Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease.
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BACKGROUND: Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may help to prevent Alzheimer's disease. The results, however, are inconsistent. METHODS: We studied the association between the use of NSAIDs and Alzheimer's disease and vascular dementia in a prospective, population-based cohort study of 6989 subjects 55 years of age or older who were free of dementia at base line, in 1991. To detect new cases of dementia, follow-up screening was performed in 1993 and 1994 and again in 1997 through 1999. The risk of Alzheimer's disease was estimated in relation to the use of NSAIDs as documented in pharmacy records. We defined four mutually exclusive categories of use: nonuse, short-term use (1 month or less of cumulative use), intermediate-term use (more than 1 but less than 24 months of cumulative use), and long-term use (24 months or more of cumulative use). Adjustments were made by Cox regression analysis for age, sex, education, smoking status, and the use or nonuse of salicylates, histamine Hz-receptor antagonists, antihypertensive agents, and hypoglycemic agents. RESULTS: During an average follow-up period of 6.8 years, dementia developed in 394 subjects, of whom 293 had Alzheimer's disease, 56 vascular dementia, and 45 other types of dementia. The relative risk of Alzheimer's disease was 0.95 (95 percent confidence interval, 0.70 to 1.29) in subjects with short-term use of NSAIDs, 0.83 (95 percent confidence interval, 0.62 to 1.11) in those with intermediate-term use, and 0.20 (95 percent confidence interval, 0.05 to 0.83) in those with long-term use. The risk did not vary according to age. The use of NSAIDs was not associated with a reduction in the risk of vascular dementia. CONCLUSIONS: The long-term use of NSAIDs may protect against Alzheimer's disease but not against vascular dementia. (+info)
Codon 311 (Cys --> Ser) polymorphism of paraoxonase-2 gene is associated with apolipoprotein E4 allele in both Alzheimer's and vascular dementias.
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The gene of an esterase enzyme, called paraoxonase (PON, EC.3.1.8.1.) is a member of a multigene family that comprises three related genes PON1, PON2, and PON3 with structural homology clustering on the chromosome 7.(1,2) The PON1 activity and the polymorphism of the PON1 and PON2 genes have been found to be associated with risk of cardiovascular diseases such as hypercholesterolaemia, non-insulin-dependent diabetes, coronary heart disease (CHD) and myocardial infaction.(3-8) The importance of cardiovascular risk factors in the pathomechanism of Alzheimer's disease (AD) and vascular dementia (VD)(9-13) prompted us to examine the genetic effect of PON2 gene codon 311 (Cys-->Ser; PON2*S) polymorphism and the relationship between the PON2*S allele and the other dementia risk factor, the apoE polymorphism in these dementias. The PON2*C and PON2*S allele frequencies were similar in both AD (25% and 75%) and VD groups (23% and 77%), respectively, compared with the controls (27% and 73%). The ratio of the PON2*S carriers was significantly higher among the apoE4 allele carrier AD (27%) and VD (25%) groups than in the control (12%). Our results indicate that the PON2*S and apoE4 alleles have interactive effect on the development of the two most common forms of dementias AD and VD, and further support the hypothesis that cardiovascular factors contribute to the development of AD. (+info)
Vascular dementia: a diagnosis running out of time.
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BACKGROUND: The concept of vascular dementia has a long history but its usefulness as a diagnostic category has been called into question. AIMS: To evaluate vascular disease as a risk factor for dementia and the interface between cerebrovascular pathology and Alzheimer's disease. METHOD: The literature on this topic was selectively reviewed and synthesised. RESULTS: Risk factors for cerebrovascular disease are also risk factors for dementia. However, the course of dementia, once it has developed, appears to be frequently determined by Alzheimer's disease. CONCLUSIONS: As a public health measure, modification of vascular risk represents a potentially powerful means to prevent dementia through delaying its onset. However, an effect on progression of dementia, once it has developed, has yet to be established. The traditional view of vascular dementia and Alzheimer's disease as distinguishable conditions is becoming steadily less tenable. (+info)
MR analysis of the substantia innominata in normal aging, Alzheimer disease, and other types of dementia.
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BACKGROUND AND PURPOSE: The substantia innominata can be visualized on coronal thin-section T2-weighted MR images. The purpose of this study was to investigate the morphologic changes of the substantia innominata in normal aging by using MR imaging and to determine whether the changes in this structure on MR images were specific to Alzheimer disease (AD). METHODS: The thickness of the substantia innominata was measured on the coronal T2-weighted image obtained through the anterior commissure in 39 healthy control subjects (age range, 25-86 y; mean age, 62 y); 39 patients with AD; and 36 patients with non-AD dementia, including vascular dementia, frontotemporal dementia, and Parkinson disease with dementia. RESULTS: In the control subjects, the thickness of the substantia innominata significantly decreased with age. Compared with age-matched control subjects, both patients with AD and patients with non-AD dementia had significant atrophy of the substantia innominata. The thickness of the substantia innominata significantly correlated with scores from the Mini-Mental State Examination in patients with AD but not in patients with non-AD dementia. CONCLUSION: MR analysis reveals age-related shrinkage of the substantia innominata. Atrophy of the substantia innominata, which reflects degeneration in the nucleus basalis of Meynert, is pronounced both in patients with AD and in those with non-AD dementia. MR imaging features in this structure may not be specific to AD. (+info)
Volumetric MRI study of the caudate nucleus in patients with dementia with Lewy bodies, Alzheimer's disease, and vascular dementia.
