| 1. |
- Mangialasche, Francesca, et al.
(författare)
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Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults
- 2013
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 48:12, s. 1428-1435
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin E includes eight natural antioxidant compounds (four tocopherols and four tocotrienols), but a-tocopherol has been the main focus of investigation in studies of cognitive impairment and Alzheimer's disease. Objective: To investigate the association between serum levels of tocopherols and tocotrienols, markers of vitamin E oxidative/nitrosative damage (alpha-tocopherylquinone, 5-nitro-gamma-tocopherol) and incidence of cognitive impairment in a population-based study. Design: A sample of 140 non-cognitively impaired elderly subjects derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed-up for 8 years to detect cognitive impairment, defined as development of mild cognitive impairment (MCI) or Alzheimer's dementia. The association between baseline serum vitamin E and cognitive impairment was analyzed with multiple logistic regression after adjusting for several confounders. Results: The risk of cognitive impairment was lower in subjects in the middle tertile of the alpha-tocopherol/cholesterol ratio than in those in the lowest tertile: the multiadjusted odds ratio (OR) with 95% confidence interval (CI) was 0.27 (0.10-0.78). Higher incidence of cognitive impairment was found in the middle [OR (95% CI): 3.41 (1.29-9.06)] and highest [OR (95% CI): 2.89 (1.05-7.97)] tertiles of the 5-NO2-gamma-tocopherol/gamma-tocopherol ratio. Analyses of absolute serum levels of vitamin E showed lower risk of cognitive impairment in subjects with higher levels of gamma-tocopherol, beta-tocotrienol, and total tocotrienols. Conclusions: Elevated levels of tocopherol and tocotrienol forms are associated with reduced risk of cognitive impairment in older adults. The association is modulated by concurrent cholesterol concentration. Various vitamin E forms might play a role in cognitive impairment, and their evaluation can provide a more accurate measure of vitamin E status in humans.
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| 2. |
- Wang, Rui, et al.
(författare)
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MRI load of cerebral microvascular lesions and neurodegeneration, cognitive decline, and dementia
- 2018
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 91:16, s. 1487-1497
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Tidskriftsartikel (refereegranskat)abstract
- Objective To explore the differential associations of neurodegeneration and microvascular lesion load with cognitive decline and dementia in older people and the modifying effect of the APOE genotype on these associations. Methods A sample of 436 participants (age >= 60 years) was derived from the population-based Swedish National study on Aging and Care in Kungsholmen, Stockholm, and clinically examined at baseline (2001-2003) and 3 occasions during the 9-year follow-up. At baseline, we assessed microvascular lesion load using a summary score for MRI markers of lacunes, white matter hyperintensities (WMHs), and perivascular spaces and neurodegeneration load for markers of enlarged ventricles, smaller hippocampus, and smaller gray matter. We assessed cognitive function using the Mini-Mental State Examination (MMSE) test and diagnosed dementia following the Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. We analyzed data using linear mixed-effects, mediation, and random-effects Cox models. Results During the follow-up, 46 participants were diagnosed with dementia. Per 1-point increase in microvascular lesion and neurodegeneration score (range 0-3) was associated with multiple adjusted beta-coefficients of -0.35 (95% confidence interval, -0.51 to -0.20) and -0.44 (-0.56 to -0.32), respectively, for the MMSE score and multiple adjusted hazard ratios of 1.68 (1.12-2.51) and 2.35 (1.58-3.52), respectively, for dementia; carrying APOE epsilon 4 reinforced the associations with MMSE decline. WMH volume changes during the follow-up mediated 66.9% and 12.7% of the total association of MMSE decline with the baseline microvascular score and neurodegeneration score, respectively. Conclusions Both cerebral microvascular lesion and neurodegeneration loads are strongly associated with cognitive decline and dementia. The cognitive decline due to microvascular lesions is exacerbated by APOE epsilon 4 and is largely attributed to progression and development of microvascular lesions.
