The study of sex differences in Alzheimer’s disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer’s disease (>90% in the 7th decade). Yet, sex differences in Alzheimer’s disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-center, cross-sectional study of 628 adults with Down syndrome (46% female, 44.4 [34.6; 50.7] years) we compared Alzheimer’s disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG-DS), modified cued recall test (mCRT), and determinations of brain amyloidosis (CSF amyloid-β (Aβ)42/40, amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament-light (NfL), total-tau, fluorodeoxyglucose(FDG)-PET, MRI). We used within-group locally estimated scatterplot smoothing (LOESS) models to compare the trajectory of biomarker changes with age in women versus men, as well as by apolipoprotein (APOE) ε4 carriership. Our work revealed similar prevalence, age at diagnosis, and CAMCOG-DS scores by sex, but men showed lower mCRT scores from age 45 compared with women. AT(N) biomarkers were comparable in men and women. When considering APOE ε4, women ε4 carriers showed a 3-year earlier age at diagnosis compared with women non-carriers (50.5 versus 53.2 years, p=0.01). This difference was not seen in men (52.2 vs 52.5 years, p=0.76). Our exploratory analyses considering sex, APOE ε4, and biomarkers showed that women ε4 carriers tended to exhibit lower CSF Aβ42/Aβ40 ratio and lower hippocampal volume compared with women without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer’s disease in adults with Down syndrome. Consideration of APOE ε4 haplotype, particularly in women, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting, and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine.

Aim To assess if digital PET/CT improves liver lesion detectability compared to analog PET/CT in patients with known or suspected liver metastases. Materials and methods We prospectively included 83 cancer patients, with one or more of these conditions: history of liver metastases, clinical risk of having liver metastases or presence of suspected liver metastases on the first of the two PET/CTs. All patients were consecutively scanned on each PET/CT on the same day after a single [18F]fluorodeoxyglucose dose injection. The order of acquisition was randomly assigned. Three nuclear medicine physicians assessed both PET/CTs by counting the foci of high uptake suspicious of liver metastases. Findings were correlated with appropriate reference standards; 19 patients were excluded from the analysis due to insufficient lesion nature confirmation. The final sample consisted of 64 patients (34 women, mean age 68 ± 12 years). Results As per-patient analysis, the mean number of liver lesions detected by the digital PET/CT (3.84 ± 4.25) was significantly higher than that detected by the analog PET/CT (2.91 ± 3.31); P < 0.001. Fifty-five patients had a positive PET/CT study for liver lesions. In 26/55 patients (47%), the digital PET/CT detected more lesions; 7/26 patients (27%) had detectable lesions only by the digital system and had <10 mm of diameter. Twenty-nine patients had the same number of liver lesions detected by both systems. In nine patients both PET/CT systems were negative for liver lesions. Conclusion Digital PET/CT offers improved detectability of liver lesions over the analog PET/CT in patients with known or suspected liver metastases.

Approximately 20% of type 1 diabetes (T1D) patients have an impaired awareness of hypoglyceamia (IAH). IAH represents a risk factor for severe and recurrent hypoglycaemic events, which can lead to brain damage. Because no effective treatments are currently available to prevent IAH in this population, characterising the set of brain alterations associated with IAH may reveal novel preclinical diagnostic or therapeutic strategies. Using state‐of‐the art neuroimaging techniques, we compared 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) uptake at rest between 10 T1D patients with IAH and nine patients with normal awareness of hypoglycaemia (NAH). T1D‐IAH patients showed a pattern of increased FDG‐PET uptake with respect to NAH patients (P < .05 corrected). Topographically, glucose metabolism was increased in the frontal and precuneus regions. Importantly, within the IAH group, this abnormal hypermetabolism correlated with IAH severity. This hypermetabolic state appeared to be unrelated to compensatory mechanisms as a result of reduced grey matter density or a neuroinflammatory state. We observed an abnormal increase in FDG‐uptake in T1D patients with IAH in brain regions strongly related to cognition. Because this hypermetabolic state correlated with IAH severity, its biological characterisation could reveal new preventive or therapeutic strategies. A possible mechanism could be that glucose transport is increased in hypoglycaemia unawareness to compensate for recurrent hypoglycaemia, although this need to be confirmed in further research.