| 1. |
- Adedeji, Dickson O., et al.
(författare)
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Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients
- 2023
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Ingår i: Brain, Behavior, and Immunity - Health. - : Elsevier. - 2666-3546. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allostatic load (AL) is defined as the cumulative dysregulation of neuroendocrine, immunological, metabolic, and cardiovascular systems that increases the susceptibility to stress-related health problems. Several dementia and Alzheimer's disease (AD) risk factors have been identified, yet little is known about the role of AL and its associations with AD biomarkers (e.g., beta-amyloid (Aβ) or tau) and cognitive function among memory clinic patients. Hence, this study aims to assess the association between AL and AD biomarkers, cognitive performance, and cognitive decline after 3-years of follow-up.Methods: Data from 188 memory clinic patients were derived from the Cortisol and Stress in AD (Co-STAR) study in Sweden. Participants underwent baseline assessments including blood tests for AL measures (including cortisol, thyroid stimulating hormone, cobalamin, homocysteine, leukocytes, glycated hemoglobin, albumin, high-density and low-density lipoprotein cholesterol, triglycerides, and creatinine), cerebrospinal fluid (CSF) sampling for AD biomarkers and neuropsychological tests including five cognitive domains. Linear regressions were conducted, adjusting for age, sex, and education.Results: Higher AL was associated with lower CSF Aβ1-42 levels (β = −0.175, p = 0.025), reflecting higher brain levels of Aβ1-42. Stratified analyses suggested a significant association among women but not men, although the AL-sex interaction was not statistically significant. AL was not significantly associated with T-tau level (β = −0.030, p = 0.682) and P-tau level (β = 0.091, p = 0.980). There were no significant associations between AL and cognition or cognitive decline after 3 years.Conclusion: This study showed that higher AL was associated with increased brain amyloid accumulation. This suggests that AL may play a role in AD/dementia pathophysiology. Potential sex-related differences should be assessed in further larger studies.
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| 2. |
- Adedeji, Dickson O., et al.
(författare)
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Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients
- 2023
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Ingår i: Brain, Behavior, and Immunity - Health. - : Elsevier BV. - 2666-3546. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allostatic load (AL) is defined as the cumulative dysregulation of neuroendocrine, immunological, metabolic, and cardiovascular systems that increases the susceptibility to stress-related health problems. Several dementia and Alzheimer's disease (AD) risk factors have been identified, yet little is known about the role of AL and its associations with AD biomarkers (e.g., beta-amyloid (Aβ) or tau) and cognitive function among memory clinic patients. Hence, this study aims to assess the association between AL and AD biomarkers, cognitive performance, and cognitive decline after 3-years of follow-up.Methods: Data from 188 memory clinic patients were derived from the Cortisol and Stress in AD (Co-STAR) study in Sweden. Participants underwent baseline assessments including blood tests for AL measures (including cortisol, thyroid stimulating hormone, cobalamin, homocysteine, leukocytes, glycated hemoglobin, albumin, high-density and low-density lipoprotein cholesterol, triglycerides, and creatinine), cerebrospinal fluid (CSF) sampling for AD biomarkers and neuropsychological tests including five cognitive domains. Linear regressions were conducted, adjusting for age, sex, and education.Results: Higher AL was associated with lower CSF Aβ1-42 levels (β = −0.175, p = 0.025), reflecting higher brain levels of Aβ1-42. Stratified analyses suggested a significant association among women but not men, although the AL-sex interaction was not statistically significant. AL was not significantly associated with T-tau level (β = −0.030, p = 0.682) and P-tau level (β = 0.091, p = 0.980). There were no significant associations between AL and cognition or cognitive decline after 3 years.Conclusion: This study showed that higher AL was associated with increased brain amyloid accumulation. This suggests that AL may play a role in AD/dementia pathophysiology. Potential sex-related differences should be assessed in further larger studies.
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| 3. |
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| 4. |
- Andersson, Christin, et al.