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| 3. |
- Wu, Yu-Tzu, et al.
(författare)
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The changing prevalence and incidence of dementia over time - current evidence.
- 2017
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Ingår i: Nature reviews. Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.
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| 4. |
- Heiland, Emerald G, et al.
(författare)
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Cardiovascular Risk Burden and Future Risk of Walking Speed Limitation in Older Adults
- 2017
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 65:11, s. 2418-2424
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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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| 5. |
- Hooshmand, Babak, et al.
(författare)
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Association of Methionine to Homocysteine Status With Brain Magnetic Resonance Imaging Measures and Risk of Dementia
- 2019
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 76:11, s. 1198-1205
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Impairment of methylation status (ie, methionine to homocysteine ratio) may be a modifiable risk factor for structural brain changes and incident dementia.OBJECTIVE To investigate the association of serum markers of methylation status and sulfur amino acids with risk of incident dementia, Alzheimer disease (AD), and the rate of total brain tissue volume loss during 6 years.DESIGN, SETTING, AND PARTICIPANTS This population-based longitudinal study was performed from March 21, 2001, to October 10, 2010, in a sample of 2570 individuals aged 60 to 102 years from the Swedish Study on Aging and Care in Kungsholmen who were dementia free at baseline and underwent comprehensive examinations and structural brain magnetic resonance imaging (MRI) on 2 to 3 occasions during 6 years. Data analysis was performed from March 1, 2018, to October 1, 2018.MAIN OUTCOMES AND MEASURES Incident dementia, AD, and the rate of total brain volume loss.RESULTS This study included 2570 individuals (mean [SD] age, 73.1 [10.4] years; 1331 [56.5%] female). The methionine to homocysteine ratio was higher in individuals who consumed vitamin supplements (median, 1.9; interquartile range [IQR], 1.5-2.6) compared with those who did not (median, 1.8; IQR, 1.3-2.3; P<.001) and increased per each quartile increase of vitamin B-12 or folate. In the multiadjusted model, an elevated baseline serum total homocysteine level was associated with an increased risk of dementia and AD during 6 years: for the highest homocysteine quartile compared with the lowest, the hazard ratios (HRs) were 1.60 (95% CI, 1.01-2.55) for dementia and 2.33 (95% CI, 1.26-4.30) for AD. In contrast, elevated concentrations of methionine were associated with a decreased risk of dementia (HR, 0.54; 95% CI, 0.36-0.81) for the highest quartile compared with the lowest. Higher values of the methionine to homocysteine ratio were significantly associated with lower risk of dementia and AD: for the fourth methionine-homocysteine quartile compared with the first quartile, the HR was 0.44 (95% CI, 0.27-0.71) for incident dementia and 0.43 (95% CI, 0.23-0.80) for AD. In the multiadjusted linear mixed models, a higher methionine to homocysteine ratio was associated with a decreased rate of total brain tissue volume loss during the study period (beta [SE] per 1-SD increase, 0.038 [0.014]; P=.007).CONCLUSIONS AND RELEVANCE The methionine to homocysteine status was associated with dementia development and structural brain changes during the 6-year study period, suggesting that a higher methionine to homocysteine ratio may be important in reducing the rate of brain atrophy and decreasing the risk of dementia in older adults.
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| 6. |
- Welmer, Anna-Karin, et al.
