPPA-high than lvPPA-low. Parietal hypometabolism was greater in lvPPA-high than lvPPA-low. Conclusions: Unusually high occipital Aβ deposition is associated with widespread cognitive impairment and different imaging findings in lvPPA. These findings help explain clinical heterogeneity in lvPPA and suggest that Aβ influences severity of overall cognitive impairment but not aphasia.

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U2 - 10.1136/jnnp-2013-305628

DO - 10.1136/jnnp-2013-305628

M3 - Article

C2 - 23946416

AN - SCOPUS:84888039861

VL - 84

SP - 1357

EP - 1364

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

IS - 12

ER -