Excessive daytime sleepiness and topographic expansion of Lewy pathology

Robert D. Abbott, G. Webster Ross, John E. Duda, Chol Shin, Jane H. Uyehara-Lock, Kamal H. Masaki, Lenore J. Launer, Lon R. White, Caroline M. Tanner, Helen Petrovitch

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: While excessive daytime sleepiness (EDS) can predate the clinical diagnosis of Parkinson disease (PD), associations with underlying PD pathogenesis are unknown. Our objective is to determine if EDS is related to brain Lewy pathology (LP), a marker of PD pathogenesis, using clinical assessments of EDS with postmortem follow-up. METHODS: Identification of LP was based on staining for α-synuclein in multiple brain regions in a sample of 211 men. Data on EDS were collected at clinical examinations from 1991 to 1999 when participants were aged 72-97 years. RESULTS: Although EDS was more common in the presence vs absence of LP (p = 0.034), the association became stronger in neocortical regions. When LP was limited to the olfactory bulb, brainstem, and basal forebrain (Braak stages 1-4), frequency of EDS was 10% (4/40) vs 17.5% (20/114) in decedents without LP (p = 0.258). In contrast, compared to the absence of LP, EDS frequency doubled (36.7% [11/30], p = 0.023) when LP reached the anterior cingulate gyrus, insula mesocortex, and midfrontal, midtemporal, and inferior parietal neocortex (Braak stage 5). With further infiltration into the primary motor and sensory neocortices (Braak stage 6), EDS frequency increased threefold (51.9% [14/27], p < 0.001). Findings were similar across sleep-related features and persisted after adjustment for age and other covariates, including the removal of PD and dementia with Lewy bodies. CONCLUSIONS: The association between EDS and PD includes relationships with extensive topographic LP expansion. The neocortex could be especially vulnerable to adverse relationships between sleep disorders and aggregation of misfolded α-synuclein and LP formation.

Original languageEnglish
Pages (from-to)e1425-e1432
JournalNeurology
Volume93
Issue number15
DOIs
Publication statusPublished - 2019 Oct 8
Externally publishedYes

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Pathology
Parkinson Disease
Neocortex
Synucleins
Lewy Body Disease
Olfactory Bulb
Gyrus Cinguli
Brain
Prednisolone
Brain Stem
Sleep
Staining and Labeling

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Abbott, R. D., Ross, G. W., Duda, J. E., Shin, C., Uyehara-Lock, J. H., Masaki, K. H., ... Petrovitch, H. (2019). Excessive daytime sleepiness and topographic expansion of Lewy pathology. Neurology, 93(15), e1425-e1432. https://doi.org/10.1212/WNL.0000000000008241

Excessive daytime sleepiness and topographic expansion of Lewy pathology. / Abbott, Robert D.; Ross, G. Webster; Duda, John E.; Shin, Chol; Uyehara-Lock, Jane H.; Masaki, Kamal H.; Launer, Lenore J.; White, Lon R.; Tanner, Caroline M.; Petrovitch, Helen.

In: Neurology, Vol. 93, No. 15, 08.10.2019, p. e1425-e1432.

Research output: Contribution to journalArticle

Abbott, RD, Ross, GW, Duda, JE, Shin, C, Uyehara-Lock, JH, Masaki, KH, Launer, LJ, White, LR, Tanner, CM & Petrovitch, H 2019, 'Excessive daytime sleepiness and topographic expansion of Lewy pathology', Neurology, vol. 93, no. 15, pp. e1425-e1432. https://doi.org/10.1212/WNL.0000000000008241
Abbott RD, Ross GW, Duda JE, Shin C, Uyehara-Lock JH, Masaki KH et al. Excessive daytime sleepiness and topographic expansion of Lewy pathology. Neurology. 2019 Oct 8;93(15):e1425-e1432. https://doi.org/10.1212/WNL.0000000000008241
Abbott, Robert D. ; Ross, G. Webster ; Duda, John E. ; Shin, Chol ; Uyehara-Lock, Jane H. ; Masaki, Kamal H. ; Launer, Lenore J. ; White, Lon R. ; Tanner, Caroline M. ; Petrovitch, Helen. / Excessive daytime sleepiness and topographic expansion of Lewy pathology. In: Neurology. 2019 ; Vol. 93, No. 15. pp. e1425-e1432.
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AU - Abbott, Robert D.

