Unravelling the relation among fatigue, fatigability and attention in Parkinson's disease

Fatigue is one of the most disabling non-motor symptoms in Parkinson's disease (PD). Evidence suggests that it may be underpinned by altered central fatigability mechanisms and deficits in attentional control. This study investigated the relationships among subjective fatigue, executive-attentional dysfunction, and central fatigability in PD. Twenty-seven PD patients and 21 age- and education-matched healthy controls underwent a multidimensional assessment including subjective fatigue (16-item Parkinson Fatigue Scale; PFS), perceived cognitive difficulties (Perceived Cognitive Difficulties Scale; PCDS), executive functioning (Frontal Assessment Battery; FAB), and sustained attention measured through a computerized reaction time task (Sustained Attention Task; SAT). Central fatigability was assessed using transcranial magnetic stimulation (TMS), measuring post-exercise depression (PED) of cortical excitability via changes in resting motor threshold (RMT), motor evoked potential (MEP) amplitude, and cortical silent period (CSP) duration before (PRE) and after (POST) a fatiguing pinching task. PD patients reported higher fatigue, more cognitive complaints, lower FAB scores, and longer SAT latencies. PED was impaired in PD, with lower PRE/POST % of change of RMT, MEP amplitude, and CSP as compared to HCs. PFS correlated with PCDS (r = 0.513), FAB (r = -0.410), SAT latency (r = 0.519), PRE/POST % of change of CSP (r = -0.497). All p < 0.01. SAT latency, PRE/POST % change of MEP, PRE/POST % of change of CSP independently predicted fatigue. These results indicate that fatigue in PD may arise from disrupted inhibitory PED mechanisms and reduced attentional efficiency, converging toward the hypothesis that GABAergic dysfunction could impair cortical adaptability to effort.