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A coding mutation in APP , the gene that encodes the amyloid-β precursor protein, is found to protect against Alzheimer’s disease and cognitive decline in the elderly without Alzheimer’s disease. 'Natural' protection against Alzheimer's disease Alzheimer's disease is characterized by the existence in the brain of amyloid plaques, which form as a consequence of proteolic cleavage of amyloid precursor protein (APP). By screening almost 2,000 genomes, Kari Stefansson and colleagues find a coding mutation in the APP gene that protects against Alzheimer's disease and cognitive decline in elderly people who lack symptoms of Alzheimer's disease. The mutation causes an approximately 40% reduction in the formation of amyloidogenic peptides in vitro . The strong protective effect of this mutation, which lies next to the aspartyl protease beta-site in APP, provides support for the hypothesis that reducing the beta-cleavage of APP may protect against Alzheimer's. The results also raise the possibility that Alzheimer's disease and cognitive decline in the elderly are mechanistically related. The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer’s disease 1 , 2 , 3 , 4 . The age-specific prevalence of Alzheimer’s disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3 ). Here, to search for low-frequency variants in the amyloid-β precursor protein ( APP ) gene with a significant effect on the risk of Alzheimer’s disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer’s disease and cognitive decline in the elderly without Alzheimer’s disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro . The strong protective effect of the A673T substitution against Alzheimer’s disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer’s disease, the two may be mediated through the same or similar mechanisms.

Background Policymakers advocate extended residence in private homes as people age, rather than relocation to long-term care facilities. Consequently, it is expected that older people living in their own homes will be frailer and have more complex health problems over time. Therefore, community care for aging people is becoming increasingly important to facilitate prevention of decline in physical and cognitive abilities and unnecessary hospital admission and transfer to a nursing home. The aim of this study was to examine changes in the characteristic of home care clients and home care provided in five European countries between 2001 and 2014 and to explore whether home care clients who are most in need of care receive the care required. Methods This descriptive study used data from two European research projects, Aged in Home Care (AdHOC; 2001–2002) and Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of Community Care (IBenC; 2014–2016). In both projects, the InterRAI-Home Care assessment tool was used to assess a random sample of home care clients 65 years and older in five European countries. These data facilitate a comparison of physical and cognitive health and the provided home care between countries and study periods. Results In most participating countries, both cognitive (measured on the Cognitive Performance Scale) and functional ability (measured on the Activities of Daily Living Hierarchy scale) of home care clients deteriorated over a 10-year period. Home care provided increased between the studies. Home care clients who scored high on the physical and cognitive scales also received home care for a significantly higher duration than those who scored low. Conclusion Older people in several European countries remain living in their own homes despite deteriorating physical and cognitive skills. Home care services to this group have increased. This indicates that the government policy of long-term residence at own home among older people, even in increased frailty, has been realised.

Since the advent of topological insulators hosting Dirac surface states, efforts have been made to gap these states in a controllable way. A new route to accomplish this was opened up by the discovery of topological crystalline insulators where the topological states are protected by crystal symmetries and thus prone to gap formation by structural changes of the lattice. Here we show a temperature-driven gap opening in Dirac surface states within the topological crystalline insulator phase in (Pb,Sn)Se. By using angle-resolved photoelectron spectroscopy, the gap formation and mass acquisition is studied as a function of composition and temperature. The resulting observations lead to the addition of a temperature- and composition-dependent boundary between massless and massive Dirac states in the topological phase diagram for (Pb,Sn)Se (001). Overall, our results experimentally establish the possibility to tune between massless and massive topological states on the surface of a topological system. The opening of a Dirac point gap in topologically non-trivial materials is key to potential applications. Here, the authors use photoelectron spectroscopy to study gap formation and carrier mass acquisition in a topological crystalline insulator as a function of composition and temperature.

