Relation between nicotine intake and Alzheimer's disease.

OBJECTIVE--To study the association between Alzheimer''s disease and nicotine intake through smoking. DESIGN--Population based case-control study. SETTING--City of Rotterdam and four northern provinces of The Netherlands. SUBJECTS--198 patients with early onset Alzheimer''s disease, 198 controls matched for age and sex, and families of 17 patients in whom Alzheimer''s disease was apparently inherited as an autosomal dominant disorder. MAIN OUTCOME MEASURES--Age of onset of dementia, relative risk of Alzheimer''s disease. RESULTS--89 of 193 patients with Alzheimer''s disease had a history of smoking compared with 102 of 195 controls. Among the patients and controls with a family history of dementia, smoking was significantly less common in those with dementia (40/95 with dementia v 55/96 controls; relative risk 0.35; 95% confidence interval 0.16 to 0.78). The risk of Alzheimer''s disease decreased with increasing daily number of cigarettes smoked before onset of disease (relative risk 0.3 in those smoking greater than 21/day v 1 in non-smokers). In six families in which the disease was apparently inherited as an autosomal dominant disorder, the mean age of onset was 4.17 years later in smoking patients than in non-smoking patients from the same family (p = 0.03). CONCLUSIONS--These findings suggest an inverse association between smoking and Alzheimer''s disease, although smoking cannot be advocated for other health reasons. We speculate that nicotine may have a role in the aetiology of both Alzheimer''s disease and Parkinson''s disease.     

Association of apolipoprotein E phenotypes with late onset Alzheimer's disease: population based study.

OBJECTIVE--To determine the association between the e4 allele of apolipoprotein E and Alzheimer''s disease in a randomly selected population sample. DESIGN--Cross sectional population based study. SUBJECTS--980 people aged 69 to 78 (349 men, 631 women). SETTING--Population of Kuopio, eastern Finland. MAIN OUTCOME MEASURES--Presence of e4 allele and diagnosis of Alzheimer''s disease by detailed neurological and neurophysiological evaluation. RESULTS--46 (4.7%) subjects were classified as having probable or possible Alzheimer''s disease. The frequency of the apolipoprotein E e4 allele was 0.359 in patients with Alzheimer''s disease and 0.165 subjects without dementia (P < 0.0001). The prevalence of Alzheimer''s disease was 2.9% in subjects with no e4 alleles, 7.6% in subjects with one e4 allele, and 21.4% in subjects with two e4 alleles of apolipoprotein E. CONCLUSIONS--Allele e4 of apolipoprotein is associated with Alzheimer''s disease in a dose-response fashion in a randomly selected elderly population.     

Epidemiology of Alzheimer's presenile dementia in Scotland, 1974-88.

OBJECTIVE--To describe the epidemiology of presenile Alzheimer''s disease in Scotland from 1974 to 1988. DESIGN--Retrospective review of hospital records of patients aged less than 73 years admitted to psychiatric hospital with various diagnoses of dementia. Diagnoses were classified by National Institute for Communicative Disorders and Stroke and Alzheimer''s Disease and Related Disorders Association Criteria and the Hachinski score. Completeness of the study sample was evaluated by scrutiny of neurology outpatient and general hospital records. SETTING--All general psychiatric hospitals in Scotland. SUBJECTS--All patients with onset of dementia aged 40-64. MAIN OUTCOME MEASURES--Probable and broad Alzheimer''s disease, sex of patient, age at onset. RESULTS--5874 psychiatric hospital records, 129 neurology outpatient records, and 89 records from non-psychiatric hospitals were examined. 317 patients met criteria for probable Alzheimer''s disease, 569 met criteria for broad Alzheimer''s disease, and 267 met those for multi-infarct dementia. Minimal incidences per 100,000 population aged 40-64 years were 22.6 (95% confidence interval, 20.2 to 25.2) and 40.5 (38.9 to 42.3) per 100,000 for probable and broad Alzheimer''s disease. In the 1981 census year the annual incidence of probable Alzheimer''s disease was 1.6 (1.0 to 2.6). Women were at greater risk with incidence rates for probable Alzheimer''s disease of 28.2 (24.5 to 32.4) per 100,000 compared with 16.5 (13.8 to 19.8) per 100,000 for men. The incidence per 100,000 for multi-infarct dementia was greater in men (25.1, 23.3 to 27.1) than women (13.4, 12.1 to 14.8). CONCLUSION--Female sex seems to be positively associated with development of Alzheimer''s disease before age 65 years.     

Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study.

OBJECTIVE: To determine the association between features of the insulin resistance syndrome and Alzheimer''s disease. DESIGN: Cross sectional population based study. SUBJECTS: 980 people aged 69 to 78 (349 men, 631 women). SETTING: Population of Kuopio, eastern Finland. MAIN OUTCOME MEASURES: Presence of features of the insulin resistance syndrome and diagnosis of Alzheimer''s disease by detailed neurological and neuropsychological evaluation. RESULTS: 46 (4.7%) subjects were classified as having probable or possible Alzheimer''s disease. In univariate analyses, apolipoprotein E4 phenotype (odds ratio; 95% confidence interval 3.24: 1.77 to 5.92), age (1.16; 1.05 to 1.29), low level of education (0.82; 0.72 to 0.93), low total cholesterol concentration (0.77; 0.59 to 1.00), high systolic blood pressure (1.01; 1.00 to 1.03), high fasting and 2 hour plasma glucose concentrations (1.11; 1.01 to 1.23 and 1.08; 1.03 to 1.13, respectively), high fasting and 2 hour insulin concentrations (1.05; 1.02 to 1.08 and 1.003; 1.00 to 1.01, respectively), and abnormal glucose tolerance (1.86; 1.23 to 2.80) were significantly associated with Alzheimer''s disease. In multivariate analysis including apolipoprotein E4 phenotype, age, education, systolic blood pressure, total cholesterol concentration, fasting glucose concentration, and insulin concentration, apolipoprotein E4 phenotype, age, education, total cholesterol, and insulin were significantly associated with Alzheimer''s disease. In 532 non-diabetic subjects without the e4 allele hyperinsulinaemia was associated with an increased risk for Alzheimer''s disease (prevalence of disease 7.5% v 1.4% in normoinsulinaemic subjects, P = 0.0004). In contrast, in the 228 with the e4 allele hyperinsulinaemia had no effect on the risk of disease (7.0% v 7.1%, respectively). CONCLUSION: Features of the insulin resistance syndrome are associated with Alzheimer''s disease independently of apolipoprotein E4 phenotype.     

Colonic Crohn's disease and use of oral contraception.

The prevalence of use of oral contraception before the onset of disease was established in 100 consecutive women attending follow up clinics for inflammatory bowel disease. A significant excess of women with Crohn''s disease confined to the colon had taken oral contraceptives in the year before developing symptoms (10/16 (63%] compared with women with small-intestinal Crohn''s disease (12/49 (24%); p less than 0.02) and women with ulcerative colitis (3/35 (9%); p less than 0.0005). When the patient groups were matched for age and year of onset of disease usage of oral contraception before the onset of disease was still more common among women with isolated colonic Crohn''s disease (9/12, 75%) than among those with ulcerative colitis (2/12 (17%); p less than 0.02) and was also more common than would be expected from reported figures for oral contraception in England and Wales (31.4% of women aged under 41; p less than 0.005). A survey of current patient records showed that isolated colonic disease was at least twice as common among women with Crohn''s disease (63/218, 29%) compared with men (25/181, 14%; p less than 0.001). These data support the suggestion made previously that oral contraceptives may predispose to a colitis that resembles colonic Crohn''s disease.     

