| 1. |
- Vestin, Erika, et al.
(författare)
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Herpes Simplex Viral Infection Doubles the Risk of Dementia in a Contemporary Cohort of Older Adults : A Prospective Study
- 2024
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 97:4, s. 1841-1850
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence indicates that herpes simplex virus (HSV) participates in the pathogenesis of Alzheimer's disease (AD). Objective: We investigated AD and dementia risks according to the presence of herpesvirus antibodies in relation to antiherpesvirus treatment and potential APOE epsilon 4 carriership interaction. Methods: This studywas conducted with 1002 dementia-free 70-year-olds living in Sweden in 2001-2005 who were followed for 15 years. Serum samples were analyzed to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels. Diagnoses and drug prescriptions were collected from medical records. Cox proportional-hazards regression models were applied. Results: CumulativeADand all-cause dementia incidences were 4% and 7%, respectively. Eighty-two percent of participants were anti-HSV IgG carriers, of whom 6% received anti-herpesvirus treatment. Anti-HSV IgG was associated with a more than doubled dementia risk (fully adjusted hazard ratio = 2.26, p = 0.031). No significant association was found with AD, but the hazard ratio was of the same magnitude as for dementia. Anti-HSV IgM and anti-CMV IgG prevalence, anti-herpesvirus treatment, and anti-HSV and -CMV IgG levels were not associated with AD or dementia, nor were interactions between anti-HSV IgG and APOE epsilon 4 or anti-CMV IgG. Similar results were obtained for HSV-1. Conclusions: HSV (but not CMV) infection may be indicative of doubled dementia risk. The low AD incidence in this cohort may have impaired the statistical power to detect associations with AD.
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| 2. |
- Weidung, Bodil, et al.
(författare)
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Longitudinal Effects of Herpesviruses on Multiple Cognitive Outcomes in Healthy Elderly Adults
- 2023
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 94:2, s. 751-762
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Tidskriftsartikel (refereegranskat)abstract
- Background: Herpesviruses have been proposed to be involved in Alzheimer's disease development as potentially modifiable pathology triggers. Objective: To investigate associations of serum antibodies for herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) and anti-herpesvirus treatment with cognitive outcomes in relation to interactions with APOE epsilon 4.Methods: The study included 849 participants in the population-based Prospective Investigation of the Vasculature in Uppsala Seniors study. Cognitive performance at the ages of 75 and 80 years was assessed using the Mini-Mental State Examination (MMSE), trail-making test (TMT) A and B, and 7-minute screening test (7MS).Results: Anti-HSV-1 IgG positivity was associated cross-sectionally with worse performance on the MMSE, TMT-A, TMT-B, 7MS, enhanced free recall, and verbal fluency tests (p = 0.016, p = 0.016, p < 0.001, p = 0.001, p = 0.033, and p < 0.001, respectively), but not orientation or clock drawing. Cognitive scores did not decline over time and longitudinal changes did not differ according to HSV-1 positivity. Anti-CMV IgG positivity was not associated cross-sectionally with cognition, but TMT-B scores declined more in anti-CMV IgG carriers. Anti-HSV-1 IgG interacted with APOE epsilon 4 in association with worse TMT-A and better enhanced cued recall. Anti-HSV IgM interacted with APOE epsilon 4 and anti-herpesvirus treatment in association with worse TMT-A and clock drawing, respectively.Conclusion: These findings indicate that HSV-1 is linked to poorer cognition in cognitively healthy elderly adults, including impairments in executive function, memory, and expressive language. Cognitive performance did not decline over time, nor was longitudinal decline associated with HSV-1.
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| 3. |
- Lindvall, Elias, et al.
