Monetary value of informal caregiving in dementia from a societal perspective

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Effect of Exercise on Drug-Related Falls Among Persons with Alzheimer's Disease : A Secondary Analysis of the FINALEX Study

Introduction No study has investigated how exercise modifies the effect of fall-related drugs (FRDs) on falls among people with Alzheimer's disease (AD). Objective The aim of this study was to investigate how exercise intervention and FRDs interact with fall risk among patients with AD. Methods In the FINALEX trial, community-dwelling persons with AD received either home-based or group-based exercise twice weekly for 1 year (n = 129); the control group received normal care (n = 65). The number of falls was based on spouses' fall diaries. We examined the incidence rate ratios (IRRs) for falls among both non-users and users of various FRDs (antihypertensives, psychotropics, drugs with anticholinergic properties [DAPs]) in both control and combined intervention groups. Results Between the intervention and control groups, there was no difference in the number of falls among those without antihypertensives or psychotropics. In the intervention group taking antihypertensives, the IRR was 0.5 falls/person-year (95% confidence interval [CI] 0.4-0.6), while in the control group, the IRR was 1.5 falls/person-year (95% CI 1.2-1.8) [p <0.001 for group, p = 0.067 for medication, p <0.001 for interaction]. Among patients using psychotropics, the intervention group had an IRR of 0.7 falls/person-year (95% CI 0.6-0.9), while the control group had an IRR of 2.0 falls/person-year (95% CI 1.6-2.5) [p <0.001 for group, p = 0.071 for medication, p <0.001 for interaction]. There was a significant difference in falls between the intervention and control groups not using DAPs (0.6, 95% CI 0.5-0.7; 1.2, 95% CI 1.0-1.4), and between the intervention and control groups using DAPs (1.1, 95% CI 0.8-1.3; 1.5, 95% CI 1.0-2.1) [p <0.001 for group, p = 0.014 for medication, p = 0.97 for interaction]. Conclusion Exercise has the potential to decrease the risk for falls among people with AD using antihypertensives and psychotropics.Peer reviewe

How Do Community-Dwelling Persons with Alzheimer Disease Fall? Falls in the FINALEX Study

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Education-Based Cutoffs for Cognitive Screening of Alzheimer’s Disease

Introduction: The educational background and size of the elderly population are undergoing significant changes in Finland during the 2020s. A similar process is likely to occur also in several European countries. For cognitive screening of early Alzheimer’s disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy. The aim of the present study was to examine the effects of education, age, and gender on the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery (CERAD-nb) in a large register-based, clinical sample of patients with mild AD and nondemented at-risk persons from the general population (controls) and to examine whether corrected cutoff scores would increase the accuracy of differentiation between the 2 groups. Methods: CERAD-nb scores were obtained from AD patients (n = 389, 58% women, mean age 74.0 years) and from controls (n = 1,980, 52% women, mean age 68.5 years). The differences in CERAD-nb performance were evaluated by univariate GLM. Differentiation between the 2 groups was evaluated using a receiver operating characteristic (ROC) curve, where a larger area under the ROC curve represents better discrimination. Youden’s J was calculated for the overall performance and accuracy of each of the measures. Results: Of the demographic factors, education was the strongest predictor of CERAD-nb performance, explaining more variation than age or gender in both the AD patients and the controls. Education corrected cutoff scores had better diagnostic accuracy in discriminating between the AD patients and controls than existing uncorrected scores. The highest level of discrimination between the 2 groups overall was found for two CERAD-nb total scores. Conclusions: Education-corrected cutoff scores were superior to uncorrected scores in differentiating between controls and AD patients especially for the highest level of education and should therefore be used in clinical cognitive screening, also as the proportion of the educated elderly is increasing substantially during the 2020s. Our results also indicate that total scores of the CERAD-nb are better at discriminating AD patients from controls than any single subtest score. A digital tool for calculating the total scores and comparing education-based cutoffs would increase the efficiency and usability of the test.Peer reviewe

Exercise rehabilitation on home-dwelling patients with Alzheimer's disease - a randomized, controlled trial. Study protocol

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Recombinant Human FSH Treatment Outcomes in Five Boys With Severe Congenital Hypogonadotropic Hypogonadism

ConclusionsSpermatogenesis can be induced with gonadotropins even in boys with HH who have extremely small testes, and despite low-dose T treatment given in early puberty. Induction of puberty with gonadotropins allows preservation of fertility.</p

Human pluripotent stem cell-derived cells endogenously expressing follicle-stimulating hormone receptors : modeling the function of an inactivating receptor mutation

Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells. FSH stimulation of the wild-type (WT), but not the inactivating Finnish founder mutant (A189V) receptor, activated the canonical cyclic adenosine monophosphate (cAMP)-dependent signaling pathway and downstream mediators. To investigate protein-protein interaction partners of FSHR at resting state and upon FSH stimulation, we expressed FSHR in HEK293 cells followed by affinity purification mass spectrometry analyses. We found 19 specific high-confidence interacting proteins for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility. Interestingly, while only WT FSHR interacted with FSH, insulin-like growth factor 1 receptor (IGF1R), for example, interacted with both WT and A189V FSHR upon FSH stimulation. In conclusion, our protocol allows detailed studies of FSH action and disease modeling in human cells endogenously expressing FSHR.Peer reviewe