ABCA1基因多态性R219K与帕金森症和阿尔兹海默症发病率的相关性研究

目的:探讨与研究三磷酸腺苷结合盒转运体A1 (Adenosine triphosphate (ATP)-binding cassette transporter A1)基因多态性R219K与帕金森症(Parkinson disease,PD)和阿尔兹海默症(Alzheimer disease,AD)发病率的相关性。方法:选择2016年2月到2019年8月在本院门诊与住院的帕金森症患者42例作为PD组,同期选择本院门诊与住院的阿尔兹海默症患者42例作为AD组,同期选择本院门诊健康体检者84例作为对照组。调查入选者的一般资料,检测三组血液样本的ABCA1基因多态性R219K情况并进行相关性分析。结果:AD组低密度脂蛋白(low-density lipoprotein,LDL-C)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)与尿酸(Uric acid,UA)均低于对照组,而高密度脂蛋白(high-density lipoprotein,HDL-C)、同型半胱氨酸(homocysteine,Hcy)值高于对照组(P0.05);AD组TC均低于PD组,而HDL高于PD组。PD患者HDL-C均低于对照组,而LDL、TC和TG与对照组无差异(P0.05),三组空腹血糖(Fasting blood glucose,FBG)值对比差异无统计学意义(P0.05)。PD组与AD组的ABCA1 R219K GA基因型、A等位基因频率都显著高于对照组(P0.05),PD组与AD组对比差异无统计学意义(P0.05)。在168例入选者中,直线相关分析显示ABCA1 R219K GA基因型与A等位基因与帕金森症或阿尔兹海默症发生有显著相关性(P0.05)。结论:ABCA1基因多态性R219K在帕金森症和阿尔兹海默症患者中比较常见,ABCA1 R219K GA基因型与A等位基因可诱发帕金森症和阿尔兹海默症的发生。     

Active Surveillance of Hansen's Disease (Leprosy): Importance for Case Finding among Extra-domiciliary Contacts

Hansen''s disease (leprosy) remains an important health problem in Brazil, where 34,894 new cases were diagnosed in 2010, corresponding to 15.3% of the world''s new cases detected in that year. The purpose of this study was to use home visits as a tool for surveillance of Hansen''s disease in a hyperendemic area in Brazil. A total of 258 residences were visited with 719 individuals examined. Of these, 82 individuals had had a previous history of Hansen''s disease, 209 were their household contacts and 428 lived in neighboring residences. Fifteen new Hansen''s disease cases were confirmed, yielding a detection rate of 2.0% of people examined. There was no difference in the detection rate between household and neighbor contacts (p = 0.615). The two groups had the same background in relation to education (p = 0.510), household income (p = 0.582), and the number of people living in the residence (p = 0.188). Spatial analysis showed clustering of newly diagnosed cases and association with residential coordinates of previously diagnosed multibacillary cases. Active case finding is an important tool for Hansen''s disease control in hyperendemic areas, enabling earlier diagnosis, treatment, decrease in disability from Hansen''s disease and potentially less spread of Mycobacterium leprae.     

Association of IRGM Gene Mutations with Inflammatory Bowel Disease in the Indian Population

Background

Mutations in the IRGM gene have been associated with Crohn''s disease in several populations but have not been explored in Indian patients with this disease. This study examined the association of IRGM mutations with ulcerative colitis and Crohn''s disease in Indian patients with inflammatory bowel disease.

Methods

The IRGM gene was amplified in four segments and Sanger-sequenced in 101 participants (42 Crohn''s disease, 39 ulcerative colitis, and 20 healthy controls). Ten single nucleotide polymorphisms (SNP) were genotyped in 1200 participants (352 Crohn''s disease, 400 ulcerative colitis, and 448 healthy controls) using Sequenom MassARRAY iPLEX. Disease associations were evaluated for each of the ten SNPs.

Results

Thirty one mutations were identified in the IRGM gene, of which two had not hitherto been reported (150226250- ss947429272 & 150227858- ss947429273). Ten SNPs (6 from the above and 4 from the literature) were evaluated. Significant associations with Crohn''s disease were noted with the T allele of rs1000113 (OR 1.46, 95% CI 1.12–1.90), T allele of rs9637876 (OR 1.25, 95% CI 1.005–1.561) and C allele of rs 13361189 (OR 1.33, 95% CI 1.07–1.669). Two SNPs – rs11747270 and rs180802994 – did not exhibit Hardy-Weinberg equilibrium but were associated with both Crohn''s disease and ulcerative colitis in this population. The remaining SNPs did not show significant associations with either Crohn''s disease or ulcerative colitis.

