New research provides evidence that the presence of early minor hallucinations in Parkinson’s disease patients, along with specific patterns of brainwave activity, can serve as indicators of more rapid cognitive decline. The findings, published in Nature Mental Health, have important implications for the early identification of cognitive impairment and the potential for interventions to mitigate its effects in patients with Parkinson’s disease.
There is a pressing need to detect and intervene in neurodegenerative diseases like Parkinson’s disease at an early stage, before they advance to a point where treatment options are limited. The researchers aimed to investigate whether there were changes in brain oscillations associated with minor hallucinations and if these changes could predict cognitive decline over a five-year period. They also wanted to determine if EEG data combined with neuropsychological and neuropsychiatric assessments could serve as an early marker for cognitive decline in Parkinson’s disease patients with minor hallucinations.
“We are neuroscientists working on perception, we are particularly interested in how the brain processes stimuli, and how it generates false perceptions (i.e. hallucinations),” explained study author Fosco Bernasconi, a postdoctoral researcher at the Laboratory of Cognitive Neuroscience at the École Polytechnique Fédérale de Lausanne. “Hallucinations are of high clinical relevance in Parkinson’s disease because they may be an indicator of cognitive decline. In our research we are interested in understanding the brain mechanisms underlying hallucinations and the (possible) related cognitive decline. We hope that our research will help in future to develop new diagnostic tools and therapies.”
To conduct the study, the researchers recruited 75 patients aged 60 to 70 who had been diagnosed with Parkinson’s disease. These patients were divided into two groups: those with minor hallucinations and those without minor hallucinations. The researchers collected data through a combination of clinical evaluations, neuropsychiatric interviews, neuropsychological assessments, and electroencephalography (EEG) measurements.
The patients’ cognitive functions were evaluated using the Parkinson’s Disease Cognitive Rating Scale (PD-CRS), which includes various cognitive tasks. The presence of minor hallucinations was assessed using the hallucinations and psychosis item of the MDS-UPDRS-I clinical scale. Resting-state EEG data were recorded from 19 scalp sites while participants had their eyes open.
The researchers found that among patients with Parkinson’s disease, those who experienced early hallucinations exhibited a more rapid decline in frontal executive cognitive functions over the following five years compared to patients without such hallucinations.
“Although Parkinson’s disease is traditionally and predominantly defined as a motor disease, characterized by tremor, there are also numerous non-motor symptoms (e.g. hallucinations), which are very frequent in Parkinson’s disease,” Bernasconi told PsyPost. “Certain non-motor symptoms appear years before the onset of the motor symptoms and have therefore been identified as prodromal markers for the disease. Concerning hallucinations, we believe that it is important for the person experiencing the hallucinations to share this information with the partner, family. Even the so-called ‘minor’ hallucinations (i.e. presence hallucinations, passage hallucinations and visual illusions) are of clinical relevance, as demonstrated by our recent work.
“Hallucinations should be shared with the treating physician, because treatments may have to be adapted. Also, previous results show that complex visual hallucinations are a good predictor for dementia in Parkinson’s disease. However, complex visual hallucinations usually occur at a rather mid-late stage of the disease, not making them an optimal candidate for an early identification of individuals at risk of cognitive decline. Our results show that minor hallucinations, which usually anticipate complex visual hallucinations, are associated with a more rapid decline of (frontal) cognitive functions. This should raise the attention on the possible role of minor hallucinations as a possible marker for dementia. However, more data and longer studies are needed to confirm the role of minor hallucinations in predicting dementia.”
There was a significant association between the degree of cognitive decline observed over the five-year period and specific alterations in frontal theta (4-8Hz) oscillatory activity, as measured by EEG during the initial assessment.
Frontal theta oscillatory activity refers to a specific pattern of brain wave activity that occurs in the frontal region of the brain. These waves are commonly associated with various cognitive and mental states, including different levels of consciousness, attention, memory, and learning.
Importantly, the researchers found that changes in frontal theta oscillations were unique to patients with Parkinson’s disease who had early hallucinations. These oscillatory alterations were not present in patients with Parkinson’s disease who did not report hallucinations. These findings suggests that changes in the pattern of frontal theta activity may be a biomarker for cognitive decline in these patients.
“Previous evidence has indicated that complex visual hallucinations in Parkinson’s disease are associated with cognitive decline and dementia,” Bernasconi explained. “Yet, visual hallucinations usually occur at a middle to advanced stage of the disease and this does not make them suitable as an early marker or predictor of the later appearing dementia, sometimes 5 years or more. However, growing evidence suggest that complex visual hallucinations are very often preceded years by many of the so-called ‘minor’ hallucinations. Those hallucinations may even precede motor symptoms and the diagnosis of Parkinson’s disease.”
“We therefore hypothesized that ‘minor’ hallucinations might also play a role in identifying cognitive decline. We were surprised that our data aligned up beautifully when integrating the presence of these ‘minor’ hallucinations with frontal brain activity changes that were further associated with changes in frontal lobe function. Hence we were surprised to find this clear, selective and early involvement of changes in the frontal brain associated with minor hallucinations.”
But the study, like all research, includes some limitations.
“Despite the large number of patients included in our study, the results should be replicated in another study to confirm the results,” Bernasconi told PsyPost. “In our current research, we demonstrated that patients with minor hallucinations have a more rapid cognitive decline compared to patients without hallucinations. Future results should follow those patients for even a longer period, to evaluate the progression of the cognitive functions for a period even longer.”
“While there is no approved treatment for Parkinson’s disease and cognitive decline, a better understanding of the underlying mechanisms allowing the development of therapies that aim at slowing down Parkinson’s disease (and therefore cognitive decline) is part of major effort conducted by academic and pharmaceutical industries,” the researcher added. “At the moment various non-pharmacological strategies have been shown to somewhat slow down the progression of cognitive decline in some individuals.”
“For instance, cognitive training, increased social engagement, physical exercise, improved sleep quality and nutrition, and practice mindfulness are among the suggested possibilities to slow down cognitive decline. While those methods may have an effect, it’s essential for individuals with Parkinson’s disease to work closely with their healthcare team to develop a personalized plan that addresses their specific needs and challenges.”
The study, “Theta oscillations and minor hallucinations in Parkinson’s disease reveal decrease in frontal lobe functions and later cognitive decline“, was authored by Fosco Bernasconi, Javier Pagonabarraga, Helena Bejr-Kasem, Saul Martinez-Horta, Juan Marín-Lahoz, Andrea Horta-Barba, Jaime Kulisevsky, and Olaf Blanke.