Conference Coverage
Poor cognitive function is associated with an increased risk of incident parkinsonism, including probable Parkinson’s disease, according to research published online ahead of print September 25 in JAMA Neurology. The association is strong beyond eight years of follow-up and holds for patients with incident parkinsonism without dementia.
Sirwan K. L. Darweesh, MD
Cognitive loss is not among the Movement Disorder Society’s criteria for prodromal Parkinson’s disease because prospective evidence about this variable was lacking when the criteria were developed. “Our results, as well as those of other published studies, suggest that cognitive dysfunction now warrants inclusion as a prodromal marker,” said Sirwan K. L. Darweesh, MD, of the Department of Epidemiology at Erasmus MC University Medical Center in Rotterdam, the Netherlands.
Prospective Data From the Rotterdam Study
Dr. Darweesh and colleagues conducted research to test their hypothesis that poor cognitive function is associated with an increased risk of parkinsonism. They examined participants in the prospective, population-based Rotterdam Study, which began in 1990. The study instituted a comprehensive battery of cognitive tests between 2002 and 2008, and Dr. Darweesh and colleagues used this period as the baseline of their investigation. During this time, researchers assessed cognitive function in 7,386 participants who were free of parkinsonism and dementia. The assessments included the Stroop color word test, letter-digit substitution, verbal fluency, and word learning.
During follow-up, participants presented for serial in-person examinations, and investigators had full access to participants’ medical records. Follow-up ended on January 1, 2015. The main outcome was the hazard ratio for incident parkinsonism per standard deviation decrease in global cognition. The researchers adjusted the data for age and sex.
Education Did Not Affect the Association
The population’s mean age was 65, and 57.4% of the population was female. During a median follow-up of 8.3 years, 79 participants (1.1%) received a diagnosis of incident parkinsonism. Of these patients, 57 (72.2%) received a diagnosis of probable Parkinson’s disease. Among participants with incident parkinsonism, 24 (30.4%) received a diagnosis of incident dementia. In addition, 446 people (6.1%) who remained free of incident parkinsonism received a diagnosis of incident dementia.
Each standard-deviation decrease in global cognition was associated with a 79% increase in the risk of incident parkinsonism. After the researchers censored people with incident dementia and restricted the analysis to patients with incident parkinsonism who were examined by a neurologist or geriatrician, the association remained strong beyond the first eight years of follow-up. Adjustment for education did not affect the association, but adjustment for subtle motor signs weakened it slightly. Poor cognitive functioning also was associated with probable Parkinson’s disease (hazard ratio [HR], 1.52) and with a joint end point of probable Parkinson’s disease or dementia with Lewy bodies (HR, 1.59).
Incident parkinsonism was associated with lower scores on letter-digit substitution (HR, 1.59), verbal fluency (HR, 1.61), and inverted interference task Stroop color word test (HR, 1.56). The association with word learning delayed-task scores was weaker (HR, 1.18).
A possible explanation for the association is that “low baseline cognitive scores may indicate ongoing cognitive decline in prediagnostic patients who probably will develop parkinsonism, most of whom have prediagnostic Parkinson’s disease.” Another possible explanation is that people who probably will develop parkinsonism in mid- or late life never attain a high level of cognitive functioning in early life, said the researchers.
Results May Prompt Screening and Interventions
The study results are broadly applicable because they come from a large, community-based cohort with low attrition, said Ethan G. Brown, MD, a clinical fellow, and Caroline M. Tanner, MD, PhD, Professor of Neurology, both at the University of California, San Francisco, in an accompanying editorial. The researchers may have overlooked some participants’ cognitive impairment, however, because the neuropsychologic assessment was not as thorough as recommended. Also, the study design made specialist adjudication of all diagnoses of Parkinson’s disease impossible, and the primary outcome was incident parkinsonism, rather than incident Parkinson’s disease.
The findings nevertheless reiterate the presence of cognitive impairment early in Parkinson’s disease, thus emphasizing the need for therapeutic trials to target this symptom, said Drs. Brown and Tanner. The study also provides guidance for identifying people most at risk for Parkinson’s disease.
In addition, Dr. Darweesh’s group has found evidence that supports the Braak hypothesis about Parkinson’s disease progression, said Drs. Brown and Tanner. The data challenge the idea that synuclein pathology always spreads through the vagus and substantia nigra.
“Now we … know that people with early mild cognitive impairment, especially in the setting of subtle motor findings, may have prodromal Parkinson’s disease,” said Drs. Brown and Tanner. “This recognition can allow physicians to screen for falls or other nonmotor aspects of Parkinson’s disease in these cases and provide early treatment for these symptoms. Physicians may recommend interventions, such as physical activity, that are helpful for motor and cognitive changes in Parkinson’s disease.”
—Erik Greb
Suggested Reading
Brown EG, Tanner CM. Impaired cognition and the risk of Parkinson disease: Trouble in mind. JAMA Neurol. 2017 Sep 25 [Epub ahead of print].
Darweesh SKL, Wolters FJ, Postuma RB, et al. Association between poor cognitive functioning and risk of incident parkinsonism: The Rotterdam Study. JAMA Neurol. 2017 Sep 25 [Epub ahead of print].