Gerd Faxén-Irving

Omega-3 fatty acids enhance phagocytosis of Alzheimer's disease-related amyloid-β42 by human microglia and decrease inflammatory markers.

The use of supplements with omega-3 (ω3) fatty acids (FAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is widespread due to proposed beneficial effects on the nervous and cardiovascular systems. Many effects of ω3 FAs are believed to be caused by down-regulation and resolution of inflammation. Alzheimers disease (AD) is associated with inflammation mediated by microglia and astrocytes, and ω3 FAs have been proposed as potential treatments for AD. The focus of the present study is on the effects of DHA and EPA on microglial phagocytosis of the AD pathogen amyloid-β (Aβ), on secreted and cellular markers of immune activity, and on production of brain-derived neurotrophic factor (BDNF). Human CHME3 microglial cells were exposed to DHA or EPA, with or without the presence of Aβ42. Phagocytosis of Aβ42 was analyzed by flow cytometry in conjunction with immunocytochemistry using antibodies to cellular proteins. Secreted proteins were analyzed by ELISA. Both DHA and EPA were found to stimulate microglial phagocytosis of Aβ42. Phagocytosis of Aβ42 was performed by microglia with a predominance of M2 markers. EPA increased the levels of BDNF in the culture medium. The levels of TNF-α were decreased by DHA. Both DHA and EPA decreased the pro-inflammatory M1 markers CD40 and CD86, and DHA had a stimulatory effect on the anti-inflammatory M2 marker CD206. DHA and EPA can be beneficial in AD by enhancing removal of Aβ42, increasing neurotrophin production, decreasing pro-inflammatory cytokine production, and by inducing a shift in phenotype away from pro-inflammatory M1 activation.

Physical activity and energy expenditure in haemodialysis patients: an international survey

BACKGROUND The assessment of physical activity and energy expenditure is relevant to the care of maintenance haemodialysis (MHD) patients. In the current study, we aimed to evaluate measurements of physical activity and energy expenditure in MHD patients from different centres and countries and explored the predictors of physical activity in these patients. METHODS In this cross-sectional multicentre study, 134 MHD patients from four countries (France, Switzerland, Sweden and Brazil) were included. The physical activity was evaluated for 5.0 ± 1.4 days (mean ± SD) by a multisensory device (SenseWear Armband) and comprised the assessment of number of steps per day, activity-related energy expenditure (activity-related EE) and physical activity level (PAL). RESULTS The number of steps per day, activity-related EE and PAL from the MHD patients were compatible with a sedentary lifestyle. In addition, all parameters were significantly lower in dialysis days when compared to non-dialysis days (P < 0.001). The multivariate regression analysis revealed that diabetes and higher body mass index (BMI) predicted a lower PAL and older age and diabetes predicted a reduced number of steps. CONCLUSIONS The physical activity parameters of MHD patients were compatible with a sedentary lifestyle. This inactivity was worsened by aging, diabetes and higher BMI. Our results indicate that MHD patients should be encouraged by the health care team to increase their physical activity.

Effects of Omega-3 Fatty Acids on Inflammatory Markers in Cerebrospinal Fluid and Plasma in Alzheimer’s Disease: The OmegAD Study

Background: ω-3 fatty acids (ω-3 FAs) found in dietary fish or fish oils are anti-inflammatory agents that may influence Alzheimer’s disease (AD). Objective: To study the effects of dietary ω-3 FA supplementation on inflammatory markers in cerebrospinal fluid (CSF) and plasma from patients with mild to moderate AD. Methods: Thirty-five patients (70.3 ± 8.2 years) were randomized to a daily intake of 2.3 g ω-3 FAs or placebo for 6 months. The inflammatory markers interleukin (IL)-6, tumour necrosis factor-α and soluble interleukin-1 receptor type II (sIL-1RII) were analysed in CSF and plasma at baseline and at 6 months. The AD markers tau-protein, hyperphosphorylated tau-protein and β-amyloid (Aβ1–42) were assessed in CSF. High-sensitivity C-reactive protein was assessed in plasma. A possible relation to the APOE genotype was investigated. Results: There was no significant treatment effect of ω-3 FAs on inflammatory and AD biomarkers in CSF or on inflammatory markers in plasma, nor was there any relation with APOE. A significant correlation was observed at baseline between sIL-1RII and Aβ1–42 levels in CSF. Conclusions: Treatment of AD patients with ω-3 FAs for 6 months did not influence inflammatory or biomarkers in CSF or plasma. The correlation between sIL-1RII and Aβ1–42 may reflect the reciprocal interactions between IL-1 and Aβ peptides.

