Background Given the projected trends in population ageing and population growth, the number of people with dementia is expected to increase. In addition, strong evidence has emerged supporting the importance of potentially modifiable risk factors for dementia. Characterising the distribution and magnitude of anticipated growth is crucial for public health planning and resource prioritisation. This study aimed to improve on previous forecasts of dementia prevalence by producing country-level estimates and incorporating information on selected risk factors. MethodsWe forecasted the prevalence of dementia attributable to the three dementia risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 (high body-mass index, high fasting plasma glucose, and smoking) from 2019 to 2050, using relative risks and forecasted risk factor prevalence to predict GBD risk-attributable prevalence in 2050 globally and by world region and country. Using linear regression models with education included as an additional predictor, we then forecasted the prevalence of dementia not attributable to GBD risks. To assess the relative contribution of future trends in GBD risk factors, education, population growth, and population ageing, we did a decomposition analysis. FindingsWe estimated that the number of people with dementia would increase from 57•4 (95% uncertainty interval 50•4-65•1) million cases globally in 2019 to 152•8 (130•8-175•9) million cases in 2050. Despite large increases in the projected number of people living with dementia, age-standardised both-sex prevalence remained stable between 2019 and 2050 (global percentage change of 0•1% [-7•5 to 10•8]). We estimated that there were more women with dementia than men with dementia globally in 2019 (female-to-male ratio of 1•69 [1•64-1•73]), and we expect this pattern to continue to 2050 (female-to-male ratio of 1•67 [1•52-1•85]). There was geographical heterogeneity in the projected increases across countries and regions, with the smallest percentage changes in the number of projected dementia cases in high-income Asia Pacific (53% [41-67]) and western Europe (74% [58-90]), and the largest in north Africa and the Middle East (367% [329-403]) and eastern sub-Saharan Africa (357% [323-395]). Projected increases in cases could largely be attributed to population growth and population ageing, although their relative importance varied by world region, with population growth contributing most to the increases in sub-Saharan Africa and population ageing contributing most to the increases in east Asia. Interpretation Growth in the number of individuals living with dementia underscores the need for public health planning efforts and policy to address the needs of this group. Country-level estimates can be used to inform national planning efforts and decisions. Multifaceted approaches, including scaling up interventions to address modifiable risk factors and investing in research on biological mechanisms, will be key in addressing the expected incr...

Objectives To estimate initial levels of symptoms of depression and anxiety, and their changes during the early months of the COVID‐19 pandemic in Australia; to identify trajectories of symptoms of depression and anxiety; to identify factors associated with these trajectories. Design, setting, participants Longitudinal cohort study; seven fortnightly online surveys of a representative sample of 1296 Australian adults from the beginning of COVID‐19‐related restrictions in late March 2020 to mid‐June 2020. Main outcome measures Symptoms of depression and anxiety, measured with the Patient Health Questionnaire (PHQ‐9) depression and Generalised Anxiety Disorder (GAD‐7) scales; trajectories of symptom change. Results Younger age, being female, greater COVID‐19‐related work and social impairment, COVID‐19‐related financial distress, having a neurological or mental illness diagnosis, and recent adversity were each significantly associated with higher baseline depression and anxiety scores. Growth mixture models identified three latent trajectories for depression symptoms (low throughout the study, 81% of participants; moderate throughout the study, 10%; initially severe then declining, 9%) and four for anxiety symptoms (low throughout the study, 77%; initially moderate then increasing, 10%; initially moderate then declining, 5%; initially mild then increasing before again declining, 8%). Factors statistically associated with not having a low symptom trajectory included mental disorder diagnoses, COVID‐19‐related financial distress and social and work impairment, and bushfire exposure. Conclusion Our longitudinal data enabled identification of distinct symptom trajectories during the first three months of the COVID‐19 pandemic in Australia. Early intervention to ensure that vulnerable people are clinically and socially supported during a pandemic should be a priority.

