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  • 1.
    Bergfrid, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Littbrand, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Olofsson, Birgitta
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Having plans for the future in very old people2024In: The International Journal of Aging & Human Development, ISSN 0091-4150, E-ISSN 1541-3535Article in journal (Refereed)
    Abstract [en]

    This study aimed to investigate the prevalence of having plans for the future among very old people and the factors associated with having such plans. A longitudinal population-based study with home visits for 85-, 90-, and ≥95-year-old participants in Sweden and Finland was used. Multivariate logistic regression and Cox proportional-hazards regression models with a maximum 5-year follow-up period were used. The prevalence of having plans for the future was 18.6% (174/936). More men than women and more people living in Sweden than in Finland had plans for the future. In multivariate models, having plans for the future was associated with speaking Swedish, being dentate, and living in the community in the total sample; speaking Swedish and being dentate among women; and speaking Swedish, having a lower Geriatric Depression Scale score, and urban residence among men. Having plans for the future was associated univariately, but not multivariately, with increased survival.

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  • 2.
    Hemmingsson, Eva-Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Hjelmare, Ellen
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Antiviral treatment associated with reduced risk of clinical Alzheimer's disease: A nested case-control study2021In: Alzheimer’s & Dementia: Translational Research & Clinical Interventions, E-ISSN 2352-8737, Vol. 7, no 1, article id e12187Article in journal (Refereed)
    Abstract [en]

    Introduction: In this nested case-control study, we investigated if antiviral treatment given prior to onset of Alzheimer's disease (AD) could influence incident AD.

    Methods: From a large population-based cohort study in northern Sweden, 262 individuals that later developed AD were compared to a non-AD matched control group with respect to prescriptions of herpes antiviral treatment. All included subjects were herpes simplex virus 1 (HSV1) carriers and the matching criteria were age, sex, apolipoprotein E genotype (ε4 allele carriership), and study sample start year.

    Results: Among those who developed AD, 6 prescriptions of antivirals were found, compared to 20 among matched controls. Adjusted for length of follow-up, a conditional logistic regression indicated a difference in the risk for AD development between groups (odds ratio for AD with an antiviral prescription 0.287, P = .018).

    Discussion: Antiviral treatment might possibly reduce the risk for later development of HSV1-associated AD.

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  • 3.
    Hörnsten, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Littbrand, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    High blood pressure as a risk factor for incident stroke among very old people: a population-based cohort study2016In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 34, no 10, p. 2059-2065Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: High blood pressure (BP) increases the risk of stroke, but there is limited evidence from studies including very old people. The aim was to investigate risk factors for incident stroke among very old people.

    METHODS: A prospective population-based cohort study was performed among participants aged at least 85 years in northern Sweden. The 955 participants were tested at their homes. BP was measured manually after 5-min supine rest. Incident stroke data were collected from medical charts guided by hospital registry, death records, and 5-year reassessments. Cox proportional hazards models were used.

    RESULTS: The stroke incidence was 33.8/1000 person-years (94 stroke events) during a mean follow-up period of 2.9 years. In a comprehensive multivariate model, atrial fibrillation [hazard ratio 1.85, 95% confidence interval (CI) 1.07-3.19] and higher SBP (hazard ratio 1.19, 95% CI 1.08-1.30 per 10-mmHg increase) were associated with incident stroke overall. However, higher SBP was not associated with incident stroke in participants with SBP less than 140 mmHg (hazard ratio 0.90, 95% CI 0.53-1.53 per 10-mmHg increase). In additional multivariate models, DBP at least 90 mmHg (hazard ratio 2.45, 95% CI 1.47-4.08) and SBP at least 160 mmHg (vs. <140 mmHg; hazard ratio 2.80, 95% CI 1.53-5.14) were associated with incident stroke. The association between BP and incident stroke was not affected by interactions related to sex, dependence in activities of daily living, or cognitive impairment.

