| 1. |
- Al-Adili, Lina
(författare)
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The evaluation process of nutrition interventions for patients at risk of malnutrition : From a person-centred perspective
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is aimed at exploring the process of evaluating nutrition interventions for patients at risk of malnutrition from a person-centred perspective. An explorative cross-sectional study was conducted based on data from the International Nutrition Care Process and Terminology Implementation Survey (INIS). Associations between the reported documentation of goals and outcomes and the reported implementation of the nutrition care process and its terminology, demographic factors, and factors associated with the workplace were explored. Responses were received from 347 Scandinavian dietitians. Strong associations were found between the implementation of nutrition monitoring and evaluation terminology and the documentation of goals and outcomes. Standardisation may support the documentation of goals and outcomes, and improve nutrition monitoring and evaluation. Focus group interviews were held with Swedish dietitians working in hospital and primary healthcare settings. The dietitians’ reflections on the process of nutrition monitoring and evaluation (Paper II) and the goal-setting process (Paper III) with patients at risk of malnutrition in nutrition intervention were explored. A lack of routine and structure in the process of evaluation and a lack of shared decision-making (SDM) in goal-setting was found. Dietitians described qualitative subjective outcomes as being most important to patients but that these are only implied in the nutrition intervention. They highlighted discrepancies between their clinically oriented goals and the patients’ own goals. The clarification of patients’ perspectives in the evaluation process is necessary to promote person-centredness, improve communication, and support the evidence-informed practice of nutrition intervention.An interview study with patients at risk of malnutrition was conducted. Patients’ experiences, perspectives and needs concerning goals in nutrition intervention were explored. Patients rarely reflected on goals in nutrition interventions, instead they described striving towards increased strength and energy. Goal-setting is part of the dietitian’s structured way of working, while the patient’s life-world is complex and unstructured. Elucidating patients’ goals may counteract the discrepancies between the dietitians’ clinically oriented goals and patients’ perspectives.In summary, this thesis highlights the need for tools and strategies for the improvement of the evaluation process in nutrition intervention. The person-centred practice of the evaluation process is described in this thesis as key to improving this process. This can be achieved through exploring what matters to patients in terms of perspectives, goals, and priorities, creating partnerships through involving patients in goal-setting and communicating feedback, and documenting and evaluating outcomes that are meaningful to patients.
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| 2. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 3. |
- Ferencz, Beata, et al.
(författare)
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The Benefits of Staying Active in Old Age : Physical Activity Counteracts the Negative Influence of PICALM, BIN1, and CLU Risk Alleles on Episodic Memory Functioning
- 2014
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Ingår i: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 29:2, s. 440-449
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Tidskriftsartikel (refereegranskat)abstract
- PICALM, BIN1, CLU, and APOE are top candidate genes for Alzheimer's disease, and they influence episodic memory performance in old age. Physical activity, however, has been shown to protect against age-related decline and counteract genetic influences on cognition. The aims of this study were to assess whether (a) a genetic risk constellation of PICALM, BIN1, and CLU polymorphisms influences cognitive performance in old age; and (b) if physical activity moderates this effect. Data from the SNAC-K population-based study were used, including 2,480 individuals (age range = 60 to 100 years) free of dementia at baseline and at 3- to 6-year follow-ups. Tasks assessing episodic memory, perceptual speed, knowledge, and verbal fluency were administered. Physical activity was measured using self-reports. Individuals who had engaged in frequent health-or fitness-enhancing activities within the past year were compared with those who were inactive. Genetic risk scores were computed based on an integration of risk alleles for PICALM (rs3851179 G allele, rs541458 T allele), BIN1 (rs744373 G allele), and CLU (rs11136000 T allele). High genetic risk was associated with reduced episodic memory performance, controlling for age, education, vascular risk factors, chronic diseases, activities of daily living, and APOE gene status. Critically, physical activity attenuated the effects of genetic risk on episodic memory. Our findings suggest that participants with high genetic risk who maintain a physically active lifestyle show selective benefits in episodic memory performance.
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| 4. |
- Ferencz, Beata, et al.
