Brain Lewy-Type Synucleinopathy Density Is Associated with a Lower Prevalence of Atherosclerotic Cardiovascular Disease Risk Factors in Patients with Parkinson's Disease

Erika M Driver-Dunckley, Nan Zhang, Charles Howard Adler, Geidy E. Serrano, Lucia I. Sue, Holly A. Shill, Shyamal Mehta, Christine M. Belden, Edward Y. Zamrini, Kathryn Davis, Thomas G. Beach

Research output: Contribution to journalArticle

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Abstract

Background: Some epidemiology studies suggest that atherosclerotic cardiovascular disease (ASCVD) risk factors increase the risk of developing Parkinson's disease (PD). However, conflicting data suggest lower rates of ASCVD in PD. Objective: The objective of this study is to determine, with data from a longitudinal clinicopathological study, whether ASCVD risk factors are associated with a PD diagnosis and/or increased brain or peripheral load of Lewy-type synucleinopathy (LTS). Methods: All subjects were followed to autopsy and neuropathological examination in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Multivariable regression models, including age, gender, and smoking history, were used to investigate the association of a PD diagnosis or brain or submandibular gland LTS load with ASCVD risk factors. Results: 150 subjects were included (PD n=60, controls n=90). Univariable comparisons and regression models showed a general trend to inverse associations. The multivariable odds ratio (OR) of brain LTS load for carotid artery disease was 0.93 (95% CI: 0.86 to 0.98; p=0.02), for anticoagulant use 0.95 (95% CI: 0.90 to 0.99; p=0.04) and for abnormal heart weight 0.96 (95% CI: 0.92 to 0.99; p=0.01). Composite clinical and overall (clinical + pathology composite risk scores) composite risk scores were also significantly lower in the PD subjects (p=0.0164 and 0.0187, respectively). Submandibular gland LTS load was not significantly related to ASCVD conditions. Conclusions: This study shows associations of higher brain LTS with lower prevalence of both clinical and pathological indices of ASCVD in PD subjects versus age-similar controls. We suggest that this is due to α-synuclein pathology-induced sympathetic denervation in PD.

Original languageEnglish (US)
Pages (from-to)543-552
Number of pages10
JournalJournal of Parkinson's disease
Volume9
Issue number3
DOIs
StatePublished - Jan 1 2019

Fingerprint

Parkinson Disease
Cardiovascular Diseases
Brain
Submandibular Gland
Synucleins
Carotid Artery Diseases
Clinical Pathology
Sympathectomy
Neurodegenerative Diseases
Anticoagulants
Longitudinal Studies
Autopsy
Epidemiology
Smoking
History
Odds Ratio
Pathology
Weights and Measures

Keywords

  • atherosclerotic cardiovascular disease
  • Parkinson's disease
  • sympathetic nervous system
  • α-synuclein

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Brain Lewy-Type Synucleinopathy Density Is Associated with a Lower Prevalence of Atherosclerotic Cardiovascular Disease Risk Factors in Patients with Parkinson's Disease. / Driver-Dunckley, Erika M; Zhang, Nan; Adler, Charles Howard; Serrano, Geidy E.; Sue, Lucia I.; Shill, Holly A.; Mehta, Shyamal; Belden, Christine M.; Zamrini, Edward Y.; Davis, Kathryn; Beach, Thomas G.

In: Journal of Parkinson's disease, Vol. 9, No. 3, 01.01.2019, p. 543-552.

Research output: Contribution to journalArticle

Driver-Dunckley, Erika M ; Zhang, Nan ; Adler, Charles Howard ; Serrano, Geidy E. ; Sue, Lucia I. ; Shill, Holly A. ; Mehta, Shyamal ; Belden, Christine M. ; Zamrini, Edward Y. ; Davis, Kathryn ; Beach, Thomas G. / Brain Lewy-Type Synucleinopathy Density Is Associated with a Lower Prevalence of Atherosclerotic Cardiovascular Disease Risk Factors in Patients with Parkinson's Disease. In: Journal of Parkinson's disease. 2019 ; Vol. 9, No. 3. pp. 543-552.
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abstract = "Background: Some epidemiology studies suggest that atherosclerotic cardiovascular disease (ASCVD) risk factors increase the risk of developing Parkinson's disease (PD). However, conflicting data suggest lower rates of ASCVD in PD. Objective: The objective of this study is to determine, with data from a longitudinal clinicopathological study, whether ASCVD risk factors are associated with a PD diagnosis and/or increased brain or peripheral load of Lewy-type synucleinopathy (LTS). Methods: All subjects were followed to autopsy and neuropathological examination in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Multivariable regression models, including age, gender, and smoking history, were used to investigate the association of a PD diagnosis or brain or submandibular gland LTS load with ASCVD risk factors. Results: 150 subjects were included (PD n=60, controls n=90). Univariable comparisons and regression models showed a general trend to inverse associations. The multivariable odds ratio (OR) of brain LTS load for carotid artery disease was 0.93 (95{\%} CI: 0.86 to 0.98; p=0.02), for anticoagulant use 0.95 (95{\%} CI: 0.90 to 0.99; p=0.04) and for abnormal heart weight 0.96 (95{\%} CI: 0.92 to 0.99; p=0.01). Composite clinical and overall (clinical + pathology composite risk scores) composite risk scores were also significantly lower in the PD subjects (p=0.0164 and 0.0187, respectively). Submandibular gland LTS load was not significantly related to ASCVD conditions. Conclusions: This study shows associations of higher brain LTS with lower prevalence of both clinical and pathological indices of ASCVD in PD subjects versus age-similar controls. We suggest that this is due to α-synuclein pathology-induced sympathetic denervation in PD.",
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AU - Adler, Charles Howard

AU - Serrano, Geidy E.

AU - Sue, Lucia I.

AU - Shill, Holly A.

AU - Mehta, Shyamal

AU - Belden, Christine M.

AU - Zamrini, Edward Y.

AU - Davis, Kathryn

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