| 1. |
- Classon, Elisabet, et al.
(author)
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Relations between Concurrent Longitudinal Changes in Cognition, Depressive Symptoms, Self-Rated Health and Everyday Function in Normally Aging Octogenarians
- 2016
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:8, s. e0160742-
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Journal article (peer-reviewed)abstract
- Ability to predict and prevent incipient functional decline in older adults may help prolong independence. Cognition is related to everyday function and easily administered, sensitive cognitive tests may help identify at-risk individuals. Factors like depressive symptoms and self-rated health are also associated with functional ability and may be as important as cognition. The purpose of this study was to investigate the relationship between concurrent longitudinal changes in cognition, depression, self-rated health and everyday function in a well-defined cohort of healthy 85 year olds that were followed-up at the age of 90 in the Elderly in Linkoping Screening Assessment 85 study. Regression analyses were used to determine if cognitive decline as assessed by global (the Mini-Mental State Examination) and domain specific (the Cognitive Assessment Battery, CAB) cognitive tests predicted functional decline in the context of changes in depressive symptoms and self-rated health. Results showed deterioration in most variables and as many as 83% of these community-dwelling elders experienced functional difficulties at the age of 90. Slowing-down of processing speed as assessed by the Symbol Digits Modality Test (included in the CAB) accounted for 14% of the variance in functional decline. Worsening self-rated health accounted for an additional 6%, but no other variables reached significance. These results are discussed with an eye to possible preventive interventions that may prolong independence for the steadily growing number of normally aging old-old citizens.
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| 2. |
- Domert, Jakob, 1986-
(author)
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Neuron-to-neuron propagation of neurodegenerative proteins; relation to degradative systems
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Alzheimer’s disease (AD) and Parkinson’s disease (PD) are defined by neurodegeneration and accumulations of misfolded proteins that spread through the brain in a well characterized manner. In AD these accumulations consist mainly of β-amyloid (Aβ) and tau, while in PD, α-synuclein (α-syn) make up the characteristic lewy pathology. The general aim of this thesis was to investigate mechanisms associated with neurotoxic peptide activity by Aβ, tau and α-syn in relation to cellular degradation and transfer with a cell-to-cell transfer model system. We found that intercellular transfer of oligomeric Aβ occurs independently of isoform. However, the amount of transfer correlates with each isoforms ability to resist degradation or cellular clearance. The Aβ1-42 isoform showed particular resistance to clearance, which resulted in higher levels of cell-to-cell transfer of the isoform and lysosomal stress caused by accumulation. As Aβ accumulations can inhibit the proteasomal degradation we investigated how reduced proteasomal degradation affected neuron-like cells. We found increased levels of phosphorylated tau protein, disturbed microtubule stability and impaired neuritic transport after reduced proteasomal activity. These changes was partly linked to c-Jun and ERK 1/2 kinase activity. We could also show that α-syn transferred from cell-to-cell in our model system, with a higher degree of transfer for the larger oligomer and fibrillar species. Similar to Aβ, α-syn mainly colocalized with lysosomes, before and after transfer. Lastly, we have developed our cell-to-cell transfer system into a model suitable for high throughput screening (HTS). The type of cells have been upgraded from SH-SY5Y cells to induced pluripotent stem cells (iPSCs), with a differentiation profile more similar to mature neurons. The next step will be screening a small molecular library for substances with inhibitory effect on cell-to-cell transfer of Aβ peptides. The importance of the degradative systems in maintaining protein homeostasis and prevent toxic accumulations in general is well known. Our findings shows the importance of these systems for neurodegenerative diseases and also highlight the link between degradation and cell-to-cell transfer. To restore or enhance the degradative systems would be an interesting avenue to treat neurodegenerative diseases. Another way would be to inhibit the transfer of misfolded protein aggregates. By using the HTS model we developed, a candidate substance with good inhibitory effect on transfer can hopefully be found.
