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Sökning: WFRF:(Qiu Chengxuan)

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1.
  • Heiland, Emerald G, et al. (författare)
  • Association of mobility limitations with incident disability among older adults : a population-based study.
  • 2016
  • Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 45:6, s. 812-819
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: mobility-related limitations predict future disability; however, the extent to which individual and combined mobility tests may predict disability remains unclear.OBJECTIVES: to estimate the odds of developing disability in activities of daily living (ADL) according to limitations in walking speed, balance or both; and explore the role of chronic diseases and cognitive function.DESIGN: a prospective cohort study.SETTING: urban area of Stockholm, Sweden.SUBJECTS: one thousand nine hundred and seventy-one disability-free persons (age ≥60 years, 63% women) from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K), who underwent baseline examination in 2001-04 and follow-up assessments for 6 years.MEASUREMENTS: mobility limitation was defined as a one-leg balance stand <5 s or walking speed <0.8 m/s. ADL disability was defined as the inability to complete one or more ADL: bathing, dressing, using the toilet, transferring and eating.RESULTS: during a total of 11,404 person-years (mean per person 5.8 years, SD 0.30) of follow-up, 119 (incidence 1.5/100 person-years) participants developed ADL disability. The demographic adjusted odds ratios (OR) (95% confidence intervals, CI) of incident ADL disability related to balance stand and walking speed limitations were 3.8 (2.3-6.3) and 8.4 (5.2-13.3), respectively. The associations remained statistically significant after controlling for number of chronic diseases and cognitive status. People with limitations in both balance and walking speed had an OR of 12.9 (95% CI 7.0-23.7) for incident disability compared with no limitation.CONCLUSION: balance and walking speed tests are simple clinical procedures that can indicate hierarchical risk of ADL dependence in older adults.
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2.
  • Wimo, Anders, et al. (författare)
  • Cohort Effects in the Prevalence and Survival of People with Dementia in a Rural Area in Northern Sweden
  • 2016
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 50:2, s. 387-396
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recent studies suggest that trends in cardiovascular risk may result in a decrease in age-specific prevalence of dementia. Studies in rural areas are rare.Objectives: To study cohort effects in dementia prevalence and survival of people with dementia in a Swedish rural area.Methods: Participants were from the 1995-1998 Nordanstig Project (NP) (n = 303) and the 2001-2003 Swedish National study on Aging and Care in Nordanstig (SNAC-N) (n = 384). Overall 6-year dementia prevalence and mortality in NP and SNAC-N were compared for people 78 years and older. Logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for dementia occurrence using the NP study population as the reference group. Cox regression models were used to analyze time to death.Results: The crude prevalence of dementia was 21.8% in NP and 17.4% in SNAC-N. When the NP cohort was used as the reference group, the age- and gender-adjusted OR of dementia was 0.71 (95% CI 0.48-1.04) in SNAC-N; the OR was 0.47 (0.24-0.90) for men and 0.88 (0.54-1.44) for women. In the extended model, the OR of dementia was significantly lower in SNAC-N than in the NP cohort as a whole (0.63; 0.39-0.99) and in men (0.34; 0.15-0.79), but not in women (0.81; 0.46-1.44). The Cox regression models indicated that the hazard ratio of dying was lower in the SNAC-N than NP population.Conclusions: Trends toward a lower prevalence of dementia in high-income countries seem to be evident in this Swedish rural area, at least in men.
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3.
  • Anstey, Kaarin J., et al. (författare)
  • A Self-Report Risk Index to Predict Occurrence of Dementia in Three Independent Cohorts of Older Adults : The ANU-ADRI
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1, s. e86141-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer's disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts. Methods: This study included three validation cohorts, i.e., the Rush Memory and Aging Study (MAP) (n = 903, age >= 53 years), the Kungsholmen Project (KP) (n = 905, age >= 75 years), and the Cardiovascular Health Cognition Study (CVHS) (n = 2496, age >= 65 years) that were each followed for dementia. Baseline data were collected on exposure to the 15 risk factors included in the ANU-ADRI of which MAP had 10, KP had 8 and CVHS had 9. Risk scores and C-statistics were computed for individual participants for the ANU-ADRI and the CAIDE index. Results: For the ANU-ADRI using available data, the MAP study c-statistic was 0.637 (95% CI 0.596-0.678), for the KP study it was 0.740 (0.712-0.768) and for the CVHS it was 0.733 (0.691-0.776) for predicting AD. When a common set of risk and protective factors were used c-statistics were 0.689 (95% CI 0.650-0.727), 0.666 (0.628-0.704) and 0.734 (0.707-0.761) for MAP, KP and CVHS respectively. Results for CAIDE ranged from c-statistics of 0.488 (0.427-0.554) to 0.595 (0.565-0.625). Conclusion: A composite risk score derived from the ANU-ADRI weights including 8-10 risk or protective factors is a valid, self-report tool to identify those at risk of AD and dementia. The accuracy can be further improved in studies including more risk factors and younger cohorts with long-term follow-up.
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4.
  • Chen, Huashuai, et al. (författare)
  • Trends in the prevalence of cognitive impairment at old age in China, 2002–2018
  • 2024
  • Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 20:2, s. 1387-1396
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: China has the world's largest number of older adults with cognitive impairment (CI). We aimed to examine secular trends in the prevalence of CI in China from 2002 to 2018.METHODS: Generalized estimating equations (GEE) was used to assess changes in CI trend in 44,154 individuals (72,027 observations) aged 65 to 105 years old.RESULTS: The prevalence of CI increased from 2002 to 2008 and then decreased until 2018. The age-standardized prevalence increased from 25.7% in 2002, 26.1% in 2005, to 28.2% in 2008, then decreased to 26.0% in 2011, 25.3% in 2014, and 24.9% in 2018. Females and those ≥ 80 years old had greater CI prevalence.DISCUSSION: The prevalence of CI showed an inverted U shape from early 2000s to late 2010s with a peak in 2008. Follow-up studies are needed to confirm the decreasing trend after 2008 and examine the contributing factors and underlying mechanisms of this trend.
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5.
  • Cong, Lin, et al. (författare)
  • Mild cognitive impairment among rural-dwelling older adults in China : A community-based study
  • 2023
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:1, s. 56-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological studies of mild cognitive impairment (MCI) and subtypes of MCI have rarely focused on rural residents in China.Methods: This population-based study included 5068 participants (age >= 60 years) who were living in rural communities. We defined MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) following the Petersen's criteria that integrated neuropsychological assessments with in-person clinical evaluations.Results: The overall prevalence of MCI, aMCI, and naMCI was 26.48%, 22.30%, and 4.18%, respectively. The prevalence of MCI increased with age. The adjusted odds ratio (OR) of MCI was 0.71 (95% confidence interval [CI] 0.61 to 0.82) for primary school (vs. illiteracy), 0.30 (0.24 to 0.39) for middle school or above, 1.35 (1.09 to 1.67) for being farmers, 0.65 (0.54 to 0.78) for alcohol consumption, 1.43 (1.20 to 1.70) for stroke history, and 1.14 (0.95 to 1.36) for any apolipoprotein E (APOE) epsilon 4 allele (vs epsilon 3/epsilon 3).Conclusions: MCI affects over one-fourth of rural older adults in China. Overall MCI was associated with demographic factors, non-alcohol consumption, and stroke, but not with APOE genotype and cardiometabolic factors.
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6.
  • Cong, Lin, et al. (författare)
  • Use of Cardiovascular Drugs for Primary and Secondary Prevention of Cardiovascular Disease Among Rural-Dwelling Older Chinese Adults
  • 2020
  • Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiovascular risk factors and related disorders are common among older adults, and use of various classes of cardiovascular (CV) drugs could reduce the risk of cardiovascular disease (CVD). However, data are sparse with regard to the use of CV drugs among rural-dwelling older adults in China. Therefore, this population-based study aimed to describe use of CV drugs among older adults living in the rural communities in China, while taking into account the use of CV drugs for primary and secondary prevention of CVDs. This study included 5,246 participants (age >= 65 years; 57.17% women; 40.68% illiteracy) in the baseline examination of the MIND-China study. In March-September 2018, data on health-related factors, CVDs (ischemic heart disease, atrial fibrillation, heart failure, and stroke), and CV drug use were collected via face-to-face survey, clinical examination, and laboratory tests. We classified CV drugs according to the Anatomical Therapeutic Chemical classification system for western medications and specific cardiovascular effects for the products of traditional Chinese medicine (TCM). We conducted descriptive analysis. The overall prevalence of major cardiovascular risk factors ranged from 14.30% in diabetes and 23.81% in dyslipidemia to 66.70% in hypertension, and CVDs affected 35.07% of all participants (36.28% in women vs. 33.47% in men, p = 0.035). In the total sample, calcium channel blockers (C08) were most commonly used (10.39%), followed by TCM products (7.64%), hypoglycemic agents (A10, 4.73%), renin-angiotensin system (RAS)-acting agents (C09, 4.61%), and lipid-lowering agents (C10, 4.17%). The proportions of CV drugs for primary prevention (i.e., use of CV drugs among people without CVD) were 3.14% for antithrombotic agents (mainly aspirin), 1.38% for lipid-lowering agents, and 3.11% for RAS-acting agents; the corresponding figures for secondary prevention (i.e., use of CV drugs among people with CVD) were 13.97%, 9.35%, and 7.39%. In conclusion, despite highly prevalent cardiovascular risk factors and CVDs, a fairly low proportion of the rural-dwelling older adults take CV medications for primary and secondary prevention. Notably, TCM products are among the most commonly used CV drugs. These results call for additional efforts to promote implementation of the evidence-based recommendations for prevention of CVDs in the primary care settings.
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7.