(författare)
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Lifestyle Factors and Subjective Cognitive Impairment in Patients Seeking Help at a Memory Disorder Clinic : The Role of Negative Life Events
- 2019
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 48:3-4, s. 196-206
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: A large proportion of patients at memory disorders clinics are classified as having subjective cognitive impairment (SCI). Previous research has investigated whether particular lifestyle factors known to affect cognition can be useful in differentiating patients who do not show objective evidence of memory decline. There may also exist subgroups of patients with respect to lifestyle factors that could help clinicians to understand the patient group that presents to memory clinics. These may differ in diagnostic outcome. Very little is known about potential subgroups; however, but such information may help guide interventions and potentially eliminate unnecessary diagnostic procedures. The current study investigated patterns of lifestyle-related variables, including stress, sleep, sensory sensitivity, depression, and negative life events in patients presenting to a memory disorders clinic. The aim was to determine whether subgroups existed and whether it was possible to distinguish those with objectively impaired cognition. Methods: One hundred and seventy-eight patients (mean age 58 years) from a University Hospital Memory Disorders Clinic. Results: Cluster analysis identified three groups of lifestyle-related variables. Strong determinants of clusters were negative life events and age. Patients with a high number of negative life events also tended to have highest self-reported memory complaint, higher levels of stress, depression, and sensory sensitivity. However, they did not perform the worst on memory testing. In contrast, individuals who performed the worst on memory tests were older, tended to have the least memory complaints, and less negative lifestyle factors; this group also included the highest proportion of patients with mild cognitive impairment and had the lowest median amyloid A-beta 42 (A beta 42). The group with the best cognitive performance were younger, included the highest proportion of patients with SCI and the highest median A beta 42. On lifestyle variables, their ratings fell in between the other groups. Conclusions: Lifestyle subgroups of patients were determined by stress, emotional problems, and age. The groups were significantly associated with A beta 42 and diagnostic outcome. This pattern may confound the differentiation between objective and subjective memory problems. Asking about lifestyle variables, in conjunction with neuropsychological testing, could potentially identify individuals who are not likely to have objective memory impairment and guide interventions.
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| 5. |
- Arendt, Maja Louise, et al.
(författare)
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The ABCC4 gene is associated with pyometra in golden retriever dogs
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Pyometra is one of the most common diseases in female dogs, presenting as purulent inflammation and bacterial infection of the uterus. On average 20% of intact female dogs are affected before 10 years of age, a proportion that varies greatly between breeds (3-66%). The clear breed predisposition suggests that genetic risk factors are involved in disease development. To identify genetic risk factors associated with the disease, we performed a genome-wide association study (GWAS) in golden retrievers, a breed with increased risk of developing pyometra (risk ratio: 3.3). We applied a mixed model approach comparing 98 cases, and 96 healthy controls and identified an associated locus on chromosome 22 (p = 1.2 x 10(-6), passing Bonferroni corrected significance). This locus contained five significantly associated SNPs positioned within introns of the ATP-binding cassette transporter 4 (ABCC4) gene. This gene encodes a transmembrane transporter that is important for prostaglandin transport. Next generation sequencing and genotyping of cases and controls subsequently identified four missense SNPs within the ABCC4 gene. One missense SNP at chr22:45,893,198 (p.Met787Val) showed complete linkage disequilibrium with the associated GWAS SNPs suggesting a potential role in disease development. Another locus on chromosome 18 overlapping the TESMIN gene, is also potentially implicated in the development of the disease.
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| 6. |
- Bendt, Martina, et al.
(författare)
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Adults with spina bifida : A cross-sectional study of health issues and living conditions
- 2020
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Ingår i: Brain and Behavior. - : John Wiley & Sons. - 2162-3279 .- 2162-3279. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe health issues and living conditions in a cohort of adults living with Spina bifida.MATERIAL AND METHODS: A cross-sectional study was conducted by a multidisciplinary team. Adults with spina bifida (n = 219) were invited to participate. One-hundred-and-ninety-six persons (104 women and 92 men; 18-73 years, median age 33 years) were included. Structured interviews, questionnaires, and clinical assessments for medical, social, physical, and cognitive functions were used.RESULTS: There was large variation among participants as regards the consequences of their spina bifida. Individuals < 46 years seemed to have more secondary conditions such as hydrocephalus, Chiari II malformation, tethered cord symptoms, and latex allergy. A higher proportion of the individuals >46 years and older was able to walk, and they had performed better in primary school and on tests of psychomotor speed and executive function.CONCLUSIONS: This study demonstrates that adults with spina bifida have a complex set of physical, cognitive, and social needs that need to be addressed in order to improve their health issues and living conditions. The high prevalence of urinary and fecal incontinence, pain, and overweight underline that these issues need much attention during follow-up. The future generations of older adults may need more attention in many ways, since they at a younger age do have more complex medical conditions, lower physical and cognitive functions, and lower prerequisites for independent living and participation in society than those > 46 years today. This elucidates that adults with spina bifida need systematic follow-up services and social support throughout life.
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| 7. |
- Bendt, Martina, et al.