Background/objectives: A few previous studies indicate that protein supplementation increases gains in muscle mass and strength during a resistance exercise program. The purpose of this study was to investigate whether whey protein supplementation results in greater increases in lean body mass, muscle strength and physical function in elderly individuals during 12 weeks of resistance exercise when compared to isocaloric carbohydrate supplementation. Subjects/Methods: A total of 161 men and women, 65–91 years old, participated in a randomized, controlled, double-blind intervention study, involving dietary supplementation and a 12-week resistance exercise program, designed to increase muscle mass and strength of all major muscle groups. Participants exercised three times a week and received either 20 g of whey protein ( n =83) or isocaloric carbohydrate ( n =78) in liquid form immediately after each workout. Data were obtained at baseline and end point. Results: The primary outcomes, lean body mass, strength and physical function increased significantly during the course of the study. Type of dietary supplementation did not influence gains in lean body mass ( P =0.365), quadriceps strength ( P =0.776) or performance during a 6-min walk ( P =0.726) or a timed up-and-go test ( P =0.151). Twenty participants discontinued the intervention. Conclusions: Ingestion of 20 g of whey protein immediately after resistance exercise three times per week, does not lead to greater gains in lean body mass, strength and physical function in elderly people with sufficient energy and protein intakes when compared to isocaloric carbohydrate.

Background/objectivesMalnutrition is common among older adults. Dietary intervention studies in older adults aiming to improve anthropometrics measures and physical function have been inconsistent. We aimed to investigate the effects of nutrition therapy in combination with home delivered meals and oral nutritional supplements (ONS) in community-dwelling older adults discharged from hospital.MethodsA total of 106 participants (>65 years) were randomized into the intervention group (n = 53) and into the control group (n = 53). The intervention group received individual nutrition therapy (five in person visits and three phone calls) and freely delivered energy- and protein- rich foods, while the control group received standard care. Dietary intake, anthropometrics, and short physical performance battery (SPPB) were assessed at baseline and at endpoint.ResultsEnergy intake at baseline was similar in both groups (~1500 kcal at the hospital) but there was a significant increase in energy intake and body weight in the intervention group (+919 kcal/day and 1.7 kg, P < 0.001 in both cases) during the study period, compared to a significant decrease in both measures among controls (−815 kcal/day and −3.5 kg, P < 0.001 in both cases). SPPB score increased significantly in the intervention group while no changes were observed among controls.ConclusionsMost Icelandic older adults experience substantial weight loss after hospital discharge when receiving current standard care. However, a 6-month multi-component nutrition therapy, provided by a clinical nutritionist in combination with freely delivered supplemental energy- and protein-dense foods has beneficial effects on body weight, physical function, and nutritional status.Study registrationThis study was registered at ClinicalTrials.gov (NCT03995303).

Sjögren’s syndrome (SS) is an autoimmune disease affecting the salivary and lacrimal glands. Symptoms range from dryness to severe extra-glandular disease involving manifestations in the skin, lungs, nervous system, and kidney. Fatigue occurs in 70% of patients, characterizing primary SS (pSS) and significantly impacting the patient’s quality of life. There are some generic and specific instruments used to measure fatigue in SS. The mechanisms involved with fatigue in SS are still poorly understood, but it appears fatigue signaling pathways are more associated with cell protection and defense than with pro-inflammatory pathways. There are no established pharmacological treatment options for fatigue in pSS. So far, exercise and neuromodulation techniques have shown positive effects on fatigue in pSS. This study briefly reviews fatigue in pSS, with special attention to outcome measures, biomarkers, and possible treatment options.

Malnutrition is frequently observed in older adults and is associated with hospital readmissions, length of stay (LOS), and mortality in discharged patients. The aim of this study was to investigate effects of six-month nutrition therapy on hospital readmissions, LOS, mortality and need for long-term care residence 1-, 6-, 12- and 18-months post-discharge in older Icelandic adults. Secondary analysis of a randomized controlled trial. Participants (>65 years) were randomised into intervention (n=53) and control (n=53) before discharge from a geriatric unit. The intervention group received nutrition therapy based on the Nutrition Care Process, including home visits, phone calls, freely delivered energy- and protein-rich foods and supplements for six months after hospital discharge. The Icelandic electronic hospital registry was accessed to gain information on emergency room visits (ER), hospital readmissions, LOS, mortality and need for long-term care residence. The intervention group had a lower proportion of participants with at least one readmission compared to control (1 month: 1.9% vs 15.8%, P=0.033; 6 months: 25.0% vs 46.2%, P=0.021; 12 months: 38.5% vs 55.8%, P=0.051; and 18 months: 51.9% vs 65.4%, P=0.107). There was also a lower total number of readmissions per participant (1 month: 0.02 vs 0.19, P=0.015; 6 month: 0.33 vs 0.77, P=0.014; 0.62 vs 1.12, P=0.044) and a shorter LOS (1 month: 0.02 vs 0.92, P=0.013; 6 months: 2.44 vs 13.21; P=0.006; 12 months: 5.83 vs 19.40, P=0.034; 18 months: 10.42 vs 26.00, P=0.033) in the intervention group. However, there were no differences between groups in ER visits, mortality and need for long-term care residence. A six-month nutrition therapy in older Icelandic adults discharged from hospital reduced hospital readmissions and shortens LOS at the hospital up to 18-months post-discharge. However, it did neither affect mortality, ER, nor need of long-term care residence in this group.