  • Dekker, Joost, et al. (författare)
  • Behavioral medicine in China
  • 2014
  • Ingår i: International Journal of Behavioral Medicine. - : Springer Science and Business Media LLC. - 1070-5503 .- 1532-7558. ; 21:4, s. 571-573
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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8.
  • Ding, Mozhu, et al. (författare)
  • Atrial fibrillation and use of antithrombotic medications in older people : A population-based study
  • 2017
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 249, s. 173-178
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Trends in the use of antithrombotic drugs in elderly patients with atrial fibrillation (AF) are largely unknown. We estimated the prevalence of AF in an older population, and examined whether use of anticoagulant and antiplatelet drugs in older AF patients has changed over time. Methods: Data from the population-based Swedish National study on Aging and Care in Kungsholmen (n = 3363, age = 60 years, 64.9% women) were used (2001-2004 and 2007-2010). AF cases were identified through 12-lead electrocardiogram, physician examinations, and patient register records (ICD-10 code I48). We used the CHADS(2) and CHA(2)DS(2)-VASc scores to estimate stroke risk, and an incomplete HAS-BLED score to estimate bleeding risk. Results: At baseline (2001-2004), 328 persons (9.8%) were ascertained to have AF. The prevalence of AF increased significantly with age from 2.8% in people aged 60-66 years to 21.2% in those = 90 years, and was more common in men than in women (11.2% vs. 9.0%). Among AF patients with CHADS2 score = 2 at baseline, 25% were taking anticoagulant drugs and 54% were taking antiplatelet drugs. High bleeding risk was significantly associated with not using anticoagulant drugs in AF patients (multi-adjusted OR = 2.50, p = 0.015). Between 2001-2004 and 2007-2010, use of anticoagulant drugs increased significantly, especially in AF patients with CHA2DS2-VASc score >= 2 (23% vs. 33%, p = 0.008) and in those with HAS-BLED score <3 (32% vs. 53%, p = 0.004). Conclusion: AF is common among old people. The use of anticoagulant drugs increased over time in AF patients, yet still two-thirds of those with high stroke risk remained untreated.
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9.
  • Ding, Mozhu, et al. (författare)
  • Atrial fibrillation, antithrombotic treatment, and cognitive aging : A population-based study
  • 2018
  • Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 91:19, s. e1732-e1740
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo examine the association of atrial fibrillation (AF) with cognitive decline and dementia in old age, and to explore the cognitive benefit of antithrombotic treatment in patients with AF.MethodsThis population-based cohort study included 2,685 dementia-free participants from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001-2004 to 2010-2013. AF was ascertained from clinical examination, ECG, and patient registry. Global cognitive function was assessed using the Mini-Mental State Examination. We followed the DSM-IV criteria for the diagnosis of dementia, the NINDS-AIREN (National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences) criteria for vascular dementia, and the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer disease. Data were analyzed using multiple linear mixed-effects and Cox regression models.ResultsWe identified 243 participants (9.1%) with AF at baseline. During the 9-year follow-up period, 279 participants (11.4%) developed AF and 399 (14.9%) developed dementia. As a time-varying variable, AF was significantly associated with a faster annual Mini-Mental State Examination decline (beta coefficient = -0.24, 95% confidence interval [ CI]: -0.31 to -0.16) and an increased hazard ratio (HR) of all-cause dementia (HR = 1.40, 95% CI: 1.11-1.77) and vascular and mixed dementia (HR = 1.88, 95% CI: 1.09-3.23), but not Alzheimer disease (HR = 1.33, 95% CI: 0.92-1.94). Among people with either prevalent or incident AF, use of anticoagulant drugs, but not antiplatelet treatment, was associated with a 60% decreased risk of dementia (HR = 0.40, 95% CI: 0.18-0.92).Conclusion AF is associated with a faster global cognitive decline and an increased risk of dementia in older people. Use of anticoagulant drugs may reduce dementia risk in patients with AF.
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10.
  • Ding, Mozhu, et al. (författare)
  • Cerebral Small Vessel Disease Associated With Atrial Fibrillation Among Older Adults : A Population-Based Study.
  • 2021
  • Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 52:8, s. 2685-2689
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults.METHODS: Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001-2004) and follow-ups (2004-2007 and 2007-2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models.RESULTS: At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (β coefficient=0.45 [95% CI, 0.04-0.86]) and lateral ventricular volume (0.58 [0.13-1.02]). There was no significant association of AF with annual changes in perivascular spaces number (β coefficient=0.53 [95% CI, -0.27 to 1.34]) or lacune number (-0.01 [-0.07 to 0.05]).CONCLUSIONS: Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.
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11.
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12.
  • Ding, Mozhu, et al. (författare)
  • Tracing temporal trends in dementia incidence over 25 years in central Stockholm, Sweden
  • 2020
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:5, s. 770-778
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Recent reports from high-income countries have suggested a declining incidence of dementia.Methods: Trends in dementia incidence over 25 years among people >= 75 years of age were examined using two population-based cohort studies: the Kungsholmen Project (KP, n = 1473, 1987-1998) and the Swedish National study on Aging and Care in Kungsholmen (SNAC-K, n = 1746, 2001-2013).Results: We identified 440 (29.9%) and 388 (22.2%) incident dementia cases in the KP and SNAC-K cohorts, respectively. The incidence of dementia declined by 30% (hazard ratio [HR] = 0.70; 95% confidence interval [CI] 0.61-0.80) during the second decade. Adjustment of education, psychosocial working conditions, lifestyle, and vascular diseases did not substantially change the results (HR = 0.77, 95% CI 0.65-0.90). This decline was observed particularly in women and people with elementary education.Discussion: Our study provides direct evidence of a declining trend in dementia incidence. Improved cognitive reserve and cardiovascular health could partially explain the decline.
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13.
  • Dong, Yi, et al. (författare)
  • Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults
  • 2023
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:2, s. 589-601
  • Tidskriftsartikel (refereegranskat)abstract
    • Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population-based study included 4214 dementia-free participants (age ≥65 years). Olfaction was assessed using the 16-item Sniffin’ Sticks identification test. In the subsamples, we measured plasma amyloid beta (Aβ)40, Aβ42, total tau, and neurofilament light chain (NfL; n = 1054); and quantified hippocampal, entorhinal cortex, and white matter hyperintensity (WMH) volumes, and Alzheimer's disease (AD)-signature cortical thickness (n = 917). Data were analyzed with logistic and linear regression models. In the total sample, mild cognitive impairment (MCI) was diagnosed in 1102 persons (26.2%; amnestic MCI, n = 931; non-amnestic MCI, n = 171). Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non-amnestic MCI. In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD-signature cortical thickness. These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults.
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14.
  • Dong, Yi, et al. (författare)
  • Dementia screening in rural-dwelling Chinese older adults : The utility of a smell test and the self-rated AD8
  • 2022
  • Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 70:4, s. 1106-1116
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Olfactory impairment is associated with dementia in clinical settings. We examined the relationship of olfactory identification function with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) and assessed the discriminative ability of the Sniffin' Sticks Identification Test (SSIT), the self-rated Ascertain Dementia 8-item Questionnaire (AD8), and their combination for dementia detection among rural-dwelling older adults in China.Methods: This population-based cross-sectional study included 4481 participants (age ≥ 65 years; 56.8% women; 38.1% illiteracy) living in rural communities. The 16-item SSIT was performed to assess olfactory identification function. The self-rated AD8 was administered to participants for cognitive status. We diagnosed dementia, AD, and VaD following the international criteria. Data were analyzed with logistic regression models and receiver operating characteristic curve.Results: Of the 4481 participants, dementia was diagnosed in 139 persons (3.1%), including 92 with AD and 42 with VaD. The SSIT score (range, 0–16) was associated with multiadjusted odds ratios of 0.83 (95% CI: 0.79–0.88) for dementia, 0.84 (0.79–0.90) for AD, and 0.79 (0.71–0.87) for VaD. The area under the curve for the discrimination between participants with and without dementia was 0.73 (95% CI: 0.69–0.77) for SSIT score ≤ 8 alone, 0.86 (0.82–0.89) for self-rated AD8 score ≥ 3 alone, and 0.89 (0.86–0.92) for their combination using a logistic model.Conclusions: Olfactory impairment is a clinical marker for all-cause dementia, AD, and VaD. The smell identification test, in combination with the brief self-rated cognitive screening tool, is accurate for screening dementia among rural-dwelling Chinese older adults with no or limited education.
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15.
  • Dong, Yi, et al. (författare)
  • Olfactory Impairment Among Rural-Dwelling Chinese Older Adults : Prevalence and Associations With Demographic, Lifestyle, and Clinical Factors
  • 2021
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Olfactory impairment (OI) refers to decreased (hyposmia) or absent (anosmia) ability to smell. We sought to estimate the prevalence and correlates of OI among rural-dwelling Chinese older adults.Methods: This population-based cross-sectional analysis included 4,514 participants (age >= 65 years; 56.7% women) from the Multidomain Interventions to Delay Dementia and Disability in Rural China (MIND-China). The 16-item Sniffin' Sticks identification test (SSIT) was used to assess olfactory function. Olfactory impairment was defined as the SSIT score <= 10, hyposmia as SSIT score of 8-10, and anosmia as SSIT score <8. Multivariable logistic regression models were used to examine factors associated with OI. Results: The overall prevalence was 67.7% for OI, 35.3% for hyposmia, and 32.5% for anosmia. The prevalence increased with age for OI and anosmia, but not for hyposmia. The multivariable-adjusted odds ratio (OR) of OI was 2.10 (95% CI 1.69-2.61) for illiteracy and 1.41 (1.18-1.70) for elementary school (vs. middle school or above), 1.30 (1.01-1.67) for current smoking (vs. never smoking), 0.86 (0.74-0.99) for overweight and 0.73 (0.61-0.87) for obesity (vs. normal weight), 4.21 (2.23-7.94) for dementia, 1.68 (1.23-2.30) for head injury, and 1.44 (1.14-1.83) for sinonasal disease. Illiteracy in combination with either male sex or diabetes was significantly associated with an over two-fold increased OR of OI (p for interactions <0.05).Conclusion: Olfactory impairment is highly prevalent that affects over two-thirds of rural-dwelling older adults in China. OI is correlated with illiteracy, current smoking, dementia, head injury, and sinonasal disease, but negatively associated with overweight or obesity. Olfactory impairment as a potential clinical marker of neurodegenerative disorders among older adults deserves further investigation.
