The European Journal of Neuroscience recently published a report (“The Prodromes of Parkinson’s Disease”) that delineates some of the symptoms you may get before your doctor concludes that you have Parkinson’s. As many of us know from first-hand experience, things went wrong which we lived with for years before a doctor identified PD.
From the report’s introductory paragraph (minus all the references to previously published research, but preserving the spelling “whilst”):
“Parkinson’s disease (PD) is diagnosed when bradykinesia occurs along with rigidity or tremor, with consideration of additional supporting and exclusionary features. However, patients frequently report having had symptoms for years before the diagnosis, and database analyses have shown that a number of clinical features occur more frequently in patients with a later diagnosis of PD than controls. Whilst it is now accepted that a long prodromal phase can exist, the progression of clinical features and the underlying pathological correlates during this phase are poorly understood, and reliably identifying people in this phase remains a challenge. Neuropathological studies suggest that at the time of diagnosis there has been significant neuronal loss in the substantia nigra, and within 4 years of diagnosis, there is almost complete loss of dopamine terminals in the dorsal putamen. Through extrapolation of these data, it has been estimated that the disease process, in the brain at least, has been developing for 5 to 10 years before diagnosis. Understanding the clinical and pathophysiological aspects of this prodromal phase of PD is a key challenge in PD research to enable earlier diagnosis, investigation of the pathophysiological cascade and, ultimately, disease-modifying treatment.”
This sounds frustrating, scary and annoying. Frustrating, because if only you and your doctor had realized that you were displaying precursor symptoms to PD, you might have jumped on the “let me lead a healthier life” bandwagon earlier, with exercise, the right foods, and medications. Scary, because since you’re now getting a late start on fighting the disease, you’re so far behind in the race to save your substantia nigra and dopamine terminals that you may never come out ahead. And annoying, due (to my ears, at least) to the poetic-yet-hyperbolic term “pathophysiological cascade” – did the authors think that Parkies would never read this?
The bulk of the article deals with well-known prodromal features:
- Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD)
- Idiopathic anosmia (inability to smell)
- Families with certain genetic mutations that often accompany PD
Let’s review them one-by-one.
REM Sleep Behavior Disorder (RBD)
RBD occurs when you’re sleeping and your muscles snap out of their relaxed state while you simultaneously dream vividly. Even though you’re technically asleep, you may start shouting and thrashing about, possibly injuring yourself or your bed partner(s). According to the authors, this typically happens in older men (ages 50-65). To measure this accurately, you need to be monitored in a sleep lab while you sleep.
But the RBD prodrome is more than that. Again from the article (and minus the citations): “As well as the sleep disorder, the RBD prodrome of PD includes objective motor and non-motor deficits, with impaired balance, abnormal gait, and other fine and gross motor slowing…. In [a] 10-year prospective study in an RBD cohort, abnormal color vision, anosmia and mild motor dysfunction were all strongly predictive of conversion to PD.”
In other words, a lot happens before your first visit to the neurologist.
Anosmia
Lots of people lose their ability to smell, especially as they age. Most don’t get PD. Thus, it’s hard to count anosmia alone as a predictor of future Parkinson’s disease. However, one study found that individuals with impaired olfaction who also had a first-degree relative with Parkinson’s, had an increased risk of developing Parkinson’s themselves within two years.
Genes
The two sections on genetic mutations in this report are beyond my ability to comprehend. One focuses on a mutation in the LRRK2 gene, which causes about 1% of all PD cases. The other section discusses mutations in the GBA gene. Click here for the actual report if this interests you and you want to learn more.
Bottom Line
I’ll quote again from the conclusion: “Retrospective studies and examination of newly diagnosed patients with PD have suggested a long prodromal phase of PD, beginning several years before definite features of PD.”
Which is why now, more than ever, we need the time-traveling DeLorean that Michael J. Fox used in Back to the Future, so we can examine and forestall not only Michael’s blossoming into Parkinson’s disease, but also everyone else’s.
