The Alzheimer conundrum

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Het wegwerplichaam : over de rol van het immuunsysteem tijdens de levensloop

De levensverwachting in Nederland is vanaf de 19e eeuw sterk toegenomen. Tot 1870 lag de gemiddelde levensverwachting beneden de 50 jaar,daarna begon de epidemiologische transitie, een overgang van sterfte door infectieziekten op jonge leeftijd naar sterfte door kanker en harten vaatziekten op hogere leeftijd. Deze transitie kan verklaard worden door verbeterde hygiëne, sociaal-economische ontwikkelingen en toegenomen medische kennis. Door deze ontwikkelingen is de kindersterfte vrijwel verdwenen en de gemiddelde levensverwachting fors gestegen. Op dit moment heeft een Nederlandse man een kans van 86 procent om de leeftijd van 65 jaar te bereiken en voor vrouwen is dit zelfs 90 procent. Daarbij is de levensverwachting voor mannen 77 jaar en voor vrouwen 81 jaar. Het resultaat van dit succes is dat er nu meer oude mensen zijn dan ooit te voren. Dat wil echter niet zeggen dat veroudering een nieuw fenomeen is. Ook in vroeger tijden waren er mensen die een hoge leeftijd bereikten, alleen waren er veel minder mensen die dit geluk mochten smaken. In dit hoofdstuk gaan we in op de factoren die de levensverwachting beïnvloeden, waarbij we ons concentreren op de rol die het immuunsysteem speelt gedurende de levensloop.Wetensch. publicati

Perspectives on the etiology of violence in later life

This article focuses on the development of a conceptual framework for explaining the etiology of violence in later life by various groups involved in the field of elder abuse. In this study, we explore this through eight focusgroups with different professionals involved in the field of elder abuse and older persons themselves and in interviews with 35 experts in the field. Our findings show that dependency, vulnerability, power and control, social isolation, stress, and care burden play a central role in their explanations for the occurrence of violence in later life. The role of a history of violence in violence in later life is equivocal. The complexity and ambiguity of dependency and vulnerability, the notion of mutual dependency, and diverse attitudes and expectations toward them that arise with the aging process are distinct features of violence in later life that were found.Dissertati

Framing abuse : explaining the incidence, perpetuation, and intervention in elder abuse

The role of individual characteristics in incidences of elder abuse has long been highest on research and policy agendas. Now, it is timely to discuss factors that go beyond victim and perpetrator. Environmental factors also play an important role in elder abuse. In this paper, we address the framing of elder abuse as a social and health problem. Attention is paid to the factors that influence societal context and the Healthcare system, its organization, structure, and principlesWetensch. publicati

Expressions of self-ageism in four European countries:a comparative analysis of predictors across cultural contexts

Self-ageism has a significant negative impact on older people's ageing experiences and health outcomes. Despite ample evidence on cross-cultural ageism, studies have rarely looked into the way cultural contexts affect self-ageism. In this article, we compare expressions of self-ageism and its possible predictors across four European countries based on two questionnaires in a study sample of 2,494 individuals aged 55 and older. We explore how predictors of self-ageism are moderated by cultural values in a comparative fixed-effects regression model. We empirically show that similarly to ageism, self-ageism is not present in the same way and to the same extent in every country. Moreover, the level to which cultures value hierarchy and intellectual autonomy significantly moderates the association between self-ageism and individual predictors of self-ageism. Our study adds to the small existing body of work on self-ageism by confirming empirically that certain expressions of self-ageism and individual predictors are susceptible to change in different cultural contexts. Our research results suggest that self-ageism interventions may benefit from a culturally sensitive approach and imply that more culturally diverse comparisons of self-ageism are necessary to figure out fitting ways to reduce self-ageism

Do psychosocial factors modify the negative association between disability and life satisfaction in old age?

CONTEXT: Many assume that having poor physical health in old age lowers life satisfaction, but in fact there are large differences in life satisfaction among older people who experience disability. OBJECTIVE: To investigate whether psychosocial factors modify the negative association between disability and life satisfaction in older people and whether these differ across the life course. DESIGN: Cross sectional study. SETTING: 66,561 community-dwelling Survey of Health, Ageing, and Retirement in Europe (SHARE) participants aged 50-106 with a mean age of 67.8 ± 9.9 (SD) years from 17 European countries and Israel. METHODS: Psychosocial factors included depression (EURO-D scale), perceived loneliness, having a spouse, having children, contact with children, and participation in social activities. Disability was assessed by limitations in (Instrumental) Activities of Daily Living ((I)ADL) and life satisfaction by Cantril's ladder. We also ran the analyses with the Control Autonomy Self-realization Pleasure (CASP-12) Index, a normative measure of quality of life. We used multiple linear regressions to estimate associations and proportion of variance explained. RESULTS: The variance in life satisfaction that could be attributed uniquely to ADL and IADL disability was 0.17% and 0.33% respectively (both p < 0.001). The impact of (I)ADL disabilities on life satisfaction was strongest at age 50 and gradually decreased with increasing age (p trend < 0.001). Mental health explained more variance; 5.75% for depressive symptoms and 2.50% for loneliness and for social resources this ranged from 0.09% to 0.47% (all p < 0.001). While disability has a negative effect on life satisfaction, the effect was not stronger in older persons who were depressed, neither in those who felt lonely nor in those without social resources. Similar outcomes were found when using CASP-12 as the explained variable. CONCLUSION: The impact of (I)ADL disabilities on life satisfaction in community-dwelling older people decreases with age. These associations are not affected by psychosocial factors and these patterns cannot be explained by people changing their norms and values