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| 3. |
- Dong, Huan-Ji, et al.
(author)
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Obese very old women have low relative handgrip strength, poor physical function, and difficulty in daily living
- 2015
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In: The Journal of Nutrition, Health & Aging. - : Springer. - 1279-7707 .- 1760-4788. ; 19:1, s. 20-25
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Journal article (peer-reviewed)abstract
- Objectives: To investigate how anthropometric and body composition variables, and handgrip strength (HS) affect physical function and independent daily living in 88-year-old Swedish women.Participants: A cross-sectional analysis of 83 community-dwelling women, who were 88 years old with normal weight (n=30), overweight (n=29), and obesity (n=24) in Linköping, Sweden, was performed.Measures: Assessments of body weight (Wt), height, waist circumference (WC), and arm circumference were performed by using an electronic scale and measuring tape. Tricep skinfold thickness was measured by a skinfold calliper. Fat mass (FM) and fat-free mass (FFM) were measured by bioelectrical impedance analysis, and HS was recorded with an electronic grip force instrument. Linear regression was used to determine the contributions of parameters as a single predictor or as a ratio with HS to physical function (Short Form-36, SF-36PF) and instrumental activities of daily living (IADL).Results: Obese women had greater absolute FM and FFM, and lower HS corrected for FFM and HS-based ratios (i.e., HS/Wt, HS/body mass index [BMI]) than their normal weight and overweight counterparts. After adjusting for physical activity levels and the number of chronic diseases, HS-based ratios explained more variance in SF-36PF scoring (R2: 0.52–0.54) than single anthropometric and body composition variables (R2: 0.45–0.51). WC, HS, and HS-based ratios (HS/Wt and HS/FFM) were also associated with the number of IADL with no difficulty.Conclusion: Obese very old women have a high WC, but their HS is relatively low in relation to their Wt and FFM. These parameters are better than BMI for predicting physical function and independent daily living.
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| 4. |
- Dong, Huan-Ji, et al.
(author)
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Unaltered image of health maintenance : An observation of non-participants in a swedish cohort study of 85 to 86 years olds
- 2015
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In: Journal of Frailty & Aging. - Paris, France : Editions S E R D I. - 2260-1341 .- 2273-4309. ; 4:2, s. 93-99
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Journal article (peer-reviewed)abstract
- Background: Selection bias is often inevitable in epidemiologic studies. It is not surprising that study conclusions based on participants’ health status are frequently questioned. Objective: This study aimed to assess whether the non-participants affected the characteristics of a general population of the very old people. Design, Setting and Participants: Prospective, cross-sectional (N=650, aged 85 years old) analysis and 1-year follow-up (n=273), in Linköping, Sweden. Measurements: We analysed data on health-related factors from a postal questionnaire, a home visit and a clinic visit at baseline and at the 1-year follow-up. We calculated the effect size to evaluate the degree of differences between the groups. Results: A greater proportion of non-participants resided in sheltered accommodation or nursing homes (participants vs non-response vs refusal, 11% vs 22% vs 40, P<0.001, φ=0.24). During the home visit or clinic visit, a higher proportion of dropouts reported mid-severe problems in EQ-5D domains (mobility and self-care) and limitations in personal activities of daily living, but the differences between participants and dropouts were very small (φ<0.2). No significant difference was found between the groups with regard to emergency room visits or hospital admissions, despite the fact that more participants than dropouts (φ=0.23) had multimorbidities (≥2 chronic diseases). Living in sheltered accommodation or a nursing home (odds ratio (OR), 2.8; 95% confidence interval (CI), 1.5-5), female gender (OR, 1.8; 95% CI, 1.1-3.1) and receiving more home visits in primary care (OR, 1.03; 95% CI, 1-1.06) contributed positively to drop out in the data collection stages over the study period. Conclusion: Non-participants were not considered to be a group with worse health. Mobility problems may influence very old people when considering further participation, which threatens attrition.