(författare)
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Adults with spina bifida : Ambulatory performance and cognitive capacity in relation to muscle function
- 2022
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Ingår i: Spinal Cord. - : Springer Science and Business Media LLC. - 1362-4393 .- 1476-5624. ; 60:2, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: Cross-sectional study.OBJECTIVE: Describe and compare ambulatory performance and cognitive capacity in relation to muscle function in an adult cohort with spina bifida. Also, explore factors associated with ambulation in participants with muscle function level 3.SETTING: Specialist clinic for adults with spinal cord disorders in Stockholm, Sweden.METHODS: A total regional cohort of adults (n = 219) with spina bifida was invited, 196 (104 women, mean age 35 years, SD 13 years) participated. Mode of mobility, cognitive capacity and muscle function were investigated. For participants with muscle function level 3, factors associated with ambulation were investigated using multivariate logistic regression analysis.RESULTS: In all, 84 participants (42%) were community ambulators, 22 (12%) household ambulators and 90 (46%) wheelchair users. There was a linear association between the lower degree of muscle function and scoliosis (P < 0.001). Mode of mobility varied despite similar muscle prerequisites in participants with muscle function level 3 (n = 58). Factors associated with ambulation in participants with muscle function level 3 were the absence of scoliosis, lower BMI and higher cognitive capacity.CONCLUSIONS: Cognitive capacity and mode of mobility varied widely across the cohort. However, in participants with muscle function level 3, despite similar muscular prerequisites, a large variation in the mode of mobility was found, suggesting that other factors were involved. It is important to prevent scoliosis, support a healthy lifestyle, as well as offer cognitive screening and support to promote ambulatory function and optimise independence in the everyday lives of adults with spina bifida.
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| 8. |
- Bendt, Martina, et al.
(författare)
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Gait and dynamic balance in adults with spina bifida
- 2022
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Ingår i: Gait & Posture. - : Elsevier BV. - 0966-6362 .- 1879-2219. ; 96, s. 343-350
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Spina bifida (SB) is a complex congenital malformation, often causing impaired gait performance depending on the level and extent of malformation. Research regarding gait and balance performance in adults with SB, has not been sufficiently described yet.RESEARCH QUESTION: What are the characteristics of spatiotemporal gait parameters and balance performance in adults with SB? Further, do persons with muscle function (MF) level 3 differ regarding gait and balance performance from those with MF level 1-2?METHODS: Cross-sectional observational study at an outpatient clinic. 41 adults with SB (18-65 years), who walked regularly. Spatiotemporal parameters of gait was assessed with the APDM system and balance performance with the Mini Balance Evaluation Systems Test (Mini-BESTest). Muscle strength in the legs was assessed with 0-5 manual muscle test, and participants were classified according to level of MF into groups MF1, MF2, and MF3. Two-sided t-test was used for parametric independent variables, and Cohen's d was used for effect sizes. The Mann-Whitney U test was used for non-parametric independent data and effect size was calculated by the z value (r = z/√n).RESULTS: Mean gait speed was 0.96 (SD 0.20) m/s and mean stride length 1.08 m (SD 0.17), individuals with MF3 showed significantly slower gaitspeed and shorter stride length (p < 0.05). Lumbar rotation was 21° (SD 11), and thoracic lateral sway 15° (IQR 15) with significantley difference (p < 0.001 and p < 0.05) for individuals in MF3. Mini-BESTest showed a mean score of 11.3 (SD 6.9), and individuals with MF3 showed significantly lower scores (p ≤ 0.001).SIGNIFICANCE: Gait and balance performance was reduced compared to normative data in almost all parameters, especially in persons with less muscle function. Increased knowledge from advanced gait analysis may help healthcare professionals to design rehabilitation programmes, in order to achieve and maintain a sustainable gait and balance performance.
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| 9. |
- Bendt, Martina, et al.
(författare)
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Living and health conditions for adults with spina bifida in Sweden – a comprehensive prevalence group study
- 2018
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Konferensbidrag (refereegranskat)abstract
- Introduction Seventy-five per-cents of children born with Spina Bifida (SB) are expected to live into adulthood, meaning that the adults will need more attention in the future. Adulthood involves great demands for persons with SB, but also for their families, the social well-fare and healthcare systems, as the group has a persistent need for care and support. The aim is to describe the living and health conditions for adults with Spina Bifida in different life stages including medical, physical, psychological, cognitive and social aspects. Methods A cross-sectional study conducted by a multidisciplinary team. Data collection was performed through structured interviews, questionnaires and clinical assessments. All individuals > 18 years with SB (n=219) registered at a regional outpatient clinic were offered participation; 196 persons (104 women, 92 men 18-73 years) were included. Results There was a great variation in the group concerning problems related to their congenital injury. The persons > 45 years and especially > 61 years seems to have less problems such as less prevalence of hydrocephalus, Chiari II malformation, tethered cord syndrome and they also walked to a higher extent. They passed elementary school to a higher extent and performed better on the tests for psychomotor speed and executive function. Conclusions The study shows the multifaceted problems this group is facing as adults with SB and contributes to increased knowledge concerning the living and health conditions. Increased knowledge can lead to targeted interventions and better care, thereby decreasing secondary complications, reducing costs for society and hopefully increasing quality of life for persons with SB and their families.
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| 10. |
- Ehrén, Ingrid, et al.
(författare)
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Cognitive challenges in persons with spina bifida : Bearing on urological dysfunctions?