(författare)
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The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age
- 2013
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction is implicated in neurodegenerative disorders, such as Alzheimer's disease (AD). Translocase of outer mitochondrial membrane 40 (TOMM40) may be influential in this regard by influencing mitochondrial neurotoxicity. Little is known about the influence of the TOMM40 gene on hippocampal (HC) volume and episodic memory (EM), particularly in healthy older adults. Thus, we sought to discern the influence of TOMM40 single nucleotide polymorphisms (SNPs), which have previously been associated with medial temporal lobe integrity (rs11556505 and rs2075650), on HC volume and EM. The study sample consisted of individuals from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who were free of dementia and known neurological disorders, and 6087 years of age (n = 424). EM was measured by using a 16-item word list with a 2-min free recall period and delineation of the HC was performed manually. The influence of Apolipoprotein E (APOE) and TOMM40 was assessed by 2 x 2 ANOVAs and partial correlations. There was no effect of APOE and TOMM40 on EM performance and HC volume. However, partial correlations revealed that HC volume was positively associated with free recall performance (r = 0.21, p < 0.01, r(2) = 0.04). When further stratified for TOMM40, the observed association between HC volume and free recall in APOE epsilon 4 carriers was present in combination with TOMM40 rs11556505 any T (r = 0.28, p < 0.01, R-2 = 0.08) and rs2075650 any G (r = 0.28, p < 0.01, R-2 = 0.08) risk alleles. This pattern might reflect higher reliance on HC volume for adequate EM performance among APOE epsilon 4 carriers with additional TOMM40 risk alleles suggesting that the TOMM40 gene cannot merely be considered a marker of APOE genotype. Nevertheless, neither APOE nor TOMM40 influenced HC volume or EM in this population-based sample of cognitively intact individuals over the age of 60.
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| 5. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 6. |
- Kalpouzos, Grégoria, et al.
(författare)
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Telomerase Gene (hTERT) and Survival : Results From Two Swedish Cohorts of Older Adults
- 2016
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 71:2, s. 188-195
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Tidskriftsartikel (refereegranskat)abstract
- Telomere length has been associated with longevity. As telomere length is partly determined by the human telomerase reverse transcriptase (hTERT), we investigated the association between an hTERT polymorphism located in its promoter region ((-) (1327)T/C) and longevity in two cohorts of older adults. Participants from the Kungsholmen project (KP; n = 1,205) and the Swedish National study of Aging and Care in Kungsholmen (SNAC-K; n = 2,764) were followed for an average period of 7.5 years. The main outcomes were hazard ratios (HR) of mortality and median age at death. In both cohorts, mortality was lower in female T/T carriers, aged 75+ years in KP (HR = 0.8, 95% CI: 0.5-0.9) and 78+ years in SNAC-K (HR = 0.6, 95% CI: 0.4-0.8) compared with female C/C carriers. T/T carriers died 1.8-3 years later than the C/C carriers. This effect was not present in men, neither in SNAC-K women aged 60-72 years. The association was not modified by presence of cancer, cardiovascular diseases, number of chronic diseases, or markers of inflammation, and did not interact with APOE genotype or estrogen replacement therapy. The gender-specific increased survival in T/T carriers can be due to a synergistic effect between genetic background and the life-long exposure to endogenous estrogen.
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| 7. |
- Keller, Lina, et al.
(författare)
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A Functional Polymorphism In The Hmgcr Promoter Affects Transcriptional Activity But Not The Risk For Alzheimer Disease In Swedish Populations
- 2010
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Ingår i: Brain Research. - Amsterdam : Elsevier. - 0006-8993 .- 1872-6240. ; 1344, s. 185-91
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Tidskriftsartikel (refereegranskat)abstract
- Variations in genes associated with cholesterol homeostasis have been reported to modify the risk of developing Alzheimer disease (AD). To date there have been few investigations into variations in genes directly involved in cholesterol biosynthesis and AD. We investigated the influence of the -911C>A polymorphism (rs3761740) in the hydroxy-methyl-glutaryl CoA reductase (HMGCR) gene promoter on basal and regulated transcription, plasma cholesterol levels and the association with AD. Under in vitro conditions the A allele was found to be significantly more responsive to SREBP-2 mediated regulation than the C allele. In an age and sex matched case-control study, the genotype distribution and allele frequency of this polymorphism were not associated with AD (OR=1.03; 95% CI=0.72-1.48). However, we did find evidence supporting an interaction between the HMGCR A allele, the APOE E4 allele and an altered risk of AD (OR=2.41; 95% CI=0.93-6.22).
