Maternal serum screening for Down's syndrome in early pregnancy.

The possibility of improving the effectiveness of antenatal screening for Down''s syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Down''s syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Down''s syndrome in the United Kingdom from about 900 a year to about 350 a year.     

Screening for Down's syndrome in the North East Thames region.

The suggested strategies for a screening programme for Down''s syndrome by maternal serum alpha fetoprotein concentration were examined and tested on the experience of the North East Thames Regional. Screening by maternal serum alpha fetoprotein concentration may be used to identify pregnancies at increased risk, but this is useful only in women aged over 32 whose collective risk is greater than one in 200. The absolute probability of carrying babies with Down''s syndrome for individuals in this high risk group can then be calculated and used to decide whether further diagnosis by amniocentesis is desired.     

Screening for Down's syndrome based on individual risk.

OBJECTIVE--To evaluate the effectiveness of biochemical screening of individual pregnancies for Down''s syndrome risk. DESIGN--Retrospective determination of risk. SETTING--Obstetric and cytogenetic services in Tayside, Scotland. SUBJECTS--3436 pregnant women who had screening for neural tube defects in the second trimester during November 1988 to March 1990 and whose pregnancies were dated by ultrasonography. Three women with pregnancies associated with Down''s syndrome reported later in 1990. MAIN OUTCOME MEASURES--Individual risk calculated from age at estimated date of delivery; chorionic gonadotrophin and alpha fetoprotein concentrations in serum samples obtained at precisely determined gestational ages in second trimester. Results of karyotype determination and outcome of pregnancy. RESULTS--During November 1988 to March 1990 karyotypes were determined for 5% of pregnancies for reasons of maternal age and genetic history and one of the eight affected fetuses was detected. Individual risk could not be calculated for 347 pregnancies, but screening on this basis would have detected five of the cases and required screening in 194 out of 3089 (6.3%) pregnancies; all three affected pregnancies reported later in 1990 would also have been detected, giving a success rate of 73% (95% confidence interval 39% to 94%). The age distribution of women according to individual risk suggests that women over 35 would be screened effectively. CONCLUSION--Screening based on individual risk would use resources more effectively than screening based on maternal age and genetic history without affecting detection rates in older women.     

Antenatal maternal serum screening for Down's syndrome: results of a demonstration project.

OBJECTIVES--To assess the implementation of antenatal screening for Down''s syndrome in practice, using individual risk estimates based on maternal age and the three serum markers: alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin. DESIGN--Demonstration project of Down''s syndrome screening; women with a risk estimate at term of 1 in 250 or greater were classified as "screen positive" and offered diagnostic amniocentesis. SETTING--Hospital and community antenatal clinics in four health districts in London. SUBJECTS--12,603 women of all ages with singleton pregnancies seen between February 1989 and the end of May 1991, with follow up of the outcome of pregnancy completed to the end of 1991. MAIN OUTCOME MEASURES--Uptake of screening, detection rate for Down''s syndrome, false positive rate, odds of being affected given a positive result, and uptake of amniocentesis in women with positive screening results, together with the costs of the screening programme. RESULTS--The uptake of screening was 74%. The detection rate was 48% (12/25), and the false positive rate was 4.1%, consistent with results expected from previous work based on observational studies. There was a loss of detection due to the selective use of ultrasound scans among women with positive screening results. One affected pregnancy occurred among 205 reclassified as negative; this illustrated the danger of false negatives occurring in this group and lends weight to the view that if an ultrasound estimate of gestational age is used it should be carried out routinely on all women rather than selectively among those with positive results. The estimated cost of avoiding the birth of a baby with Down''s syndrome was about 38,000 pounds, substantially less than the lifetime costs of care. CONCLUSION--Antenatal maternal serum screening for Down''s syndrome is effective in practice and can be readily integrated into routine antenatal care. It is cost effective and performs better than selection for amniocentesis on the basis of maternal age alone.     

Results of first year (1989) of a national register of Down's syndrome in England and Wales.