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16.
  • Dong, Yi, et al. (författare)
  • Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer's Disease Clinical Spectrum: A Population-Based Study
  • 2023
  • Ingår i: JOURNAL OF ALZHEIMERS DISEASE. - 1387-2877 .- 1875-8908. ; 96:2, s. 845-858
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Plasma biomarkers have emerged as a promising approach for characterizing pathophysiology in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Objective: We aimed to characterize plasma biomarkers for AD and neurodegeneration across the AD clinical continuum, and to assess their ability to differentiate between AD, MCI, and normal cognition. Methods: This population-based study engaged 1,446 rural-dwelling older adults (age >= 60 years, 61.0% women) derived from MIND-China; of these, 402 were defined with MCI and 142 with AD. Plasma amyloid-beta (A beta), total tau (t-tau), and neurofilament light chain (NfL) concentrations were analyzed using the Simoa platform. Data were analyzed using linear and logistic regression models, and receiver operating characteristic (ROC) analysis. Results: Across the AD clinical spectrum, plasma A beta(40) and NfL increased, whereas A beta(42)/A beta(40) ratio decreased. Plasma t-tau was higher in people withADdementia than those with MCI or normal cognition. Plasma NfL outperformed other biomarkers in differentiating AD from normal cognition (area under the ROC curve [AUC] = 0.75), but all plasma biomarkers performed poorly to distinguish MCI from normal cognition (AUC <0.60). Plasma NfL in combination with age, sex, education, and APOE genotype yielded the AUC of 0.87 for differentiating between AD and normal cognition, 0.79 between AD and MCI, and 0.64 between MCI and normal cognition. Conclusions: In this Chinese population, AD plasma biomarkers vary by age, sex, and APOE genotype. Plasma A beta, t-tau, and NfL differ across the AD clinical spectrum, and plasma NfL appears to be superior to plasma A beta and t-tau for defining the clinical spectrum.
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17.
  • Duan, Haiping, et al. (författare)
  • Heritability of Age-Related Hearing Loss in Middle-Aged and Elderly Chinese : A Population-Based Twin Study
  • 2019
  • Ingår i: Ear and Hearing. - 0196-0202 .- 1538-4667. ; 40:2, s. 253-259
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The heritability of age-related hearing loss has been studied mostly in developed countries. The authors aimed to estimate the heritability of better ear hearing level (BEHL), defined as hearing level of the better ear at a given frequency, and pure-tone averages at the middle (0.5, 1.0, and 2.0 kHz) and high (4.0, 8.0, and 12.5 kHz) frequencies among middle-aged and elderly Chinese twins, and to explore their genetic correlations.Design: This population-based twin study included 226 monozygotic and 132 dizygotic twin-pairs and 1 triplet (age range, 33 to 80 years; mean age, 51.55 years). Pure-tone air-conducted hearing thresholds in each ear were measured at the frequencies of 0.5, 1.0, 2.0, 4.0, 8.0, and 12.5 kHz with a diagnostic audiometer. Univariate and multivariate twin models were fitted to evaluate heritability and genetic correlations.Results: Our data showed a reverse J-shaped pattern of BEHLs at six frequencies by age and sex. Univariate analysis showed that the heritability of BEHLs at the frequencies between 2.0 and 12.5 kHz ranged from 47.08 to 54.20%, but the heritability at the frequencies of 0.5 and 1.0 kHz was 1.65% and 18.68%, respectively. The heritability of pure-tone average at the middle and high frequencies was 34.77% and 43.26%, respectively. Multivariate analysis showed significant genetic correlations among BEHLs at all six frequencies, with the correlation coefficients ranging from 0.48 to 0.83 at middle frequencies, and from 0.46 to 0.75 at high frequencies.Conclusions: This population-based twin study suggests that genetic factors are associated with age-related hearing loss at middle and high frequencies among middle-aged and elderly Chinese.
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18.
  • Fa, Wenxin, et al. (författare)
  • Associations of Blood Absolute Neutrophil Count and Cytokines With Cognitive Function in Dementia-Free Participants : A Population-Based Cohort Study
  • 2023
  • Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - 1079-5006 .- 1758-535X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The relationships of neutrophils and cytokines with cognitive dysfunction are poorly defined. We aimed to investigate the association of peripheral blood absolute neutrophil count (ANC) with cognitive function in older adults and to further explore the mediating role of serum cytokines in this association.Methods: This population-based cohort study included 1 666 dementia-free participants (age ≥60 years) derived from baseline examinations (March–September 2018) of the Multimodal Intervention to Delay Dementia and Disability in Rural China (MIND-China); of these, 1 087 participants completed follow-up examinations in October–December 2019. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, and executive function at the baseline and follow-up examinations. We used Mindray BC-6800 automated hematology analyzer to measure ANC and Meso Scale Discovery to measure serum interleukin-6 (IL-6) and eotaxin-3.Results: The linear regression analysis of cross-sectional data at baseline (n = 1 666) suggested that increased ANC was significantly associated with a lower episodic memory z score (β coefficient: −0.149, 95% CI: −0.274 to −0.023) and lower long-delayed free recall z score (−0.216, −0.361 to −0.070). Serum IL-6 and eotaxin-3 could mediate 16.16% to 20.21% and 7.55% to 9.35%, respectively, of these associations. The analysis of longitudinal data (n = 1 087) showed a J-shaped relationship of ANC with decline in episodic memory z score (p for nonlinear = .049), and a U-shaped relationship between ANC and decline in long-delayed free recall z score (p for nonlinear = .043).Conclusions: Increased neutrophils are associated with poor cognitive performance and accelerated decline in episodic memory, and the cross-sectional association is partly mediated by serum cytokines.
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19.
  • Fan, Dong, et al. (författare)
  • Cardiovascular health profiles, systemic inflammation, and physical function in older adults : A population-based study
  • 2023
  • Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 109
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined the association of modifiable cardiovascular health (CVH) metrics with physical function among rural older adults in China and the potential role of inflammatory mechanisms in the association. This study included 3733 stroke-and dementia-free participants (age >= 65 years; 56.9% women) in the baseline survey of a multimodal intervention study in rural China. From March-September 2018, data were collected via face-to-face interviews, clinical assessments, and laboratory tests. The Short Performance Physical Battery (SPPB) test was performed to assess physical function. We defined six modifiable CVH metrics according to the modified American Heart Association's recommendations. Serum interleukin (IL)-6 was measured in a subsample (n = 1156). Data were analyzed with multiple general linear and logistic regression models and structural equation modeling. Poor physical function (SPPB score <= 9) was defined in 1443 participants. Ideal CVH (vs. poor CVH) was associated with multivariable-adjusted odds ratio of 0.60 (95%CI 0.48-0.75) for poor physical function. Ideal CVH was significantly associated with higher scores on balance, chair stand, and walking speed tests (all p < 0.05). Moreover, ideal CVH profile was associated with lower serum IL-6 (multivariable-adjusted beta=-0.04; 95% CI-0.06,-0.01). Mediation analysis revealed that serum IL-6 accounted for 14% of the association of CVH with total SPPB score and 10% of the association with walking speed score (p < 0.05). This study suggests that an ideal CVH profile is associated with better physical function among stroke-and dementia-free older adults, partly via inflammatory mechanisms. The preventive implications of these findings warrant further investigation in cohort studies.
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20.
  • Feng, Lei, et al. (författare)
  • Tea Consumption and Depressive Symptoms in Older People in Rural China
  • 2013
  • Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 61:11, s. 1943-1947
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo examine the association between tea consumption and depressive symptoms in Chinese older people and to explore the mediating role of cerebrovascular disease in the association. DesignPopulation-based cross-sectional study. SettingA rural community near Qufu in Shandong, China. ParticipantsCommunity-dwelling individuals aged 60 and older (mean 68.6; 59.3% female) from the Confucius Hometown Aging Project (N=1,368). MeasurmentsData were collected through interviews, clinical examinations, and psychological testing, following a standard procedure. Presence of high depressive symptoms was defined as a score of 5 or greater on the 15-item Geriatric Depression Scale. ResultsOf the 1,368 participants, 165 (12.1%) were weekly and 489 (35.7%) were daily tea consumers. Compared with no or irregular tea consumption, controlling for age, sex, education, leisure activities, number of comorbidities, and Mini-Mental State Examination score, the odds ratios of having high depressive symptoms were 0.86 (95% confidence interval (CI)=0.56-1.32) for weekly and 0.59 (95% CI=0.43-0.81) for daily tea consumption (P for linear trend=.001); the linear trend of the association remained statistically significant when further controlling for history of stroke, transient ischemic attacks, and presence of carotid plaques. ConclusionsDaily tea consumption is associated with a lower likelihood of depressive symptoms in Chinese older people living in a rural community. The association appears to be independent of cerebrovascular disease and atherosclerosis.
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21.
  • Ferrari, Camilla, et al. (författare)
  • How can elderly apolipoprotein E epsilon 4 carriers remain free from dementia?
