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

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

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

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