(författare)
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The impact of stroke on the ability to live an independent life at old age : a community-based cohort study of Swedish men
- 2023
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Ingår i: BMC Geriatrics. - : BioMed Central (BMC). - 1471-2318 .- 1471-2318. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Few studies with controls from the same cohort have investigated the impact of stroke on the ability to live an independent life at old age. We aimed to analyze how great an impact being a stroke survivor would have on cognition and disability. We also analyzed the predictive value of baseline cardiovascular risk factors.METHODS: We included 1147 men, free from stroke, dementia, and disability, from the Uppsala Longitudinal Study of Adult Men, between 69-74 years of age. Follow-up data were collected between the ages of 85-89 years and were available for 481 of all 509 survivors. Data on stroke diagnosis were obtained through national registries. Dementia was diagnosed through a systematic review of medical charts and in accordance with the current diagnostic criteria. The primary outcome, preserved functions, was a composite outcome comprising four criteria: no dementia, independent in personal activities of daily living, ability to walk outside unassisted, and not living in an institution.RESULTS: Among 481 survivors with outcome data, 64 (13%) suffered a stroke during the follow-up. Only 31% of stroke cases, compared to 72% of non-stroke cases (adjusted OR 0.20 [95% CI 0.11-0.37]), had preserved functions. The chance of being free of dementia was 60% lower in the stroke group, OR 0.40 [95% CI 0.22-0.72]. No cardiovascular risk factors were independently able to predict preserved functions among stroke cases.CONCLUSION: Stroke has long lasting consequences for many aspects of disability at very high age.
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| 4. |
- Tan, Xiao, et al.
(författare)
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Reverse Dipping of Systolic Blood Pressure Is Associated With Increased Dementia Risk in Older Men : A Longitudinal Study Over 24 Years
- 2021
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Ingår i: Hypertension. - : Wolters Kluwer. - 0194-911X .- 1524-4563. ; 77:4, s. 1383-1390
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Tidskriftsartikel (refereegranskat)abstract
- A lower day-to-night systolic blood pressure (BP) dip has previously been associated with poor brain health and cognitive functions. Here, we sought to examine whether reduced (nighttime/daytime ratio of systolic BP >0.9 and ≤1) and reverse (nighttime/daytime ratio of systolic BP >1) dipping of systolic BP is associated with the prospective risk of being diagnosed with any dementia in Swedish older men. Twenty-four-hour ambulatory BP monitoring was used to estimate the nocturnal systolic BP dipping status of men at mean age 71 (n=997; 35% on antihypertensive medication) and 77.6 (n=611; 41% on antihypertensive medication). Dementia incidence during the observational period up to 24 years (n=286 cases) was determined by reviewing participants' medical history and independently confirmed by at least 2 experienced geriatricians. Using time-updated Cox regression (ie, time-updated information on covariates and exposure), we found that reverse systolic BP dipping was associated with a higher risk of being diagnosed with any dementia (adjusted HR, 1.64 [95% CI, 1.14-2.34], P=0.007) and Alzheimer's disease (1.67 [1.01-2.76], P=0.047) but not vascular dementia (1.29 [0.55-3.06], P=0.559). In contrast, reduced dipping of nocturnal systolic BP was not associated with a higher risk of being diagnosed with dementia. Our findings suggest that reverse systolic BP dipping may represent an independent risk factor for dementia and Alzheimer's disease in older men. Future studies should decipher whether therapies lowering nocturnal systolic BP below daytime levels, such as bedtime dosing of antihypertensive medication, can meaningfully curb the development of dementia.
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| 5. |
- Vestin, Erika, et al.
(författare)
-
Herpes simplex viral infection doubles the risk of dementia in a contemporary cohort of older adults : a prospective study
- 2024
-
Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 97:4, s. 1841-1850
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence indicates that herpes simplex virus (HSV) participates in the pathogenesis of Alzheimer’s disease (AD).Objective: We investigated AD and dementia risks according to the presence of herpesvirus antibodies in relation to anti-herpesvirus treatment and potential APOE ε4 carriership interaction.Methods: This study was conducted with 1002 dementia-free 70-year-olds living in Sweden in 2001–2005 who were followed for 15 years. Serum samples were analyzed to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels. Diagnoses and drug prescriptions were collected from medical records. Cox proportional-hazards regression models were applied.Results: Cumulative AD and all-cause dementia incidences were 4% and 7%, respectively. Eighty-two percent of participants were anti-HSV IgG carriers, of whom 6% received anti-herpesvirus treatment. Anti-HSV IgG was associated with a more than doubled dementia risk (fully adjusted hazard ratio = 2.26, p = 0.031). No significant association was found with AD, but the hazard ratio was of the same magnitude as for dementia. Anti-HSV IgM and anti-CMV IgG prevalence, anti-herpesvirus treatment, and anti-HSV and -CMV IgG levels were not associated with AD or dementia, nor were interactions between anti-HSV IgG and APOE ε4 or anti-CMV IgG. Similar results were obtained for HSV-1.Conclusions: HSV (but not CMV) infection may be indicative of doubled dementia risk. The low AD incidence in this cohort may have impaired the statistical power to detect associations with AD.
