Estimating demand for potential disease-modifying therapies for Alzheimer's disease in the UK.

BACKGROUND: Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring. AIMS: To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK. METHOD: We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment. RESULTS: We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally. CONCLUSIONS: Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.

Rapid pre-attentive processing of a famous speaker: Electrophysiological effects of Angela Merkel's voice.

The recognition of human speakers by their voices is a remarkable cognitive ability. Previous research has established a voice area in the right temporal cortex involved in the integration of speaker-specific acoustic features. This integration appears to occur rapidly, especially in case of familiar voices. However, the exact time course of this process is less well understood. To this end, we here investigated the automatic change detection response of the human brain while listening to the famous voice of German chancellor Angela Merkel, embedded in the context of acoustically matched voices. A classic passive oddball paradigm contrasted short word stimuli uttered by Merkel with word stimuli uttered by two unfamiliar female speakers. Electrophysiological voice processing indices from 21 participants were quantified as mismatch negativities (MMNs) and P3a differences. Cortical sources were approximated by variable resolution electromagnetic tomography. The results showed amplitude and latency effects for both MMN and P3a: The famous (familiar) voice elicited a smaller but earlier MMN than the unfamiliar voices. The P3a, by contrast, was both larger and later for the familiar than for the unfamiliar voices. Familiar-voice MMNs originated from right-hemispheric regions in temporal cortex, overlapping with the temporal voice area, while unfamiliar-voice MMNs stemmed from left superior temporal gyrus. These results suggest that the processing of a very famous voice relies on pre-attentive right temporal processing within the first 150 ms of the acoustic signal. The findings further our understanding of the neural dynamics underlying familiar voice processing.

The impact of high-end ultrasound in the management of a patient with neuroendocrine tumor of the ileum.

Diagnostic imaging of jejuno-ileal neuroendocrine tumors (NETs) has been described as challenging. Follow-up requires the detection of metastatic spread as well as screening for local recurrence. Multimodal imaging concepts must often be applied.We report the case of a 45-year-old man with a history of ileal NET. At 2 points in follow-up of our patient, information provided by high-end ultrasound changed prognosis and treatment considerably: when positron emission tomography/computed tomography newly detected suspected hepatic metastases, contrast-enhanced ultrasound correctly identified the lesions as intrahepatic vascular shunts. Moreover, profound B-mode ultrasound solely detected ileal recurrence, leading to early removal of the tumor.