Predicting alpha-synuclein pathology by REM sleep behavior disorder diagnosis

David R. Shprecher, Charles Howard Adler, Nan Zhang, Joseph G. Hentz, Geidy E. Serrano, Brittany N. Dugger, Holly A. Shill, Rodolfo Savica, John Nathaniel Caviness, Marwan N. Sabbagh, Christine M. Belden, Erika M Driver-Dunckley, Shyamal Mehta, Lucia I. Sue, Kathryn J. Davis, Edward Zamrini, Thomas G. Beach

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Inability to accurately diagnose Lewy type alpha-synucleinopathy (LTS) pre-mortem has been a major obstacle to clinical care and research. Probable REM sleep behavior disorder (PRBD) diagnosed with support of instruments such as the Mayo Sleep Questionnaire (MSQ) may provide a cost effective means of predicting LTS. Since 2007, 602 subjects in the Arizona Study of Aging and Neurodegenerative Disorders had clinician assessment for PRBD (298 with, 304 without support of the MSQ), completed cognitive and movement examinations, and had neuropathological assessment. Mean age at death was 84.8 years. Histological evidence of LTS was found in 80/101(79.2%) cases with PRBD and 198/501 (39.5%) without PRBD (p < 0.001). Overall sensitivity for predicting LTS by PRBD diagnosis was 28.8%, specificity 93.5%, positive predictive value (PPV) 79.2%, negative predictive value (NPV) 60.5%. Diagnosis of PRBD was less frequently present in subjects without LTS [4/105 (3.8%) of healthy controls, 42/255 (16.5%) AD, 2/33 (6.1%) progressive supranuclear palsy (PSP) without LTS] than in subjects with LTS [11/46 (23.9%) DLB, 58/104 (55.8%) PD, and 4/16 (25.0%) PSP with LTS.] PRBD was not present in any of 46 subjects with incidental Lewy body disease (ILBD). MSQ-supported diagnosis of PRBD appears useful for predicting LTS in manifest neurodegenerative disease, but not necessarily ILBD. Additional prospective autopsy research, including well-characterized polysomnogram-confirmed RBD subjects, is needed to elucidate the earliest tissue abnormalities in the “idiopathic” (premotor/pre-dementia) stage of RBD.

Original languageEnglish (US)
JournalParkinsonism and Related Disorders
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

REM Sleep Behavior Disorder
alpha-Synuclein
Pathology
Progressive Supranuclear Palsy
Lewy Body Disease
Sleep
Neurodegenerative Diseases
Research
Dementia
Autopsy
Costs and Cost Analysis

Keywords

  • Dementia with Lewy bodies
  • Parkinson disease
  • Parkinson disease dementia
  • REM sleep behavior disorder

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Shprecher, D. R., Adler, C. H., Zhang, N., Hentz, J. G., Serrano, G. E., Dugger, B. N., ... Beach, T. G. (Accepted/In press). Predicting alpha-synuclein pathology by REM sleep behavior disorder diagnosis. Parkinsonism and Related Disorders. https://doi.org/10.1016/j.parkreldis.2018.05.020

Predicting alpha-synuclein pathology by REM sleep behavior disorder diagnosis. / Shprecher, David R.; Adler, Charles Howard; Zhang, Nan; Hentz, Joseph G.; Serrano, Geidy E.; Dugger, Brittany N.; Shill, Holly A.; Savica, Rodolfo; Caviness, John Nathaniel; Sabbagh, Marwan N.; Belden, Christine M.; Driver-Dunckley, Erika M; Mehta, Shyamal; Sue, Lucia I.; Davis, Kathryn J.; Zamrini, Edward; Beach, Thomas G.

In: Parkinsonism and Related Disorders, 01.01.2018.

Research output: Contribution to journalArticle

Shprecher, DR, Adler, CH, Zhang, N, Hentz, JG, Serrano, GE, Dugger, BN, Shill, HA, Savica, R, Caviness, JN, Sabbagh, MN, Belden, CM, Driver-Dunckley, EM, Mehta, S, Sue, LI, Davis, KJ, Zamrini, E & Beach, TG 2018, 'Predicting alpha-synuclein pathology by REM sleep behavior disorder diagnosis', Parkinsonism and Related Disorders. https://doi.org/10.1016/j.parkreldis.2018.05.020
Shprecher, David R. ; Adler, Charles Howard ; Zhang, Nan ; Hentz, Joseph G. ; Serrano, Geidy E. ; Dugger, Brittany N. ; Shill, Holly A. ; Savica, Rodolfo ; Caviness, John Nathaniel ; Sabbagh, Marwan N. ; Belden, Christine M. ; Driver-Dunckley, Erika M ; Mehta, Shyamal ; Sue, Lucia I. ; Davis, Kathryn J. ; Zamrini, Edward ; Beach, Thomas G. / Predicting alpha-synuclein pathology by REM sleep behavior disorder diagnosis. In: Parkinsonism and Related Disorders. 2018.
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abstract = "Inability to accurately diagnose Lewy type alpha-synucleinopathy (LTS) pre-mortem has been a major obstacle to clinical care and research. Probable REM sleep behavior disorder (PRBD) diagnosed with support of instruments such as the Mayo Sleep Questionnaire (MSQ) may provide a cost effective means of predicting LTS. Since 2007, 602 subjects in the Arizona Study of Aging and Neurodegenerative Disorders had clinician assessment for PRBD (298 with, 304 without support of the MSQ), completed cognitive and movement examinations, and had neuropathological assessment. Mean age at death was 84.8 years. Histological evidence of LTS was found in 80/101(79.2{\%}) cases with PRBD and 198/501 (39.5{\%}) without PRBD (p < 0.001). Overall sensitivity for predicting LTS by PRBD diagnosis was 28.8{\%}, specificity 93.5{\%}, positive predictive value (PPV) 79.2{\%}, negative predictive value (NPV) 60.5{\%}. Diagnosis of PRBD was less frequently present in subjects without LTS [4/105 (3.8{\%}) of healthy controls, 42/255 (16.5{\%}) AD, 2/33 (6.1{\%}) progressive supranuclear palsy (PSP) without LTS] than in subjects with LTS [11/46 (23.9{\%}) DLB, 58/104 (55.8{\%}) PD, and 4/16 (25.0{\%}) PSP with LTS.] PRBD was not present in any of 46 subjects with incidental Lewy body disease (ILBD). MSQ-supported diagnosis of PRBD appears useful for predicting LTS in manifest neurodegenerative disease, but not necessarily ILBD. Additional prospective autopsy research, including well-characterized polysomnogram-confirmed RBD subjects, is needed to elucidate the earliest tissue abnormalities in the “idiopathic” (premotor/pre-dementia) stage of RBD.",
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AU - Adler, Charles Howard

AU - Zhang, Nan

AU - Hentz, Joseph G.

AU - Serrano, Geidy E.

AU - Dugger, Brittany N.

AU - Shill, Holly A.

AU - Savica, Rodolfo

AU - Caviness, John Nathaniel

AU - Sabbagh, Marwan N.

AU - Belden, Christine M.

AU - Driver-Dunckley, Erika M

AU - Mehta, Shyamal

AU - Sue, Lucia I.

AU - Davis, Kathryn J.

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