血压、白质损伤和颞叶内侧萎缩之间的联系

Background: Blood pressure level is associated with the risk of clinical Alzheimer disease (AD), yet the underlying mechanisms are unclear. High blood pressure levels may cause cerebral small- vessel pathology, which contributes to cognitive decline in patients with AD. Alternatively, in persons with high blood pressure, increased numbers of neurofibrillary tangles and amyloid plaques at autopsy have also been observed, suggesting direct links between blood pressure and AD. Abstract:Objective: To investigate the association of blood pressure and markers of small- vessel disease (white matter lesions [WMLs] on MRI)- with hippocampal and amygdalar atrophy on MRI - potential in vivo indicators of Alzheimer pathology. Methods: In 1995 to 1996, 511 nondemented elderly subjects (age 60 to 90) underwent MRI. The extent of WMLs was assessed, and volumes of the hippocampus and amygdala were measured. Blood pressure levels were assessed at the time of MRI and 5 years before the MRI. Results: Higher diastolic blood pressure 5 years before MRI predicted more hippocampal atrophy in persons untreated for hypertension (per SD increase - 0.10 mL [95% CI - 0.19 to - 0.02, p = 0.02]). Conversely, in persons treated for hypertension, a low diastolic blood pressure was associated with more severe atrophy. Persons with more WMLs on MRI more often had severe atrophy of the hippocampus and amygdala. Conclusion: Blood pressure and indicators of small- vessel disease in the brain may be associated with atrophy of

朊病毒蛋白基因中缩胆囊素反复序列的插入与早发型痴呆的相关性研究

Objectives: The most common familial early onset dementia mutations are found in the genes involved in Alzheimer’ s disease; the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and 2) genes; the prion protein gene (PRNP) may be involved. Methods: Following identification of a two octapeptide repeat insertion in PRNP, we conducted a meta analysis to investigate the relation of number of PRNP octapeptide repeats with age at disease onset and duration of illness; identifying 55 patients with PRNP octapeptide repeat insertions. We used a linear mixed effects model to assess the relation of number of repeats with age at disease onset, and studied the effect of the number of inserted octapeptide repeats on disease duration with a Cox proportional hazards regression analysis. Results: We found an increasing number of repeats associated with younger age at onset (p < 0.001). Duration of the disease decreased significantly with the length of the octapeptide repeat (p < 0,001) when adjusting for age at onset. Conclusions: Our findings showsignificant inverse associations of the length of the PRNP octapeptide repeat with age at disease onset and disease duration in the spongiform encephalopathies.

高同型半胱氨酸血症、妊娠并发症及其研究的时间选择

OBJECTIVE: To assess associations between vitamin-dependent homocysteine me ta bolism and vascular-related pregnancy complications by considering interval bet ween delivery and postpartam investigation and maternal age. METHODS: Casecontro l study performed at the University Medical Center Nijmegen in the Netherlands. Patients had experienced pregnancy-induced hypertension (n = 37), preeclampsia (n = 144), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 104), recurrent early pregnancy loss (n = 544), abruptio placentae (n = 135), intrauterine growth restriction (n = 144), or intrauterine fetal death (n = 104) . Controls comprised 176 women with uncomplicated obstetric histories. Oral meth ionine loading tests and fasting vitamin profiles were performed more than 6 wee ks after delivery. Odds ratios and 95%confidence intervals were calculated afte r logistic regression analysis. RESULTS: Hyperhomocysteinemia was associated wit h an approximately 2-fold to 3-fold increased risk for pregnancy-induced hype rtension, abruptio placentae, and intrauterine growth restriction. Cobalamin def iciency was associated with HELLP syndrome, abruptio placentae, intrauterine gro wth restriction, and intrauterine fetal death. Pyridoxal 5phosphate deficiency i ncreased the risk for pregnancy-induced hypertension 4-fold. These association s lost their significance after adjustment for time interval and maternal age. H igh red cell folate was associated with a decreased risk for abruptio placentae and intrauterine growth restriction. An increased creatinine concentration was a ssociated with pregnancy-induced hypertension, preeclampsia, HELLP syndrome, an d abruptio placentae. CONCLUSION: Hyperhomocysteinemia and vitamin deficiencies are largely determined by the interval between delivery and postpartum investiga tion and by maternal age. Time interval and maternal age should be considered in the risk estimation for vascular-related pregnancy complications.

