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Cognitive dysfunction linked to increased risk for parkinsonism

Poor cognitive functioning was associated with an increased likelihood of parkinsonism, including Parkinson’s disease, according to findings recently published in JAMA Neurology.

In addition, researchers found that cognition indicates parkinsonism probability during long intervals, extending beyond patients with disease onset after dementia.

“It is unclear whether a single global assessment of cognitive functioning is associated with an increased risk of parkinsonism over longer intervals, to what extent the different cognitive domains predict parkinsonism, and how poor cognitive functioning combines with subtle motor signs in patients with prediagnostic parkinsonism,” Sirwan K.L. Darweesh, MD, MSc, of the department of epidemiology at Erasmus MC University Medical Center in Rotterdam, The Netherlands, and colleagues wrote. “Such insight is critical because it may further unravel the prodromal phase of common parkinsonism diseases, in particular prodromal [Parkinson’s disease], a phase in which patients may still respond to putative disease-modifying interventions.”

To determine whether poor cognitive functioning yields an increased risk for parkinsonism, researchers examined 7,386 participants from the ongoing Rotterdam study who were free of dementia and parkinsonism. Participants underwent four tests: word learning, verbal fluency, letter-digit substitution and Stroop Color Word Test.

During follow-up (median, 8.3 years), 79 participants were diagnosed with incident parkinsonism, of whom 57 were diagnosed with probable Parkinson’s disease. Among patients with incident parkinsonism, 24 — 14 after the onset of parkinsonism and 10 before — also developed dementia.

In addition, poor global cognition at baseline was associated with an increased hazard of incident parkinsonism (HR = 1.79; 95% CI, 1.37-2.33). This association remained strong after the first 8 years (HR = 1.59; 95% CI, 1.01-2.59) and after removing individuals with dementia onset before parkinsonism (HR = 1.72; 95% CI, 1.28-2.27).

Researchers also wrote that poor global cognition at baseline was associated with incident probable Parkinson’s disease (HR = 1.52; 95% CI, 1.11-2.08). Verbal fluency (HR = 1.61; 95% CI, 1.23-2.08), letter-digit substitution (HR = 1.59; 95% CI, 1.22-2.04) and inverted interference task Stroop Color Word Test (HR = 1.56; 95% CI, 1.25-1.96) scores were each linked with incident parkinsonism, but the association with word learning delayed-task scores was weaker (HR = 1.18; 95% CI, 0.92-1.52).

“These findings suggest that both motor and cognitive decline are common in patients with prodromal [Parkinson’s disease], and that their sequence of occurrence is variable,” Darweesh and colleagues wrote. “Future observational studies will unravel the underlying abnormalities that drive the variable sequence of motor and cognitive decline in patients with prodromal [Parkinson’s disease].”

In a related editorial, Ethan G. Brown, MD, and Caroline M. Tanner, MD, PhD, both of the

department of neurology at the University of California, San Francisco, wrote that some of these findings provide information that health care providers can utilize in their practices immediately.

“Now we ... know that people with early mild cognitive impairment, especially in the setting of subtle motor findings, may have prodromal [Parkinson’s disease]. 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,” they wrote.

“Physicians may recommend interventions, such as physical activity, that are helpful for motor and cognitive changes in [Parkinson’s disease],” Brown and Tanner continued. “Recognition of cognitive impairment as a prodromal sign will improve our ability to detect prodromal [Parkinson’s disease]. Intervening at the earliest stages of [Parkinson’s disease] may provide the best chance for slowing disease progression and maintaining function. Clarification of the early course of [Parkinson’s disease] with studies such as this may allow identification in time to change the course of disease.” – by Janel Miller

Disclosures : Brown reports receiving compensation for serving on the fellowship advisory board for AbbVie. Tanner reports receiving grants from the Department of Defense, Michael J. Fox Foundation, NIH, Parkinson’s Disease Foundation and Sage Bionetworks; compensation for serving on data monitoring committees from Biotie Therapeutics, Intec Pharma and Voyager Therapeutics; and personal fees for consulting from Adamas Therapeutics, Neurocrine Biosciences and PhotoPharmics. The other researchers report no relevant financial disclosures.