The profile of attentional impairments and fluctuating attention is similar in PD dementia and DLB with parkinsonism. The current findings do not support the current arbitrary distinctions between these patient groups. Importantly, patients with PD do not experience fluctuating attention.

A fundamental question in neuroscience is how brain organisation gives rise to humans' unique cognitive abilities. Although complex cognition is widely assumed to rely on frontal and parietal brain regions, the underlying mechanisms remain elusive: current approaches are unable to disentangle different forms of information processing in the brain. Here, we introduce a powerful framework to identify synergistic and redundant contributions to neural information processing and cognition. Leveraging multimodal data including functional MRI, PET, cytoarchitectonics and genetics, we reveal that synergistic interactions are the fundamental drivers of complex human cognition. Whereas redundant information dominates sensorimotor areas, synergistic activity is closely associated with the brain's prefrontal-parietal and default networks; furthermore, meta-analytic results demonstrate a close relationship between high-level cognitive tasks and synergistic information. From an evolutionary perspective, the human brain exhibits higher prevalence of synergistic information than non-human primates. At the macroscale, we demonstrate that high-synergy regions underwent the highest degree of evolutionary cortical expansion. At the microscale, human-accelerated genes promote synergistic interactions by enhancing synaptic transmission. These convergent results provide critical insights that synergistic neural interactions underlie the evolution and functioning of humans' sophisticated cognitive abilities, and demonstrate the power of our widely applicable information decomposition framework.

These findings indicate that the butyrylcholinesterase enzyme is a major regulator of attention especially in cholinergic deficiency states through its ability to hydrolyse acetylcholine. Pharmacologic manipulation of this enzyme may be a viable strategy in dementia treatment and, with butyrylcholinesterase genotyping, may provide pharmacogenomic treatment of dementia.

Dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia. Siblings of affected individuals are at greater risk of developing DLB, but little is known about the underlying genetic basis of the disease. We set out to determine whether mutations in known highly penetrant neurodegenerative disease genes are found in patients with DLB. Whole-exome sequencing was performed on 91 neuropathologically confirmed cases of DLB, supplemented by independent APOE genotyping. Genetic variants were classified using established criteria, and additional neuropathological examination was performed for putative mutation carriers. Likely pathogenic variants previously described as causing monogenic forms of neurodegenerative disease were found in 4.4% of patients with DLB. The APOE ɛ4 allele increased the risk of disease (P=0.0001), conferred a shorter disease duration (P=0.043) and earlier age of death (P=0.0015). In conclusion, although known pathogenic mutations in neurodegenerative disease genes are uncommon in DLB, known genetic risk factors are present in >60% of cases. APOE ɛ4 not only modifies disease risk, but also modulates the rate of disease progression. The reduced penetrance of reported pathogenic alleles explains the lack of a family history in most patients, and the presence of variants previously described as causing frontotemporal dementia suggests a mechanistic overlap between DLB and other neurodegenerative diseases.