Researchers find predictors of cognitive impairments over time
Cognitive function in Parkinson's remained stable or declined over 4 years
Cognitive function in adults with Parkinson’s disease either remains stable or progressively declines over time, according to a four-year follow-up study that also found that early problems with several tasks related to visual processing and spatial reasoning were among predictors of eventual cognitive impairments.
Among Parkinson’s patients with cognitive decline, an increase in the power of slow brain waves associated with sleep, as assessed by electroencephalogram (EEG) at the study’s start, predicted worsening in different cognitive measures after two and four years of follow-up, the data showed.
“Development of an aggressive cognitive decline in [Parkinson’s disease] is associated with increased slow-wave power density,” the researchers wrote.
The team noted that further research with a larger patient population and more longitudinal EEG recordings are “essential … to assess the potential individual predictive power of short-term neurophysiological changes” in Parkinson’s.
The study, “Prediction of Cognitive Heterogeneity in Parkinson’s Disease: A 4-Year Longitudinal Study Using Clinical, Neuroimaging, Biological and Electrophysiological Biomarkers,” was published in the Annals of Neurology.
Cognitive impairments in Parkinson’s often vary widely
Cognitive impairment is a common nonmotor symptom of Parkinson’s, a disorder caused by the progressive death of certain nerve cells in the brain.
Such symptoms can range from subtle cognitive changes to mild cognitive impairment and dementia. Moreover, cognitive changes over time often vary widely from person to person, with some experiencing a rapid decline after years of stability, while others may even revert from more advanced cognitive impairments to normal cognition.
To identify factors that predict cognitive changes over time, a team of researchers across Spain assessed cognition in two groups of adults with Parkinson’s, alongside healthy controls, over a four-year period.
The first group comprised 82 Parkinson’s patients and the second group, added to validate the findings from the first group, totaled 393 patients who participated in the COPPADIS, a five-year observational study that followed patients across Spain.
Cognition was assessed using the Parkinson’s Disease-Cognitive Rating Scale (PD-CRS), which covers the full spectrum of cognitive changes associated with Parkinson’s. Other tests included blood biomarkers, MRI scans, and EEG recordings, along with memory, attention, language, and executive function assessments.
Cognitive function found to remain stable for 60%, decline for 40%
An analysis of the first group revealed two distinct patterns of cognitive changes over time: For about 60% of patients, cognition remained stable or improved, while progressive cognitive decline was seen in approximately 40% of these individuals. Analysis of COPPADIS data found the same two patterns.
Compared with cognitively stable patients, those with progressive cognitive decline showed significantly worse PD-CRS scores when assessed at two, three, and four years.
In PD-CRS subscales, progressors had a worse posterior cortical function after two years — that region of the brain is responsible for visual processing and spatial reasoning. These patients also had worse frontal-subcortical functions, which included declines in planning tasks, working memory, verbal fluency, and attention. Similar outcomes were found using COPPADIS data.
By year four, progressors experienced a worsening in day-to-day functionality, as assessed by the Parkinson’s Disease-Cognitive Functional Rating Scale (PD-CFRS), a patient-reported questionnaire. Motor symptoms and several aspects of cognition, including language, memory, and executive functions, also were worse by year four.
During the four-year follow-up, progressors in the first group had a twofold increased risk of mild cognitive impairment and a 4.9 times higher risk for dementia. COPPADIS progressors showed similar cognitive risks, with a 1.8 times greater risk of mild cognitive impairment and a 7.3 times higher risk for dementia.
Early changes in the performance pattern on specific posterior-cortical-dependent tasks, and early increases in [slow wave] power density in several … brain regions anticipate and predict the development of a more aggressive cognitive trajectory..
MRI scans and blood levels of neurofilament light chain, a biomarker of nerve damage, measured at the study’s start (baseline), were similar between eventual progressors or those whose cognition remained stable.
Using EEG, which measures the brain’s electrical activity, increases in the power of slow waves, a type of brain activity associated with sleep, in the progressor group at baseline, predicted worse cognitive outcomes at follow-up.
Specifically, a worsening of temporal memory — the ability to remember the timeline of events and their sequence — at four years was significantly associated with increased slow waves in multiple brain regions. Similar associations were found between the same brain regions, brain wave frequency bands, and PD-CFRS changes at four years. Even at two years, global cognitive status, as assessed with the PD-CRS, was already associated with increased slow-wave power density in several locations.
“We were able to identify [two] distinct patterns of cognitive decline in [Parkinson’s disease],” the authors concluded. “Early changes in the performance pattern on specific posterior-cortical-dependent tasks, and early increases in [slow wave] power density in several … brain regions anticipate and predict the development of a more aggressive cognitive trajectory.”
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