| 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. |
- Vuorinen, Miika, et al.
(författare)
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Changes in vascular factors 28 years from midlife and late-life cortical thickness
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:1, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- We assessed midlife blood pressure (BP), body mass index, total cholesterol, and their changes over time in relation to cortical thickness on magnetic resonance imaging 28 years later in 63 elderly at risk of dementia. Participants in the population-based Cardiovascular Risk Factors, Aging, and Dementia study were first examined at midlife. A first follow-up was conducted after 21 years, and a second follow-up after an additional 7 years. Magnetic resonance images from the second follow-up were analyzed using algorithms developed at McGill University, Montreal, Canada. Midlife hypertension was related to thinner cortex in several brain areas, including insular, frontal, and temporal cortices. In elderly with thinner insular cortex, there was a continuous decline in systolic BP and an increase in pulse pressure after midlife, while in elderly with thicker insular cortex the decline in systolic BP started at older ages, paralleled by a decline in pulse pressure. No associations were found between body mass index, cholesterol, or apolipoprotein E ε4 allele and cortical thickness in this group of elderly at risk individuals.
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| 3. |
- Enache, Daniela, et al.
(författare)
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CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 42, s. 124-131
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status. Cerebrospinal fluid was analyzed for amyloid β (Aβ), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced Aβ, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE.
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| 4. |
- 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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| 5. |
- Wallin, Karin, et al.
(författare)
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Midlife rheumatoid arthritis increases the risk of cognitive impairment two decades later : a population based study
- 2012
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 31:3, s. 669-676
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation has been associated with Alzheimer's disease (AD) and dementia. The association between rheumatoid arthritis (RA) or arthritis and dementia/AD has been investigated in several case-control or hospital- and register-based studies with mixed results. This long-term population-based study investigates the association between presence of joint disorders (RA and other joint disorders) in midlife and cognitive status later in life. 1,449 participants were first evaluated in 1972, 1977, 1982, and 1987 and follow-up was performed after 21 years. A self-administered questionnaire including questions on joint disorders was used at both evaluations. Cognitive status (control, mild cognitive impairment, dementia/AD) was assessed at follow-up. The presence of any joint disorder in midlife was significantly associated with a worse cognitive status later in life: OR (95% CI) in an ordinal logistic regression analysis adjusted for age, gender, follow-up time, education, APOE epsilon 4, body mass index, smoking, drug treatment, and diabetes was 1.96 (1.17-3.28). For RA only, OR (95% CI) was 2.77 (1.26-6.10). The correlation remained significant for RA when AD was considered instead of dementia OR (95% CI) 2.49 (1.09-5.67). The presence of joint disorders, especially RA, at midlife seems to be associated with a worse cognitive status later in life. Given the chronic inflammatory component of RA, this study suggests that inflammatory mechanisms may have an important role in increasing the risk of cognitive impairment and dementia/AD.
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| 6. |
- Norgren, Jakob, et al.
(författare)
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Capillary blood tests may overestimate ketosis : triangulation between three different measures of beta-hydroxybutyrate
- 2020
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 318:2, s. e184-E188
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Tidskriftsartikel (refereegranskat)abstract
- The ketone body beta-hydroxybutyrate (BHB), assessed by a point-of-care meter in venous whole blood (BHBv), was used as the main outcome in a study on nutritional ketosis in healthy older adults. Two other BHB measures were also used in the study for validation and exploratory purposes, and here we report findings on correlation and agreement between those three methods. Ketosis in the range of 0-1.5 mmol/L was induced in 15 healthy volunteers by intake of medium-chain fatty acids after a 12-h fast. BHBv was assessed at 12 time points for 4 h. The same point-of-care meter was also used to test capillary blood (BHBc) at three time points, and a laboratory test determined total ketones (TK) in plasma (BHBp + acetoacetate) at four time points. A total of 180 cases included simultaneous data on BHBv, BHBc, BHBp, and TK. TK correlated with BHBp (Pearson's r = 0.99), BHBv (r = 0.91), and BHBc (r = 0.91), all P < 0.0001. BHBv and BHBp had good agreement in absolute values. However, the slope between BHBc and BHBv, measured with the same device, was in the range of 0.64-0.78 in different regression models, indicating substantially higher BHB concentrations in capillary versus venous blood. We conclude that all three methods are valid to detect relative changes in ketosis, but our results highlight the importance of method considerations and the possible need to adjust cutoffs, e.g., in the management of ketoacidosis and in the evaluation and comparison of dietary interventions.
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| 7. |
- Wu, Jing, et al.
(författare)
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Can dementia risk be reduced by following the American Heart Association's Life's Simple 7? : A systematic review and dose-response meta-analysis.
