Predicting Parkinson’s disease: worthwhile but are we there yet?

Abstract

Current opinion suggests there is a preclinical phase in idiopathic Parkinson’s disease (PD) with a latent period somewhere between 6 and 40 years. 1,2 This prodrome, sometimes also termed the presymptomatic or pre -motor phase of PD, needs to be distinguished from non -motor features such as neuropsychiatric symptoms, dysautonomia, fatigue, and so on,3 only some of which start before the classical motor triad of PD (tremor, rigidity, and bradykinesia). Clearly, prediction of PD would be straight forward in those few parkinsonian patients with monogenetic disorder that in theory may be identified from birth, but most such mutations are very rare. A variety of predictive biochemical tests4 are proposed but as yet none is sufficiently reliable. Fluorodopa positron emission tomography (PET) or dopamine transporter imaging (DATScan) will detect deficiency of striatal dopamine but by this stage the motor phase–at least neurochemically–has probably begun. So might symptoms or signs foretell PD, and if so, which ones and how reliably? Such predictive research has many potential benefits as it enhances our understanding of the underlying disease mechanism, identifies subjects at risk of future PD, and provides an opportunity for neuroprotective therapy if this is eventually found to be effective. Braak pathological staging5 represents a landmark in our understanding of PD and may provide a basis for any proposed clinically based predictive features of the motor stage (see fig 1 and table). The first two stages represent the pathological substrate of preclinical PD while stage III straddles the premotor and motor phases. It is estimated that when some 50% of nigral cells are lost the first motor symptoms will appear,6 heralding the end of the premotor phase; hence tests of structures involved at this juncture such as the amygdala and pedunculopontine nucleus are unlikely to be rewarding …