    CONCLUSION: High SBP (≥160 mmHg) and DBP (≥90 mmHg) and atrial fibrillation appeared to be risk factors for incident stroke among very old people.

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  • 4.
    Lopatko Lindman, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Hemmingsson, Eva-Stina
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Brännström, Jon
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Herpesvirus infections, antiviral treatment, and the risk ofdementia: a registry-based cohort study in Sweden2021In: Alzheimer’s & Dementia: Translational Research & Clinical Interventions, E-ISSN 2352-8737, Vol. 7, no 1, article id e12119Article in journal (Refereed)
    Abstract [en]

    Introduction: Herpesviruses, including Herpes simplex virus type 1 (HSV1) and varicella zoster‐virus (VZV), have been implicated in Alzheimer's disease (AD) development. Likewise, antiviral treatment has been suggested to protect against dementia development in herpes‐infected individuals.

    Methods: The study enrolled 265,172 subjects aged ≥ 50 years, with diagnoses of VZV or HSV, or prescribed antiviral drugs between 31 December 2005 and 31 December 2017. Controls were matched in a 1:1 ratio by sex and birth year.

    Results: Antiviral treatment was associated with decreased risk of dementia (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.86 to 0.92), while herpes infection without antiviral drugs increased the risk of dementia (adjusted HR 1.50, 95% CI 1.29 to 1.74).

    Discussion: Antiviral treatment was associated with a reduced long‐term risk of dementia among individuals with overt signs of herpes infection. This is consistent with earlier findings indicating that herpesviruses are involved in the pathogenesis of AD.

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  • 5.
    Lopatko Lindman, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Jonsson, Caroline
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Pandey, Janardan P.
    Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, United States.
    Prokopenko, Dmitry
    Genetics and Aging Unit, Department of Neurology, McCance Center for Brain Health, Massachusetts General Hospital, MA, Boston, United States; Harvard Medical School, MA, Boston, United States.
    Tanzi, Rudolph E.
    Genetics and Aging Unit, Department of Neurology, McCance Center for Brain Health, Massachusetts General Hospital, MA, Boston, United States; Harvard Medical School, MA, Boston, United States.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    PILRA polymorphism modifies the effect of APOE4 and GM17 on Alzheimer’s disease risk2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 13264Article in journal (Refereed)
    Abstract [en]

    PILRA (rs1859788 A > G) has been suggested to be a protective variant for Alzheimer’s disease (AD) and is an entry co-receptor for herpes simplex virus-1. We conducted a nested case–control study of 360 1:1-matched AD subjects. Interactions between the PILRA-A allele, APOE risk variants (ε3/ε4 or ε4/ε4) and GM17 for AD risk were modelled. The associations were cross-validated using two independent whole-genome sequencing datasets. We found negative interactions between PILRA-A and GM17 (OR 0.72, 95% CI 0.52–1.00) and between PILRA-A and APOE risk variants (OR 0.56, 95% CI 0.32–0.98) in the discovery dataset. In the replication cohort, a joint effect of PILRA and PILRA × GM 17/17 was observed for the risk of developing AD (p.02). Here, we report a negative effect modification by PILRA on APOE and GM17 high-risk variants for future AD risk in two independent datasets. This highlights the complex genetics of AD.

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  • 6.
    Lopatko Lindman, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Lockman-Lundgren, Judith
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Long-term time trends in reactivated herpes simplex infections and treatment in Sweden2022In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 22, no 1, article id 547Article in journal (Refereed)
    Abstract [en]

    Background: Our aim was to describe the annual prevalence of herpes simplex virus (HSV) reactivation in relation to solar ultraviolet (UV) radiation and antiviral drug use in the Swedish adult population.

    Methods: The study comprised 2879 anti-HSV-1 immunoglobulin (Ig) G positive subjects from five different cohorts who had donated serum from 1988 to 2010. The sera were analyzed for anti-HSV IgM using enzyme-linked immunosorbent assay. Associations between the presence of anti-HSV IgM antibodies, the apolipoprotein E ε4 allele and the serum sampling year were assessed by logistic regression. Seasonality of anti-HSV IgM was evaluated in a UV radiation model. Data of antiviral drugs for the entire Swedish population were compiled from two different nationwide databases: the Swedish Prescribed Drug Register and the Swedish Association of the Pharmaceutical Industry.

