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  • 1.
    Huang, Wenyong
    et al.
    Aging Research Center, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm.
    Qiu, Chengxuan
    Aging Research Center, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm.
    von Strauss, Eva
    Aging Research Center, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm.
    Winblad, Bengt
    Aging Research Center, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm.
    Fratiglioni, Laura
    Aging Research Center, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm.
    APOE Genotype, Family History of Dementia, and Alzheimer Disease Risk: A 6-Year Follow-up Study2004In: Archives of Neurology, ISSN 0003-9942, E-ISSN 1538-3687, Vol. 61, no 12, p. 1930-1934Article in journal (Refereed)
    Abstract [en]

    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.

  • 2. Qiu, Chengxuan
    et al.
    von Strauss, Eva
    Fastbom, Johan
    Winblad, Bengt
    Fratiglioni, Laura
    Low blood pressure and risk of dementia in the Kungsholmen project: a 6-year follow-up study2003In: Archives of Neurology, ISSN 0003-9942, E-ISSN 1538-3687, Vol. 60, no 2, p. 223-228Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies have reported a higher prevalence of dementia in persons with low blood pressure.

    Objective: To examine whether low blood pressure is prospectively associated with the occurrence of Alzheimer disease and dementia in elderly people.

    Subjects and Methods: A community-based, dementia-free cohort (n = 1270) aged 75 to 101 years was longitudinally examined twice within 6 years to detect incident dementia using the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria. Cox proportional hazards models were used to analyze blood pressure in association with dementia after adjustment for several potential confounders.

    Results: During the 6-year period, 339 subjects were diagnosed with dementia, including 256 persons with Alzheimer disease. Subjects with very high systolic pressure (>180 vs 141-180 mm Hg) had an adjusted relative risk of 1.5 (95% confidence interval [CI], 1.0-2.3; P =.07) for Alzheimer disease, and 1.6 (95% CI, 1.1-2.2) for dementia. Low systolic pressure (</=140 mm Hg) was not related to incident dementia. In contrast, high diastolic pressure (>90 mm Hg) was not associated with dementia incidence, whereas extremely low diastolic pressure (</=65 vs 66-90 mm Hg) produced an adjusted relative risk of 1.7 (95% CI, 1.1-2.4) for Alzheimer disease and 1.5 (95% CI, 1.0-2.1; P =.03) for dementia. The latter association was pronounced particularly in persons who used antihypertensive drugs.

    Conclusions: Both low diastolic and high systolic pressure are associated with an increased risk of Alzheimer disease and dementia in this elderly population. The atherosclerotic process may explain the observed associations. In addition, low diastolic pressure may increase dementia risk by affecting cerebral perfusion.

  • 3.
    von Strauss, Eva
    et al.
    Stockholm Gerontology Research Center, Division of Geriatric Medicine, Neurotec, Karolinska Institute, Stockholm.
    Viitanen, Matti
    Stockholm Gerontology Research Center, Division of Geriatric Medicine, Neurotec, Karolinska Institute, Stockholm.
    De Ronchi, Diana
    Stockholm Gerontology Research Center, Division of Geriatric Medicine, Neurotec, Karolinska Institute, Stockholm.
    Winblad, Bengt
    Stockholm Gerontology Research Center, Division of Geriatric Medicine, Neurotec, Karolinska Institute, Stockholm.
    Fratiglioni, Laura
    Stockholm Gerontology Research Center, Division of Geriatric Medicine, Neurotec, Karolinska Institute, Stockholm.
    Aging and the occurrence of dementia: Findings From a Population-Based Cohort With a Large Sample of Nonagenarians1999In: Archives of Neurology, ISSN 0003-9942, E-ISSN 1538-3687, Vol. 56, no 5, p. 587-592Article in journal (Refereed)
    Abstract [en]

    Context In spite of numerous studies on the occurrence of dementia, many questions remain, such as the relation between age, aging, and dementing disorders. This question is relevant both for understanding the pathogenetic mechanism of the dementias and for the public health prospective because of the increasing number of 85-year-old or older persons in our population.

    Objective To estimate the occurrence of dementia in the very old, including nonagenarians, in relation to age, gender, and different dementia types.

    Design An epidemiological survey where all participants were clinically examined by physicians, assessed by psychologists, and interviewed by nurses. The Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria for dementia were followed. A category of "questionable dementia" was added when all criteria were not fulfilled. A double diagnostic procedure was used for all subjects.

    Setting Community-based population, including all inhabitants of 2 areas in central Stockholm, Sweden (N=1848).

    Participants Of the 1848 subjects in the study population, 168 (9.1%) had died and 56 (3%) moved before examination. Of the remaining subjects, 1424 (87.7%) were examined, and the refusal rate was 12.3%.

    Main Outcome Measures Age- and gender-specific prevalence figures, and gender- and education-adjusted odds ratios were used.

    Results At the end of the diagnostic procedure, 358 clinically definite cases of dementia and 101 questionable cases of dementia were identified. Alzheimer disease (AD) contributed to 76.5%, and vascular dementia (VaD) to 17.9%. The prevalence of dementia increases from 13% in the 77- to 84-year-old subjects to 48% among persons 95 years and older (from 18% to 61% when questionable cases were included). The odds ratio for subjects 90 to 94 years and 95 years and older in comparison with 77- to 84-year-old subjects was 3.7 (95% confidence interval [CI], 2.7-5.1) and 6.5 (95% CI, 3.9-10.8) for dementia, 4.8 (95% CI, 3.3-7.0) and 8.0 (95% CI, 4.6-14.0) for persons with AD, 2.3 (95% CI, 1.3-4.2) and 4.6 (95% CI, 1.9-11.2) for VaD, respectively.

    Conclusions Dementia prevalence continues to increase even in the most advanced ages. This increase is especially evident among women and is more clear for AD. We believe that our prevalence data reflect the differential distribution of dementia risk.

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