Conclusions

Association of IRGM gene SNPs with Crohn''s disease is reported for the first time in Indian patients. We also report, for the first time, an association of rs 9637876 in the IRGM gene with Crohn''s disease.     

A community survey of Parkinson's disease.

In a rural community of 80,000 people 69 patients were identified as having a diagnosis of Parkinson''s disease. After interview and examination we found that 55 met the generally accepted diagnostic criteria for Parkinson''s disease, 4 had possible Parkinson''s disease, 6 had essential tremor, 2 had dementia and 2 had other conditions. The patients with Parkinson''s disease had clinical and epidemiologic characteristics similar to those of patients in previous, mainly hospital-based, studies. These characteristics included mean age at onset (63 years), frequency rate of dementia (20%) and presence of postural tremor (11%). The pattern of treatment varied, some patients receiving more medication than is usual for the severity of their illness, and some patients receiving less than is usual. Parkinson''s disease can be difficult to diagnose and manage because of the clinical variation between patients in presentation and response to treatment.     

Diagnostic value of 9 am plasma adrenocorticotrophic hormone concentrations in Cushing's disease.

Morning plasma adrenocorticotrophic hormone (ACTH) concentrations were measured in 58 normal subjects and seven patients with pituitary-dependent Cushing''s syndrome (Cushing''s disease). Particular note was taken of the time of venepuncture. The range of values for the normal subjects irrespective of timing was 9-77 ng/l. The range between 9 0 am and 9 30 am was 9-24 ng/l. In the patients with Cushing''s disease the ACTH concentrations were in the range 39-109 ng/l. To distinguish patients with Cushing''s disease from normal subjects it is therefore important to define accurately the 9 am normal range, since these results show no overlap.     

Detection of inflammatory bowel disease in adults and children: evaluation of a new isotopic technique.

The distribution of radioactivity after the oral administration of sucralfate labelled with technetium-99m was studied in 33 patients with Crohn''s disease (13 adults, 20 children), 10 with ulcerative colitis (four adults), and 29 controls (23 with upper intestinal disease, four irritable bowel, one hypolactasia, and one malrotation of the gut). Positive scans were obtained in all patients with ulcerative colitis and 29 of 31 with active Crohn''s disease. The scans of two patients with inactive Crohn''s disease were negative. There were two false negative scans in patients with Crohn''s colitis and one false positive scan. Overall, sensitivity was 95% and specificity 97%. Comparison with radiology in 39 patients showed similar distribution of disease in 24 and more extensive disease in 12. The scan was inexpensive, simple to perform, well tolerated, allowed small and large bowel to be visualised simultaneously, and used a lower dose of radiation than barium studies. It may prove useful as a screening test for inflammatory bowel disease and in the serial assessment of disease activity.     

Computed tomography of abdomen in staging and clinical management of lymphoma.

During July 1976 to Demember 1977, 150 patients with Hodgkin''s disease and 138 with non-Hodgkin''s lymphoma were examined by computed tomography (CT). In 45 cases 50 repeat examinations were conducted. Concurrent laparotomy and lymphography were performed on 68 and 56 patients respectively. The overall incidence of false-positive CT examinations as confirmed by laparotomy was 7.4%. In 18 patients with non-Hodgkin''s lymphoma in the abdomen there was good correlation between the two techniques. Of the 50 patients with Hodgkin''s disease who underwent laparotomy, 17 had splenic disease and 14 minimally enlarged lymph nodes in 20 areas; CT, however, detected only four diseased spleens and five minimally enlarged lymph nodes. Nevertheless, CT often detected enlarged lymph nodes missed by lymphography and was 23% more efficient than lymphography in detecting unsuspected disease. CT also detected unsuspected disease in patients with relapse of lymphoma. CT may replace other non-invasive investigations of abdominal disease in patients with lymphoma and give a reliable guide to prognosis. It does not, however, eliminate the need for laparotomy in staging Hodgkin''s disease.     