(författare)
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Association of Cardiovascular Burden with Mobility Limitation among Elderly People : A Population-Based Study
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiovascular risk factors (CRFs) such as smoking and diabetes have been associated with mobility limitations among older adults. We seek to examine to what extent individual and aggregated CRFs and cardiovascular diseases (CVDs) are associated with mobility limitation. Methods: The study sample included 2725 participants (age >= 60 years, mean age 72.7 years, 62% women) in the Swedish National Study on Aging and Care in the Kungsholmen district of central Stockholm, Sweden, who were living either at their own home or in institutions. Data on demographic features, CRFs, and CVDs were collected through interview, clinical examination, self-reported history, laboratory tests, and inpatient register. Mobility limitation was defined as walking speed <0.8 m/s. Data were analyzed using multiple logistic models controlling for potential confounders. Results: Of the 2725 participants, 581 (21.3%) had mobility limitation. The likelihood of mobility limitation increased linearly with the increasing number of CRFs (i.e., hypertension, high C-reactive protein, obesity, diabetes and smoking) (p for linear trend<0.010) and of CVDs (i.e., ischemic heart disease, atrial fibrillation, heart failure and stroke) (p for linear trend<0.001). There were statistical interactions of aggregated CRFs with age and APOE epsilon 4 allele on mobility limitation (p(interaction)<0.05), such that the association of mobility limitation with aggregated CRFs was statistically evident only among people aged <80 years and among carriers of the APOE epsilon 4 allele. Conclusion: Aggregations of multiple CRFs and CVDs are associated with an increased likelihood of mobility limitation among older adults; however the associations of CRFs with mobility limitation vary by age and genetic susceptibility.
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| 7. |
- Marseglia, Anna, et al.
(författare)
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Cognitive Trajectories of Older Adults With Prediabetes and Diabetes : A Population-Based Cohort Study
- 2018
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 73:3, s. 400-406
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes has been linked to dementia risk; however, the cognitive trajectories in older adults with diabetes remain unclear. We aimed to investigate the effect of prediabetes and diabetes on cognitive trajectories among cognitively intact older adults in a long-term follow-up study.Methods Within the Swedish Adoption/Twin Study of Aging, 793 cognitively intact older adults aged ≥50 were identified at baseline and followed for up to 23 years. Based on standardized scores from 11 cognitive tests, administered at baseline and up to seven follow-ups, four cognitive domains (verbal abilities, spatial/fluid, memory, perceptual speed) were identified by principal-component analysis. Prediabetes was defined according to blood glucose levels in diabetes-free participants. Diabetes was ascertained based on self-report, hypoglycemic medication use and blood glucose levels. Data were analyzed with linear mixed-effect models adjusting for potential confounders.Results At baseline, 68 participants (8.6%) had prediabetes and 45 (5.7%) had diabetes. Compared to diabetes-free individuals, people with diabetes had a steeper decline over time in perceptual speed and verbal abilities. The annual declines in these domains were greater than the annual decline in memory. Prediabetes was associated with lower performance in memory in middle-age, but also associated with a less steep memory decline over the follow-up.Conclusions Diabetes is associated with a faster decline in perceptual speed and verbal abilities, while prediabetes is associated with lower memory performance in middle-age. However, the detrimental effects of hyperglycemia seem to not affect memory over time.
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| 8. |
- Clerici, Francesca, et al.
(författare)
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Does Vascular Burden Contribute to the Progression of Mild Cognitive Impairment to Dementia?
- 2012
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 34:3-4, s. 235-243
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the contribution of vascular risk factors (VRFs), vascular diseases (VDs) and white matter lesions (WMLs) to the progression of mild cognitive impairment (MCI) to dementia and Alzheimer’s disease (AD). Methods: Two hundred forty-five consecutive subjects with MCI (age 74.09 ± 6.92 years) were followed for an average of 2.4 years. The Hachinski Ischemic Score and the Framingham Stroke Risk Profile were used to summarize VRFs and VDs. WMLs were graded using the Age-Related White Matter Changes Scale. Results: One hundred twenty-nine (52.6%) out of 245 subjects at risk converted to dementia, including 87 cases of AD. When hypertension occurred in MCI with deep WMLs, a 1.8-fold increased risk of dementia was observed (95% CI = 1.0–3.4). When deep WMLs occurred in MCI with high scores (≥4) on the Hachinski scale, a 3.5-fold (95% CI = 1.6–7.4) and 3.8-fold (95% CI = 1.2–11.5) risk of progression to dementia and AD was observed, respectively. Analogously, the joint effect of WMLs and high scores (≥14) on the Framingham scale nearly doubled the risk of dementia (hazard ratio = 1.9, 95% CI = 1.1–3.3). Conclusions: Accelerated progression of MCI to dementia and AD is to be expected when VRFs and VDs occur together with WMLs.
