| 1. |
- Ferrari, Camilla, et al.
(författare)
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How can elderly apolipoprotein E epsilon 4 carriers remain free from dementia?
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:1, s. 13-21
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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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| 2. |
- Giron, Maria Stella T, et al.
(författare)
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The appropriateness of drug use in an older nondemented and demented population
- 2001
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 49:3, s. 277-83
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the extent of inappropriateness of drug use in an older nondemented and demented population. DESIGN: Descriptive analysis based on data from a sample of older subjects age 81 years and older. Data were collected from the second follow-up conducted in 1994–1996. SETTING: A population-based study of the Kungsholmen project in Stockholm, Sweden. PARTICIPANTS: Drug information was obtained from 681 subjects with a mean age of 86.9 years. The subjects were predominantly women (78%). Thirteen percent resided in institutions and 27.6% were diagnosed with dementia. MEASUREMENTS: Dementia diagnosis based on DSM III-R. Criteria for inappropriateness of drug use: use of drugs with potent anticholinergic properties, drug duplication, potential drug-drug and drug-disease interactions, and inappropriate drug dosage. RESULTS: The mean number of drugs used was 4.6: 4.5 drugs for nondemented and 4.8 for demented subjects. Nondemented subjects more commonly used cardiovascular-system drugs and demented subjects used nervous-system drugs. Demented subjects were more commonly exposed to drug duplication and to drugs with potent anticholinergic properties, both involving the use of psychotropic drugs. Nondemented subjects were more commonly exposed to potential drug-disease interactions, mostly with the use of cardiovascular drugs. The most common drug combination leading to a potential interaction was the use of digoxin with furosemide, occurring more frequently among nondemented subjects. The most common drug-disease interaction was the use of beta-blockers and calcium antagonists in subjects with congestive heart failure. The doses of drugs taken by both nondemented and demented subjects were mostly lower than the defined daily dose. CONCLUSION: There was substantial exposure to presumptive inappropriateness of drug use in this very old nondemented and demented population. The exposure of demented subjects to psychotropic drugs and nondemented subjects to cardiovascular drugs reflect the high frequency of prescribing these drugs in this population.
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| 3. |
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| 4. |
- Keller, Lina, et al.
(författare)
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The Obesity Related Gene, FTO, Interacts with APOE and is Associated with Alzheimer's Disease Risk : A Prospective Cohort Study
- 2011
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 23:3, s. 461-469
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Tidskriftsartikel (refereegranskat)abstract
- The FTO gene has been shown to have a small but robust effect on body mass index (BMI) and to increase the risk for diabetes. Both high BMI and diabetes are vascular risk factors that might play a role in the development of Alzheimer's disease (AD) and dementia. Thus, our aim was to explore the impact of FTO on AD and dementia risk. Nine years of follow-up data was gathered from the Kungsholmen project, a prospective population-based study on 1,003 persons without dementia. Cox-regression models were used to assess the relative risks of developing AD and dementia (DSM-III-R criteria) according to FTO genotypes (rs9939609), taking into account APOE, physical inactivity, BMI, diabetes, and cardiovascular disease (CVD). Compared to carriers of the FTO TT-genotype, AA-carriers had a higher risk for AD (RR 1.58, 95% CI: 1.11-2.24) and for dementia (RR 1.48, 95% CI: 1.09-2.02) after adjustment for age, gender, education, and APOE genotype. This effect remained after additional adjustment for physical inactivity, BMI, diabetes, and CVD. An interaction between FTO and APOE was found, with increased risk for dementia for those carrying both FTO AA and APOE epsilon 4. Importantly, the effect of the AA-genotype on dementia/AD risk seems to act mostly through the interaction with APOE epsilon 4. Our findings suggest that the FTO AA-genotype increases the risk for dementia, and in particular AD, independently of physical inactivity, BMI, diabetes, and CVD measured at baseline. Our results are in line with the recently reported association between FTO and reduced brain volume in cognitively healthy subjects.
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| 5. |
- Paillard-Borg, Stéphanie, et al.
(författare)
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An active lifestyle postpones dementia onset by more than one year in very old adults
- 2012
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 52, s. 216-216
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to test the hypothesis that an active lifestyle delays age at dementia onset. This study included 388 incident dementia cases (DSM-III-R criteria) that developed over a 9-year follow-up period among 1,375 baseline dementia-free community dwellers with good cognitive function (MMSE > 23) (mean age = 81.2) from the Kungsholmen Project. An active lifestyle was defined as participation in mental, physical, or social activity. We used linear regression models to estimate influence of baseline active lifestyle on age at onset of incident dementia and general linear models to estimate mean age at dementia onset. Age at onset of dementia was significantly older in persons who had higher levels of participation in mental, physical, or social activity (beta: 0.18, 0.29 and 0.23 respectively, p < 0.001 for all the activities) independent of education, medical condition, functional status, and other confounders including APOE. When the three types of activities were integrated into an index, we found that the broader the spectrum of participation in the activities, the later the onset of disease (beta = 0.93, p = 0.01 for participating in two activities, and beta = 1.42, p < 0.001 for three activities). There were 17 months difference in mean age at dementia onset between the inactive group and the most active group. An active lifestyle operates as a protective factor for dementia by delaying the clinical onset of the disease. These findings highlight the relevance of encouraging old adults to have active lifestyles, which could have a great impact on public health.
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| 6. |
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| 7. |
- Wang, Hui-Xin, et al.