Primary hypogammaglobulinaemia and arthritis.

Arthritis may be the first clinical manifestation of primary hypogammaglobulinaemia. In 16 years of 281 patients who had immunodeficiency, 30 had arthritis at presentation. It was more common in Bruton''s disease (15 (22%) of 69 patients) than in other forms of immunodeficiency (15 (7%) of 212 patients). Non-septic arthritis was more prevalent than septic arthritis, particularly monoarticular arthritis in Bruton''s disease and pauciarticular disease in common variable immunodeficiency. Boys in whom a diagnosis of Bruton''s disease was delayed were likely to develop recurrent infections complicated by arthritis. The measurement of serum immunoglobulin concentrations readily differentiates immunodeficiency from conditions such as Still''s disease and dictates subsequent management.     

Immunotherapy of Crohn's disease.

Although the initiating events of Crohn''s disease are unknown, models of experimental colitis have provided new insights in the immunologically mediated pathways of mucosal inflammation. In Crohn''s disease activated mucosal T lymphocytes produce proinflammatory cytokines within the mucosal compartment. With this understanding, there has been a shift in past years from the use of unspecific anti-inflammatory agents (corticosteroids, aminosalicylates) to the use of immunomodulatory drugs (azathioprine, methotrexate). Moreover, novel strategies have been designed for specific targets in Crohn''s disease, in particular T lymphocytes and cytokines. In an open label study treatment of steroid-refractory Crohn''s disease with anti- CD4+ antibodies was well tolerated and showed clinical benefit. However, a sustained depletion of the CD4+ cells precluded further clinical trials. In controlled clinical studies, anti-tumour necrosis factor (TNF-alpha) antibodies induced complete remissions and few side effects were observed. One study suggested efficacy in active Crohn''s disease of recombinant interleukin-10. Long term treatment studies will have to answer questions about the indications for use, benefit and toxicity. Altogether, these results hold promise for future management of Crohn''s disease, where disease-modifying interventions and strategies that effectively maintain disease remission will play a key role.     

Risk of second primary cancers after Hodgkin's disease by type of treatment: analysis of 2846 patients in the British National Lymphoma Investigation.

OBJECTIVE--To analyse the risk of second primary cancers during long term follow up of patients with Hodgkin''s disease. DESIGN--Cohort study. SETTING--The British National Lymphoma Investigation (a collaborative group of over 60 participating centres in Britain treating lymphomas). PATIENTS--2846 patients first treated for Hodgkin''s disease during 1970-87, for whom follow up was complete in 99.8%. MAIN OUTCOME MEASURES--Second primary cancers; uniform pathology reviews confirmed the diagnosis of Hodgkin''s disease and of second primary non-Hodgkin''s lymphomas. RESULTS--113 second primary cancers occurred. Relative risk of cancer other than Hodgkin''s disease was 2.7 (95% confidence interval 2.3 to 3.3) compared with the general population, with significant risk of leukaemia (16.0(9.1 to 26.0)); non-Hodgkin''s lymphoma (16.8(9.8 to 26.9)); and cancers of the colon (3.2 (1.4 to 6.2)), lung (3.8 (2.6 to 5.4)), bone (15.1 (1.8 to 54.7)), and thyroid (9.4 (1.1 to 33.9)). Absolute excess risk associated with treatment was greater for solid tumours than for leukaemia and lymphomas. Relative risk of leukaemia increased soon after treatment, reaching a peak after five to nine years. It was increased substantially after chemotherapy (27.9 (12.7 to 52.9)), combined treatment with radiotherapy and chemotherapy (21.5 (7.9 to 46.8)), and relative to number of courses of chemotherapy but was not significantly increased after radiotherapy (2.5 (0.1 to 14.1)). Relative risk of non-Hodgkin''s lymphoma increased in the first five years after treatment and remained high but showed no clear relation with type or extent of treatment. Relative risk of solid tumours was less raised initially but increased throughout follow up and for lung cancer 10 years or more after entry was 8.3 (4.0 to 15.3). The risk of solid tumours increased after treatments including radiotherapy and after chemotherapy alone. The risk after chemotherapy increased significantly with time since first treatment. CONCLUSION--The risk of solid cancer, not of leukaemia, is the major long term hazard of treatment for Hodgkin''s disease, and this seemed to apply after chemotherapy as well as after radiotherapy. These risks of second cancers are important in choice of treatment and in follow up of patients, but they are small compared with the great improvements in survival which have been brought about by modern therapeutic methods for Hodgkin''s disease.     