Listening to the voices of abused older people: should we classify system abuse?

Elder abuse is often the result of the organisation of health systems rather than the fault of individuals, argue Yuliya Mysyuk and colleagues. They call for system abuse to be acknowledged and addressed by incorporating older people’s views when designing health servicesWetensch. publicati

Gastrin Induces Nuclear Export and Proteasomal Degradation of Menin in Enteric Glial Cells

Background & aims: The multiple endocrine neoplasia, type 1 (MEN1) locus encodes the nuclear protein and tumor suppressor menin. MEN1 mutations frequently cause neuroendocrine tumors such as gastrinomas, characterized by their predominant duodenal location and local metastasis at time of diagnosis. Diffuse gastrin cell hyperplasia precedes the appearance of MEN1 gastrinomas, which develop within submucosal Brunner\u27s glands. We investigated how menin regulates expression of the gastrin gene and induces generation of submucosal gastrin-expressing cell hyperplasia. Methods: Primary enteric glial cultures were generated from the VillinCre:Men1FL/FL:Sst-/- mice or C57BL/6 mice (controls), with or without inhibition of gastric acid by omeprazole. Primary enteric glial cells from C57BL/6 mice were incubated with gastrin and separated into nuclear and cytoplasmic fractions. Cells were incubated with forskolin and H89 to activate or inhibit protein kinase A (a family of enzymes whose activity depends on cellular levels of cyclic AMP). Gastrin was measured in blood, tissue, and cell cultures using an ELISA. Immunoprecipitation with menin or ubiquitin was used to demonstrate post-translational modification of menin. Primary glial cells were incubated with leptomycin b and MG132 to block nuclear export and proteasome activity, respectively. We obtained human duodenal, lymph node, and pancreatic gastrinoma samples, collected from patients who underwent surgery from 1996 through 2007 in the United States or the United Kingdom. Results: Enteric glial cells that stained positive for glial fibrillary acidic protein (GFAP+) expressed gastrin de novo through a mechanism that required PKA. Gastrin-induced nuclear export of menin via cholecystokinin B receptor (CCKBR)-mediated activation of PKA. Once exported from the nucleus, menin was ubiquitinated and degraded by the proteasome. GFAP and other markers of enteric glial cells (eg, p75 and S100B), colocalized with gastrin in human duodenal gastrinomas. Conclusions: MEN1-associated gastrinomas, which develop in the submucosa, might arise from enteric glial cells through hormone-dependent PKA signaling. This pathway disrupts nuclear menin function, leading to hypergastrinemia and associated sequelae

Impact of physical and mental health on life satisfaction in old age:a population based observational study

Background: It is widely assumed that poor health lowers life satisfaction when ageing. Yet, research suggests this relationship is not straightforward. This study investigated how older people evaluate their life when facing disease and disabilities. Methods: The Leiden 85-plus Study, a prospectively followed cohort of a cohort of a middle-sized city in the Netherlands, all aged 85 years, that was age-representative of the general population, was used. Those with severe cognitive dysfunction were excluded (n = 501). Comorbidities, physical performance, cognitive function, functional status, residual lifespan, depressive symptoms and experienced loneliness were measured during home visits. Life satisfaction was self-reported with Cantril's ladder. All analyses were performed using regression analysis. Results: Participants reported high life satisfaction (median 8 out of 10 points) despite having representative levels of disease and disability. Comorbidity, low cognitive function, and residual lifespan as markers of health were not associated with life satisfaction. Poor physical performance and low functional status were weakly but significantly associated with lower life satisfaction (p <0.05 respectively p <0.001), but significance was lost after adjustment for depressive symptoms and perceived loneliness. Depressive symptoms and perceived loneliness were strongly related to lower life satisfaction (both p <0.001), even after adjustment for physical health characteristics. Conclusion: Poor physical health was hardly related to lower life satisfaction, whereas poor mental health was strongly related to lower life satisfaction. This indicates that mental health has a greater impact on life satisfaction at old age than physical health, and that physical health is less relevant for a satisfactory old age