The aging brain is vulnerable to a wide array of neuropathologies. Prior work estimated that the three most studied of these, Alzheimer's disease (AD), infarcts, and Lewy bodies, account for about 40% of the variation in late life cognitive decline. However, that estimate did not incorporate many other diseases that are now recognized as potent drivers of cognitive decline (e.g. limbic predominant age-related TDP-43 encephalopathy [LATE-NC], hippocampal sclerosis, other cerebrovascular conditions). We examined the degree to which person-specific cognitive decline in old age is driven by a wide array of neuropathologies. 1,164 deceased participants from two longitudinal clinical-pathologic studies, the Rush Memory and Aging Project and Religious Orders Study, completed up to 24 annual evaluations including 17 cognitive performance tests and underwent brain autopsy. Neuropathologic examinations provided 11 pathologic indices, including markers of AD, non-AD neurodegenerative diseases (i.e. LATE-NC, hippocampal 30-36% of the variation, non-AD neurodegenerative indices 4-10%, and cerebrovascular indices 3-8%. Finally, the 11 pathologic indices combined accounted for less than a third of the variation in the onset of terminal decline (28%) and rates of preterminal (32%) and terminal decline (19%). Although age-related neuropathologies account for a large proportion of the variation in late life cognitive decline, considerable variation remains unexplained even after considering a wide array of neuropathologies. These findings highlight the complexity of cognitive aging and have important implications for the ongoing effort to develop effective therapeutics and identify novel treatment targets.
  To characterise the incidence of clinically diagnosed Paget's disease of bone in the UK during 1999-2015 and to determine variation in incidence of disease by age, sex, geography and level of deprivation.
 
  Incident cases of Paget's disease occurring between 1999-2015 were identified from primary care records. Overall crude incidence and incidence stratified by age and sex was calculated each year from 1999-2015. Direct age- and sex-standardised incidence was also calculated. We used Poisson regression to look at variation in incidence by deprivation and UK region.
 
  3,592 incident cases of Paget's disease were identified between 1999-2015. Incidence increased with age and at all ages was greater in men than women. In women and men, respectively, crude incidence increased from 0.037 and 0.074 per 10 000 population per year among those aged 45-49 years to 3.7 and 6.3 per 10 000 population per year among those 85 years and older. Overall standardised incidence reduced from 0.75/10 000 person-years in 1999-0.20/10 000 person-years in 2015. After adjustment for age and sex, incidence was >30% higher in the most, compared with least deprived quintile of deprivation. There was evidence of geographic variation, with highest incidence in the North West of England, which persisted after adjustment for age, sex, and level of deprivation.
 
  The incidence of clinically diagnosed Paget's disease has continued to decrease since 1999. The reason for the decline in incidence remains unknown though the rapidity of change points to an alteration in one or more environmental determinants.
 The incidence of clinically diagnosed Paget's disease has continued to decrease since 1999. The reason for the decline in incidence remains unknown though the rapidity of change points to an alteration in one or more environmental determinants.
  To characterize the epidemiology of temporal artery biopsy-positive (TAB+) giant cell arteritis (GCA), including trends in incidence, seasonal variation, and prevalence in Skåne, the southernmost region of Sweden.
 
  All histopathology reports of TABs from 1997 through 2019 were reviewed to identify patients diagnosed with TAB+ GCA. Incidence rates based on the 23-year period and the point-prevalence at 31 December, 2014 were determined. An alternative prevalence calculation included only TAB+ GCA patients living in the study area and receiving immunosuppressant therapy on the point-prevalence date.
 
  1360 patients were diagnosed with TAB+ GCA (71% female). The average annual incidence 1997-2019 was 13.3 (95% CI 12.6-14.0) per 100 000 inhabitants aged ≥50 years and was higher in females (17.8; 95% CI 16.7-18.9) than in males (8.2; 95% CI 7.4-9.0). The age- and sex- standardized incidence declined from 17.3 in 1997-8.7 in 2019, with incidence ratio (IR) of 0.98 per year (95% CI 0.98-0.99). A seasonal variation was observed with higher incidence during spring than winter [IR 1.19 (95% CI 1.03-1.39)]. The overall point-prevalence of TAB+ GCA was 127.1 per 100 000 (95% CI 117-137.3) and was 75.5 (95% CI 67.7-83.3) when including only patients receiving immunosuppressants.
 
  Over the past two decades, the incidence of biopsy-confirmed GCA has decreased by ∼2% per year. Still, a high prevalence of GCA on current treatment was observed.  https://www.selleckchem.com/products/arv-110.html  More cases are diagnosed during spring and summer than in the winter.
 Over the past two decades, the incidence of biopsy-confirmed GCA has decreased by ∼2% per year. Still, a high prevalence of GCA on current treatment was observed. More cases are diagnosed during spring and summer than in the winter.Functional recovery after stroke is dose-dependent on the amount of rehabilitative training. However, rehabilitative training is subject to motivational hurdles. Decision neuroscience formalizes drivers and dampers of behaviour and provides strategies for tipping motivational trade-offs and behaviour change. Here, we used one such strategy, upfront voluntary choice restriction ('precommitment'), and tested if it can increase the amount of self-directed rehabilitative training in severely impaired stroke patients. In this randomized controlled study, stroke patients with working-memory deficits (n = 83) were prescribed daily self-directed gamified cognitive training as an add-on to standard therapy during post-acute inpatient neurorehabilitation. Patients allocated to the precommitment intervention could choose to restrict competing options to self-directed training, specifically the possibility to meet visitors. This upfront choice restriction was opted for by all patients in the intervention group and highly effective.