- 2020
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Ingår i: Neurourology and Urodynamics. - : John Wiley & Sons. - 0733-2467 .- 1520-6777. ; 39:8, s. 2139-2145
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate if adult persons with spina bifida (SB) who have urinary tract complications have cognitive difficulties that can be identified by neuropsychological tests.METHODS: All individuals with SB ≥ 18 years of age registered at a regional outpatient clinic (n = 219) were invited, of which, 154 persons were included. Neuropsychological assessment of their cognitive status was performed with Wechsler Adult Intelligence Scale®-Fourth Edition: Coding, Block design, Arithmetic's, FAS (word generation), Rey Auditory Verbal Test for learning, and delayed recall 30 min. Bladder and bowel function were assessed with questions used by the Nordic Spinal Cord Injury Registry (NSCIR) in structured interviews, by questionnaires, and by chart reviews.RESULTS: Average neuropsychological test results for this SB population was shown to be approximately 1 SD under the median for the general population. The Coding test showed significantly lower test results as compared with the whole SB group in persons with urinary tract complications, especially urinary tract infections, reduced kidney function, dependent emptying of the bladder, and the bowel and accidental bowel leakage. The Arithmetic's test showed a significant difference between subgroups in all parameters except reduced kidney function whereas the other neuropsychological tests were significantly correlated with some but not all urological parameters.CONCLUSION: We propose neuropsychological testing with primarily two tests to find those persons with SB who, due to cognitive challenges, might need extra support to minimize urological complications.
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| 11. |
- Forsberg, Anton, et al.
(författare)
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PET imaging of amyloid deposition in patients with mild cognitive impairment
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1456-1465
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Tidskriftsartikel (refereegranskat)abstract
- It is of great clinical value to identify subjects at a high risk of developing AD. We previously found that the amyloid positron emission tomography (PET) tracer PIB showed a robust difference in retention in the brain between AD patients and healthy controls (HC). Twenty-one patients diagnosed with MCI (mean age 63.3 ± 7.8 (S.D.) years) underwent PET studies with 11C-PIB, and 18F-fluoro-deoxy-glucose (FDG) to measure cerebral glucose metabolism, as well as assessment of cognitive function and CSF sampling. Reference group data from 27 AD patients and 6 healthy controls, respectively, were used for comparison. The mean cortical PIB retention for the MCI patients was intermediate compared to HC and AD. Seven MCI patients that later at clinical follow-up converted to AD (8.1 ± 6.0 (S.D.) months) showed significant higher PIB retention compared to non-converting MCI patients and HC, respectively (ps < 0.01). The PIB retention in MCI converters was comparable to AD patients (p > 0.01). Correlations were observed in the MCI patients between PIB retention and CSF Aβ1-42, total Tau and episodic memory, respectively.
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| 12. |
- Hagman, Göran, et al.
(författare)
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Midlife hopelessness and white matter lesions two decades later : A population-based study
- 2010
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 7:4, Supplement, s. 595-595
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hopelessness has been associated with increased cardiovas- cular disease mortality and morbidity, subclinical atherosclerosis and meta- bolic syndrome. This study investigates the relation between midlife hopelessness and white matter lesions (WMLs) 20 years later in a Finnish population of men and women. Methods: Participants of the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) study in Finland were derived from random, population-based samples previously surveyed in 1972,1977, 1982 or 1987. In 1998, 1449 (73%) individuals aged 65-79 years participated in the re-examination. A subgroup (n1⁄4112, including 39 dementia cases, 31 mild cognitive impairment (MCI) cases and 42 con- trols) underwent 1.5T MRI scanning at re-examination, and WMLs were as- sessed from FLAIR-images using a semi-quantitative visual rating scale. Hopelessness was measured by 2 questionnaire items (expectations about future and reaching goals). Results: Subjects with increased hopelessness had a significantly higher risk of developing more severe WMLs two de- cades later. OR (95% CI) was 4.35 (1.36-13.46) in ordinal regression anal- yses adjusted for age, sex education, follow-up time, presence of the APOEe4 allele, systolic blood pressure, BMI, history of stroke, heart infarct, smoking and level of midlife leisure physical activity. Conclusions: Higher levels of hopelessness at midlife seem to be related to more severe WMLs later in life. Since WMLs may contribute to late-life cognitive impairment, lifestyle management of midlife vascular risk factors (which also increase the risk of dementia and cognitive impairment) may have better effects if people’s expectations are more thoroughly discussed.
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| 13. |
- Holleman, Jasper, et al.