    Results: Cross-sectional and longitudinal analyses indicated that the prevalence of anti-HSV IgM antibodies declined between 1988 and 2010 (odds ratio [OR] = 0.912, p <.001), while the total annual use of antiviral drugs in Sweden gradually increased from 1984 to 2017. Higher UV radiation was associated with higher prevalence of anti-HSV IgM antibodies (OR = 1.071, p =.043).

    Conclusion: The declining time trend of HSV reactivation in a Swedish cohort coincides with a steady increase of antiviral drug use in the Swedish general population.

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  • 7.
    Lopatko Lindman, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Plasma Amyloid-β in Relation to Antibodies Against Herpes Simplex Virus, Cytomegalovirus, and Chlamydophila pneumoniae2021In: Journal of Alzheimer's Disease Reports, E-ISSN 2542-4823, Vol. 5, no 1, p. 229-235Article in journal (Refereed)
    Abstract [en]

    Background: Amyloid-β (Aβ), the key constituent of Alzheimer’s disease (AD) plaques, has antimicrobial properties.

    Objective: To investigate the association between plasma Aβ and antibodies against the AD-related pathogens herpes simplex virus (HSV), cytomegalovirus (CMV), and C. pneumoniae.

    Methods: Plasma from 339 AD cases, obtained on average 9.4 years (±4.00) before diagnosis, and their matched controls were analyzed for Aβ40 and Aβ42 concentrations with Luminex xMAP technology and INNOBIA plasma Aβ-form assays. Enzyme-linked immunosorbent assays were utilized for analyses of anti-HSV immunoglobulin (Ig) G, anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG. Follow-up samples were available for 150 of the cases.

    Results: Presence and levels of anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG did not correlate with concentrations of Aβ42 or Aβ40 in cases or controls.

    Conclusion: Levels of plasma Aβ were not associated with antibodies against different AD-related pathogens.

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  • 8.
    Lopatko Lindman, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Kok, Eloise
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    A genetic signature including apolipoprotein Eε4 potentiates the risk of herpes simplex-associated Alzheimer's disease2019In: Alzheimer’s & Dementia: Translational Research & Clinical Interventions, E-ISSN 2352-8737, Vol. 5, p. 697-704Article in journal (Refereed)
    Abstract [en]

    Introduction: Herpes simplex virus type 1 (HSV1) in combination with genetic susceptibility has previously been implicated in Alzheimer's disease (AD) pathogenesis.

    Methods: Plasma from 360 AD cases, obtained on average 9.6 years before diagnosis, and their age- and sex-matched controls, were analyzed for anti-HSV1 immunoglobulin (Ig) G with enzyme-linked immunosorbent assays (ELISAs). APOE genotype and nine other selected risk genes for AD were extracted from a genome-wide association study analysis by deCODE genetics, Reykjavik, Iceland.

    Results: The interaction between APOEε4 heterozygosity (APOEε24 or ε3/ε4) and anti-HSV1 IgG carriage increased the risk of AD (OR 4.55, P = .02). A genetic risk score based on the nine AD risk genes also interacted with anti-HSV1 IgG for the risk of developing AD (OR 2.35, P = .01).

    Discussion: The present findings suggest that the APOEε4 allele and other AD genetic risk factors might potentiate the risk of HSV1-associated AD.

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  • 9.
    Lövheim, Hugo
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Norman, Tove
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study2019In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 1, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Background: Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer’s disease (AD) development.

    Objective: The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOE ɛ4) in a large population-based cohort with a long follow-up time.

    Methods: The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOE ɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared.

    Results: Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOE ɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOE ɛ4 for episodic memory decline (p < 0.001).

    Conclusion: In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOE ɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.

