Parkinson's MCI Has Distinct Subtypes

Kristina Fiore 
Associate Editor, MedPage 

July 15, 2016

Most common was non-amnestic with executive dysfunction

In the observational LANDSCAPE study, the most common subtype of PD-MCI was non-amnestic single domain (39.4%), Elke Kalbe, MD, of University Hospital Cologne in Germany, and colleagues reported online in the Journal of Neurology, Neurosurgery and Psychiatry.

They also found that age, gender, and global cognition predicted disease subtype -- and they noted that additional longitudinal research is needed to determine whether these specific MCI profiles predict the development of dementia in Parkinson's patients.

About a quarter of patients with Parkinson's have MCI, and higher rates have been reported with more advanced disease severity. Some work has suggested that PD-MCI also predicts conversion to dementia.

Researchers also believe the MCI seen in Parkinson's is different from that involved in Alzheimer's disease: it appears to affect executive function rather than memory.

However, the jury is still out on PD-MCI, as results regarding the cognitive profile of patients with Parkinson's have been variable and have come from small studies. Indeed, the Movement Disorders Society's most recent (2012) guidelines on diagnosing MCI in patients with Parkinson's caution that its criteria will require validation and will likely be refined with additional research.

To further clarify the issue, Kalbe and colleagues conducted the LANDSCAPE Study, a multicenter, prospective observational trial of 269 patients with PD-MCI -- the largest number of prospectively recruited patients with PD-MCI to date, the researchers said.

About two-thirds of patients with PD-MCI had executive impairment (65.3%), followed by visuospatial (36.3%), memory (33.5%), attention (25.8%), and language impairment (6.5%).

After non-amnestic single domain MCI, the largest subtypes of participants were amnestic multiple domain (30.5%), non-amnestic multiple domain (23.4%), and amnestic single domain (6.7%).

The tests most frequently impaired were the Modified Card Scoring Test (MCST) (number of categories 43.5%), the digit span backwards (36.1%), and the word list direct recall (31.2%).

Regression analyses showed that lower global cognition, female gender, and higher age predicted PD-MCI subtypes -- but education and disease-related parameters did not.

"Our finding that executive dysfunctions are the most typical cognitive symptom in PD-MCI is in line with recent reviews and original studies and reflects the fact that the 'cognitive' frontostriatal loop projecting from the dorsal striatum to the dorsolateral prefrontal cortex, which is related to executive functions, is affected early in patients with PD," the researchers wrote. "Likewise, executive dysfunctions are most typical in newly diagnosed, drug-naïve patients with PD."

Kalbe and co-authors did acknowledge, however, that some studies have shown memory to be most frequently impacted in Parkinson's, and this could be due to methodological differences in studies, or it may reflect different neuropathological pathways that suggest different subtypes of Parkinson's disease.

The team also noted that patients with the amnestic multiple domains subtype had the lowest performance in global cognitive scores, suggesting that these patients may be the most likely to go on to develop dementia.

"Predicting the [amnestic multiple domains PD-MCI subtype] with variables that are easily available in clinical routine could be useful, as this subtype scored lowest on global cognition and ... may thus be 'closest' to dementia." The researchers cautioned, however, that commonly used cognitive tests vary greatly in their sensitivity to detect dysfunction.

The study was limited because PD-MCI diagnosis was not based on the Movement Disorders Society criteria since those were not available when the study started, and because the small size of the amnestic single domain subtype may have confounded statistical comparisons between this and other subtypes.

Kalbe et al concluded that additional longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks for developing dementia.

The study was supported by Novartis, the International Parkinson Fonds, and the German Ministry for Education and Research.

http://www.medpagetoday.com/Neurology/ParkinsonsDisease/59094?