ESPEN guidelines on nutrition in dementia

BACKGROUND Older people suffering from dementia are at increased risk of malnutrition due to various nutritional problems, and the question arises which interventions are effective in maintaining adequate nutritional intake and nutritional status in the course of the disease. It is of further interest whether supplementation of energy and/or specific nutrients is able to prevent further cognitive decline or even correct cognitive impairment, and in which situations artificial nutritional support is justified. OBJECTIVE It is the purpose of these guidelines to cover these issues with evidence-based recommendations. METHODS The guidelines were developed by an international multidisciplinary working group in accordance with officially accepted standards. The GRADE system was used for assigning strength of evidence. Recommendations were discussed, submitted to Delphi rounds and accepted in an online survey among ESPEN members. RESULTS 26 recommendations for nutritional care of older persons with dementia are given. In every person with dementia, screening for malnutrition and close monitoring of body weight are recommended. In all stages of the disease, oral nutrition may be supported by provision of adequate, attractive food in a pleasant environment, by adequate nursing support and elimination of potential causes of malnutrition. Supplementation of single nutrients is not recommended unless there is a sign of deficiency. Oral nutritional supplements are recommended to improve nutritional status but not to correct cognitive impairment or prevent cognitive decline. Artificial nutrition is suggested in patients with mild or moderate dementia for a limited period of time to overcome a crisis situation with markedly insufficient oral intake, if low nutritional intake is predominantly caused by a potentially reversible condition, but not in patients with severe dementia or in the terminal phase of life. CONCLUSION Nutritional care and support should be an integral part of dementia management. In all stages of the disease, the decision for or against nutritional interventions should be made on an individual basis after carefully balancing expected benefit and potential burden, taking the (assumed) patient will and general prognosis into account.

Body mass index in dementia

This review comprehensively examines the current knowledge on the relationship between body mass index (BMI) and dementia. The association between BMI and cognition is complex: in younger adults, higher BMIs are associated with impaired cognition. Overweight and obesity in middle age are linked to increased future dementia risk in old age. However, when examined in old age, higher BMIs are associated with better cognition and decreased mortality. Little is known about the optimal BMI for well-being and survival in populations already suffering from dementia. Lifetime trends in weight, rather than single measures, might predict prognosis better and help untangle these apparent contradictions. Thus, the need arises to properly monitor BMI trends in affected dementia patients. Registries can include BMI, improving the management of dementia patients throughout the whole course of the disease. The role of central obesity and systemic inflammation on brain pathology and cognitive decline are discussed in this review. Understanding the life-course changes in BMI and their influence on dementia risk, cognitive prognosis and mortality after diagnosis may provide new insights into the underlying pathophysiology of dementia and shape possible intervention and treatment strategies.

Prudent diet may attenuate the adverse effects of Western diet on cognitive decline

The influence of mixed dietary patterns on cognitive changes is unknown.

Plasma Fatty Acid Profiles in Relation to Cognition and Gender in Alzheimer’s Disease Patients During Oral Omega-3 Fatty Acid Supplementation: The OmegAD Study

