Independent Risk Factor For Alzheimer's Disease Research Articles

Incidence and etiology of dementia in a large elderly Italian population

To estimate age- and sex-specific incidence of dementia, Alzheimer disease (AD), and vascular dementia (VaD) in the Conselice Study of Brain Aging, an Italian prospective population-based study, and to assess whether poor education is a risk factor for dementia. In 1999 to 2000, the baseline study identified a dementia-free cohort of 937 subjects aged 65 years and older who were reexamined in 2003 to 2004 using a two-phase procedure. Information was obtained for 91% of the subjects at risk; 115 incident cases of dementia were identified. Incidence rates per 1,000 person-years were 37.8 (95% CI = 30.0 to 47.7) for dementia, 23.8 (95% CI = 17.3 to 31.7) for AD, and 11.0 (95% CI = 7.2 to 16.9) for VaD. This translates into more than 400,000 new cases of dementia expected per year in Italy. Increasing age was an independent risk factor for both AD and VaD. Poor education was an independent risk factor for AD but not VaD. Sex did not affect dementia risk. In this Italian population-based cohort, incidence of dementia increased with age, and Alzheimer disease (AD) was the most frequent type of dementia. Poor education was associated with a higher risk of AD. Our incidence rates are higher than previously reported in Italy, and provide new estimates for projection of future burden of disease in Italy.

Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism and risk of Alzheimer's disease in Italians

Monocyte chemoattractant protein-1 (MCP-1) is a key molecule for monocyte chemotaxis and tissue extravasation and for the modulation of leukocyte function during inflammation. Upregulation of MCP-1 may occur in the brain of subjects affected by Alzheimer's disease (AD) and MCP-1 levels in plasma and cerebrospinal fluid have been proposed as biological markers for the inflammatory process that accompanies AD pathogenesis. Importantly, serum levels and biological activity of MCP-1 protein are strongly influenced by a single nucleotide polymorphism occurring at position −2518 of the MCP-1 gene promoter. A recent study has investigated the possible association between this gene polymorphism and AD in a Spanish population, with negative results. Here, we performed a case–control study to test whether the risk for AD might be influenced by the −2518 A/G polymorphism of the MCP-1 gene in an ethnically homogeneous Italian population. The GG genotype and the G allele of the MCP-1 gene polymorphism were significantly more common in the AD group than in control individuals ( P<0.0001). A logistic regression analysis indicated that the GG genotype was an independent risk factor for AD in our population. This effect was not influenced by the presence of the APOE ε4 high-risk allele, nor by the presence of other gene variations associated with a pro-inflammatory phenotype. These findings indicate that the −2518 A/G polymorphism of the MCP-1 gene is associated with AD in Italians and confirm that inflammatory gene variations may be important contributors in the development and progression of neurodegenerative disorders.

Tumour necrosis factor-α gene polymorphisms and Alzheimer's disease

Recent findings suggest that production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-α), is increased in the brains of people with Alzheimer's disease (AD). We used direct sequencing methods on a section of the enhancer/promoter region and on a smaller fragment located 10.5 kb upstream of the TNF-α gene to respectively examine TNF-α polymorphisms and TNF-a and -b microsatellite alleles in a cohort of 235 post-mortem confirmed AD and 130 control cases. None of the TNF-α point mutations or microsatellite alleles investigated proved to be independent risk factors for AD. However, when −308/A, −238/G and TNF-a2 were examined as a 2-1-2 haplotype, we observed that the absence of that haplotype was significantly associated with AD ( P=0.014, Fisher's exact test) suggesting that the 2-1-2 haplotype may be protective against AD.

The role of cerebrovascular disease in dementia.

Improvements in health care over the last 50 years have lengthened average life expectancy significantly, resulting in considerable growth of the population over 65 years of age. With increased age, however, comes an increased risk for Alzheimer's disease (AD), and the prevalence of AD is predicted to reach epidemic proportions by the later half of the 21st century. The prevalence of cerebrovascular disease also increases with age, and recent evidence suggests that cerebrovascular risk factors such as hypertension and hypercholesterolemia also increase an individual's risk for AD, suggesting a potential interaction between these two very common disorders. The potential impact of cerebrovascular disease on general cognitive health is not yet well understood, but is now being actively explored and clarified. Cerebrovascular disease may manifest itself in many ways, and this review begins by discussing the possible spectrum of brain injury associated with common cerebrovascular risk factors. The prominent role of brain imaging to detect clinically silent cerebrovascular disease is recognized and reviewed. The neuropsychological consequences of cerebrovascular disease across the cognitive spectrum is also reviewed, including potential mechanisms by which cerebrovascular disease may interact with AD to increase the expression or hasten the progression of dementia. Cerebrovascular risk factors, common to the elderly, lead to pernicious brain injury and subtle cognitive impairment that most probably places the individual at greater lifetime risk for dementia. The cause of dementia among individuals with cerebrovascular disease, however, remains AD. Recognition of the potential role of cerebrovascular disease as an independent risk factor for AD offers the possibility of primary prevention through treatment of well-recognized risk factors and deserves further study. In the meantime, clinicians presented with an individual suffering from a slowly progressive dementia and findings of clinically silent cerebrovascular brain injury should recognize the potential role of cerebrovascular disease in the dementia process but not ignore the likely overwhelming effects of AD and treat appropriately.

Relationship between blood pressure and Alzheimer's disease in Linxian County, China

To investigate the relationship between hypertension and Alzheimer's disease(AD) and the change of Alzheimer's patients' blood pressure(BP) before and after the onset of AD, we conducted this epidemiological study. Subjects for this study were individuals who participated in a large scale, randomized controlled trial of nutritional intervention from 1984 to1991. Participants were initially screened for dementia using Chinese Mini-Mental State Examination (CMMS) and Activities of Daily Living (ADL). Positive subjects were subsequently administered a detailed neuropsychological and neurobehavioral examination. The diagnosis of AD was made by a consensus conference of psychiatrists using Diagnostic And Statistical Manual Of Mental Disorders-Fourth Edition(DSM-IV) criteria. 16 488 subjects were examined and 301 were diagnosed as AD. We compared the prevalence of AD in different populations that were stratified with 1984's systolic or diastolic blood pressure(those four stratifications being high blood pressure, borderline blood pressure, normal, low blood pressure), and compared the change of blood pressure of 301 AD patients between 1984 and 1999–2000, which is before and after the onset of AD respectively. Multiple Logistic Regression (1:1 nested case-control study) was used to assess if hypertension is an independent risk factor for AD, and Trend test was used to assess the relationship between blood pressure and AD. Here we demonstrate that there was a significant difference in AD prevalence among different populations stratified by systolic or diastolic blood pressure (P < 0.01).The prevalence is highest in hypertension group, and lowest in hypotension group. Multiple Logistic Regression identified high blood pressure as a risk factor for AD (OR = 1.97, 95%CI:1.09–3.54, P = 0.02). Trend test showed that there is a significant dose-response relationship between blood pressure and AD (P < 0.0002). For hypertensive AD patients, there was no significant difference in systolic blood pressure(SBP) before and after the onset of AD, but diastolic blood pressure(DBP) decreased dramatically after the onset of AD (P < 0.01), howerver, the result also showed that DBP decrease occurred in the non-demented group. Based on this, we think the DBP decrease is not related to AD. We further investigated whether BP values differed crossed-sectionally between the AD-patients and non-demented individuals. We found that regardless of SBP or DBP, the BP values of the AD group were all significantly higher than that of non-demented. In summary, these data suggest there is a strong relationship between hypertension and AD; however, the mechanism remains to be studied.