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| 8. |
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| 9. |
- Keller, Lina
(författare)
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Genetics in dementia : impact of sequence variations for families and populations
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Even though the human genome sequences are remarkably similar, there is room for genetic variability that makes every human unique. The most common form of sequence variation in the genome is an exchange of a single nucleotide. The effect of sequence variations on the phenotype can be considered to be a continuum, from common polymorphisms with none or relatively mild effects, to severe and dramatic effects for mutations. Dementia is a devastating disorder, which severely affects cognitive functions and eventually leads to death. Dementia is, not always but most of the time, caused by neurodegeneration, as in the case of Alzheimer disease (AD) and Frontotemporal dementia (FTD). The genetics in dementia is complex. The majority of cases are caused by a combination of variations in many genes, polymorphisms, in addition to an increased vulnerability due to exposure to harmful environmental factors during the life course. The effects of these variations are studied in populations, where both genetic and environmental factors can be assessed. In a few percent of dementia cases, the disease is caused by mutations in single genes. By identifying mutations in the affected families, important features about the disease etiology can be revealed. In this thesis, variations in four genes were studied. Study I focuses on the impact of the widely confirmed genetic risk factor for dementia, APOE, on mortality in a prospective community-based study, The Kungsholmen Project. The risk for mortality was increased for epsilon4 carriers, and decreased for epsilon2 carriers. The increased mortality was mainly explained by dementia. In addition, a gender specific effect was observed. In Study II, a G35fsX19 mutation was identified in the GRN gene, causing FTD in a Swedish family. Members in this family developed dementia with behavioral disturbances and progressive aphasia with an age at onset around 55 years. At autopsy, neurodegeneration and immunoreactivity for TDP-43 was observed. The G35fsX19 mutation resulted in a frameshift and was predicted to create a premature stop codon. Functional analyses of mRNA showed about 50% less expression of GRN. The mutated mRNA was not detected by cDNA sequencing, suggesting it was degraded by nonsense mediated mRNA decay. In Study III, an I143T mutation was identified in PSEN1 in a Swedish family with early onset AD. The onset age was around 36 years. The mutation carriers were severely affected by cognitive deficits, in addition to neurological symptoms such as myoclonia. Neuropathologically, they were severely affected by Alzheimer pathology. Since one of the pathological hallmarks of AD, the amyloid plaques, consists of the Abeta peptide, the distribution of Abeta species in the postmortem brain of mutation carriers was investigated. Abeta42 was abundantly present both in plaques and vessels while Abeta40 was mainly present in vessels. Interestingly, we found Abeta43, which has rarely been studied in AD, to be present in all investigated brain regions, emphasizing a role for Abeta43 in the disease etiology. In Study IV, the FTO gene, which has been known for its involvement in body weight, was shown to influence the risk for dementia and AD for the first time, in persons 75+ years derived from the Kungsholmen project. The AA-genotype of the FTO rs9939609 polymorphism increased the risk about 50% compared to TT-carriers. This effect could not be explained by vascular risk factors measured at baseline, such as diabetes, high BMI, CVD or physical activity. Interaction between FTO and APOE was found, and together the two risk alleles increased the dementia risk almost three times. This finding supports a role for metabolic dysregulation in the dementia etiology. To conclude, four genomic sequence variations were investigated for their impact onneurodegenerative diseases and mortality. Two mutations were identified, in GRN and PSEN1 in two families suffering from FTD and AD, respectively. The APOE gene was found to increase mortality whereas FTO, the obesity-associated gene, was for the first time shown to increase the risk of dementia and AD in the old Kungsholmen population.
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| 10. |
- Keller, Lina, et al.
(författare)
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The Obesity Related Gene, FTO, Interacts with APOE and is Associated with Alzheimer's Disease Risk : A Prospective Cohort Study
- 2011
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 23:3, s. 461-469
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Tidskriftsartikel (refereegranskat)abstract
- The FTO gene has been shown to have a small but robust effect on body mass index (BMI) and to increase the risk for diabetes. Both high BMI and diabetes are vascular risk factors that might play a role in the development of Alzheimer's disease (AD) and dementia. Thus, our aim was to explore the impact of FTO on AD and dementia risk. Nine years of follow-up data was gathered from the Kungsholmen project, a prospective population-based study on 1,003 persons without dementia. Cox-regression models were used to assess the relative risks of developing AD and dementia (DSM-III-R criteria) according to FTO genotypes (rs9939609), taking into account APOE, physical inactivity, BMI, diabetes, and cardiovascular disease (CVD). Compared to carriers of the FTO TT-genotype, AA-carriers had a higher risk for AD (RR 1.58, 95% CI: 1.11-2.24) and for dementia (RR 1.48, 95% CI: 1.09-2.02) after adjustment for age, gender, education, and APOE genotype. This effect remained after additional adjustment for physical inactivity, BMI, diabetes, and CVD. An interaction between FTO and APOE was found, with increased risk for dementia for those carrying both FTO AA and APOE epsilon 4. Importantly, the effect of the AA-genotype on dementia/AD risk seems to act mostly through the interaction with APOE epsilon 4. Our findings suggest that the FTO AA-genotype increases the risk for dementia, and in particular AD, independently of physical inactivity, BMI, diabetes, and CVD measured at baseline. Our results are in line with the recently reported association between FTO and reduced brain volume in cognitively healthy subjects.
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