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OBJECTIVES: To determine whether parkinsonian symptoms in dementia with Lewy bodies (DLB) are associated with greater atrophy of the caudate nucleus in comparison with patients with Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: T1weighted MR scans were acquired in elderly patients with DLB, AD, VaD, and healthy controls. Normalised volumetric measurements of the caudate nucleus were obtained and parkinsonian symptoms rated using Hoehn and Yahr staging. RESULTS: There were no significant differences in the volume of the caudate nucleus between patients with dementia. However, the left caudate volume was significantly reduced in AD and DLB compared with controls. Parkinsonian symptoms did not correlate with caudate nucleus volume. CONCLUSIONS: Parkinsonian symptoms in DLB may be more closely coupled to neurochemical rather than structural changes in the caudate nucleus, and volumetric MRI analysis of caudate nucleus does not discriminate between patients with DLB, AD, and VaD. (+info)
Islington study of dementia subtypes in the community.
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BACKGROUND: Epidemiological studies of dementia subtypes have revealed widely varying distribution rates. There are almost no published community prevalence data for dementia with Lewy bodies (DLB) or the frontal lobe dementias (FLD). AIMS: To identify the distribution of dementia subtypes in a representative community population of older people. METHOD: People aged > or = 65 years in randomised enumeration districts in Islington, north London, were screened using a reliable and valid questionnaire. People screened as having dementia were assessed in detail and diagnoses were made according to standard diagnostic criteria. RESULTS: Of 1085 people interviewed, 107 (9.86%) met screening criteria for dementia. Diagnoses were made for 72 people (67.3%). Distribution of subtypes varied according to the criteria used; the best-validated criteria yielding: Alzheimer's disease 31.3%; vascular dementia 21.9%; DLB 10.9%; and FLD 7.8%. CONCLUSIONS: Alzheimer's disease is confirmed as the most common cause of dementia in older people, followed by vascular dementia. However, DLB and FLD occur sufficiently often to be seen frequently in clinical practice and should be incorporated into future editions of standard diagnostic criteria. (+info)
Hypertension and cerebral white matter lesions in a prospective cohort study.
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White matter lesions are frequently found on cerebral MRI scans of elderly people and are thought to be important in the pathogenesis of dementia. Hyper tension has been associated with the presence of white matter lesions but this has been investigated almost exclusively in cross-sectional studies. We studied prospectively the association of these lesions with the duration and treatment of hypertension. We randomly sampled 1077 subjects aged between 60 and 90 years from two prospective population-based studies. One-half of the study subjects had their blood pressure measured between 1975 and 1978 and the other half between 1990 and 1993. All subjects underwent 1.5 T MRI scanning; white matter lesions in the subcortical and periventricular regions were rated separately. Subjects with hypertension had increased rates of both types of white matter lesion. Duration of hypertension was associated with both periventricular and subcortical white matter lesions. This relationship was influenced strongly by age. For participants with >20 years of hypertension and aged between 60 and 70 years at the time of follow-up, the relative risks for subcortical and periventricular white matter lesions were 24.3 [95% confidence interval (CI) 5.1-114.8] and 15.8 (95% CI 3.4-73.5), respectively, compared with normotensive subjects. Subjects with successfully treated hypertension had only moderately increased rates of subcortical white matter lesions and periventricular white matter lesions (relative risk 3.3, 95% CI 1.3-8.4 and 2.6, 95% CI 1.0-6.8, respectively) compared with normotensive subjects. For poorly controlled hypertensives, these relative risks were 8.4 (95% CI 3.1-22.6) and 5.8 (95% CI 2.1-16.0), respectively. In conclusion, we found a relationship between long-standing hypertension and the presence of white matter lesions. Our findings are consistent with the view that effective treatment may reduce the rates of both types of white matter lesion. Adequate treatment of hypertension may therefore prevent white matter lesions and the associated cognitive decline. (+info)
Hypertensive pontine microhemorrhage.
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BACKGROUND AND PURPOSE: This study investigated whether the topography of hypertensive pontine microhemorrhages (hPMHs) resembles that of larger primary pontine hemorrhages. METHODS: Sixty-nine consecutive patients with small-vessel disease underwent imaging with gradient-echo MRI, and 27 patients with hPMH were detected. Lesion size and location along the rostrocaudal (longitudinal), lateral (coronal), and anteroposterior (sagittal) axes were determined. RESULTS: A total of 52 hPMHs were identified in the 27 patients (mean, 1.93+/-2.4 per patient). The lesions showed a nonrandom distribution, with a propensity to occur in the middle pons in the rostrocaudal axis, posterior half of the basis pontis in the anteroposterior axis, and central subdivision within the lateral axis. The area of hPMH ranged from 1.3 to 19.0 mm2 (mean, 5.06+/-3.72 mm2). The size of hPMH did not vary as a function of lesion location. CONCLUSIONS: Previous studies reported that primary pontine hemorrhages tend to occur in the middle pons and at the junction of basis pontis and tegmentum. Therefore, topographical correspondences between large and small pontine hemorrhages may provide evidence that the 2 lesions share some etiological basis. Further investigation may determine whether hPMHs portend future symptomatic primary pontine hemorrhages. (+info)