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| 9. |
- Dekhtyar, Serhiy, et al.
(författare)
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Genetic risk of dementia mitigated by cognitive reserve : A cohort study
- 2019
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 86:1, s. 68-78
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Tidskriftsartikel (refereegranskat)abstract
- Objective We investigated whether cognitive reserve modifies the risk of dementia attributable to apolipoprotein epsilon 4 (APOE-epsilon 4), a well-known genetic risk factor for dementia. Methods We followed 2,556 cognitively intact participants aged >= 60 years from the ongoing prospective community-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Dementia was ascertained through clinical and neuropsychological assessments and diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Structural equation modeling was used to generate a cognitive reserve indicator from 4 previously validated contributors: early life education, midlife substantive work complexity, late life leisure activities, and late life social networks. Cox proportional hazard models estimated dementia risk in relation to cognitive reserve indicator. The interaction between the cognitive reserve indicator and APOE-epsilon 4 was assessed on multiplicative and additive scales. Results After an average of 6.3 years (range = 2.1-10.7) of follow-up, 232 dementia cases were ascertained. Relative to individuals in the lowest tertile of cognitive reserve indicator, those with moderate and high reserve were at a reduced risk of dementia. There was no multiplicative interaction between APOE-epsilon 4 status and cognitive reserve indicator (p = 0.113). Additive interaction was statistically significant. Relative to APOE-epsilon 4 carriers with low cognitive reserve, epsilon 4 carriers with high reserve had a reduced risk of dementia (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.13-0.59). The magnitude of risk reduction was similar in epsilon 4 noncarriers with a high cognitive reserve indicator (HR = 0.24, 95% CI = 0.15-0.40). Interpretation Lifelong engagement in reserve-enhancing activities attenuates the risk of dementia attributable to APOE-epsilon 4. Promoting cognitive reserve might be especially effective in subpopulations with high genetic risk of dementia. ANN NEUROL 2019
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| 10. |
- Ferrari, Camilla, et al.
(författare)
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Alzheimer's Disease Progression : Factors Influencing Cognitive Decline
- 2018
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 61:2, s. 785-791
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Tidskriftsartikel (refereegranskat)abstract
- Background:Alzheimer's disease (AD) patients present high variability in the rate of cognitive decline. Despite the wide knowledge on factors influencing dementia risk, little is known on what accounts for AD progression. Previous studies on this topic have mainly analyzed each factor separately without taking into account the interaction between genetic and non-genetic factors.Objective:The aim of the present study is to evaluate the role of demographic, clinical, therapeutic, and genetic factors and their interaction on cognitive decline among newly diagnosed AD patients.Methods:We retrospectively selected 160 AD patients diagnosed at the Neurology Unit of Careggi University Hospital of Florence. We evaluated the occurrence of rapid cognitive changes defined as the worsening of more than four points at the Mini-Mental State Examination after 2-year follow up period.Results:Among the 160 AD patients, 50% presented rapid disease progression. Extrapyramidal signs at disease onset were predictors of worse outcome (OR 2.2), especially among Apolipoprotein E (APOE) epsilon 4 allele carriers, while the presence of family history for dementia decreased the risk of rapid progression by about 50%. Higher educated epsilon 4-carriers showed a slower AD progression. We identified the chronic use of aspirin as potential secondary preventative strategy for the non epsilon 4-carriers.Conclusion:At dementia onset, some clinical and demographic data can be predictors of future progression. The outcomes of the present study support the already hypothesized interaction between genetic and non-genetic factors during disease course and suggest genetic-based approaches.
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