Background/Objectives: Low intake of long chain polyunsaturated fatty acids (PUFAs) are associated with physical disability; however, prospective studies of circulating PUFAs are scarce. We examined associations between plasma phospholipid n −3 and n −6 PUFAs with risk of incident mobility disability and gait speed decline. Subjects/Methods: Data are from a subgroup of the Age, Gene/Environment Susceptibility–Reykjavik Study, a population-based study of risk factors for disease and disability in old age. In this subgroup ( n =556, mean age 75.1±5.0 years, 47.5% men), plasma phospholipid PUFAs were assessed at baseline using gas chromatography. Mobility disability and usual gait speed were assessed at baseline and after 5.2±0.2 years. Mobility disability was defined as the following: having much difficulty, or being unable to walk 500 m or climb up 10 steps; decline in gait speed was defined as change ⩾0.10 m/s. Logistic regression analyses were performed to determine associations between sex-specific s.d. increments in PUFAs with risk of incident mobility disability and gait speed decline. Odds ratios (95% confidence intervals) adjusted for demographics, follow-up time, risk factors and serum vitamin D were reported. Results: In women, but not men, every s.d. increment increase of total n −3 PUFAs and docosahexaenoic acid (DHA) was associated with lower mobility disability risk, odds ratio 0.48 (0.25; 0.93) and odds ratio 0.45 (0.24; 0.83), respectively. There was no association between n −6 PUFAs and the risk of incident mobility disability or gait speed decline. Conclusions: Higher concentrations of n −3 PUFAs and, particularly, DHA may protect women from impaired mobility but does not appear to have such an effect in men.

Background Physical function is an important domain of healthy ageing and previous studies have suggested socioeconomic status, including education to be influential. Also, lifestyle factors such as physical activity can play a crucial role in maintaining physical function. Furthermore, birth size as an indicator of nutritional status during gestation can add insight into the interplay between factors that influence physical functioning. Thus, examining healthy ageing from a life course perspective can broaden our scope for possible preventive measures for maintaining independence and quality of life at late-life. Our objective was to investigate the longitudinal association between midlife education and late-life physical function, over the mean time-period of 25 years, and to investigate whether birth size modifies the association. Methods Participants were 1604 men and women from the Age Gene/Environment Susceptibility (AGES) - Reykjavik Study who had measures from birth, midlife and late-life. Multivariate linear regression included gait speed (GS) and timed up and go test (TUG) at late-life as outcomes and midlife educational level as exposure. To examine effect modification, data was stratified by birth size as ponderal index (PI) in three groups. Results Participants with primary education had slower GS of 0.05 m/s ( p  < 0.001) and longer TUG time of 0.66 s ( p  = 0.006) compared to college/university (reference). Birth size modified the association, with the low PI group having a slower GS of 0.1 m/s ( p  < 0.001) and taking 1.35s longer to complete TUG between educational groups (primary education vs. reference). There was no association between GS nor TUG with education in the high PI group. Conclusion Our results imply that for those born small, having lower educational level is associated with having worse physical function at late-life, partly through less physical activity throughout the life-course.

B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are members of the tumour necrosis factor superfamily. We have examined circulating BAFF and APRIL in relation to serological deviations and lymphoid organization in the salivary glands of the chronic, autoimmune disorder Sjögren's syndrome. Lymphoid organization in the shape of ectopic germinal centers were detected in 33 of 130 consecutive minor salivary gland biopsies and coincided with increased focus score and elevated levels of serum IgG. Follicular dendritic cell networks, proliferation of mononuclear cells and altered B/T cell ratio also separated the two subgroups. Serum levels of sBAFF and sAPRIL were increased in Sjögren's syndrome compared to healthy blood donors, especially in anti-Ro/La+ patients. Though the differences could not be related to germinal center formation, positive correlations between serum levels of sBAFF and sAPRIL, focus score and IgG denotes their possible role in the disease progression of primary Sjögren's syndrome.