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| 5. |
- Edvardsson, Maria, et al.
(author)
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Differences in levels of albumin, ALT, AST, gamma-GT and creatinine in frail, moderately healthy and healthy elderly individuals
- 2018
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In: Clinical Chemistry and Laboratory Medicine. - : WALTER DE GRUYTER GMBH. - 1434-6621 .- 1437-4331. ; 56:3, s. 471-478
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Journal article (peer-reviewed)abstract
- Background: Reference intervals are widely used as decision tools, providing the physician with information about whether the analyte values indicate ongoing disease process. Reference intervals are generally based on individuals without diagnosed diseases or use of medication, which often excludes elderly. The aim of the study was to assess levels of albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and gamma-glutamyl transferase (gamma-GT) in frail, moderately healthy and healthy elderly indivuduals. Methods: Blood samples were collected from individuals amp;gt; 80 years old, nursing home residents, in the Elderly in Linkoping Screening Assessment and Nordic Reference Interval Project, a total of 569 individuals. They were divided into three cohorts: frail, moderately healthy and healthy, depending on cognitive and physical function. Albumin, ALT, AST, creatinine and gamma-GT were analyzed using routine methods. Results: Linear regression predicted factors for 34% of the variance in albumin were activities of daily living (ADL), gender, stroke and cancer. ADLs, gender and weight explained 15% of changes in ALT. For AST levels, ADLs, cancer and analgesics explained 5% of changes. Kidney disease, gender, Mini Mental State Examination (MMSE) and chronic obstructive pulmonary disease explained 25% of the variation in creatinine levels and MMSE explained three per cent of gamma-GT variation. Conclusions: Because a group of people are at the same age, they should not be assessed the same way. To interpret results of laboratory tests in elderly is a complex task, where reference intervals are one part, but far from the only one, to take into consideration.
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| 6. |
- Franzon, Kristin
(author)
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Independent Ageing in Very Old Swedish Men
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Predictors for survival have been investigated thoroughly, but less is known about how to reach high age with preserved physical and cognitive function. These functions are crucial to stay independent in daily life, which is highly valued by the oldest old.This thesis was based on data from the Uppsala Longitudinal Study in Adult Men. In 1970, all men born in 1920-24 and living in Uppsala were invited to the study, and 82% (n=2,322) participated in the first investigation. In this thesis, data are used from the investigations cycles at the ages of 50, 71, 87 and 92 years. Independent ageing was defined as follows: having independency in personal care and the ability to walk outdoors alone, being community-dwelling, having a Mini-Mental State Examination score of 25 points or greater, and having no diagnosed dementia.Thirty-seven percent of the original cohort survived to the age of 85. At a mean age of 87, 74% of the participants were independently aged, while at a mean age of 92 the prevalence of independent ageing was 64%. In Paper I, non-smoking and normal weight at a mean age of 50 were associated with independent ageing at a mean age of 87 years. In Paper II, never smoking, not being obese, and a high adherence to a Mediterranean-like diet at a mean age of 71 were associated with independent ageing at a mean age of 87. In both Papers I and II, high leisure time physical activity was associated with survival, but not with independent ageing. In Paper III, higher gait speed and hand grip strength and a faster chair stand test were cross-sectionally associated with independent ageing at a mean age of 87. Higher gait speed was also longitudinally associated with independent ageing five years. However, muscle mass and sarcopenia were not associated with the outcome. In Paper IV, a history of stroke, osteoarthritis, hip fracture and chronic obstructive pulmonary disease were associated with loss of independent ageing at a mean age of 92.Smoking, weight and diet are all modifiable risk factors associated with independent ageing. If decreased smoking and a normalised weight in the population could diminish stroke, hip fracture, chronic obstructive pulmonary disease and osteoarthritis, the prevalence of independent ageing could rise, even in nonagenarians. Additionally, a Mediterranean-like diet may contribute to both survival and independent ageing.