  • 2013
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:1, s. 13-21
  • Tidskriftsartikel (refereegranskat)abstract
    • Apolipoprotein E (APOE) epsilon 4 is a major risk factor for Alzheimer's disease (AD) and dementia, but not all epsilon 4 carriers develop dementia. We sought to identify factors that may play a role in modifying the risk of dementia due to epsilon 4. A cognitively intact cohort (n = 932, age >= 75) was followed for 9 years to detect incident dementia cases. At baseline, information on education, leisure activities, and vascular risk factors was collected, and APOE was genotyped. During the follow-up, 324 subjects developed dementia, including 247 AD cases. The hazard ratio (HR, 95% confidence interval [95% CI]) of dementia related to the epsilon 4 was 1.39 (1.11-1.76), while the risk was reduced when epsilon 4 carriers had high education, no vascular risk factors, or high score of leisure activities. Among epsilon 4 carriers, the multiadjusted HRs of dementia that were associated with high education, high level of leisure activities, and absence of vascular risk factors were 0.59 (0.40-0.87), 0.49 (0.29-0.85), and 0.61 (0.41-0.90), respectively. The epsilon 4 carriers with these factors had about 1.2 years delayed time to dementia onset compared with those without these factors. High education, active leisure activities, or maintaining vascular health seems to reduce the risk of dementia related to APOE epsilon 4. The epsilon 4 carriers with these characteristics appear to have similar dementia-free survival time to non-epsilon 4 carriers.
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22.
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23.
  • Gallo, Federico, et al. (författare)
  • Cognitive Trajectories and Dementia Risk : A Comparison of Two Cognitive Reserve Measures.
  • 2021
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives: Cognitive reserve (CR) is meant to account for the mismatch between brain damage and cognitive decline or dementia. Generally, CR has been operationalized using proxy variables indicating exposure to enriching activities (activity-based CR). An alternative approach defines CR as residual variance in cognition, not explained by the brain status (residual-based CR). The aim of this study is to compare activity-based and residual-based CR measures in their association with cognitive trajectories and dementia. Furthermore, we seek to examine if the two measures modify the impact of brain integrity on cognitive trajectories and if they predict dementia incidence independent of brain status.Methods: We used data on 430 older adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, followed for 12 years. Residual-based reserve was computed from a regression predicting episodic memory with a brain-integrity index incorporating six structural neuroimaging markers (white-matter hyperintensities volume, whole-brain gray matter volume, hippocampal volume, lateral ventricular volume, lacunes, and perivascular spaces), age, and sex. Activity-based reserve incorporated education, work complexity, social network, and leisure activities. Cognition was assessed with a composite of perceptual speed, semantic memory, letter-, and category fluency. Dementia was clinically diagnosed in accordance with DSM-IV criteria. Linear mixed models were used for cognitive change analyses. Interactions tested if reserve measures modified the association between brain-integrity and cognitive change. Cox proportional hazard models, adjusted for brain-integrity index, assessed dementia risk.Results: Both reserve measures were associated with cognitive trajectories [β × time (top tertile, ref.: bottom tertile) = 0.013; 95% CI: -0.126, -0.004 (residual-based) and 0.011; 95% CI: -0.001, 0.024, (activity-based)]. Residual-based, but not activity-based reserve mitigated the impact of brain integrity on cognitive decline [β (top tertile × time × brain integrity) = -0.021; 95% CI: -0.043, 0.001] and predicted 12-year dementia incidence, after accounting for the brain-integrity status [HR (top tertile) = 0.23; 95% CI: 0.09, 0.58].Interpretation: The operationalization of reserve based on residual cognitive performance may represent a more direct measure of CR than an activity-based approach. Ultimately, the two models of CR serve largely different aims. Accounting for brain integrity is essential in any model of reserve.
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24.
  • Grande, Giulia, et al. (författare)
  • Multimorbidity burden and dementia risk in older adults : The role of inflammation and genetics
  • 2021
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:5, s. 768-776
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: We investigate dementia risk in older adults with different disease patterns and explore the role of inflammation and apolipoprotein E (APOE) genotype.Methods: A total of 2,478 dementia-free participants with two or more chronic diseases (ie, multimorbidity) part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) were grouped according to their multimorbidity patterns and followed to detect clinical dementia. The potential modifier effect of C-reactive protein (CRP) and apolipoprotein E (APOE) genotype was tested through stratified analyses.Results: People with neuropsychiatric, cardiovascular, and sensory impairment/cancer multimorbidity had increased hazards for dementia compared to the unspecific (Hazard ration (HR) 1.66, 95% confidence interval [CI] 1.13-2.42; 1.61, 95% CI 1.17-2.29; 1.32, 95% CI 1.10-1.71, respectively). Despite the lack of statistically significant interaction, high CRP increased dementia risk within these patterns, and being APOE epsilon 4 carriers heightened dementia risk for neuropsychiatric and cardiovascular multimorbidity.Discussion: Individuals with neuropsychiatric, cardiovascular, and sensory impairment/cancer patterns are at increased risk for dementia and APOE epsilon 4, and inflammation may further increase the risk. Identifying such high-risk groups might allow tailored interventions for dementia prevention.
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25.
  • Grande, Giulia, et al. (författare)
  • Prevention of dementia in an ageing world : Evidence and biological rationale
  • 2020
  • Ingår i: Ageing Research Reviews. - : Elsevier BV. - 1568-1637 .- 1872-9649. ; 64
  • Forskningsöversikt (refereegranskat)abstract
    • As the population ages, the number of people with dementia is expected to increase in the coming decades, with consequences at the societal and individual levels. In this narrative review, we provide a summary of the scientific evidence concerning dementia prevention, with a focus on the following three strategies: 1) Targeting the body to protect the brain, including prevention and treatment of cardiovascular morbidity; 2) Compensatory interventions to counteract brain ageing, including education and life-long engagement in cognitively and socially stimulating activities; and 3) Lifespan health promotion, such as a physically active lifestyle, smoking cessation, and a healthy and balanced diet. Next, we consider the biological mechanisms by which these strategies may act by taking into account the main pathways implicated in the development and progression of dementia: neurodegeneration, brain resilience, vascular damage, neuroinflammation, and oxidative stress. Based on the current evidence, and in line with the declining trends of dementia incidence in high-income countries, we conclude that timely multidomain preventive actions are promising strategies to reduce the dementia epidemic worldwide. There is still a considerable gap between the epidemiological evidence and its underlying biological mechanisms. Filling this gap will be crucial to move forward in dementia prevention worldwide.
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26.
  • Gui, Wenjun, et al. (författare)
  • Associations of Vascular Risk Factors, APOE and TOMM40 Polymorphisms With Cognitive Function in Dementia-Free Chinese Older Adults : A Community-Based Study
  • 2021
  • Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The associations of vascular risk factors (VRFs), apolipoprotein E (APOE), and translocase of outer mitochondrial membrane 40 (TOMM40) with cognitive function have been investigated mostly in western societies. In the present study, we sought to examine the associations of VRFs [i.e., current smoking, current drinking, physical inactivity, obesity, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), diabetes, and hypertension] and variants located in APOE (epsilon 2/3/4) and TOMM40 (rs2075650) with global cognitive function in Chinese older adults, with a focus on their potential interactions.Methods: This is a cross-sectional study that included 422 permanent residents (mean age 69.2 years, 54.3% female) living in Beijing, who were free of dementia. Data were collected through interviews, clinical examinations, and laboratory tests. The two genetic polymorphisms were genotyped, and participants were dichotomized as carriers vs. non-carriers of APOE epsilon 4 or TOMM40 G. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Data were analyzed with multivariable linear regression models.Results: Physical inactivity and diabetes were independently associated with a lower MMSE score (all p < 0.05). When four putative VRFs (i.e., current smoking, physical inactivity, high LDL-C, and diabetes) were aggregated, an increasing number of having these factors was associated with a decreasing MMSE score in a dose-response manner (p = 0.001). TOMM40 polymorphisms, independent of the APOE epsilon 4 allele, interacted with aggregated VRFs to influence cognitive performance, such that having one or more of these VRFs was particularly detrimental to the cognition of TOMM40 carriers. Further analyses revealed interactions of the TOMM40 polymorphism with (i) physical inactivity and (ii) diabetes, such that having either physical inactivity or diabetes in combination with carrying a TOMM40 G allele, compared to having neither, was significantly associated with a markedly lower MMSE score (all p < 0.05).Conclusion: This study provides some evidence supporting the association of vascular risk factors with poor cognitive performance among dementia-free Chinese older adults and further revealed their interactions with the TOMM40 polymorphism. The results underscore the vulnerability of global cognitive function to VRFs, which could be reinforced by carrying the TOMM40 rs2075650 G allele. These findings have potential implications for developing tailored intervention programs to maintain cognitive function.
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27.
  • Han, Xiaolei, et al. (författare)
  • Accelerometer-assessed sedentary behaviour among Chinese rural older adults : Patterns and associations with physical function
  • 2022
  • Ingår i: Journal of Sports Sciences. - : Informa UK Limited. - 0264-0414 .- 1466-447X. ; 40:17, s. 1940-1949
  • Tidskriftsartikel (refereegranskat)abstract
    • Sedentary behaviour is associated with a range of adverse health conditions. Population-based studies have rarely examined the distribution and associated factors of accelerometer-measured sedentary behaviour patterns in rural-dwelling older adults. This population-based study included 2096 rural-dwelling older adults (age ≥60 years; 59.0% women) derived from baseline participants of the MIND-China Study. Total sedentary time and patterns (e.g., uninterrupted bouts and breaks) were derived from the hip-worn accelerometers for 7 days. Physical function was assessed using the Short Physical Performance Battery test. Data were analysed using general linear models. Overall, participants spent 58.8% of daily waking time in sedentary behaviour, with nearly half of sedentary time being accumulated through sedentary bouts of 30+ minutes. Men spent more total and accumulated sedentary time than women in each sedentary bout duration, while women had more daily 1+ minute sedentary bouts than men (all P < 0.001). Controlling for moderate-to-vigorous physical activity and other confounders, more prolonged sedentary time and fewer breaks were significantly associated with poor physical function, balance, lower limb strength, and walking speed (all P < 0.001). In older adults living in rural communities, prolonged sedentary behaviour and less frequent breaks are associated with poor physical function.