(författare)
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Diurnal cortisol, neuroinflammation, and neuroimaging visual rating scales in memory clinic patients
- 2024
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Ingår i: Brain, behavior, and immunity. - : Elsevier. - 0889-1591 .- 1090-2139. ; 118, s. 499-509
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neuroinflammation is a hallmark of the Alzheimer's disease (AD) pathogenic process. Cortisol dysregulation may increase AD risk and is related to brain atrophy. This cross-sectional study aims to examine interactions of cortisol patterns and neuroinflammation markers in their association with neuroimaging correlates.METHOD: 134 participants were recruited from the Karolinska University Hospital memory clinic (Stockholm, Sweden). Four visual rating scales were applied to magnetic resonance imaging or computed tomography scans: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), white matter lesions (WML), and posterior atrophy. Participants provided saliva samples for assessment of diurnal cortisol patterns, and underwent lumbar punctures for cerebrospinal fluid (CSF) sampling. Three cortisol measures were used: the cortisol awakening response, total daily output, and the ratio of awakening to bedtime levels. Nineteen CSF neuroinflammation markers were categorized into five composite scores: proinflammatory cytokines, other cytokines, angiogenesis markers, vascular injury markers, and glial activation markers. Ordinal logistic regressions were conducted to assess associations between cortisol patterns, neuroinflammation scores, and visual rating scales, and interactions between cortisol patterns and neuroinflammation scores in relation to visual rating scales.RESULT: Higher levels of angiogenesis markers were associated with more severe WML. Some evidence was found for interactions between dysregulated diurnal cortisol patterns and greater neuroinflammation-related biomarkers in relation to more severe GCA and WML. No associations were found between cortisol patterns and visual rating scales.CONCLUSION: This study suggests an interplay between diurnal cortisol patterns and neuroinflammation in relation to brain structure. While this cross-sectional study does not provide information on causality or temporality, these findings suggest that neuroinflammation may be involved in the relationship between HPA-axis functioning and AD.
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| 14. |
- Holleman, Jasper, et al.
(författare)
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Life-course stress, cognition, and diurnal cortisol in memory clinic patients without dementia
- 2024
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Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier. - 0167-4943 .- 1872-6976. ; 119
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To examine associations of life-course stress with cognition and diurnal cortisol patterns in older adulthood, as well as potential mediation effects of diurnal cortisol patterns and perceived stress on the association between life-course stress and cognition.METHODS: 127 participants without dementia were selected from a cohort of Swedish memory clinic patients. Cross-sectional associations between scores on two chronic stress questionnaires (perceived stress, stressful life events (SLEs)), five cognitive domains (overall cognition, memory, working memory, processing speed, perceptual reasoning), and two measures of diurnal cortisol patterns (total daily output, diurnal cortisol slope), as well as potential mediation effects of diurnal cortisol patterns and perceived stress on associations between life-course stress and cognition, were assessed using linear regressions.RESULTS: Greater lifetime exposure to SLEs was associated with worse memory, working memory, and processing speed performance, but not with diurnal cortisol patterns. A greater number of SLEs in late childhood was associated with worse working memory and processing speed, while a greater number of SLEs in non-recent adulthood were associated with better overall cognition and perceptual reasoning. Greater perceived stress was associated with a flattened diurnal cortisol slope, but not with cognition. No evidence for interplay between self-reported and physiological stress markers was found in relation to cognition, although there appeared to be a significant positive indirect association between economic/legal SLEs and the diurnal cortisol slope via perceived stress.CONCLUSIONS: The associations between SLEs and cognition depend on the period during which SLEs occur, but seem independent of late-life cortisol dysregulation.
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| 15. |
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| 16. |
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| 17. |
- Jonell, Patrik, et al.
(författare)
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Multimodal Capture of Patient Behaviour for Improved Detection of Early Dementia : Clinical Feasibility and Preliminary Results
- 2021
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Ingår i: Frontiers in Computer Science. - : Frontiers Media SA. - 2624-9898. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive automatic screening for Alzheimer's disease has the potential to improve diagnostic accuracy while lowering healthcare costs. Previous research has shown that patterns in speech, language, gaze, and drawing can help detect early signs of cognitive decline. In this paper, we describe a highly multimodal system for unobtrusively capturing data during real clinical interviews conducted as part of cognitive assessments for Alzheimer's disease. The system uses nine different sensor devices (smartphones, a tablet, an eye tracker, a microphone array, and a wristband) to record interaction data during a specialist's first clinical interview with a patient, and is currently in use at Karolinska University Hospital in Stockholm, Sweden. Furthermore, complementary information in the form of brain imaging, psychological tests, speech therapist assessment, and clinical meta-data is also available for each patient. We detail our data-collection and analysis procedure and present preliminary findings that relate measures extracted from the multimodal recordings to clinical assessments and established biomarkers, based on data from 25 patients gathered thus far. Our findings demonstrate feasibility for our proposed methodology and indicate that the collected data can be used to improve clinical assessments of early dementia.
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| 18. |
- Kadir, Ahmadul, et al.
(författare)
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Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease.