(författare)
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Psychosocial stress at work is associated with increased dementia risk in late life
- 2012
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 8:2, s. 114-120
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To test the hypothesis that high job stress during working life might lead to an increased risk of dementia and Alzheimer's disease (AD) in late life. Methods: A dementia-free cohort of 913 community dwellers, aged 75+ years, from the Kungsholmen Project, a population-based follow-up study carried out in Stockholm, Sweden, was followed up for an average of 6 years to detect incident dementia and AD (third revised Diagnostic and Statistical Manual of Mental Disorders). Information on the lifespan work activities was collected. Psychological stress at work was estimated for the longest period of occupation as well as for all occupations by using a validated psychosocial job exposure matrix on two dimensions: job control and job demands. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of dementia and AD in relation to different levels of job stress. Results: Low level of job control was associated with higher multivariate adjusted risk of dementia (HR = 1.9, 95% CI: 1.2-3.0) and AD (HR = 2.2, 95% CI: 1.2-3.9). Low level of job demands alone was not significantly associated with increased dementia risk. When the two dimensions were combined into a four-category job strain model, both high job strain (low control/high demands) and passive strain (both low control and demands) were related to higher risk of dementia and AD as compared with active job strain (both high). Vascular disorders did not mediate the observed associations. Conclusion: Lifelong work-related psychosocial stress, characterized by low job control and high job strain, was associated with increased risk of dementia and AD in late life, independent of other known risk factors.
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| 8. |
- Xu, Weili, et al.
(författare)
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Accelerated progression from mild cognitive impairment to dementia in people with diabetes
- 2010
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:11, s. 2928-35
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The effect of diabetes on mild cognitive impairment (MCI) and its conversion to dementia remains controversial. We sought to examine whether diabetes and pre-diabetes are associated with MCI and accelerate the progression from MCI to dementia.RESEARCH DESIGN AND METHODS: In the Kungsholmen Project, 963 cognitively intact participants and 302 subjects with MCI (120 with amnestic MCI [aMCI] and 182 with other cognitive impairment no dementia [oCIND]) age ≥ 75 years were identified at baseline. The two cohorts were followed for 9 years to detect the incident MCI and dementia following international criteria. Diabetes was ascertained based on a medical examination, hypoglycemic medication use, and random blood glucose level ≥ 11.0 mmol/l. Pre-diabetes was defined as random blood glucose level of 7.8-11.0 mmol/l in diabetes-free participants. Data were analyzed using standard and time-dependent Cox proportional-hazards models.RESULTS: During the follow-up period, in the cognitively intact cohort, 182 people developed MCI (42 aMCI and 140 oCIND), and 212 developed dementia. In the MCI cohort, 155 subjects progressed to dementia, the multi-adjusted hazard ratio (95% CI) of dementia was 2.87 (1.30-6.34) for diabetes, and 4.96 (2.27-10.84) for pre-diabetes. In a Kaplan-Meier survival analysis, diabetes and pre-diabetes accelerated the progression from MCI to dementia by 3.18 years. Diabetes and pre-diabetes were neither cross-sectionally nor longitudinally associated with MCI.CONCLUSIONS: Diabetes and pre-diabetes substantially accelerate the progression from MCI to dementia, and anticipate dementia occurrence by more than 3 years in people with MCI. The association of diabetes with the development of MCI is less evident in old people.
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| 9. |
- Xu, Wei-Li, et al.
(författare)
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Accelerated Progression from Mild Cognitive Impairment to Dementia Among APOE epsilon 4 epsilon 4 Carriers
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33:2, s. 507-515
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Tidskriftsartikel (refereegranskat)abstract
- The impact of APOE ε4 on mild cognitive impairment (MCI) and its progression to dementia remain controversial. We aimed to examine the association of APOE ε4 with MCI, and to verify the hypothesis that ε4 accelerates progression from MCI to dementia. In the Kungsholmen project, 756 cognitively healthy participants and 212 people with MCI aged ≥75 years were identified at baseline. Amnestic MCI (aMCI) and other cognitive impairment no dementia (oCIND) as two subtypes of MCI were assessed based on standard definitions. The two cohorts were followed for 9 years to detect incident cases of MCI and dementia following international criteria. APOE genotypes were assessed at baseline. Data were analyzed using Cox models. During the follow-up, in the cognitively healthy cohort, 165 people developed MCI (40 aMCI and 125 oCIND) and 176 developed dementia; in the MCI cohort, 118 persons progressed to dementia. Compared with APOE ε3ε3, the hazard ratios (HRs) (95% CIs) of ε2ε4/ε3ε4 were 2.24 (1.10-4.57) for aMCI and 1.78 (1.15-2.75) for oCIND, while the ε4ε4 was related to dementia with a HR of 4.35 (1.97-9.63) in the cognitively healthy cohort. In the MCI cohort, the ε4ε4 genotype led to a multi-adjusted HR of 2.89 (1.12-7.48) for dementia and accelerated the progression to dementia by 3.36 years. The APOE ε4 heterozygotes are associated with an increased risk of aMCI and oCIND. The ε4 homozygote substantially accelerates progression from MCI to dementia, and anticipate dementia occurrence by more than 3 years in people with MCI.
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| 10. |
- Xu, Wei-Li, et al.
(författare)
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HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease : A Population-Based Longitudinal Study
- 2015
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Background Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. Methods and Findings The first cohort, which included dementia-free adults aged >= 75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged >= 60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19-2.32) and 1.66 (95% CI 1.06-2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.407.18) and 4.81 (95% CI 1.88-8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63-8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45-9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04-2.99) and 1.64 (1.02-2.33) for the diabetes-AD and dementia-AD associations, respectively, and 4.06 (95% CI 1.06-7.58, p = 0.039) and 3.29 (95% CI 1.02-8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups. Conclusions A variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people.
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