Featured Research

from universities, journals, and other organizations

Higher levels of cerebrospinal fluid predict faster cognitive loss in Parkinson's disease

Date:
March 11, 2014
Source:
Elsevier
Summary:
A characteristic pathological feature of Parkinson's disease (PD) is the presence of Lewy bodies, which are formed by intracellular deposits of the protein α-synuclein in neurons. Although several large studies have examined α-synuclein levels in the cerebrospinal fluid of PD patients, its role in cognitive decline and dementia had been unexplored. Now, counterintuitive findings offer new insights into PD pathology.

The course of Parkinson's disease (PD) can vary from gradual deterioration to precipitous decline in motor or cognitive function. Therefore identifying predictors of progression can benefit understanding of PD disease progression and impact management. Data from 304 PD patients followed for up to 8 years indicate that patients with higher cerebrospinal fluid (CSF) α-synuclein levels experienced faster cognitive decline in the following months, although no associations were found between α-synuclein levels and motor changes. The results are published in The American Journal of Pathology.

A characteristic pathological feature of PD is the presence of Lewy bodies, which are formed by intracellular deposits of the protein α-synuclein in neurons. Although several large studies have shown that α-synuclein levels are lower in the CSF of PD patients and those with related synucleinopathies compared to controls, its role in cognitive decline and dementia had been unexplored.

Researchers were able to access CSF samples from the deprenyl and tocopherol antioxidative therapy of Parkinsonism (DATATOP) study, which is the largest cohort assembled to date with longitudinal collection of biological fluids and clinical data from PD patients. "DATATOP subjects were recruited at early disease stages, without apparent signs of dementia and prior to needing dopamine-supplementing drugs, making this cohort ideal for studying PD progression," explains Jing Zhang, MD, PhD, Department of Pathology at the University of Washington School of Medicine (Seattle).

Cognitive performance and other clinical measures, including the United Parkinson Disease Rating Scale (UPDRS), Mini-Mental State Exam (MMSE), and Hoehn and Yahr scales, were assessed at the beginning of the study and subsequently every 6 months, with an average follow-up time of 1.8 years and maximum of 8 years. Data were separated into Phase I (the time between study entry and a clinician's determination that levodopa therapy was required) and Phase II (the time between initiation of levodopa therapy and the conclusion of follow-up). CSF samples were collected at the beginning of Phases I and II. Although the study began as a randomized trial that divided subjects into four treatment groups (placebo, deprenyl, α-tocopherol, and deprenyl/α-tocopherol), this was terminated early because positive effects of deprenyl were observed and all subjects then received deprenyl for approximately 18 months.

The investigators found that although α-synuclein levels decreased significantly over the course of the study, in agreement with previous studies lacking the longitudinal component, its values did not predict the worsening of motor symptoms (as measured by UPDRS) over Phase I or Phase II. "One possible explanation is that UPDRS reflects primarily deficits arising from nigrostriatal degeneration, whereas CSF α-synuclein levels are influenced by the whole brain and may serve as a proxy for total brain pathology," says Dr. Zhang.

The findings for cognition were quite different: Higher CSF α-synuclein levels predicted faster cognitive decline. The results were significant during Phase II. Analyses were controlled for age, sex, education, exposure to study drug, and prescribed dose of levodopa. The tests evaluated multiple modes of cognition, including verbal learning and memory and visuospatial working memory/processing speed. Similar trends were found for all tests.

"The finding that α-synuclein levels decrease as PD progresses, yet those with higher α-synuclein levels experience faster cognitive decline, is somewhat counterintuitive," comments Dr. Zhang. He and his colleagues, including first author, Tessandra Stewart, PhD, suggest that the decrease in CSF α-synuclein may be the result of a compensatory process, reflecting greater retention of the protein in the brain. This may allow damaged or degenerating neurons to maintain their function for longer than those who are less efficient at retaining α-synuclein.

Dr. Zhang points out that the unique value of this study derives from the ability to perform longitudinal assessments of cognition in PD patients over a long time period and access to data from a large cohort that began when patients were in the earliest stage of disease.

PD is the second most common neurodegenerative disorder in the United States, affecting approximately one million Americans and five million people worldwide. Its prevalence is projected to double by 2030. The most obvious symptoms are movement-related, such as involuntary shaking and muscle stiffness; non-motor symptoms, including cognitive impairments and dementia, anxiety, and sleep disturbances, are also seriously debilitating.


Story Source:

The above story is based on materials provided by Elsevier. Note: Materials may be edited for content and length.


Journal Reference:

  1. Tessandra Stewart, Changqin Liu, Carmen Ginghina, Kevin C. Cain, Peggy Auinger, Brenna Cholerton, Min Shi, Jing Zhang. Cerebrospinal Fluid α-Synuclein Predicts Cognitive Decline in Parkinson's Disease Progression in the DATATOP Cohort. The American Journal of Pathology, 2014; DOI: 10.1016/j.ajpath.2013.12.007

Cite This Page:

Elsevier. "Higher levels of cerebrospinal fluid predict faster cognitive loss in Parkinson's disease." ScienceDaily. ScienceDaily, 11 March 2014. <www.sciencedaily.com/releases/2014/03/140311124028.htm>.
Elsevier. (2014, March 11). Higher levels of cerebrospinal fluid predict faster cognitive loss in Parkinson's disease. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2014/03/140311124028.htm
Elsevier. "Higher levels of cerebrospinal fluid predict faster cognitive loss in Parkinson's disease." ScienceDaily. www.sciencedaily.com/releases/2014/03/140311124028.htm (accessed July 24, 2014).

Share This




More Mind & Brain News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Newsy (July 23, 2014) An 8-year-old boy helped his younger brother, who has a rare genetic condition that's confined him to a wheelchair, finish a triathlon. Video provided by Newsy
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. Video provided by Newsy
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Do Obese Women Have 'Food Learning Impairment'?

Do Obese Women Have 'Food Learning Impairment'?

Newsy (July 18, 2014) Yale researchers tested 135 men and women, and it was only obese women who were deemed to have "impaired associative learning." Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins