From the Journals

Early cognitive impairment associated with later Parkinson’s disease

Key clinical point: Mild cognitive impairment may appear early in adults who go on to develop Parkinson’s disease.

Major finding: Poor global cognition at baseline was associated with a greater risk of incident parkinsonism (hazard ratio, 1.79) over approximately 8 years.

Data source: The data come from 7,386 adults in the population-based Rotterdam Study.

Disclosures: This study was supported in part by Stichting ParkinsonFonds. The researchers had no financial conflicts to disclose.

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Use early cognitive impairment to detect prodromal PD

The long-term nature of the Rotterdam Study makes it an excellent source for examining the association between poor cognition and parkinsonism, wrote Ethan G. Brown, MD, and Caroline M. Tanner, MD, in an accompanying editorial.

“This study reiterates the presence of cognitive impairment very early in PD, emphasizing the need for therapeutic trials to target this symptom as an outcome. Although only some patients with cognitive impairment progress to PD, the study provides some clues on how to distinguish those most at risk. Progression to parkinsonism was more likely with baseline impairment of several individual cognitive tests, but only changes in semantic fluency predicted probable PD. Semantic fluency has been previously found to be specific for progression of cognitive impairment in PD, and this study again suggests the importance of this cognitive test early on,” they wrote.

“Yet the presence of cognitive impairment so early also gives rise to questions about the underlying pathology of PD progression. A commonly cited mechanism for progression of PD involves prion-like spread of synuclein pathology up through the dorsal nucleus of the vagus and substantia nigra. This spread presumably causes the autonomic, sleep, and motor dysfunction common in PD and supposedly leads to cognitive impairment only once Lewy bodies enter the neocortex. The current evidence that cognitive impairment can be evident in the prodromal stage challenges the universality of the model of vagal spread,” they noted.

However, recognizing the role of cognitive impairment as an early sign of PD can help clinicians plan screening and care, they said.

“This recognition can allow physicians to screen for falls or other nonmotor aspects of PD 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 PD,” they added (JAMA Neurol. 2017. doi: 10.1001/jamaneurol.2017.1474).

Dr. Brown and Dr. Tanner are affiliated with the Movement Disorders and Neuromodulation Center in the department of neurology at the University of California, San Francisco. Dr. Brown disclosed compensation for serving on the Fellowship Advisory Board for AbbVie. Dr. Tanner disclosed grants from a variety of nonprofit sources, as well as compensation for serving on Data Monitoring Committees for Biotie Therapeutics, Voyager Therapeutics, and Intec Pharma. Dr. Tanner also disclosed personal consulting fees from Neurocrine Biosciences, Adamas Therapeutics, and PhotoPharmics.



Adults with early cognitive impairment are at greater risk for developing parkinsonism than those without cognitive impairment, based on data from 7,386 adults participating in the ongoing Rotterdam Study. The findings were published online Sept. 25 in JAMA Neurology.

“Between 15% and 43% of patients with newly diagnosed Parkinson disease (PD) are cognitively impaired,” wrote Sirwan K. L. Darweesh, MD, of Erasmus MC University Medical Center, Rotterdam, the Netherlands, and his colleagues. However, data on the predictive value of cognitive impairment for parkinsonism has not been well studied, they wrote (JAMA Neurol. 2017. doi: 10.1001/jamaneurol.2017.2248).

The researchers reviewed data from participants in the Rotterdam Study with an average age of 65 years; 57% were women. Dementia was assessed using either the Mini-Mental State Examination or the Geriatric Mental State Schedule organic level, followed by the Cambridge Examination for Mental Disorders of the Elderly.

Over approximately 8 years’ follow-up, 1% of the participants were diagnosed with incident parkinsonism.

“Poor global cognition at baseline was associated with a higher risk of incident parkinsonism” with a hazard ratio of 1.79, the researchers said.

“To enable translation of our findings to clinical practice, we present likelihood ratios (LRs) for the baseline presence of isolated or combined cognitive dysfunction and subtle motor features for incident parkinsonism during follow-up,” they noted.

Approximately half of participants diagnosed with incident parkinsonism during the study period had subtle motor features, cognitive dysfunction, or both, at baseline. Baseline cognitive impairment alone showed a likelihood ratio of 1.76 for development of parkinsonism, but the likelihood ratio was greater when both cognitive impairment and subtle motor findings were present (2.66).

“In individuals who received a diagnosis of both incident dementia and incident parkinsonism, baseline cognitive dysfunction was not associated with incident dementia,” the researchers noted.

The researchers determined that the most likely explanation for the association between cognitive decline and increased Parkinson’s risk was that “low baseline cognitive scores may indicate ongoing cognitive decline in prediagnostic patients who probably will develop parkinsonism, most of whom have prediagnostic PD,” they said.

The study findings were limited by several factors including the potential misclassification of parkinsonism diagnosis, the researchers noted. However, the association between poor cognitive function and the risk of parkinsonism and probably Parkinson’s disease remained for the executive, attention, cognitive speed, and memory domains of cognition, they said. “Our findings suggest that poor cognitive functioning can be considered a prodromal sign of PD,” they concluded.

This study was supported in part by Stichting ParkinsonFonds. The researchers had no financial conflicts to disclose.

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