- 2023
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Ingår i: Ageing Research Reviews. - : Elsevier. - 1568-1637 .- 1872-9649. ; 83
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to quantify the relationships between the American Heart Association (AHA) Cardiovascular Health (CVH) metrics, namely AHA Life's Simple 7, and cognitive outcomes. We searched PubMed and Embase (January 1, 2010-August 24, 2022) and finally included 14 longitudinal studies (311654 participants with 8006 incident dementia cases). Random-effects meta-analysis and one-stage linear mixed-effects models were performed. Increased CVH score seemed to associate with decreased risk of incident dementia in a linear manner, but this relationship varied by the measurement age of CVH metrics. That is, midlife CVH tended to have a linear association with late-life dementia risk, whereas a J-shaped association was observed between the late-life CVH score and dementia. In addition, late-life dementia risk was reduced significantly if individuals maintained an ideal level of AHA's CVH guidelines of physical activity, fasting plasma glucose, total cholesterol, and smoking. However, our meta-analysis did not show a significant association between CVH score and global cognitive decline rate. Following AHA's CVH guidelines and maintaining CVH at an optimal level would substantially reduce the late-life dementia risk. More research is required to explore the link between a favorable CVH score and cognitive trajectories among cognitively asymptomatic older populations.
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| 8. |
- Ibáñez, Clara, et al.
(författare)
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Toward a predictive model of Alzheimer's disease progression using capillary electrophoresis-mass spectrometry metabolomics
- 2012
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 84:20, s. 8532-8540
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is the most prevalent form of dementia with an estimated worldwide prevalence of over 30 million people, and its incidence is expected to increase dramatically with an increasing elderly population. Up until now, cerebrospinal fluid (CSF) has been the preferred sample to investigate central nervous system (CNS) disorders since its composition is directly related to metabolite production in the brain. In this work, a nontargeted metabolomic approach based on capillary electrophoresis–mass spectrometry (CE–MS) is developed to examine metabolic differences in CSF samples from subjects with different cognitive status related to AD progression. To do this, CSF samples from 85 subjects were obtained from patients with (i) subjective cognitive impairment (SCI, i.e. control group), (ii) mild cognitive impairment (MCI) which remained stable after a follow-up period of 2 years, (iii) MCI which progressed to AD within a 2-year time after the initial MCI diagnostic and, (iv) diagnosed AD. A prediction model for AD progression using multivariate statistical analysis based on CE–MS metabolomics of CSF samples was obtained using 73 CSF samples. Using our model, we were able to correctly classify 97–100% of the samples in the diagnostic groups. The prediction power was confirmed in a blind small test set of 12 CSF samples, reaching a 83% of diagnostic accuracy. The obtained predictive values were higher than those reported with classical CSF AD biomarkers (Aβ42 and tau) but need to be confirmed in larger samples cohorts. Choline, dimethylarginine, arginine, valine, proline, serine, histidine, creatine, carnitine, and suberylglycine were identified as possible disease progression biomarkers. Our results suggest that CE–MS metabolomics of CSF samples can be a useful tool to predict AD progression.
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| 9. |
- Kivipelto, Miia, et al.
(författare)
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The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) : Study design and progress
- 2013
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:6, s. 657-665
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Tidskriftsartikel (refereegranskat)abstract
- Background: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland. Materials: Participants (1200 individuals at risk of cognitive decline) are recruited from previous population-based non-intervention studies. Inclusion criteria are CAIDE Dementia Risk Score >= 6 and cognitive performance at the mean level or slightly lower than expected for age (but not substantial impairment) assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. The 2-year multidomain intervention consists of: nutritional guidance; exercise; cognitive training and social activity; and management of metabolic and vascular risk factors. Persons in the control group receive regular health advice. The primary outcome is cognitive performance as measured by the modified Neuropsychological Test Battery, Stroop test, and Trail Making Test. Main secondary outcomes are: dementia (after extended follow-up); disability; depressive symptoms; vascular risk factors and outcomes; quality of life; utilization of health resources; and neuroimaging measures. Results: Screening began in September 2009 and was completed in December 2011. All 1200 persons are enrolled and the intervention is ongoing as planned. Baseline clinical characteristics indicate that several vascular risk factors and unhealthy lifestyle related factors are present, creating a window of opportunity for prevention. The intervention will be completed during 2014. Conclusions: The FINGER is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.
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| 10. |
- Munoz-Ruiz, Miguel Angel, et al.
(författare)
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Structural MRI in Frontotemporal Dementia : Comparisons between Hippocampal Volumetry, Tensor-Based Morphometry and Voxel-Based Morphometry
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods. Objective: To compare FTD with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy. Methods: Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups. Results: We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55). Conclusion: Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.
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