BACKGROUND ω3 fatty acids (ω3 FAs) may slow the rate of decline in cognitive performance in mild forms of cognitive impairment and Alzheimers disease (AD). However, the relationship between changes of plasma ω3 FA levels and cognitive performance, as well as effects of gender, are poorly known. OBJECTIVE To study the effect of 6-month administration of DHA-rich ω3 FA supplementation on plasma FA profiles in patients with mild to moderate AD in relation to cognitive performance and gender. This investigation is part of the OmegAD Study. METHODS 174 AD patients (74 ± 9 years) were randomized to a daily intake of 2.3 g ω3 FA or placebo for 6 months; subsequently all received the ω3 FA preparation for the next 6 months. Baseline as well as changes in plasma levels of the main ω3 FAs in 165 patients, while receiving ω3 FA supplementation for 6 months, were analyzed for association to cognitive performance (assessed by ADAS-cog and MMSE scores) as well as to gender. RESULTS Preservation of cognitive functioning, assessed by ADAS-cog or its sub-items (but not MMSE) scores, was significantly associated to increasing plasma ω3 FA levels over time. Thus, the higher ω3 FA plasma levels rose, the lower was the rate of cognitive deterioration. This effect was not related to gender; since although females displayed higher ω3 FA plasma levels than did males after 6 months of supplementation, this difference disappeared when adjusted for body weight. CONCLUSIONS Since our study suggests dose-response relationships between plasma levels of ω3 FA and preservation of cognition, future ω3 FA trials in patients with mild AD should consider exploring graded (and body weight adjusted) doses of ω3 FA.

Body Mass Index in Different Dementia Disorders: Results from the Swedish Dementia Quality Registry (SveDem)

Background: Most patients with dementia lose body weight over the course of the disease and have a lower body mass index (BMI) than subjects with normal cognition. Aims: To examine body mass index and how it correlates with cognitive status, age and gender in patients with different dementia disorders. Materials and Methods: Data from newly diagnosed dementia patients in the Swedish Dementia Quality Registry (SveDem) and recorded information about age, gender, cognitive status and BMI was analyzed using independent samples t tests and one-way analysis of variance. Results: A total of 12,015 patients, 7,121 females and 4,894 males were included in the study. The average BMI was 24. More than a quarter of the patients had a BMI of <22. Females were significantly older (p < 0.001) and males had a significantly higher BMI (p < 0.001) at the time of diagnosis. BMI differed significantly by gender in various dementia disorders and correlated significantly with cognitive status and age. Conclusion: At the time of diagnosis, patients with various dementia disorders had a BMI within the normal range. However, a significant number had a BMI in a lower, suboptimal range for older persons stressing the need for nutritional assessment as part of the dementia work up. Further analyses with longitudinal follow-up are needed to investigate BMI changes over time.

The Nordic Prudent Diet Reduces Risk of Cognitive Decline in the Swedish Older Adults: A Population-Based Cohort Study

Appropriate dietary pattern for preserving cognitive function in northern Europe remains unknown. We aimed to identify a Nordic dietary pattern index associated with slower cognitive decline compared to the Mediterranean-DASH Intervention for Neurodegenerative Delay, Mediterranean Diet, Dietary Approaches to Stop Hypertension, and Baltic Sea Diet indices. A total of 2223 dementia-free adults aged ≥60 were followed for 6 years. Mini-Mental State Examination was administrated at baseline and follow-ups. Dietary intake was assessed by 98-item food frequency questionnaire, and the Nordic Prudent Dietary Pattern (NPDP) was identified. Data were analysed using mixed-effects and parametric survival models and receiver operating characteristic curves with adjustment for potential confounders. Moderate (β = 0.139, 95% CI 0.077−0.201) and high adherence (β = 0.238, 95% CI 0.175−0.300) to NPDP were associated with less cognitive decline compared to other four indices. High adherence to NPDP was also associated with the lowest risk of MMSE decline to ≤24 (HR = 0.176, 95% CI 0.080−0.386) and had the greatest ability to predict such decline (area under the curve = 0.70). Moderate-to-high adherence to the NPDP may predict a better-preserved cognitive function among older adults in Nordic countries. Regional dietary habits should be considered in developing dietary guidelines for the prevention of cognitive impairment and dementia.

A practical approach to low protein diets in Sweden– 45 years of clinical use

This review provides an overview of the development, implementation and practise of low protein diets (LPD) in Sweden. While the current practice is discussed in general terms emphasizing the interplay between nephrologists and dieticians, the ”self-selected” LPD model is explained as a practical approach to facilitated patient’s adherence to the nutritional therapy. This model is currently implemented in most clinics of the country and gives considerable flexibility regarding variation in meal planning, food selection, amounts consumed, cooking methods as well as adaptations to day-to-day changes. Current LPD use in Sweden is presented through analysis of the Swedish Renal Registry. Finally two patient cases are illustrated, with examples on their diets, attempts to reduce the protein content to the desired thresholds and their clinical course.