- 2008
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 63:5, s. 621-31
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The effects of (-)-phenserine (phenserine) and placebo/donepezil treatment on regional cerebral metabolic rate for glucose (rCMRglc) and brain amyloid load were investigated by positron emission tomography in 20 patients with mild Alzheimer's disease in relation to cerebrospinal fluid (CSF) and plasma biomarkers, and cognitive function. METHODS: The first 3 months of the study was a randomized, double-blind, placebo-controlled phase, during which 10 patients received phenserine (30 mg/day) and 10 patients the placebo. Three to 6 months was an open-label extension phase, during which the placebo group received donepezil (5 mg/day) and the phenserine group remained on phenserine. After 6 months, all patients received phenserine treatment up to 12 months. The patients underwent positron emission tomography examinations to measure rCMRglc (8F-FDG) and amyloid load (11C-PIB) at baseline and after 3 and 6 months of the treatment. Neuropsychological and biomarker data were collected at the three times of positron emission tomography imaging. RESULTS: Statistically significant effects on a composite neuropsychological test score were observed in the phenserine-treated group compared with the placebo and donepezil group at 3 and 6 months, respectively. Values of rCMRglc were significantly increased in several cortical regions after 3 months of phenserine treatment, compared with baseline, and correlated positively with cognitive function and CSF beta-amyloid 40 (Abeta40). Cortical Pittsburgh Compound B retention correlated negatively with CSF Abeta40 levels and the ratio Abeta/beta-secretase-cleaved amyloid precursor protein. In CSF, Abeta40 correlated positively with the attention domain of cognition. INTERPRETATION: Phenserine treatment was associated with an improvement in cognition and an increase in rCMRglc.
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| 19. |
- Larsson, Liss Elin, et al.
(författare)
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Association of sarcopenia and its defining components with the degree of cognitive impairment in a memory clinic population
- 2023
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 96:2, s. 777-788
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sarcopenia and cognitive impairment are two leading causes of disabilities.Objective: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients.Methods:368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer’s disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0–3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied.Results: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06–0.90) and AD (OR: 0.12, 95% CI: 0.03–0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45–11.92).Conclusion: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.
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| 20. |
- Lee, Wai Tung, et al.
(författare)
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Polarisation Development at the European Spallation Source
- 2023
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Ingår i: EPJ Web of Conferences. - 2100-014X. ; 286, s. 03004-03004
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Tidskriftsartikel (refereegranskat)abstract
- To meet the ever-increasing user demand, eleven of the fifteen European Spallation Source (ESS) instruments under construction aim to offer polarised neutrons for user experiments. They include an imaging instrument, a SANS instruments, two reflectometers, three diffractometers, and four spectrometers. In conjunction with in-kind contributions and instrumentation grants, the ESS Polarisation Project will support the incorporation of polarisation analysis on eight of the eleven instruments. The project aims to deliver polarised neutrons for first-science experiments as instruments enter operation. Different polariser and polarisation analyser techniques will be available to accommodate the specifics of experiments on a given instrument. Polarised 3He neutron spin filter using either Metastable Optical Pumping (MEOP) or Spin-Exchange Optical Pumping (SEOP) techniques will provide shared-use equipment among many instruments, with SEOP’s main application being in situ beam-polarisation. Several instruments will also use polarising-supermirror devices. To provide wide-bandwidth spin-flipping capability to the time-of-flight instruments, Adiabatic Fast Passage (AFP) neutron spin flippers, also known as gradient-field radiofrequency spin flippers will be the main method of choice. Devices based on the same AFP principle will also be used to flip 3He nuclear spins. We are constructing our first 3He polariser setup, including field coils to produce highly uniform magnetic field. Monte Carlo simulations are being done for the supermirror polarisers. To ensure science-focused development, we are working with university partners in doing scientific experiments with polarised neutrons. These are some of the activities developing polarisation analysis for ESS instruments in our project.
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| 21. |
- Marchesi, Silvia, MD, 1985-
(författare)
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The effect of mechanical ventilation on abdominal organs : Analysing the role of PEEP and perfusion.