OBJECTIVE--To examine the feasibility of a national register of Down''s syndrome and its effectiveness in evaluating prenatal screening for the syndrome. DESIGN--Information for the register was obtained from all eligible cytogenetic laboratories on relevant cytogenetic diagnoses, including date and place of birth or termination, maternal age, indication for karyotyping, and type of diagnostic test used. SETTING--Cytogenetic laboratories in England and Wales. SUBJECTS--All fetuses with trisomy 21 diagnosed prenatally and live births with Down''s syndrome diagnosed at birth. MAIN OUTCOME MEASURES--Number of prenatal and postnatal diagnoses of Down''s syndrome. National and maternal age specific prevalence of Down''s syndrome. RESULTS--For 1989 there were 1060 registrations--323 prenatal diagnoses and 737 postnatal diagnoses--after exclusion of postnatally diagnosed miscarriages and stillbirths. The estimated national rate of affected births for mothers resident in England and Wales was 1.4/1000 live births, assuming no terminations of affected pregnancies and after correction for natural losses which would have occurred in the absence of termination. The corrected maternal age specific rates were close to those found in previous population based studies. The proportion of affected pregnancies diagnosed prenatally in mothers aged 35 to 39 was 44%, and for those aged 40 or more it was 71%. Abnormal findings on ultrasonography played an unexpectedly important part in initiating cytogenetic investigation (13% of the prenatal diagnoses). CONCLUSIONS--The findings establish the feasibility of a national Down''s syndrome register and its use in evaluating prenatal screening services. Together with information held by the Office of Population Censuses and Surveys on congenital malformations, data from the register will permit studies of environmental variables affecting the prevalence of the syndrome.     

Screening for Down's syndrome using serum alpha fetoprotein: a retrospective study indicating caution.

A report was made on the outcome of a four year retrospective study in 27 064 pregnancies, of the clinical efficiency, sensitivity, and specificity of a screening programme for Down''s syndrome based on reported strategies related to the measurement of maternal serum alpha fetoprotein. This study identified 27 pregnancies affected by Down''s syndrome with a median multiple of the median maternal serum alpha fetoprotein concentration of 0.82. This figure is considerably higher than that obtained from previous reports on this subject. With an age related multiple of the median maternal serum alpha fetoprotein strategy, 30.8% of Down''s affected pregnancies were identified as well as 11.6% of unaffected pregnancies. Perhaps a United Kingdom collaborative study should begin to investigate the reasons for such wide population variance in the reports for the median multiple of the median for Down''s affected pregnancies. Until such studies are carried out, screening for Down''s syndrome based on low maternal serum alpha fetoprotein concentration is premature.     

Risk assessment adjusted for gestational age in maternal serum screening for Down's syndrome.

OBJECTIVE--To investigate the relation between errors in calculation of gestational age and assessment of risk of Down''s syndrome and to analyse the implications for screening programmes. DESIGN--Retrospective analysis of dating of gestational age by menstrual history v ultrasound scan. Computer program with maternal age and concentrations of alpha fetoprotein and free beta human chorionic gonadotrophin to calculate risk for a range of expected dates of delivery. Computer simulated prospective application of new screening programme. SETTING--Teaching hospitals in Nottingham. SUBJECTS--31,561 women with singleton pregnancies with gestational age based on routine ultrasound scan. Computer simulation of 20,000 women in three age ranges (up to 37; up to 40; all). MAIN OUTCOME MEASURES--Distribution of error between gestational age based on ultrasound scan v menstrual history. Proportion of women in the population who require precise dating of pregnancy; proportion of women who require amniocentesis. RESULTS--With gestational age derived from ultrasound scan as reference the 95% confidence interval for gestational age by menstrual history was -27 to +9 days. A screening programme for Down''s syndrome for women up to age 40 would yield a low risk (< 1:250) for this range of days in 86.0% of cases. The 14.0% of women remaining would have one or more high risk values in their report and would thus require an ultrasound scan for precise dating of the pregnancy; 30% of these--that is, 3.7% of the screened population--would be identified as high risk and require consideration for amniocentesis. CONCLUSIONS--Screening programmes for Down''s syndrome require the facility for precise dating of pregnancy to improve the accuracy of risk assessment. This can be achieved without introducing additional scans for early dating in the whole population but by selecting only those cases (about 14%) when an error in dates is likely to affect the risk of Down''s syndrome.     