AU - Ross, G. Webster

AU - Duda, John E.

AU - Shin, Chol

AU - Uyehara-Lock, Jane H.

AU - Masaki, Kamal H.

AU - Launer, Lenore J.

AU - White, Lon R.

AU - Tanner, Caroline M.

AU - Petrovitch, Helen

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N2 - OBJECTIVE: While excessive daytime sleepiness (EDS) can predate the clinical diagnosis of Parkinson disease (PD), associations with underlying PD pathogenesis are unknown. Our objective is to determine if EDS is related to brain Lewy pathology (LP), a marker of PD pathogenesis, using clinical assessments of EDS with postmortem follow-up. METHODS: Identification of LP was based on staining for α-synuclein in multiple brain regions in a sample of 211 men. Data on EDS were collected at clinical examinations from 1991 to 1999 when participants were aged 72-97 years. RESULTS: Although EDS was more common in the presence vs absence of LP (p = 0.034), the association became stronger in neocortical regions. When LP was limited to the olfactory bulb, brainstem, and basal forebrain (Braak stages 1-4), frequency of EDS was 10% (4/40) vs 17.5% (20/114) in decedents without LP (p = 0.258). In contrast, compared to the absence of LP, EDS frequency doubled (36.7% [11/30], p = 0.023) when LP reached the anterior cingulate gyrus, insula mesocortex, and midfrontal, midtemporal, and inferior parietal neocortex (Braak stage 5). With further infiltration into the primary motor and sensory neocortices (Braak stage 6), EDS frequency increased threefold (51.9% [14/27], p < 0.001). Findings were similar across sleep-related features and persisted after adjustment for age and other covariates, including the removal of PD and dementia with Lewy bodies. CONCLUSIONS: The association between EDS and PD includes relationships with extensive topographic LP expansion. The neocortex could be especially vulnerable to adverse relationships between sleep disorders and aggregation of misfolded α-synuclein and LP formation.

AB - OBJECTIVE: While excessive daytime sleepiness (EDS) can predate the clinical diagnosis of Parkinson disease (PD), associations with underlying PD pathogenesis are unknown. Our objective is to determine if EDS is related to brain Lewy pathology (LP), a marker of PD pathogenesis, using clinical assessments of EDS with postmortem follow-up. METHODS: Identification of LP was based on staining for α-synuclein in multiple brain regions in a sample of 211 men. Data on EDS were collected at clinical examinations from 1991 to 1999 when participants were aged 72-97 years. RESULTS: Although EDS was more common in the presence vs absence of LP (p = 0.034), the association became stronger in neocortical regions. When LP was limited to the olfactory bulb, brainstem, and basal forebrain (Braak stages 1-4), frequency of EDS was 10% (4/40) vs 17.5% (20/114) in decedents without LP (p = 0.258). In contrast, compared to the absence of LP, EDS frequency doubled (36.7% [11/30], p = 0.023) when LP reached the anterior cingulate gyrus, insula mesocortex, and midfrontal, midtemporal, and inferior parietal neocortex (Braak stage 5). With further infiltration into the primary motor and sensory neocortices (Braak stage 6), EDS frequency increased threefold (51.9% [14/27], p < 0.001). Findings were similar across sleep-related features and persisted after adjustment for age and other covariates, including the removal of PD and dementia with Lewy bodies. CONCLUSIONS: The association between EDS and PD includes relationships with extensive topographic LP expansion. The neocortex could be especially vulnerable to adverse relationships between sleep disorders and aggregation of misfolded α-synuclein and LP formation.

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