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The effect of mechanical ventilation on abdominal organs is not well understood and investigated yet. Previous studies, using an animal sepsis-like model, found an association between mechanical ventilation (MV) and abdominal edema and inflammation.The presented thesis was aimed to investigate the role of perfusion in edema formation and inflammation, and to study the abdomen during mechanical ventilation in an ARDS model to reduce the confounding effect of inflammation related to sepsis.Methods: In the first paper presented, inflammation and edema in the abdomen were investigated in an endotoxin model. The study subjects were divided into two groups with different mean arterial pressures (MAP), another small group of healthy controls were studied as well. MRI analyses were used to measure perfusion in the different abdominal organs. In the second paper presented, differences in abdominal edema and inflammation were assessed in two groups of subjects, one group underwent MV and one group had spontaneously breathing.Results: In the first study, MRI analyses confirm that the group with higher MAP had better perfusion than the low MAP group. In the liver, perfusion was lower in LowMAP group compared to HighMAP group, but the HighMAP group had lower perfusion than the healthy controls. However, in the other studied organs HighMAP group and healthy controls had similar perfusion.Edema did not differ between the groups. Inflammation was globally higher in LowMAP group and correlated with hemodynamics. TNFα in liver tissue and portal vein serum correlated with intra-abdominal pressure (IAP).In the second study, the cytokine concentration was higher in serum in the MV group. MV did not increase abdominal edema or inflammation, compared to spontaneous breathing. Discussion and conclusion: Abdominal edema and inflammation are multifactorial phenomena, and many elements have to be included in the analysis. Perfusion plays an important role in determining inflammation and IAP. MV per se was not found to be related to increased edema and inflammation. In a previous study, the role of different levels of PEEP and different respiratory rate between mechanically ventilated and spontaneously breathing animals were not analyzed, but could have contributed to the results. The efforts made in this study to maintain similar respiratory rate and PEEP in both groups, could have contributed to the presented results.It is important to underline that, even if MV was not related to inflammation in abdomen, it was related to an increase in systemic inflammation, most probably because of an enhanced lung production of inflammatory mediators.Further studies, focusing on the role of respiratory rate and PEEP on abdomen, as well as the analysis of the inter-relations among inflammation, perfusion and edema, are needed to increase the pathophysiological understanding of these phenomena.
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| 22. |
- Mravinacová, Sára, et al.
(författare)
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CSF protein ratios with enhanced potential to reflect Alzheimer’s disease pathology and neurodegeneration
- 2024
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Ingår i: Molecular Neurodegeneration. - : Springer Nature. - 1750-1326. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyloid and tau aggregates are considered to cause neurodegeneration and consequently cognitive decline in individuals with Alzheimer’s disease (AD). Here, we explore the potential of cerebrospinal fluid (CSF) proteins to reflect AD pathology and cognitive decline, aiming to identify potential biomarkers for monitoring outcomes of disease-modifying therapies targeting these aggregates. Method: We used a multiplex antibody-based suspension bead array to measure the levels of 49 proteins in CSF from the Swedish GEDOC memory clinic cohort at the Karolinska University Hospital. The cohort comprised 148 amyloid- and tau-negative individuals (A-T-) and 65 amyloid- and tau-positive individuals (A+T+). An independent sample set of 26 A-T- and 26 A+T+ individuals from the Amsterdam Dementia Cohort was used for validation. The measured proteins were clustered based on their correlation to CSF amyloid beta peptides, tau and NfL levels. Further, we used support vector machine modelling to identify protein pairs, matched based on their cluster origin, that reflect AD pathology and cognitive decline with improved performance compared to single proteins. Results: The protein-clustering revealed 11 proteins strongly correlated to t-tau and p-tau (tau-associated group), including mainly synaptic proteins previously found elevated in AD such as NRGN, GAP43 and SNCB. Another 16 proteins showed predominant correlation with Aβ42 (amyloid-associated group), including PTPRN2, NCAN and CHL1. Support vector machine modelling revealed that proteins from the two groups combined in pairs discriminated A-T- from A+T+ individuals with higher accuracy compared to single proteins, as well as compared to protein pairs composed of proteins originating from the same group. Moreover, combining the proteins from different groups in ratios (tau-associated protein/amyloid-associated protein) significantly increased their correlation to cognitive decline measured with cognitive scores. The results were validated in an independent cohort. Conclusions: Combining brain-derived proteins in pairs largely enhanced their capacity to discriminate between AD pathology-affected and unaffected individuals and increased their correlation to cognitive decline, potentially due to adjustment of inter-individual variability. With these results, we highlight the potential of protein pairs to monitor neurodegeneration and thereby possibly the efficacy of AD disease-modifying therapies.
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| 23. |
- Riedel, Dorothee, et al.
(författare)
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Cognitive function and performance of everyday activities in adults with spina bifida
- 2021
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Ingår i: Journal of Rehabilitation Medicine. - : Foundation for Rehabilitation Information. - 1650-1977 .- 1651-2081. ; 53:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Individuals with spina bifida often have cognitive impairments leading to dif-ficulties in education and daily activities. The aims of this study were to explore cognitive impairments in adults with spina bifida and to consider associations between impairments, educational outcome and per-formance of daily activities, comparing individuals with and without intellectual disability.METHODS: Data were collected on 35 adults with spina bifida via cognitive tests and Assessment of Motor and Process Skills (AMPS). Participants were divided into 3 groups: individuals without intellectual disability who completed compulsory education (NID-C); those without intellectual disability, who failed to successfully pass compulsory education (NID-F); and those with intellectual disability failed to successfully pass compulsory education (ID-F).RESULTS: All individuals with intellectual disability failed to successfully pass compulsory education (group ID-F) and had poorer scores across almost all measures than group NID-F and significantly poorer scores than group NID-C. All except 6 individuals scored below cut-off levels for effort and safety on both AMPS motor and process scales; more significant associations were seen between the cognitive tests and the motor rather than process scale.CONCLUSION: Cognitive impairments, irrespective of intellectual disability, impact on the performance of eve-ryday activities and on educational achievement, and thus need to be considered in assessments and inter-ventions to improve outcomes and promote independence in people with spina bifida.