胎盘特异性基因4 mRNA基因在孕妇外周血中的检测及临床价值

目的:应用实时荧光定量PCR(RT-PCR)技术对不同孕周孕妇外周血浆胎盘特异性基因4(PLAC4)m RNA基因进行检测,寻找唐氏综合征产前诊断的可靠生物学标志物,为无创性产前诊断提供新的突破口。方法:按入组标准随机选取健康育龄未妊娠女性5例,正常健康妊娠孕妇60例(早期妊娠20例、中期妊娠20例、晚期妊娠20例),唐氏筛查高危孕妇8例,正常分娩24 h女性5例。共收集外周血浆样本78例。应用RT-PCR技术,检测样本中的PLAC4 m RNA基因含量,并进行相对定量分析。结果:健康育龄未妊娠女性及正常分娩后24 h女性外周血浆中均无游离胎儿PLAC4 m RNA基因的存在;正常健康妊娠孕妇不同孕周标本均检测到PLAC4 m RNA基因,以早期妊娠作为对照,中期妊娠是早期妊娠的1.99倍,晚期妊娠是早期妊娠的3.73倍;唐氏筛查高危孕妇均检出PLAC4 m RNA基因,含量是早期妊娠的6.36倍。结论:PLAC4 m RNA基因有望成为唐氏综合征产前诊断的可靠性生物学标志物。     

Psychological consequences for parents of false negative results on prenatal screening for Down's syndrome: retrospective interview study

ObjectiveTo determine the psychological consequences for parents of children with Down''s syndrome of having received a false negative result on prenatal screening.DesignComparison of adjustment of parents who received a false negative result with that of parents not offered a test and those who declined a test.SettingParents were interviewed in their own homes.ParticipantsParents of 179 children with Down''s syndrome (mean age 4 (range 2-6) years).ResultsOverall, regardless of screening history, parents adjusted well to having a child with Down''s syndrome. Compared with mothers who declined a test, mothers in the false negative group had higher parenting stress (mean score 81.2 v 71.8, P=0.016, 95% confidence interval for the difference 1.8 to 17.0) and more negative attitudes towards their children (124.9 v 134.2, P=0.009, −16.2 to −2.4). Fathers in the false negative group had higher parenting stress test scores (77.8 v 70.0, P=0.046, 1.5 to 14.2) than fathers not offered a test. Mothers in the false negative group were more likely to blame others for the outcome than mothers who had not been offered the test (28% v 13%, P=0.032, 3% to 27%). Mothers and fathers in the false negative group were more likely to blame others for this outcome than parents who had declined a test (mothers 28% v 0%, P=0.001, 19% to 37%; fathers 27% v 0%, P=0.004, 17% to 38%). Blaming others was associated with poorer adjustment for mothers and fathers.ConclusionsA false negative result on prenatal screening seems to have a small adverse effect on parental adjustment evident two to six years after the birth of an affected child.     

Appraisal of a new scheme for prenatal screening for Down's syndrome.

OBJECTIVE--To appraise a new method of prenatal screening for Down''s syndrome based on maternal serum concentrations of alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin combined with maternal age--the "triple test." DESIGN--Examination of the cost effectiveness of the triple test relative to screening only by maternal age over a range of population detection rates. SETTING--Leicestershire Health Authority. MAIN OUTCOME MEASURES--Costs per affected fetus detected. RESULTS--The triple test is more cost effective than screening only by maternal age for risk cut off points for amniocentesis, resulting in a detection rate over 45%. The most efficient detection rate is around 60-65%, for which the cost per case detected is around 29,000 pounds, through screening with higher detection rates is still likely to be cost beneficial. CONCLUSIONS--Prenatal screening for Down''s syndrome based on the triple test should replace screening based only on maternal age. Individual women''s preferences should be elicited by the use of structured decision analysis in order to maximise utility and so increase the benefits of the screening programme.     

Preventing the birth of infants with Down's syndrome: a cost-benefit analysis.

The costs and economical benefits of providing routine prenatal diagnosis of Down''s syndrome with termination of affected pregnancies in older pregnant women in the west of Scotland were examined. The potential economic benefits would be greater than the costs for women aged 40 and over, probably about equal to costs for those aged 35 and over, but less than costs if the service were extended to women under 35.     

Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy.

OBJECTIVE--To examine the significance of fetal nuchal translucency at 10-14 weeks'' gestation in the prediction of abnormal fetal karyotype. DESIGN--Prospective screening study. SETTING--The Harris Birthright Research Centre for Fetal Medicine, King''s College Hospital, London. SUBJECTS--827 fetuses undergoing first trimester karyotyping by amniocentesis or chorionic villus sampling. MAIN OUTCOME MEASURE--Incidence of chromosomal defects. RESULTS--The incidence of chromosomal defects was 3% (28 of 827 cases). In the 51 (6%) fetuses with nuchal translucency 3-8 mm thick the incidence of chromosomal defects was 35% (18 cases). In contrast, only 10 of the remaining 776 (1%) fetuses were chromosomally abnormal. CONCLUSION--Fetal nuchal translucency > or = 3 mm is a useful first trimester marker for fetal chromosomal abnormalities.     

Serum screening for Down's syndrome: some women's experiences.

OBJECTIVES--To describe the experiences of a small group of women who had positive results after serum screening for Down''s syndrome. DESIGN--Semistructured telephone interviews and correspondence with women after a positive screening result (four women) negative amniocentesis results (eight), or termination of a pregnancy with a confirmed abnormality (eight). SUBJECTS--20 women who contacted Support After Termination For Abnormality about their experiences of serum screening for Down''s syndrome. MAIN OUTCOME MEASURES--Women''s knowledge and understanding of the test; staff misconceptions; communication of results; how women coped with the diagnostic process; attitudes to the test and to termination of abnormal fetuses. RESULTS--All women were made anxious by their positive screening test, no matter how they were told. The women''s experiences suggested that medical staff were unclear about the implications of screening tests and how to interpret risk. Even after receipt of negative amniocentesis results some women remained anxious. Staff did not always recognise women''s concerns while awaiting amniocentesis results. CONCLUSIONS--The way in which serum screening is being implemented does not always meet the needs of women with positive results. Some of the problems were not specific to screening for Down''s syndrome. When screening tests are introduced policies should be adopted to ensure appropriate support for participants.     

Serum screening for Down's syndrome: experiences of obstetricians in England and Wales.

OBJECTIVES--To assess the experiences of obstetricians in England and Wales of serum screening for Down''s syndrome. DESIGN--Postal questionnaire survey. SUBJECTS--Questionnaires were sent to all practising obstetricians in England and Wales with nonacademic appointments who had not participated in an earlier (randomly sampled) survey of obstetricians'' attitudes (n = 555). Responses were received from 393 (71%), of which 351 were analysed. The data represent about one third of obstetric consultants in England and Wales. MAIN OUTCOME MEASURES--The extent of use of serum screening for Down''s syndrome, and the problems encountered. RESULTS--Serum screening for Down''s syndrome was being offered on some basis by virtually all obstetricians in the survey. Nearly half the sample said that they did not have adequate resources for counselling all the women to whom screening was offered. Many problems were reported, which in all cases were more common than equivalent problems encountered with serum screening for neural tube defects. Over 80% (289) said that women not understanding the test was a problem. CONCLUSIONS--There is considerable confusion associated with serum screening for Down''s syndrome. The precedent of serum screening for neural tube defects does not seem to have lessened the problems experienced, rather the contrary. Many obstetricians report inadequate resources for counselling, which is consistent with the high prevalence of problems associated with women not understanding the test. There is an urgent need to consider what counselling should consist of and who should undertake it and to ensure that necessary resources are available.     

Measurement of activity of urea resistant neutrophil alkaline phosphatase as an antenatal screening test for Down's syndrome.