  • 10.
    Lövheim, Hugo
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Interaction between Cytomegalovirus and Herpes Simplex Virus Type 1 Associated with the Risk of Alzheimer’s Disease Development2018In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 61, p. 939-945Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several environmental factors, including infectious agents, have been suggested to cause Alzheimer's disease (AD). Cytomegalovirus (CMV) has been associated with AD in several recent studies.

    OBJECTIVE: To investigate whether carriage of CMV, alone or in combination with Herpes simplex virus (HSV), increased the risk of developing AD.

    METHODS: Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years), taken an average of 9.6 years before AD diagnosis, and 360 age-, sex-, cohort-, and sampling date matched dementia-free controls were analyzed to detect anti-CMV (immunoglobulin [Ig] G and IgM), group-specific anti-HSV (IgG and IgM), and specific anti-HSV1 and HSV2 IgG antibodies by enzyme-linked immunosorbent assays. AD cases and dementia-free controls were compared using conditional logistic regression analyses.

    RESULTS: The presence of anti-CMV IgG antibodies did not increase the risk of AD (odds ratio [OR], 0.857; p = 0.497). Among AD cases, an association between CMV and HSV1 carriage was detected (OR 7.145, p < 0.001); in a conditional logistic regression model, the interaction between CMV and HSV1 was associated with AD development (OR 5.662; p = 0.007).

    CONCLUSION: The present findings do not support a direct relationship between CMV infection and the development of AD; however, an interaction between CMV and HSV1 was found to be associated significantly with AD development. These findings suggest that CMV infection facilitates the development of HSV1-associated AD, possibly via its effects on the immune system.

  • 11.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Samband mellan gånghastighet och risker vid högt blodtryck hos äldre2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 11, article id EHCIArticle in journal (Other academic)
  • 12.
    Weidung, Bodil
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Boström, Gustaf
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Toots, Annika
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Littbrand, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Blood Pressure, Gait Speed, and Mortality in Very Old Individuals: A Population-Based Cohort Study2015In: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 16, no 3, p. 208-214Article in journal (Refereed)
    Abstract [en]

    Objectives: Clinical trials and observational studies have produced contradictory results regarding the association of blood pressure (BP) and mortality in people aged 80 years or older. Gait speed at usual pace has been shown to moderate this association in a population of noninstitutionalized people aged 65 years or older. The aims of this study were to investigate the association of BP with all-cause mortality in a representative sample of people aged 85 years or older and to assess whether gait speed moderates this association.

    Design, Setting, and Participants: A total of 806 participants in the population-based prospective Umeå 85+/GERDA study aged 85, 90, and 95 years or older.

    Measurements: Gait speed at usual pace was measured over 2.4 m. The main outcome was hazard ratios (HRs) for all-cause mortality according to systolic and diastolic BP categories in the total sample and in faster-walking (≥0.5 m/s, n = 312) and slower-walking (<0.5 m/s, n = 433) subcohorts; the latter also included habitually nonwalking participants. Comprehensive adjustments were made for sociodemographic and clinical characteristics associated with death.

    Results: Mean age and baseline systolic and diastolic BP were 89.6 ± 4.6 years, 146.8 ± 23.9 mm Hg, and 74.8 ± 11.1 mm Hg, respectively. Most (n = 561 [69%]) participants were women, 315 (39%) were care facility residents, and 566 (70%) were prescribed BP-lowering drugs. Within 5 years, 490 (61%) participants died. In the total sample and slower-walking subcohort, systolic BP appeared to be inversely associated with mortality, although not independent of adjustments. Among faster-walking participants, mortality risk after adjustment was more than 2 times higher in those with systolic BP of 140 to 149 mm Hg (HR = 2.25, 95% confidence interval [CI] = 1.03–4.94) and 165 mm Hg or higher (HR = 2.13, 95% CI = 1.01–4.49), compared with systolic BP of 126 to 139 mm Hg. Mortality risk was also independently higher in faster-walking participants with diastolic BP higher than 80 mm Hg, compared with diastolic BP of 75 to 80 mm Hg (HR = 1.76, 95% CI = 1.07–2.90).