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| 6. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 7. |
- Åhman, Hanna Bozkurt, et al.
(författare)
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Dual-task tests discriminate between dementia, mild cognitive impairment, subjective cognitive impairment, and healthy controls : a cross-sectional cohort study
- 2020
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318 .- 1471-2318. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Discrimination between early-stage dementia and other cognitive impairment diagnoses is central to enable appropriate interventions. Previous studies indicate that dual-task testing may be useful in such differentiation. The objective of this study was to investigate whether dual-task test outcomes discriminate between groups of individuals with dementia disorder, mild cognitive impairment, subjective cognitive impairment, and healthy controls.METHODS: A total of 464 individuals (mean age 71 years, 47% women) were included in the study, of which 298 were patients undergoing memory assessment and 166 were cognitively healthy controls. Patients were grouped according to the diagnosis received: dementia disorder, mild cognitive impairment, or subjective cognitive impairment. Data collection included participants' demographic characteristics. The patients' cognitive test results and diagnoses were collected from their medical records. Healthy controls underwent the same cognitive tests as the patients. The mobility test Timed Up-and-Go (TUG single-task) and two dual-task tests including TUG (TUGdt) were carried out: TUGdt naming animals and TUGdt months backwards. The outcomes registered were: time scores for TUG single-task and both TUGdt tests, TUGdt costs (relative time difference between TUG single-task and TUGdt), number of different animals named, number of months recited in correct order, number of animals per 10 s, and number of months per 10 s. Logistic regression models examined associations between TUG outcomes pairwise between groups.RESULTS: The TUGdt outcomes "animals/10 s" and "months/10 s" discriminated significantly (p < 0.001) between individuals with an early-stage dementia diagnosis, mild cognitive impairment, subjective cognitive impairment, and healthy controls. The TUGdt outcome "animals/10 s" showed an odds ratio of 3.3 (95% confidence interval 2.0-5.4) for the groups dementia disorders vs. mild cognitive impairment. TUGdt cost outcomes, however, did not discriminate between any of the groups.CONCLUSIONS: The novel TUGdt outcomes "words per time unit", i.e. "animals/10 s" and "months/10 s", demonstrate high levels of discrimination between all investigated groups. Thus, the TUGdt tests in the current study could be useful as complementary tools in diagnostic assessments. Future studies will be focused on the predictive value of TUGdt outcomes concerning dementia risk for individuals with mild cognitive impairment or subjective cognitive impairment.
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| 8. |
- Åhman, Hanna Bozkurt, et al.
(författare)
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Dual-Task Tests Predict Conversion to Dementia-A Prospective Memory-Clinic-Based Cohort Study
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 17:21
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate whether Timed Up-and-Go (TUG) dual-task (TUGdt) tests predict dementia incidence among patients with subjective or mild cognitive impairment (SCI; MCI). Other study objectives were to determine whether TUGdt improves dementia prediction compared to a) demographic characteristics and standard cognitive tests alone; and b) TUG and Verbal Fluency performed separately. Patients (n = 172, age range 39-91 years, 78 women) with SCI or MCI performed TUGdt tests, including 1) naming animals and 2) reciting months backwards, and clinical cognitive tests at baseline. Diagnoses were identified at follow-up after 2.5 years. Logistic regression was used to predict dementia incidence, receiver operating characteristic (ROC) curves and c-statistics for predictive capacity. Analyses were stratified by age and gender. At follow-up, 51 patients had developed dementia. The TUGdt result "animals/10 s" was associated with dementia incidence (standardized odds ratio (OR) = 4.06, 95% confidence interval (CI) 2.28-7.23, p < 0.001), more so among patients under the median age of 72 years (standardized OR = 19.4, 95% CI 3.53-106.17, p < 0.001). TUGdt "animals/10 s" improved dementia prediction compared to demographic characteristics and standard tests alone (c-statistics 0.88 to 0.94) and single-task tests (c-statistics 0.86 to 0.89), but only in the younger patient group. TUGdt has the potential to become a useful tool for dementia prediction.
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