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| 24. |
- Sindi, Shireen, et al.
(författare)
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Mid-life work-related stress increases dementia risk in late-life : The CAIDE 30-year study
- 2014
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 10:4, Supplement, s. P746-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The associations between work-related stress and various health outcomes in mid-life are well documented, yet less is known about the effects on late-life cognitive process and dementia. The current study investigated the associations between work-related stress in mid-life and the development of cognitive impairment and Alzheimer’s disease in late-life. Methods: The data was derived from the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) study; a prospective cohort study. Participants were randomly selected from four independent population-based samples that completed cardiovascular surveys. First baseline examinations occurred when participants were 50 years old on average, in 1972, 1977, 1982, or 1987. A random sample of 2,000 individ- uals was selected for re-examinations (carried out in 1998 and 2005-2008), where 1,511 subjects participated in at least one re-examination. The re- examinations included an extensive neuropsychological and cognitive assessment. Follow-up time was on average 28 (S.E.M. 1⁄4 0.17) years. Work-related stress comprised the total score of two questions adminis- tered in mid-life. The questions asked participants to rate their stress related to meeting demands at work, and constant hurry at work. Groups were categorized so that those with high or medium levels of stress were compared to those with low levels or no work-related stress. Results: High levels of work-related stress in mid-life were associated with higherrisk of cognitive impairment (where participants with cognitive impair- ment and dementia were compared to the group with no cognitive impair- ment) [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.1], and Alzheimer’s disease [OR, 2.1; CI, 1.1-3.9], when assessed at the first or second follow-up. Results remained significant after adjusting for age, ed- ucation, marital status, chronic health conditions, apolipoprotein E ε 4 allele (APOE ε 4), measures of hopelessness and loneliness. Conclusions: High levels of mid-life work-related stress predict the risk of developing dementia in late-life. The evidence suggests that individuals experiencing high levels of work-related stress form an important at-risk population. Preventive interventions are needed for this population in order to post- pone or prevent the development of cognitive impairment and Alzheimer’s disease.
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| 25. |
- Sindi, Shireen, et al.
(författare)
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Midlife Work-Related Stress Increases Dementia Risk in Later Life : The CAIDE 30-Year Study
- 2017
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Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press (OUP). - 1079-5014 .- 1758-5368. ; 72:6, s. 1044-1053
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the associations between midlife work-related stress and mild cognitive impairment (MCI), dementia, and Alzheimer's disease later in life, in a large representative population. Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study participants were randomly selected from independent population-based surveys (mean age 50 years). A random sample of 2,000 individuals was invited for two reexaminations including cognitive tests (at mean age 71 and mean age 78), and 1,511 subjects participated in at least one reexamination (mean follow-up 28.5 years). Work-related stress was measured using two questions on work demands that were administered in midlife. Analyses adjusted for important confounders. Higher levels of midlife work-related stress were associated with higher risk of MCI (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.08-1.76), dementia (OR, 1.53; CI, 1.13-2.07), and Alzheimer's disease (OR, 1.55; CI, 1.19-2.36) at the first follow-up among the CAIDE participants. Results remained significant after adjusting for several possible confounders. Work-related stress was not associated with MCI and dementia during the extended follow-up. Midlife work-related stress increases the risk for MCI, dementia, and Alzheimer's disease in later life. The association was not seen after the extended follow-up possibly reflecting selective survival/participation, heterogeneity in dementia among the oldest old, and a critical time window for the effects of midlife stress.
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| 26. |
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| 27. |
- Tengvall, Katarina, 1980-, et al.
(författare)
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Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs
- 2016
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Ingår i: BMC Genetics. - : Springer Science and Business Media LLC. - 1471-2156. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCanine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2.ResultsAdditional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10−7) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10−5), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region.ConclusionsOur experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.
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| 28. |
- Thunborg, Charlotta, 1965-, et al.
(författare)
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Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial
- 2024
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Ingår i: Alzheimer's Research & Therapy. - : Springer. - 1758-9193. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.MethodsMIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.ResultsDuring September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.ConclusionsThe multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.Trial registrationClinicalTrials.gov NCT03249688.
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| 29. |
- Thunborg, Charlotta, 1965-, et al.
(författare)
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Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial
- 2024
-
Ingår i: Alzheimer's Research & Therapy. - : Springer Nature. - 1758-9193. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.Methods: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.Results: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.Conclusions: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.
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