MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies

Melissa E Murray, Tanis Jill Ferman, Bradley F Boeve, Scott A. Przybelski, Timothy G. Lesnick, Amanda M. Liesinger, Matthew L. Senjem, Jeffrey L. Gunter, Gregory M. Preboske, Val Lowe, Prashanthi D Vemuri, Brittany N. Dugger, David S Knopman, Glenn E. Smith, Joseph E Parisi, Michael H. Silber, Neill R Graff Radford, Ronald Carl Petersen, Clifford R Jr. Jack, Dennis W DicksonKejal M Kantarci

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Abstract

Objective: To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy. Methods: Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, b-amyloid, and a-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala. Results: pRBD was present in 21 patients (60%) with high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and b-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions. Conclusion: Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.

Original languageEnglish (US)
Pages (from-to)1681-1689
Number of pages9
JournalNeurology
Volume81
Issue number19
DOIs
StatePublished - Nov 5 2013

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REM Sleep Behavior Disorder
Lewy Body Disease
Pathology
Amygdala
Hippocampus
Synucleins
Atrophy
Amyloid
Autopsy
Sleep
Dementia
Temporal Lobe

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies. / Murray, Melissa E; Ferman, Tanis Jill; Boeve, Bradley F; Przybelski, Scott A.; Lesnick, Timothy G.; Liesinger, Amanda M.; Senjem, Matthew L.; Gunter, Jeffrey L.; Preboske, Gregory M.; Lowe, Val; Vemuri, Prashanthi D; Dugger, Brittany N.; Knopman, David S; Smith, Glenn E.; Parisi, Joseph E; Silber, Michael H.; Graff Radford, Neill R; Petersen, Ronald Carl; Jack, Clifford R Jr.; Dickson, Dennis W; Kantarci, Kejal M.

In: Neurology, Vol. 81, No. 19, 05.11.2013, p. 1681-1689.

Research output: Contribution to journalArticle

Murray, Melissa E ; Ferman, Tanis Jill ; Boeve, Bradley F ; Przybelski, Scott A. ; Lesnick, Timothy G. ; Liesinger, Amanda M. ; Senjem, Matthew L. ; Gunter, Jeffrey L. ; Preboske, Gregory M. ; Lowe, Val ; Vemuri, Prashanthi D ; Dugger, Brittany N. ; Knopman, David S ; Smith, Glenn E. ; Parisi, Joseph E ; Silber, Michael H. ; Graff Radford, Neill R ; Petersen, Ronald Carl ; Jack, Clifford R Jr. ; Dickson, Dennis W ; Kantarci, Kejal M. / MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies. In: Neurology. 2013 ; Vol. 81, No. 19. pp. 1681-1689.
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abstract = "Objective: To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy. Methods: Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, b-amyloid, and a-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala. Results: pRBD was present in 21 patients (60{\%}) with high-likelihood, 12 patients (34{\%}) with intermediate-likelihood, and 2 patients (6{\%}) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and b-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions. Conclusion: Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.",
author = "Murray, {Melissa E} and Ferman, {Tanis Jill} and Boeve, {Bradley F} and Przybelski, {Scott A.} and Lesnick, {Timothy G.} and Liesinger, {Amanda M.} and Senjem, {Matthew L.} and Gunter, {Jeffrey L.} and Preboske, {Gregory M.} and Val Lowe and Vemuri, {Prashanthi D} and Dugger, {Brittany N.} and Knopman, {David S} and Smith, {Glenn E.} and Parisi, {Joseph E} and Silber, {Michael H.} and {Graff Radford}, {Neill R} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.} and Dickson, {Dennis W} and Kantarci, {Kejal M}",
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T1 - MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies

AU - Murray, Melissa E

AU - Ferman, Tanis Jill

AU - Boeve, Bradley F

AU - Przybelski, Scott A.

AU - Lesnick, Timothy G.

AU - Liesinger, Amanda M.

AU - Senjem, Matthew L.

AU - Gunter, Jeffrey L.

AU - Preboske, Gregory M.

AU - Lowe, Val

AU - Vemuri, Prashanthi D

AU - Dugger, Brittany N.

AU - Knopman, David S

AU - Smith, Glenn E.

AU - Parisi, Joseph E

AU - Silber, Michael H.

AU - Graff Radford, Neill R

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

AU - Dickson, Dennis W

AU - Kantarci, Kejal M

PY - 2013/11/5

Y1 - 2013/11/5

N2 - Objective: To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy. Methods: Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, b-amyloid, and a-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala. Results: pRBD was present in 21 patients (60%) with high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and b-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions. Conclusion: Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.

AB - Objective: To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy. Methods: Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, b-amyloid, and a-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala. Results: pRBD was present in 21 patients (60%) with high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and b-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions. Conclusion: Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.

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