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28.
  • Han, Xiaolei, et al. (författare)
  • Accelerometer-measured sedentary behavior patterns, brain structure, and cognitive function in dementia-free older adults : a population-based study
  • 2023
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 96:2, s. 657-668
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood.Objective: To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms.Methods: This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018-2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n = 1,009). Data were analyzed using the general linear, isotemporal substitution, and mediation models.Results: In the total sample (n = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z-scores of global cognition, verbal fluency, and memory (ptrend < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (ptrend < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z-scores (p < 0.05). In the MRI subsample (n = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z-scores.Conclusion: Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association.
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29.
  • Han, Xiaolei, et al. (författare)
  • Association of Cardiovascular Health Metrics with Dementia in Rural Chinese Older Adults : A Population-Based Study
  • 2022
  • Ingår i: Clinical Interventions in Aging. - 1176-9092 .- 1178-1998. ; 17, s. 947-956
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: We explore the associations of individual and composite cardiovascular health metrics with all-cause dementia, Alzheimer’s disease, and vascular dementia among rural-dwelling older adults and the potential age variations in their associations.Patients and Methods: This community-based cross-sectional study included 4980 older adults (age ≥ 65 years; 57.23% women) from the baseline examination of MIND-China. In March–September 2018, data were collected via face-to-face interviews, clinical examinations, and laboratory test. We defined six cardiovascular health metrics according to the modified American Heart Association’s recommendations. We diagnosed dementia and its subtypes following the international criteria. Data were analyzed using logistic regression models.Results: Of all the participants, 250 were diagnosed with dementia, including 165 with Alzheimer’s disease and 75 with vascular dementia. Ideal composite global cardiovascular health metrics (vs poor composite metrics) were associated with a multi-adjusted odds ratio (95% confidence interval) of 0.62 (0.42– 0.93) for dementia, 0.88 (0.52– 1.48) for Alzheimer’s disease, and 0.31 (0.16– 0.60) for vascular dementia. Moreover, ideal biological cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.52 (0.28– 0.95) for dementia and 0.21 (0.06– 0.77) for vascular dementia in young–old adults (65– 74 years), whereas ideal behavioral cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.48 (0.26– 0.89) for dementia and 0.16 (0.06– 0.43) for vascular dementia in old–old adults (≥ 75 years).Conclusion: Our results suggest that ideal cardiovascular health metrics are cross-sectionally associated with a low likelihood of dementia and vascular dementia among rural-dwelling older Chinese adults. The associations vary with age, components of cardiovascular health metrics, and dementia subtypes.
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30.
  • Han, Xiaolei, et al. (författare)
  • KIBRA regulates amyloid β metabolism by controlling extracellular vesicles secretion
  • 2022
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 78
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Previous research has revealed that KIBRA controls secretion of extracellular vesicles (EVs) by inhibiting the proteasomal degradation of Rab27a and EVs play an important role in amyloid β (Aβ) metabolism and transmission during Alzheimer's disease (AD) pathogenesis. Here, we further test the hypothesis that KIBRA regulates Aβ metabolism via the endosomal-lysosomal system.Methods We generated KIBRA knockout mice on a 5XFAD background and KIBRA knockdown cells in murine HT22 cells with stably overexpressing APP. Various forms of Aβ and quantification of EVs were analyzed by biochemical methods and nanoparticle tracking analysis, respectively. Multivesicular bodies (MVBs) were visualized by electron microscopy and confocal fluorescent microscopy. In a population-based cohort (n = 1419), KIBRA genotypes and plasma Aβ levels were analyzed using multiple-PCR amplification and Simoa, respectively.Findings Multiple forms of Aβ were dramatically attenuated in KIBRA knockout mouse brain, including monomers, oligomers, and extracellular deposition, but KIBRA knockout had no effect on intraneuronal APP C-terminal fragment β (APP-CTFβ)/Aβ levels. KIBRA depletion also decreased APP-CTFβ/Aβ-associated EVs secretion and subsequently enhanced MVBs number. Furthermore, we found that excessive accumulation of MVBs harboring APP-CTFβ/Aβ promoted the MVBs-lysosome fusion for degradation and inhibition of lysosomal function rescued secretion of APP-CTFβ/Aβ-associated EVs. More importantly, whole exon sequencing of KIBRA in a large population-based cohort identified the association of KIBRA rs28421695 polymorphism with plasma Aβ levels.Interpretation These results demonstrate that KIBRA regulates Aβ metabolism via controlling the secretion of APP-CTFβ/Aβ-associated EVs.
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31.
  • Han, Xiaolei, et al. (författare)
  • Sex disparities in cardiovascular health metrics among rural-dwelling older adults in China : a population-based study
  • 2021
  • Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cardiovascular health (CVH) metrics among Chinese older adults are poorly understood. We investigated sex disparities in CVH metrics and their management among rural-dwelling older adults in China.Methods: This community-based study included 5026 participants (age >= 65years; 57.2% women) in the baseline survey of a multimodal intervention study in rural China. In March-September 2018, data were collected through face-to-face interviews, clinical examinations, and laboratory tests. We defined six CVH metrics (three behavioral factors-smoking, body mass index, and physical activity; three biological factors-blood pressure, total cholesterol, and blood glucose) following the modified American Heart Association's recommendations. We performed descriptive analysis separately for men and women.Results: Of all participants, only 0.8% achieved ideal levels in all six CVH metrics. Men were more likely than women to have ideal levels in all CVH metrics but smoking. Women had higher prevalence of ideal global (9.7% vs. 7.8%) and behavioral (18.3% vs. 9.5%) CVH metrics (p<0.001), whereas men had higher prevalence of ideal biological CVH metrics (5.4% vs. 3.5%, p<0.001). The prevalence of ideal global and behavioral CVH metrics increased with age in both women and men (p for trend<0.001). Women were more likely to be aware of their hypertension and diabetes, and to receive antihypertensive treatment, while men were more likely to achieve the goal of high cholesterol treatment (p<0.05).Conclusions: The CVH metrics among older adults living in the rural communities in China are characterized by an extremely low proportion of optimal global CVH metrics and distinct sex differences, alongside poor management of major biological risk factors.
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32.
  • Heiland, Emerald G, et al. (författare)
  • Cardiovascular Risk Burden and Future Risk of Walking Speed Limitation in Older Adults
  • 2017
  • Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 65:11, s. 2418-2424
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To explore the association between cardiovascular risk factor (CRF) burden and limitation in walking speed, balance, and chair stand and to verify whether these associations vary according to age and cognitive status.DESIGN: Longitudinal population-based study.SETTING: Urban area of Stockholm, Sweden.PARTICIPANTS: Individuals aged 60 and older who participated in the Swedish National Study on Aging and Care in Kungsholmen and were free of limitations in walking speed (n = 1,441), balance (n = 1,154), or chair stands (n = 1,496) at baseline (2001-04).MEASUREMENTS: At baseline, data on demographic characteristics, CRFs, other lifestyle factors, C-reactive protein, and cognitive function were collected. CRF burden was measured using the Framingham general cardiovascular risk score (FRS). Limitations in walking speed (<0.8 m/s), balance (<5 seconds), and chair stand (inability to rise 5 times) were determined at 3-, 6-, and 9-year follow-up. Data were analyzed using Cox proportional hazards models stratified according to age (<78, >= 78).RESULTS: During follow-up, 326 persons developed limitations in walking speed, 303 in balance, and 374 in chair stands. An association between the FRS and walking speed limitation was evident only in adults younger than 78 (for each 1-point increase in FRS: hazard ratio (HR) = 1.09, 95% confidence interval (CI) = 1.02-1.17) after controlling for potential confounders including cognitive function (correspondingly, in adults aged >= 78: HR = 0.98, 95% CI = 0.92-1.03). Also, higher FRS was significantly associated with faster decline in walking speed (P<.001).CONCLUSION: A higher FRS is associated with greater risk of subsequent development of walking speed limitation in adults younger than 78, independent of cognitive function. Interventions targeting multiple CRFs in younger-old people may help in maintaining mobility function.
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33.
  • Heiland, Emerald G, et al. (författare)
  • Cardiovascular Risk Factors and the Risk of Disability in Older Adults : Variation by Age and Functional Status.
  • 2019
  • Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 20:2, s. 208-212.e3
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: We aimed to quantify the increased risk of disability associated with cardiovascular risk factors among older adults, and to verify whether this risk may vary by age and functional status.DESIGN: Longitudinal population-based cohort study.SETTING: Urban area of Stockholm, Sweden.PARTICIPANTS: Community-dwelling and institutionalized adults ≥60 years in the Swedish National study on Aging and Care in Kungsholmen free of cardiovascular diseases and disability (n = 1756) at baseline (2001-2004).MEASURES: Incident disability in activities of daily living (ADL) was ascertained over 9 years. Cardiovascular risk factors (physical inactivity, alcohol consumption, smoking, high blood pressure, diabetes, high body mass index, high levels of total cholesterol, and high C-reactive protein) and walking speed were assessed at baseline. Data were analyzed using Cox proportional hazards models, stratifying by younger-old (age 60-72 years) and older-old (≥78 years).RESULTS: During the follow-up, 23 and 148 persons developed ADL-disability among the younger- and older-old, respectively. In the younger-old, the adjusted hazard ratio (HR) of developing ADL-disability was 4.10 (95% confidence interval [CI] 1.22-13.76) for physical inactivity and 5.61 (95% CI 1.17-26.82) for diabetes. In the older-old, physical inactivity was associated with incident ADL-disability (HR 1.99, 95% CI 1.36-2.93), and there was a significant interaction between physical inactivity and walking speed limitation (<0.8 m/s), showing a 6-fold higher risk of ADL-disability in those who were both physically inactive and had walking speed limitation than being active with no limitation, accounting for a population-attributable risk of 42.7%.CONCLUSIONS/IMPLICATIONS: Interventions targeting cardiovascular risk factors may be more important for the younger-old in decreasing the risk of disability, whereas improving physical function and maintaining physical activity may be more beneficial for the older-old.
