Improving fatigue and neurocognitive impairment in progressive neurological disorders: a systematic and narrative review

Objective To provide a comprehensive overview of the interventions and their effectiveness used to simultaneously improve fatigue and neurocognitive impairment in patients with progressive neurological disorders. Data sources A systematic search was conducted in four databases (PubMed, Embase.com, APA PsycInfo, and CINAHL). Study selection Two independent reviewers selected interventional studies that reported on the effects of symptom management interventions on both patient-reported fatigue and neurocognitive outcomes. Data extraction Study details, intervention characteristics, assessment tools, and outcomes were extracted. The results were synthesized through a narrative approach. Data synthesis We identified 3188 studies, of which 91 were included (MS = 80, Parkinson's disease = 8, glioma = 3). Studies investigated physical activity (n = 26), pharmacological treatments (n = 25), cognitive rehabilitation (n = 12), multimodal interventions (n = 6), mind-body and psychological interventions (n = 4), noninvasive neurostimulation (n = 4), cannabis derivatives (n = 3), and other interventions (n = 7). Overall, study designs and intervention protocols were heterogeneous across studies. Of the 91 identified studies, 24 demonstrated a positive effect on both fatigue and neurocognitive functioning (referred to as F + NCF+). Particularly, aerobic physical activity demonstrated consistent improvements in fatigue and neurocognitive functioning (12/26 studies F + NCF+). Other interventions were less successful; for example, only 2/25 pharmacological interventions and 2/12 cognitive rehabilitation programs were F + NCF+. Across studies, methodologies including guidance by a healthcare provider, on-site program administration, group-based elements, and interventional personalization contributed to intervention success. Conclusions A considerable number of heterogeneous studies explored various interventions. However, only a subset instigated improvement in fatigue and neurocognitive impairments. Physical activity emerged as a particularly promising intervention, potentially alleviating both fatigue and neurocognitive impairment across progressive neurological disorders. There is an unmet need for personalized and guided interventions targeting these co-occurring symptoms, which should be addressed in future studies.