Relation between severity of Alzheimer's disease and costs of caring

BACKGROUND: Data from the Canadian Study of Health and Aging (CSHA) were used to examine the relation between severity of Alzheimer''s disease, as measured by the Mini-Mental State Examination (MMSE), and costs of caring. METHODS: The CSHA was a community-based survey of the prevalence of dementia, including subtypes such as Alzheimer''s disease, among elderly Canadians. Survey subjects with a diagnosis of possible or probable Alzheimer''s disease were grouped into disease severity levels of mild (MMSE score 21-26), mild to moderate (MMSE score 15-20), moderate (MMSE score 10-14) and severe (MMSE score below 10). Components of care available from the CSHA were use of nursing home care, use of medications, use of community support services by caregivers and unpaid caregiver time. Costs were calculated from a societal perspective and are expressed in 1996 Canadian dollars. RESULTS: The annual societal cost of care per patient increased significantly with severity of Alzheimer''s disease. The cost per patient was estimated to be $9451 for mild disease, $16,054 for mild to moderate disease, $25,724 for moderate disease and $36,794 for severe disease. Institutionalization was the largest component of cost, accounting for as much as 84% of the cost for people with severe disease. For subjects living in the community, unpaid caregiver time and use of community services were the greatest components of cost and increased with disease severity. INTERPRETATION: The societal cost of care of Alzheimer''s disease increases drastically with increasing disease severity. Institutionalization is responsible for the largest cost component.     

Contribution of Step Length to Increase Walking and Turning Speed as a Marker of Parkinson’s Disease Progression

When increasing ambulation speed in Parkinson’s disease, step cadence increases more than stride length, indicating movement scaling difficulties that affect step generation in particular. We investigated whether step length variation when increasing ambulation speed was related to disease progression. Patients with Parkinson’s disease (N = 39) and controls (N = 152) performed two timed ambulation tasks: at a ''free'' (self-selected) pace and then at ''maximal'' speed. The total number of steps (including during turns) and time to complete the task were clinically measured. The relative contribution of step length and cadence to increased ambulation speed was determined using two methods: the ratios of change in step length or in cadence to the change in ambulation speed, and the step length index. While the relative contribution of step length and cadence to increased ambulation speed was independent of age in both control and patient groups, in Parkinson’s disease there was a negative correlation between time from diagnosis and the ratio of change in step length to change in ambulation speed (R = 0.54; p = 0.0004) and the step length index (R = 0.56, p = 0.0002). In parallel, there was a positive correlation between time since diagnosis and the ratio of change in cadence to change in ambulation speed (R = 0.57; p = 0.0002). The relative contribution of step length and cadence to increased ambulation speed is age invariant but a marker of Parkinson''s disease advancement, and can be easily determined in the clinical setting.     