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34.
  • Heiland, Emerald G, et al. (författare)
  • Cerebral small vessel disease, cardiovascular risk factors, and future walking speed in old age : a population-based cohort study.
  • 2021
  • Ingår i: BMC Neurology. - : BioMed Central. - 1471-2377. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The purpose of this study was to examine the associations between combined and individual cerebral small vessel disease (cSVD) markers on future walking speed over 9 years; and to explore whether these associations varied by the presence of cardiovascular risk factors (CRFs).METHODS: This population-based cohort study included 331 adults, aged ≥60 years, without limitation in walking speed (≥0.8 m/s). At baseline, cSVD markers, including white matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS), were assessed on magnetic resonance imaging. The modifiable CRFs (physical inactivity, heavy alcohol consumption, smoking, hypertension, high total cholesterol, diabetes, and overweight/obese) were combined into a score. The association between baseline cSVD markers and the decline in walking speed was examined using linear mixed-effects models, whereas Cox proportional hazards models were used to estimate the association with walking speed limitation (defined as < 0.8 m/s) over the follow-up.RESULTS: Over the follow-up period, 76 (23.0%) persons developed walking speed limitation. Participants in the highest tertile of the combined cSVD marker score had a hazard ratio (HR) of 3.78 (95% confidence interval [CI] 1.70-8.45) for walking speed limitation compared with people in the lowest score tertile, even after adjusting for socio-demographics, CRFs, cognitive function, and chronic conditions. When investigating the cSVD markers individually, having the highest burden of WMH was associated with a significantly faster decline in walking speed (β coefficient - 0.020; 95% CI -0.035-0.004) and a greater HR of walking speed limitation (HR 2.78; 95% CI 1.31-5.89) compared with having the lowest WMH burden. Similar results were obtained for the highest tertile of PVS (HR 2.13; 95% CI 1.04-4.36). Lacunes were associated with walking speed limitation, but only in men. Having ≥4 CRFs and high WMH volume simultaneously, showed a greater risk of walking speed limitation compared with having ≥4 CRFs and low WMH burden. CRFs did not modify the associations between lacunes or PVS and walking speed.CONCLUSIONS: Combined cSVD markers strongly predict walking speed limitation in healthy older adults, independent of cognitive function, with WMH and PVS being the strongest contributors. Improving cardiovascular health may help to mitigate the negative effects of WMH on future walking speed.
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35.
  • Huang, Wenyong, et al. (författare)
  • APOE Genotype, Family History of Dementia, and Alzheimer Disease Risk : A 6-Year Follow-up Study
  • 2004
  • Ingår i: Archives of Neurology. - : American Medical Association. - 0003-9942 .- 1538-3687. ; 61:12, s. 1930-1934
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Both family aggregation and apolipoprotein E (APOE) ε4 allele are well-known risk factors for dementia, but the relation between these two factors remains unclear.Objective To explore whether the risk of dementia and Alzheimer disease (AD) due to a positive family history is explained by APOE genotypes.Design Community-based cohort study.Setting The Kungsholmen district of Stockholm, Sweden.Participants A total of 907 nondemented people 75 years or older, followed up for 6 years to detect incident dementia and AD cases according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition.Main Outcome Measures Risk of dementia and AD by Cox proportional hazards models after controlling for several potential confounders.Results Subjects who had at least 2 siblings with dementia were at an increased risk of AD. Individuals with both APOE ε4 allele and at least 2 affected first-degree relatives had a higher risk of dementia and AD compared with those without these 2 factors. Similar results were obtained for history of dementia separately in parents or siblings. Among the ε4 allele carriers, subjects with 2 or more first-degree demented relatives had increased risk of dementia and AD, whereas no increased risk was detected among non–ε4 carriers.Conclusions Family history of dementia was associated with an increased risk of dementia and AD in this very old population, but only among APOE ε4 carriers. This suggests the existence of other genetic or environmental risk factors that may be active in the presence of the APOE ε4 allele.The role of both family history of dementia and the apolipoprotein E (APOE) gene in the development of Alzheimer disease (AD) has been extensively investigated. There is strong evidence to suggest that APOE ε4 allele carriers, as well as subjects with a family history of dementia, have an increased risk of AD.Familial aggregation and genetic risk factors appear to be most influential in AD at relatively early ages.However, there are reports supporting an effect of both familial aggregation and APOE ε4 even in late-onset AD,although a lower effect in comparison with early-onset cases has been detected.It is hypothesized that APOE ε4 allele might explain the association between family history of dementia and AD. Previous studies have tried to evaluate this hypothesis, but to what extent familial aggregation is due to the association between the ε4 allele and AD remains equivocal. Some studies indicated that ε4-positive patients with AD tended to have a higher rate of family history of dementia than ε4-negative patients. Conversely, patients with family history of AD are also more likely to carry the ε4 allele than patients without family history.Other studies, however, showed that the APOE ε4 allele was not related to familial aggregation of AD.Most previous analyses have been hospital-based case-control studies. Because of ascertainment bias and severe truncation of data, these studies might overestimate the effects of family history and APOE ε4 allele, especially in very old people. Only a small-scale prospective study has examined both family history of dementia and APOE ε4 allele in relation to AD risk among people 75 years or older.In a previous study within the Kungsholmen Project, a strong familial aggregation was detected among prevalent cases of late-onset AD, but the contribution of the APOE ε4 allele was not considered. In the present study, we examined the 6-year follow-up data from the same project to explore whether the risk of dementia and AD due to a positive family history is explained by APOE genotypes.
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36.
  • Imahori, Yume, et al. (författare)
  • Association of ischemic heart disease with long-term risk of cognitive decline and dementia : A cohort study
  • 2023
  • Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 19:12, s. 5541-5549
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: The independent and joint effect of ischemic heart disease (IHD) and coexisting atrial fibrillation (AF) and heart failure (HF) on dementia risk is largely unknown.METHODS: This population-based cohort study included 2568 dementia-free participants (age ≥60 years) in SNAC-K, who were regularly examined from 2001–2004 through 2013–2016. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. Global cognitive function was assessed using a global cognitive composite z-score derived from five cognitive domains. Data were analyzed using Cox, Fine-Gray, and linear mixed-effects models.RESULTS: Overall, IHD at baseline was associated with multivariable-adjusted hazard ratio (HR) of 1.39 (95% confidence interval = 1.06−1.82) for dementia and multivariable-adjusted β-coefficient of −0.02 (−0.03 to −0.01) for annual changes in global cognitive z-score, independent of AF, HF, and cerebrovascular disease. Coexisting AF or HF did not add further risk to dementia and cognitive decline.DISCUSSION: IHD is independently associated with dementia and cognitive decline in older adults, whereas coexisting AF/HF is not associated with an increased risk.
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37.
  • Imahori, Yume, et al. (författare)
  • Association of resting heart rate with cognitive decline and dementia in older adults : A population-based cohort study
  • 2022
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:10, s. 1779-1787
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Resting heart rate (RHR) predicts future risk for cardiovascular disease (CVD). However, longitudinal studies investigating the relationship of RHR with cognitive decline are scarce.Methods: This population-based cohort study included 2147 participants (age≥60) in SNAC-K who were free of dementia and regularly followed from 2001–2004 to 2013–2016. RHR was assessed with electrocardiogram. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders 4th Revision criteria. Global cognitive function was assessed using Mini-Mental State Examination (MMSE). Data were analyzed using Cox and linear mixed-effects models.Results: RHR≥80 (vs. 60–69) bpm was associated with a multi-adjusted hazard ratio of 1.55 (95% confidence interval 1.06−2.27) for dementia. The association remained significant after excluding participants with prevalent and incident CVDs. Similarly, RHR≥80 bpm was associated with a multi-adjusted β-coefficient of –0.13 (–0.21 to –0.04) for MMSE score.Discussion: Higher RHR is associated with increased risk for dementia and faster cognitive decline independent of CVDs in a general population of elderly people.
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38.
  • Imahori, Yume, et al. (författare)
  • Electrocardiographic Predictors of Cognitive Decline and Dementia : A Systematic Review
  • 2021
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 84:3, s. 1303-1322
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Markers of altered cardiac function might predict cognitive decline and dementia. Objective: This systematic review aims to review the literature that examines the associations of various electrocardiogram (ECG) markers with cognitive decline and dementia in middle-aged and elderly populations. Methods: We searched PubMed, Embase, and Web of Science through 1 July 2020 for literature and conducted a systematic literature review. We included studies examining the associations of ECG markers (e.g., left ventricular hypertrophy [LVH], spatial QRS-T angle, and QT prolongation) with cognitive function and dementia in adult populations regardless of study setting and design, but excluded studies examining atrial fibrillation and heart rate variability. Results: Fourteen community-based cross-sectional and longitudinal studies were identified. ECG markers were investigated in association with dementia in four prospective studies, and with cognitive decline in ten prospective studies. ECG-assessed LVH was associated with dementia in one study while five heterogeneous prospective studies yielded inconsistent associations with cognitive decline. Regarding ventricular repolarization markers, spatial QRS-T angle was associated with cognitive decline in one study while another study found no association between QT prolongation and cognitive decline. High resting heart rate was associated with both dementia and cognitive decline in one study but not associated with dementia in another study. P-wave abnormality was significantly associated with incident dementia and cognitive decline in one prospective study. Conclusion: Some ECG markers were associated with incident dementia and cognitive decline. However, limited number of heterogeneous studies did not allow us to make firm conclusions. Further studies are needed.
