Are Neuropsychiatric Symptoms an Early Sign of Parkinson’s?
WPC 2013 allowed us to present the results of a longitudinal study in patients people with Parkinson’s disease. We showed that cognitive performance is linked to changes in the brain’s structure and they can be measured over time. Specifically, some brain regions were reported to diminish their thickness, as cognitive performance diminishes. This study outlined the possibility of using brain morphology as a marker for predicting current and future cognitive performance and was published in a well renowned journal. Interestingly, the results were further confirmed by another study, performed in a larger cohort and published in the same journal.
Since then, we extended our research to assess the potential association between neuropsychiatric symptoms (NPS) and brain morphology. Indeed, we reported significant influence of depression on brain’s structure as well as cognitive performance in patients with Parkinson’s disease. Since NPS were confirmed to influence brain’s structure as well as the cognitive performance, this opened the door to our next step - verification if NPS could be a marker for predicting future development of Parkinson’s disease and whether NPS could actually show us the correct path towards rehabilitation. This became my main research direction as principal investigator at Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal, CIUSSS-CSMTL and University of Montreal.
The general understanding about Parkinson’s disease changed a lot. Initially it was considered mainly a motor-impairment due to neuronal death and loss of dopamine concentration. This neuromediator is required for proper functioning of the brain loops associated with decision-making processes, and its loss gradually impairs not only motor functioning but also cognitive performance. Nevertheless, it has been widely accepted now that Parkinson’s disease pathology includes a multitude of clinical presentations.
Initially a protein imbalance was considered as the culprit of Parkinson’s disease development. Specifically alpha-synuclein’s characteristics of forming large conglomerates that lead to neuronal death. Yet distinct results have emerged. Alpha-synuclein has been shown to be involved in regulation of neuronal functioning: release and regulation the neurotransmitters, expressing the genes, response to stress by counteracting oxidative response and toxic insults. In fact, alpha-synuclein might be a protective agent beneficial for cell survival by acting against the damage produced by dopamine.
In the context of such opposite results on the structural level, the assessment of brain’s function emerge as a potential game changer. NPS as a functional and behavioral group showed the potential for depicting early stage changes and increased the risk of neurodegenerative diseases like Parkinson's disease. An important advantage of NPS is their ease to be quantified.
Though NPS encompasses multiple presentations (depression, anxiety, apathy, hallucinations, sleep-related disorders), only some of them are associated with Parkinson’s disease. For example hallucinations can manifest in up to 60% of patients at least once in 12 years prior to disease development. Typically, these are visual hallucinations of formed images of people or animals, often occurring in the evening or at times when patients are alone in an environment with little stimulation. Depression and apathy would manifest in up to 40% of patients in the beginning of the disease. Sleep related impairments have also been linked with future development of Parkinson’s disease. Specifically, a recent study on 1280 patients reported that 73% of participants who presented “Rapid eye movement sleep behavior disorder” converted to Parkinson’s disease after 12-year follow-up. Anxiety occurs in at least one-third of patients with Parkinson’s disease long before the diagnosis or after the disease has developed. In fact, according to one study in of more than 174.000 participants in Taiwan published in 2015, participants with anxiety were more likely to develop Parkinson’s disease compared to those without anxiety. Furthermore, results were significant after adjustment for age, sex, comorbid depression and other Parkinson’s disease factors. On the other hand, impulse control disorders, which are present in up to 13% of patients, might have a protective factor against cognitive decline when compared to patients without such disorders.
It is still challenging to clearly describe the association between NPS, cognitive performance and Parkinson’s disease. Maybe this is due to low number of participants and the presence of high subjectivity in the evaluations. One approach to deal with this challenge is to increase the number of participants and increase evaluation’s objectivity, which is our current main goal.
Alexandru Hanganu is an Assistant Professor and Researcher at the University of Montreal, Department of Psychology; Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal, CIUSSS-CSMTL, Canada. He was selected as a Hot Topics presenter at the WPC 2013 where he spoke about his work.
This research was first shared as an abstract at the WPC 2013 in Montreal. WPC is pleased to support abstract authors by sharing their ongoing work. Digital versions of WPC abstract books can be downloaded from the past three Congresses HERE.
Ideas and opinions expressed in this post reflect that of the authors solely. They do not reflect the opinions or positions of the World Parkinson Coalition®