结合临床风险因素和血清胆红素水平来预测新生儿高胆红素血症

Objectives: (1) To validate a previously reported risk index for predicting total serum bilirubin (TSB) levels of 25 mg/dL (428 μmol/L) or higher; (2) to combine a subset of this index with TSB levels measured at less than 48 hours to predict subsequent TSB levels of 20 mg/dL (342 μmol/L) or higher. Design: Nested case-control study using electronic and paper records (study 1). Retrospective cohort study using electronic records only (study 2). Setting: Northern California Kaiser Permanente hospitals. Patients: Subjects for both studies were newborns weighing 2000 g or more and of 36 weeks’or more gestation. The validation study included 67 cases born 1997-1998 who developed TSB levels of 25 mg/dL or higher at less than 30 days and 208 randomly selected control subjects. Subjects for study 2 were 5706 newborns who both were discharged from the hospital and had a TSB level measured at less than 48 hours. Results: The risk index performed similarly in the validation group, born in 1997-1998, and the derivation group, born in 1995-1996 (area under the receiver operating characteristic curve = 0.83 vs 0.84). Of the 5706 newborns with TSB levels measured before 48 hours, 270 (4.7%) developed a TSB level of 20 mg/dL or higher. Of these, 254 (94%) had a TSB level at the 75th percentile or higher at less than 48 hours. The risk index improved prediction over the TSB level alone, largely owing to the effect of gestational age. For example, for those with a TSB level at the 95th percentile or higher at less than 48 hours, the risk increased from 9%for newborns born at 40 weeks’or more gestation to 42%for those born at 36 weeks. Conclusion: Clinical risk factors significantly improve prediction of subsequent hyperbilirubinemia compared with early TSB levels alone, especially in those with early TSB levels above the 75th percentile.

脑白质损害与痴呆的发病风险

Objective: To smtudy the association between white matter lesions (WML) in spe cific locations and the risk of dementia. Design: The Rotterdam Scan Study, a pr ospective population based cohort study. We scored periventricular and subcortic al WML on magnetic resonance imaging and observed participants until January 200 2 for incident dementia. Setting: General population. Participants: We included 1077 people aged 60 to 90 years who did not have dementia at baseline. Main Outc ome Measure: Incident dementia by Diagnostic and Statistical Manual of Mental Di sorders, Third Edition (DSM III R) criteria. Results: During a mean follow up of 5.2 years, 45 participants developed dementia. Higher severity of periventric ular WML increased the risk of dementia, whereas the association between subcort ical WML and dementia was less prominent. The adjusted hazard ratio of dementia for each standard deviation increase in periventricular WML severity was 1.67 (9 5%confidence interval, 1.25-2.24). This increased risk was independent of othe r risk factors for dementia and partly independent of other structural brain cha nges on magnetic resonance imaging. Conclusion: White matter lesions, especially in the periventricular region, increase the risk of dementia in elderly people.

中国原发性高血压患者中脂蛋白基因S447X多态性与脂蛋白脂质及血压水平的相关性

Objective: To investigate the association between the S447X polymorphis m of th e lipoprotein lipase (LPL) gene and lipoprotein lipid and blood pressure (BP) le vels in 904 Chinese subjects with essential hypertension. Method: Five hundred a nd sixty-three male and 341 female patients (aged 35-69 years) were randomly s elected from hypertensive patients diagnosed in the Community-based Comprehensi ve Studies on Prevention and Control of Hypertension Project in China (CCPACH) a nd not treated with antihypertensive medications for at least 2 weeks immediatel y before blood collection. Results: After multivariate adjustment for age, body mass index (BMI), smoking status, alcohol intake and serum glucose, the X447 all ele was significantly associated with low triglyceride, log triglyceride: high- density lipoprotein (HDL)-cholesterol ratio and high HDL-cholesterol levels co mpared with the S447S genotype, but not with BP levels in the whole study popula tion. However, upon stratification for dyslipidemic status, the X447 allele was associated with higher systolic blood pressure (SB P) (P< 0.05) and pulse pressure (PP) (P< 0.05) compared with the S447S genotype after multivariate adjustment in dyslipidemic subjects, but not in those without dyslipidemia. A statistically significant interaction between the LPL S447X pol ymorphism and dyslipidemic status was observed for SBP and PP levels, suggesting that dyslipidemic status might modify the effect of the LPL S447X polymorphismo n BP levels. Conclusions: Our findings suggest that a high concentration of trig lyceride and/or low concentration of HDL-cholesterol are associated with high S BP and PP in hypertensive patients with the X447 allele of the LPL gene.

普通人群中帕金森综合征和帕金森病的发病率:鹿特丹研究

Objective: To investigate the incidence of parkinsonism and Parkinson disease (PD) in the general population using inperson screening along with clinical data . Methods: In the Rotterdam study, a prospective population based cohort study of people aged ≥55 years, the authors assessed age and sex specific incidence r ates of parkinsonism and PD among 6,839 participants who were free of parkinsoni sm at baseline. Case finding involved in person screening at baseline and two f ollow up visits, and additional information was obtained through continuous mon itoring of the cohort by computer linkage to general practitionersand pharmacy records. Results: After a mean follow up period of 5.8 years, 132 subjects wit h incident parkinsonism were identified, of whom 67 (51%) had PD. The incidence of parkinsonism and PD increased with age, with incidence rates for PD increasi ng from 0.3 per 1000 person years in subjects aged 55 to 65 years, to 4.4 per 1 000 person years for those aged ≥85 years. The overall age adjusted incidence rate of any parkinsonism was not different in men and women, but men seem to ha ve a higher risk for PD (male to female ratio, 1.54; 95%CI, 0.95 to 2.51). Co nclusion: Incidence rates for parkinsonism and Parkinson disease were higher tha n those reported by most previous studies, possibly because of the authorsinte nsive case finding methods involving in person screening.