    Conclusion: The gait speed threshold of 0.5 m/s may be clinically useful for the distinction of very old people with and without increased all-cause mortality risk due to elevated systolic and diastolic BP.

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  • 13.
    Weidung, Bodil
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Littbrand, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    The association between SBP and mortality risk differs with level of cognitive function in very old individuals2016In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 34, no 4, p. 745-752Article in journal (Refereed)
    Abstract [en]

    Objective:Cognitive impairment and dementia are highly prevalent in very old populations. Cardiovascular disease is a common cause of death in people with dementia.This study investigated whether the association of blood pressure (BP) with mortality differed with respect to mini-mental state examination (MMSE) score in a representative sample of very old individuals.Methods:The sample consisted of 1115 participants aged 85, 90, and at least 95 years from the Umea85+/GErontological Regional DAtabase cohort study. The main outcome was all-cause mortality within 2 years according to BP and MMSE score, using Cox proportional-hazard regression models adjusted for sociodemographic and clinical characteristics associated with death.Results:Mean age, MMSE score, and SBP and DBP were 89.44.6 years, 21.1 +/- 7.6, 146.1 +/- 23.4mmHg, and 74.1 +/- 11.7mmHg, respectively. Within 2 years, 293 (26%) participants died. BP was not associated independently with mortality risk, except among participants with MMSE scores of 0-10 among whom mortality risk was increased in association with SBP at least 165mmHg and 125mmHg or less, compared with 126-139mmHg (adjusted hazard ratio 4.54, 95% confidence interval=1.52-13.60 and hazard ratio 2.23, 95% confidence interval=1.12-4.45, respectively). In age and sex-adjusted analyses, SBP 125mmHg or less was associated with increased mortality risk in participants with MMSE scores at least 18.Conclusion:In people aged at least 85 years, the association of SBP with mortality appears to differ with respect to MMSE score. Very old individuals with very severe cognitive impairment and low or high BP may have increased mortality risk.

  • 14.
    Weidung, Bodil
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala.
    Toots, Annika
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Systolic blood pressure decline in very old individuals is explained by deteriorating health: Longitudinal changes from Umea85+/GERDA2017In: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 51, article id e9161Article in journal (Refereed)
    Abstract [en]

    Declining systolic blood pressure (SBP) is common in very old age and is associated with adverse events, such as dementia. Knowledge of factors associated with SBP changes could explain the etiology of this decline in SBP. This study investigated longitudinal changes in socioeconomic factors, medical conditions, drug prescriptions, and assessments and their associations with SBP changes among very old followed individuals.The study was based on data from the Umea85+/Gerontological Regional Database (GERDA) cohort study, which provided cross-sectional and longitudinal data on participants aged 85, 90, and 95 years from 2000 to 2015. Follow-up assessments were conducted after 5 years. The main outcome was a change in SBP. Factors associated with SBP changes were assessed using multivariate linear regression models.In the Umea85+/GERDA study, 454 surviving individuals underwent follow-up assessment after 5 years. Of these, 297 had SBP measured at baseline and follow-up. The mean changestandard deviation in SBP was -12 +/- 25mm Hg. SBP decline was associated independently with later investigation year (P=.009), higher baseline SBP (P<.001), baseline antidepressant prescription (P=.011), incident acute myocardial infarction during follow-up (P=.003), new diuretic prescription during follow-up (P=.044), and a decline in the Barthel Activities of Daily Living index at follow-up (P<.001).In conclusion, SBP declines among very old individuals. This decline seems to be associated with initial SBP level, investigation year, and health-related factors.

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  • 15.
    Weidung, Bodil
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Toots, Annika
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Systolic blood pressure decline in very old individuals is explained by deteriorating health: Longitudinal changes from Umeå85+/GERDAManuscript (preprint) (Other academic)
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