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39.
  • Jiang, Ziying, et al. (författare)
  • Red Cell Distribution Width and Dementia Among Rural-Dwelling Older Adults : The MIND-China Study
  • 2021
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 83:3, s. 1187-1198
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence has emerged that anemia is associated with dementia, but data on the relationships of red blood cell distribution width (RDW) with dementia and cognitive function in older adults are sparse.Objective: We sought to investigate the associations of RDW with dementia and global cognitive performance among rural-dwelling Chinese older adults and further to examine their associations by anemia status.Methods: This population-based cross-sectional study included 5,115 participants (age≥65 years, 57.0%women) in the baseline examination (March-September 2018) of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-CHINA). We collected data through face-to-face interviews, clinical examinations, and laboratory tests. Global cognitive function was evaluated using the Mini-Mental State Examination (MMSE). We defined dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) following the respective international criteria. Data were analyzed using multinomial logistic and general linear regression models.Results: Of all participants, 300 were diagnosed with dementia, including 195 with AD and 95 VaD. The multiple-adjusted odds ratio of dementia associated with quartiles of RDW were 1.45 (95%CI: 0.87–2.44), 1.00 (reference), 1.77 (1.07–2.93), and 2.28 (1.40–3.72). Similar J-shaped patterns existed for the association of RDW with odds ratio of AD and VaD. Anemia was not significantly associated with dementia. The J-shaped associations of RDW with dementia and subtypes were statistically evident only among participants without anemia. There was an inverted J-shaped relationship between RDW quartiles and β-coefficients of MMSE score.Conclusion: There is a J-shaped association between RDW level and likelihood of dementias among rural-dwelling Chinese older adults, especially among people without anemia.
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40.
  • Jiang, Ziying, et al. (författare)
  • Red cell distribution width, anemia, and lower-extremity physical function among rural-dwelling older adults
  • 2022
  • Ingår i: Aging Clinical and Experimental Research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 34:10, s. 2483-2491
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Elevated red cell distribution width (RDW) has been associated with degenerative conditions in aging.Aims We aimed to evaluate the associations of RDW and anemia with lower-extremity physical function among rural-dwelling older adults. Methods This population-based cross-sectional study included 5093 rural residents (age >= 60 years, 57.3% women) who participated in the MIND-China Study in Shandong. Data were collected via face-to-face interviews, clinical examinations, and laboratory tests. RDW was categorized according to quartiles and the lower-extremity physical function was assessed using the Short Physical Performance Battery (SPPB),Results Multiple linear regression analyses suggested that the fourth quartile of RDW (vs. first quartile) was associated with lower SPPB summary score (beta-coefficient - 0.38; 95% CI - 0.58 to - 0.18) and lower scores in balance test (- 0.09; - 0.17 to - 0.01), chair stand test (- 0.17; - 0.27 to - 0.07), and walking speed test (- 0.12; - 0.19 to - 0.05). Anemia was associated with a multiple-adjusted beta-coefficient of - 0.34 (- 0.52 to - 0.16) for SPPB summary score. Stratified analysis by anemia showed that there was a linear association between RDW and SPPB in individuals without anemia but a J-shaped association in individuals with anemia.Discussion This large-scale population-based study revealed the associations of high RDW and anemia with poor lower-extremity physical function among rural-dwelling Chinese older adults. These findings suggest that an elevated RDW might be a biochemical marker for poor lower-extremity physical function among older adults.Conclusions Anemia and an elevated RDW are associated with poor performance in lower-extremity physical function among rural-dwelling Chinese older adults.
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41.
  • Khanam, Masuma Akter, et al. (författare)
  • The metabolic syndrome : prevalence, associated factors, and impact on survival among older persons in rural Bangladesh
  • 2011
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6, s. e20259-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To describe the prevalence of the metabolic syndrome (MetS) among older persons in rural Bangladesh, to investigate whether the prevalence varies by age, sex, literacy, marital status, nutritional status and socio-economic status, and to assess the impact of MetS on survival.Methods: The study consisted of 456 persons who were aged ≥60 years living in a rural area of Bangladesh during July 2003-March 2004. Data were collected through interview, clinical examination, and laboratory tests, and their survival status until 30(th) June 2009 was ascertained through the Matlab surveillance system. We defined MetS following the NCEP ATP III criteria, with minor modifications, i.e., presence of any three of the following: hypertension (BP ≥130/85 mm Hg); random blood glucose (RBG) level ≥7.0 mmol/L; hyper-triglyceridemia (≥2.28 mmol/L); low level of HDL-cholesterol (<1.04 mmol/L for men and <1.29 mmol/L for women); and BMI ≥25.0 kg/m(2). Data were analysed with logistic regressions for the influential factors of MetS, and with Cox models for the association of MetS with the survival status.Findings: The overall prevalence of MetS was 19.5%, 20.8% in women, and 18.0% in men. Asset-index and nutritional status were independently associated with MetS. During 4.93 years of follow-up, 18.2% died. In the presence of high RBG, MetS has a significant negative effect on survival (69.4% vs 95.2%, log rank p = 0.02).Conclusion: This study highlights the importance of the metabolic syndrome in rural Bangladesh. Our findings suggest that there is a need for screening programmes involving the metabolic syndrome to prevent diabetes and cardiovascular diseases.
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42.
  • Kivipelto, Miia, et al. (författare)
  • World-Wide FINGERS Network : A global approach to risk reduction and prevention of dementia
  • 2020
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:7, s. 1078-1094
  • Tidskriftsartikel (refereegranskat)abstract
    • Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.
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43.
  • Kootar, S., et al. (författare)
  • Validation of the CogDrisk Instrument as Predictive of Dementia in Four General Community-Dwelling Populations
  • 2023
  • Ingår i: The Journal of Prevention of Alzheimer's Disease. - : SERDI. - 2274-5807 .- 2426-0266. ; :10, s. 478-487
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lack of external validation of dementia risk tools is a major limitation for generalizability and translatability of prediction scores in clinical practice and research.Objectives: We aimed to validate a new dementia prediction risk tool called CogDrisk and a version, CogDrisk-AD for predicting Alzheimer’s disease (AD) using cohort studies.Design, Setting, Participants and Measurements: Four cohort studies were identified that included majority of the dementia risk factors from the CogDrisk tool. Participants who were free of dementia at baseline were included. The predictors were component variables in the CogDrisk tool that include self-reported demographics, medical risk factors and lifestyle habits. Risk scores for Any Dementia and AD were computed and Area Under the Curve (AUC) was assessed. To examine modifiable risk factors for dementia, the CogDrisk tool was tested by excluding age and sex estimates from the model.Results: The performance of the tool varied between studies. The overall AUC and 95% CI for predicting dementia was 0.77 (0.57, 0.97) for the Swedish National study on Aging and Care in Kungsholmen, 0.76 (0.70, 0.83) for the Health and Retirement Study - Aging, Demographics and Memory Study, 0.70 (0.67,0.72) for the Cardiovascular Health Study Cognition Study, and 0.66 (0.62,0.70) for the Rush Memory and Aging Project.Conclusions: The CogDrisk and CogDrisk-AD performed well in the four studies. Overall, this tool can be used to assess individualized risk factors of dementia and AD in various population settings.
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44.
  • Laveskog, Anna, et al. (författare)
  • Associations of Vascular Risk Factors and APOE Genotype With Perivascular Spaces Among Community-Dwelling Older Adults
  • 2020
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 9:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence suggests that enlarged perivascular spaces (PVSs) may represent a marker for cerebral small‐vessel disease. We investigated whether vascular risk factors are correlated with visible PVS in older adults.Methods and Results: This population‐based study included 530 participants (age ≥60 years) who were free from dementia and functional dependence, derived from the Swedish National study on Aging and Care in Kungsholmen (2001–2003). We collected data on demographics, vascular risk factors, and health conditions through interviews, clinical examinations, laboratory tests, and patient registers. Cerebral PVSs and white matter hyperintensities on magnetic resonance images were visually assessed with semiquantitative visual rating scales. Data were analyzed using the general linear regression models. After controlling for demographics and cardiovascular disease, very high blood pressure (≥160/100 mm Hg) was significantly associated with global PVS score (β‐coefficient, 1.30; 95% CI, 0.06–2.53) and orthostatic hypotension was associated with PVS score in the basal ganglia (β‐coefficient 0.37; 0.03–0.70), but the associations became non‐significant when adjusting for white matter hyperintensity load. Orthostatic hypotension was significantly associated with global and lobar PVS scores in carriers but not in noncarriers of the APOE ε4 allele. Global or regional PVS score was not significantly associated with other traditional vascular risk factors such as smoking, diabetes mellitus, physical inactivity, and overweight or obesity.Conclusions: This study provides limited evidence supporting a correlation of magnetic resonance imaging–visible PVS with traditional vascular risk factors in older adults. The association of orthostatic hypotension with lobar PVS among APOE ε4 carriers suggests that lobar PVS may be a marker for amyloid‐associated small‐vessel disease.
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45.