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| 7. |
- Jansen, Willemijn J, et al.
(author)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
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Journal article (peer-reviewed)abstract
- Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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| 8. |
- Jansen, Willemijn J, et al.
(author)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Journal article (peer-reviewed)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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| 9. |
- Johansson, Maria, et al.
(author)
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Cognitive impairment and its consequences in everyday life : experiences of people with mild cognitive impairment or mild dementia and their relatives
- 2015
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In: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 27:6, s. 949-958
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Journal article (peer-reviewed)abstract
- Background: The aim of this study was to explore experiences of cognitive impairment, its consequences in everyday life and need for support in people with mild cognitive impairment (MCI) or mild dementia and their relatives.Methods: A qualitative approach with an explorative design with interviews was chosen. The participants included five people with MCI and eight people with mild dementia and their relatives. All participants were recruited at a geriatric memory clinic in Sweden. The Grounded Theory method was used.Results: The following categories emerged: noticing cognitive changes; changed activity patterns; coping strategies; uncertainty about own ability and environmental reactions; support in everyday life; support from the healthcare system; consequences in everyday life for relatives; and support for relatives. The main findings were that people with MCI and dementia experienced cognitive changes that could be burdensome and changed activity patterns. Most of them, however, considered themselves capable of coping on their own. The relatives noticed cognitive changes and activity disruptions to a greater extent and tried to be supportive in everyday life. Degree of awareness varied and lack of awareness could lead to many problems in everyday life.Conclusions: Perceived cognitive impairment and its consequences in everyday life were individual and differed among people with MCI or dementia and their relatives. Thus, healthcare professionals must listen to both people with cognitive impairment and their relatives for optimal individual care planning. Support such as education groups and day care could be more tailored towards the early stages of dementia.
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| 10. |
- Johansson, Maria, 1967-
(author)
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Cognitive impairment and its consequences in everyday life
- 2015
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Doctoral thesis (other academic/artistic)abstract
- The overall aim was to improve knowledge of the consequences of cognitive dysfunction in everyday life and of instruments to make these assessments. The thesis contains four studies each of different design using different populations.In study I, the relationship between cognitive function, ability to perform activities of daily living and perceived health-related quality of life were investigated in a population of 85-year-old individuals in the community of Linköping (n = 373). The study was part of the Elderly in Linköping Screening Assessment 85 (ELSA 85). Even mild cognitive dysfunction correlated with impaired ability to perform activities of daily living and lower health-related quality of life.In study II, the diagnostic accuracy and clinical utility of Cognistat, a cognitive screening instrument, were evaluated for identifying individuals with cognitive impairment in a primary care population. Cognistat has relatively good diagnostic accuracy with a sensitivity of 0.85, a specificity of 0.79 and a Clinical Utility Index (CUI) of 0.72. The corresponding values were 0.59, 0.91 and 0.53 for the Mini Mental State Examination (MMSE), and 0.26, 0.88 and 0.20 for the Clock Drawing Test (CDT).In study III, the aim was to develop an instrument measuring self-perceived or caregiver reported ability to perform everyday life activities in persons with suspected cognitive impairment or dementia and to perform psychometric testing of this instrument, named the Cognitive Impairment in Daily Life (CID). The CID was found to have good content validity.In study IV, experiences of cognitive impairment, its consequences in everyday life and the need for support in persons with mild cognitive impairment (MCI) or mild dementia and their relatives were explored. Interviews were performed with five people with MCI, eight people with mild dementia and their relatives (n = 13). The main finding was that persons with MCI and dementia experienced cognitive changes that could be burdensome and result in changed activity patterns.In conclusion, the findings support earlier research and show that cognitive dysfunction even at mild stages has an impact on everyday life and reduces perceived quality of life. To improve interventions for persons with cognitive impairment, it is important to assess not only cognitive function but also its consequences in everyday life activities.
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