Did Osler suffer from "paranoia antitherapeuticum baltimorensis"?: A comparative content analysis of The Principles and Practice of Medicine and Harrison's Principles of Internal Medicine, 11th edition

One of the most important legacies of Sir William Osler was his textbook The Principles and Practice of Medicine. A common criticism of the book when it was first published was its deficiency in the area of therapeutics. In this article, the 1st edition of The Principles and Practice of Medicine is compared with the 11th edition of Harrison''s Principles of Internal Medicine. The analysis focuses on the treatment recommendations for 4 conditions that were covered in both books (diabetes mellitus, ischemic heart disease, pneumonia and typhoid fever). Osler''s textbook dealt with typhoid fever and pneumonia at greater length, whereas Harrison''s placed more emphasis on diabetes mellitus and ischemic heart disease. Notwithstanding Osler''s reputation as a therapeutic nihilist, the 2 books devoted equivalent space to treatment (in terms of proportion of total sentences for the conditions). For all conditions except ischemic heart disease, Osler concentrated on general measures and symptomatic care. Throughout Osler''s textbook numerous negative comments are made about the medicinal treatment of various conditions. A more accurate statement about Osler''s therapeutic approach was that he was a "medicinal nihilist." His demand for proof of efficacy before use of a medication remains relevant.     

No association of PTPN22 polymorphisms with susceptibility to ocular Behcet's disease in two Chinese Han populations

Background

Behcet''s disease is known as a recurrent, multisystem inflammation and immune-related disease. Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and polymorphisms of the PTPN22 gene have been shown to be associated with various immune-related diseases. The present study was performed to assess the association between PTPN22 polymorphisms and Behcet''s disease in two Chinese Han populations.

Methodology/Principal Findings

A total of 516 patients with ocular Behcet''s disease and 690 healthy controls from two Chinese Han populations were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for three single nucleotide polymorphisms (SNPs). Hardy-Weinberg equilibrium was tested using the χ² test. Genotype frequencies were estimated through direct counting. Allele and genotype frequencies were compared between patients and controls using logistic regression analysis. The results revealed that there was no association between the tested three PTPN22 SNPs (rs2488457, rs1310182 and rs3789604) and ocular Behcet''s disease (p>0.05). Categorization analysis according to the clinical features did not show any association of these three polymorphisms with these parameters (p>0.05).

Conclusions/Significance

The investigated PTPN22 gene polymorphisms (rs2488457, rs1310182 and rs3789604) were not associated with ocular Behcet''s disease in two Chinese Han populations, and showed that it may be different from other classical autoimmune diseases. More studies are needed to confirm these findings for Behcet''s disease in other ethnic backgrounds.     

Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal,population based study

Objective To examine the relation of midlife raised blood pressure and serum cholesterol concentrations to Alzheimer''s disease in later life.Design Prospective, population based study.SettingPopulations of Kuopio and Joensuu, eastern Finland.ParticipantsParticipants were derived from random, population based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average of 21 years'' follow up, a total of 1449 (73%) participants aged 65-79 took part in the re-examination in 1998.Results People with raised systolic blood pressure (⩾160 mm Hg) or high serum cholesterol concentration (⩾6.5 mmol/l) in midlife had a significantly higher risk of Alzheimer''s disease in later life, even after adjustment for age, body mass index, education, vascular events, smoking status, and alcohol consumption, than those with normal systolic blood pressure (odds ratio 2.3, 95% confidence interval 1.0 to 5.5) or serum cholesterol (odds ratio 2.1, 1.0 to 4.4). Participants with both of these risk factors in midlife had a significantly higher risk of developing Alzheimer''s disease than those with either of the risk factors alone (odds ratio 3.5, 1.6 to 7.9). Diastolic blood pressure in midlife had no significant effect on the risk of Alzheimer''s disease.Conclusion Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increase the risk of Alzheimer''s disease in later life.

What is already known on this topic

Vascular risk factors may play an important part as risk factors for Alzheimer''s diseaseNo population based studies have evaluated prospectively the impact of both midlife blood pressure and cholesterol concentration in both men and women on the subsequent development of Alzheimer''s disease

What this study adds

Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increased the risk of Alzheimer''s disease in later lifeRaised systolic blood pressure and hypercholesterolaemia may have a role in the pathogenesis of Alzheimer''s disease; more emphasis should be placed on identification and appropriate treatment of these conditions