  • Li, Yuanjing, et al. (författare)
  • Association Between Behavioral, Biological, and Genetic Markers of Cardiovascular Health and MRI Markers of Brain Aging : A Cohort Study
  • 2023
  • Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 100:1, s. e38-e48
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objective The life’s simple 7 approach was proposed to define cardiovascular health (CVH) metrics. We sought to investigate the associations between behavioral, biological, and genetic markers for CVH and vascular brain aging in older adults.Methods This population-based cohort study included participants who had repeated brain MRI measures from 2001 to 2003 to 2007–2010 (i.e., count of perivascular spaces, volumes of white matter hyperintensity [WMH] and gray matter, and lacunes). At baseline, global, behavioral, and biological CVH metrics were defined and scored following the life’s simple 7 approach and categorized into unfavorable, intermediate, and favorable profiles according to tertiles. The metabolic genetic risk score was calculated by counting 15 risk alleles associated with hypertension, diabetes, or dyslipidemia. Data were analyzed using linear mixed-effects and Cox proportional hazards models, adjusting for age, sex, and education.Results The study sample consisted of 317 participants (age 60 years or older; 61.8% women). Favorable and intermediate (vs unfavorable) global CVH profiles were related to slower WMH progression, with β-coefficients (95% CI) being −0.019(-0.035–0.002) and −0.018(-0.034–0.001), respectively. Favorable and intermediate (vs unfavorable) biological CVH profiles were significantly related to slower WMH increase only in people aged 60–72 years. CVH profiles were not related to progression of other brain measures. Furthermore, a higher metabolic genetic risk score (range: 6–21) was associated with faster WMH increase (β-coefficient = 0.005; 95% CI: 0.003–0.008). There were statistical interactions of metabolic genetic risk score with global and behavioral CVH profiles on WMH accumulation. A higher metabolic genetic risk score was related to faster WMH accumulation, with β-coefficients being 0.015(0.007–0.023), 0.005(0.001–0.009), and 0.003(-0.001 to 0.006) among people with unfavorable, intermediate, and favorable global CVH profiles, respectively; the corresponding β-coefficients were 0.013(0.006–0.020), 0.006(0.003–0.009), and 0.002(-0.002 to 0.006) among people with unfavorable, intermediate, and favorable behavioral CVH profiles.Discussion Intermediate to favorable global CVH profiles in older adults are associated with slower vascular brain aging. The association of metabolic genetic risk load with accelerated vascular brain aging was evident among people with unfavorable to intermediate, but not favorable, CVH profiles. These findings highlight the importance of adhering to favorable CVH profiles, especially healthy behaviors, in vascular brain health.
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46.
  • Li, Yuanjing, et al. (författare)
  • Association of Lifelong Cognitive Reserve with Dementia and Mild Cognitive Impairment among Older Adults with Limited Formal Education : A Population-Based Cohort Study 
  • 2023
  • Ingår i: Dementia and Geriatric Cognitive Disorders. - 1420-8008 .- 1421-9824. ; 52:4, s. 258-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. Methods: This population-based cohort study included 2,127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. Results: During the total of 8,330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with Alzheimer's disease (AD) and 26 with vascular dementia (VaD). The high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratios (95% confidence interval) of 0.28 (0.14–0.55) for dementia and 0.18 (0.07–0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60–74 but not in those aged ≥75 years (p for interaction = 0.011). Similarly, among MCI-free people at baseline (n = 1,635), the high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratios of 0.51 (0.38–0.69) for MCI and 0.46 (0.33–0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. Discussion: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in maintaining late-life cognitive health even among people with no or limited education.
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47.
  • Li, Yuanjing, et al. (författare)
  • Association of white matter hyperintensity accumulation with domain-specific cognitive decline : a population-based cohort study
  • 2023
  • Ingår i: Neurobiology of Aging. - 0197-4580 .- 1558-1497. ; 132, s. 100-108
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the association of load and accumulation of white matter hyperintensities (WMHs) with rate of cognitive decline. This population-based study included 510 dementia-free people (age ≥60 years) who had repeated measures of global and regional (lobar, deep, periventricular) WMHs up to 6 years (from 2001–2003 to 2007–2010) and repeated measures of cognitive function (episodic memory, semantic memory, category fluency, letter fluency, executive function, perceptual speed) up to 15 years (from 2001–2004 to 2016–2019). We found that greater baseline loads of global and regional WMHs were associated with faster decline in letter fluency, perceptual speed, and global cognition. Furthermore, faster accumulation of global, deep, and periventricular WMHs was related to accelerated cognitive decline, primarily in perceptual speed. These data show that WMHs are associated with decline in perceptual speed rather than episodic or semantic memory and that cognitive change is more vulnerable to WMH accumulations in deep and periventricular regions.
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48.
  • Li, Yuanjing, et al. (författare)
  • Characterizing Global and Regional Brain Structures in Amnestic Mild Cognitive Impairment Among Rural Residents : A Population-Based Study
  • 2021
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 80:4, s. 1429-1438
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Structural brain magnetic resonance imaging (MRI) scans may provide reliable neuroimaging markers for defining amnestic mild cognitive impairment (aMCI).Objective: We sought to characterize global and regional brain structures of aMCI among rural-dwelling older adults with limited education in China.Methods: This population-based study included 180 participants (aged >= 65 years, 42 with aMCI and 138 normal controls) in the Shandong Yanggu Study of Aging and Dementia during 2014-2016. We defined aMCI following the Petersen's criteria. Global and regional brain volumes were automatically segmented on MRI scans and compared using a region-of-interest approach. Data were analyzed using general linear regression models.Results: Multi-adjusted beta-coefficient (95% confidence interval) of brain volumes (cm(3)) associated with aMCI was -12.07 (-21.49, -2.64) for global grey matter (GM), -18.31 (-28.45, -8.17) for global white matter (WM), 28.17 (12.83, 44.07) for cerebrospinal fluid (CSF), and 2.20 (0.24, 4.16) for white matter hyperintensities (WMH). Furthermore, aMCI was significantly associated with lower GM volumes in bilateral superior temporal gyri, thalamus and right cuneus, and lower WM volumes in lateral areas extending from the frontal to the parietal, temporal, and occipital lobes, as well as right hippocampus (p < 0.05).Conclusion: Brain structure of older adults with aMCI is characterized by reduced global GM and WM volumes, enlarged CSF volume, increased WMH burden, reduced GM volumes in bilateral superior temporal gyri, thalamus, and right cuneus, and widespread reductions of lateral WM volumes.
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49.
  • Li, Yuanjing, et al. (författare)
  • Lifelong Cognitive Reserve, Imaging Markers of Brain Aging, and Cognitive Function in Dementia-Free Rural Older Adults : A Population-Based Study
  • 2023
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 92:1, s. 261-272
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cognitive reserve (CR) partly explains cognitive variability in the presence of pathological brain aging.Objective: We investigated the interplay of lifelong CR with age, sex, and brain aging markers in cognitive phenotypes among older adults with very limited education.Methods: This population-based cross-sectional study included 179 dementia-free participants (age ≥65 years; 39.7% women; 67.0% had no or elementary education) examined in 2014–2016. We assessed lacunes and volumes of hippocampus, ventricles, grey matter, white matter (WM), and white matter hyperintensities. Lifelong CR score was generated from six lifespan intellectual factors (e.g., education and social support). We used Mini-Mental State Examination (MMSE) score to assess cognition and Petersen’s criteria to define mild cognitive impairment (MCI). Data were analyzed using general linear and logistic models.Results: The association of higher lifelong CR score (range: –4.0–5.0) with higher MMSE score was stronger in women (multivariable-adjusted β-coefficient and 95% CI: 1.75;0.99–2.51) than in men (0.68;0.33–1.03) (pinteraction = 0.006). The association of higher CR with MCI (multivariable-adjusted odds ratio and 95% CI: 0.77;0.60–0.99) did not vary by age or sex. Among participants with low CR (<1.4[median]), greater hippocampal and WM volumes were related to higher MMSE scores with multivariable-adjusted β-coefficients being 1.77(0.41–3.13) and 0.44(0.15–0.74); the corresponding figures in those with high CR were 0.15(–0.76–1.07) and –0.17(–0.41–0.07) (pinteraction <0.01). There was no statistical interaction of CR with MRI markers on MCI.Conclusion: Greater lifelong CR capacity is associated with better late-life cognition among people with limited education, possibly by compensating for impact of neurodegeneration.
  •  
50.
  • Li, Yuanjing, et al. (författare)
  • Progression of neuroimaging markers of cerebral small vessel disease in older adults : A 6-year follow-up study
  • 2022
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 112, s. 204-211
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated progression and interrelationships of cerebral small vessel disease (cSVD) markers. This population-based cohort study included 325 participants (age ≥ 60 years) who had repeated measures of cSVD markers over 6 years: white-matter hyperintensity (WMH), perivascular spaces (PVS), lacunes, and grey-matter (GM) and ventricular volumes. We found that all cSVD markers, except PVS, progressed faster with increasing age. Regional WMH progressed faster in males and less-educated people (p < 0.05). Each 10-point increment in global WMH score was associated with multi-adjusted hazard ratio of 1.78 (95% CI = 1.50‒2.10) for incident lacunes and multi-adjusted β-coefficients of 0.15 (0.08–0.22), -0.37 (-0.58‒-0.16), and 0.11 (0.03‒0.18) for annual changes of global WMH score, GM volume, and ventricular volume, respectively. The corresponding figures associated with per 10-PVS increment were 1.14 (1.01‒1.28), 0.07 (0.03‒0.11), -0.18 (-0.32‒-0.04), and 0.02 (-0.03‒0.07). Prevalent lacunes were related to multi-adjusted β-coefficients of 0.29 (0.00‒0.58), 0.22 (0.05‒0.38), 0.10 (0.01‒0.18), and -0.93 (-1.83‒-0.03) for annual changes of global, deep, and periventricular WMH scores and GM volume, respectively. These results suggest that cSVD progresses faster in older, male, and less-educated people, and that greater loads of WMH, PVS, and lacunes anticipate faster cSVD progression.
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