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90 Y-microsphere selective internal radiation therapy (SIRT) is a valuable treatment in unresectable hepatocellular carcinoma (HCC). Partition-model predictive dosimetry relies on differential tumor-to-nontumor perfusion evaluated on pretreatment 99m Tcmacroaggregated albumin (MAA) SPECT/CT. The aim of this study was to evaluate agreement between the predictive dosimetry of in tumor volumes (TVs) and nontumor volumes (NTVs) for glass and resin spheres. The Lin concordance (r c ) was used to measure accuracy (C b ) and precision (r). Results: Administered activity ranged from 0.8 to 1.9 GBq for glass spheres and from 0.6 to 3.4 GBq for resin spheres, and the respective TVs ranged from 2 to 125 mL and from 6 to 1,828 mL. The mean dose D In selective internal radiation therapy (SIRT), 90 Y-microsphere radioembolization is a valuable therapeutic option in patients presenting with unresectable hepatocellular carcinoma (HCC) not eligible for other therapeutic options (1-3).SIRT with 90 Y-charged microspheres relies on differential vascularization between tumor and nontumor liver parenchyma, resulting in favorable, potentially tumoricidal, deposition of microsphere activity in tumors while minimizing absorbed dose to the functional parenchyma, thus preventing toxicity. Two microsphere types are clinically available: resin spheres (SIR spheres; SirTex Medical Ltd.) and glass spheres (TheraSphere; Nordion Inc.). Despite being of similar size (;30 mm), these two types of sphere differ in specific activity, density (ffi 4 · 10 5 glass spheres/GBq; ffi 2 · 10 7 resin spheres/GBq), and injection solution (NaCl for glass spheres; water for resin spheres), leading to potential differences in embolic effect and local variations in the radiation dose deposited in tissues.Predictive dosimetry has included hepatic CT angiography for catheter positioning and partition modeling based on 99m Tcmacroaggregate albumin (MAA) SPECT/CT acquisition (4,5).The manufacturer-recommended activity for resin spheres is based on a semiempiric formula including body surface area (6,7) and tumor burden. This approach can be refined using a 3-compartment partition model (4) including the lungs, liver TVs, and liver NTVs derived from a pretreatment 99m Tc-MAA SPECT/CT scan. The prescribed glass sphere activity is based on a 2-compartment model (lungs and targeted liver regions) aiming to deliver a dose of 80-150 Gy to the targeted liver volume.90 Y time-of-flight (TOF) PET/CT dosimetry (8) provides a valuable tool to verify 99m Tc-MAA SPECT/CT-based predictive dosimetry.

Purpose To present the acceptance and the commissioning, to define the reference dose, and to prepare the reference data for a quality assessment (QA) program of an ultra‐high dose rate (UHDR) electron device in order to validate it for preclinical animal FLASH radiotherapy (FLASH RT) experiments and for FLASH RT clinical human protocols. Methods The Mobetron® device was evaluated with electron beams of 9 MeV in conventional (CONV) mode and of 6 and 9 MeV in UHDR mode (nominal energy). The acceptance was performed according to the acceptance protocol of the company. The commissioning consisted of determining the short‐ and long‐term stability of the device, the measurement of percent depth dose curves (PDDs) and profiles at two different positions (with two different dose per pulse regimen) and for different collimator sizes, and the evaluation of the variability of these parameters when changing the pulse width and pulse repetition frequency. Measurements were performed using a redundant and validated dosimetric strategy with alanine and radiochromic films, as well as Advanced Markus ionization chamber for some measurements. Results The acceptance tests were all within the tolerances of the company's acceptance protocol. The linearity with pulse width was within 1.5% in all cases. The pulse repetition frequency did not affect the delivered dose more than 2% in all cases but 90 Hz, for which the larger difference was 3.8%. The reference dosimetry showed a good agreement within the alanine and films with variations of 2.2% or less. The short‐term (resp. long‐term) stability was less than 1.0% (resp. 1.8%) and was the same in both CONV and UHDR modes. PDDs, profiles, and reference dosimetry were measured at two positions, providing data for two specific dose rates (about 9 Gy/pulse and 3 Gy/pulse). Maximal beam size was 4 and 6 cm at 90% isodose in the two positions tested. There was no difference between CONV and UHDR mode in the beam characteristics tested. Conclusions The device is commissioned for FLASH RT preclinical biological experiments as well as FLASH RT clinical human protocols.

Sex differences in late-life memory decline may be explained by sex differences in dementia risk factors. Episodic memory and dementia risk factors were assessed in young, middle-aged and older adults over 12 years in a population-based sample (N = 7485). For men in midlife and old age, physical, cognitive and social activities were associated with less memory decline, and financial hardship was associated with more. APOE e4 and vascular risk factors were associated with memory decline for women in midlife. Depression, cognitive and physical activity were associated with memory change in older women. Incident midlife hypertension (β = − 0.48, 95% CI − 0.87, − 0.09, p = 0.02) was associated with greater memory decline in women and incident late-life stroke accounted for greater memory decline in men (β = − 0.56, 95% CI − 1.12, − 0.01), p = 0.05). Women have fewer modifiable risk factors than men. Stroke and hypertension explained sex differences in memory decline for men and women respectively.

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This study aimed to determine whether sulcal morphology differs between middle age (MA) and older healthy individuals. Furthermore, we sought to determine whether age-related differences in sulcal characteristics were more strongly associated with differences in local or global cortical volumes. Participants (age 44–50, N = 403; age 64–70, N = 390) from the Personality and Total Health Through Life (PATH) study were included. Sulci were 17.3% wider, on average, in old age (OA) compared to MA participants, with the largest difference in the left superior frontal sulcus. Differences in sulcal width were generally higher in males than females. Differences in the width of the superior frontal and central sulci were significantly associated with differences in the volume of adjacent local gyri, while age-related differences in the width of lateral and superior temporal sulci were associated with differences in whole brain cortical volume. These findings suggest that sulcal characteristics provide unique information about changes in local and global brain structure in aging.