OBJECTIVE--To investigate the value of measuring maternal urea resistant neutrophil alkaline phosphatase activity as an antenatal screening test for Down''s syndrome. DESIGN--Case-control study of blood samples collected at nine to 27 weeks of pregnancy. SETTING--Antenatal clinics in London and Oxford. PATIENTS--72 Women whose fetuses had been diagnosed by amniocentesis or chorionic villus sampling as having Down''s syndrome and 156 women whose fetuses did not have the syndrome. Only singleton pregnancies were studied. MAIN OUTCOME MEASURE--Activity of urea resistant neutrophil alkaline phosphatase measured cytochemically. RESULTS--The median enzyme activity in the index patients was 1.65 times the expected median for the controls at the same duration of pregnancy (p less than 0.0001; 95% confidence interval 1.56 to 1.74). A cut off value that identified the 5% of control patients with the highest activities yielded a rate of detection of Down''s syndrome of 79% (95% confidence interval 70 to 89%). CONCLUSION--Activity of urea resistant neutrophil alkaline phosphatase is an effective maternal blood marker for Down''s syndrome. Its use in antenatal screening could lead to a substantial improvement in the detection of this disorder. Before introducing the test into routine medical practice it will have to be automated so that it can be used on a large scale and is less subjective.     

Birth weight of offspring and insulin resistance in late adulthood: cross sectional survey

ObjectiveTo investigate the association between birth weight of offspring and mothers'' insulin resistance in late adulthood.DesignCross sectional survey.SettingGeneral practitioner''s surgeries in 23 towns in Great Britain.Participants4286 women aged 60-79 years.ResultsBirth weight of offspring was inversely related to maternal insulin resistance in late adulthood. For each 1 kg higher birth weight of offspring, women had a 15% reduction in the odds of being in the fourth with highest insulin resistance, compared to other fourths (odds ratio 0.85; 95% confidence interval 0.71 to 1.00). This increased to 27% (0.73; 0.60 to 0.90) after adjusting data for potential confounders. A U shaped relation between birth weight of offspring and diabetes in older age was found; women with the lightest and heaviest offspring had the highest prevalence of diabetes.ConclusionsBirth weight of offspring is inversely related to the mother''s insulin resistance in late adulthood, despite the association of glucose intolerance during pregnancy with heavier offspring at birth. Common genetic factors contribute to the relation between birth weight and risk of cardiovascular disease and diabetes in adults.

What is already known on this topic

Small birth weight is related to increased risk of cardiovascular disease and diabetes in adulthood; the underlying mechanisms are unclearSmall birth weight of offspring is related to parental cardiovascular disease, suggesting that common genetic factors affect birth weight and the risk of disease in adulthoodGenetic factors associated with the metabolism of insulin are plausible in linking birth weight and cardiovascular disease (the fetal insulin hypothesis)

What this study adds

Birth weight of offspring is inversely related to maternal insulin resistance in older ageGenetic factors related to both insulin resistance and birth weight explain at least part of the association between birth weight and risk of cardiovascular disease and diabetes in adulthood     

Fetal nuchal translucency thickness

In the early 1990s Nicolaides introduced screening for trisomy 21 by fetal nuchal translucency thickness measurement with ultrasound between 11-13(+6) weeks. Already in 1866 L. Down noted that common features of patients with trisomy 21 are a skin being too large for the body and a flat face with a small nose. While detection rates for trisomy 21, given an invasive testing rate of 5%, were only 30% for screening by maternal age and 65% for screening by maternal serum triple test, the detection rate for screening by nuchal translucency combined with maternal age was 75% and this could be increased to 90% in combination with maternal serum screening (serum B-human chorionic gonadotropin and pregnancy-associated plasma protein-A) at 11-13(+6) weeks. The additional soft markers in the first trimester are the fetal nasal bone, the Doppler velocity waveform in the ductus venosus and tricuspid regurgitation and these markers can be used to further increase the detection rate of trisomy 21. In addition increased nuchal translucency thickness can also identify other chromosomal defects (mainly trisomy 13 and 18 and monosomy X) and major congenital malformations (mainly cardiac defects) and genetic syndromes.     

Impact of Community-Based Maternal Health Workers on Coverage of Essential Maternal Health Interventions among Internally Displaced Communities in Eastern Burma: The MOM Project

Background

Access to essential maternal and reproductive health care is poor throughout Burma, but is particularly lacking among internally displaced communities in the eastern border regions. In such settings, innovative strategies for accessing vulnerable populations and delivering basic public health interventions are urgently needed.

Methods

Four ethnic health organizations from the Shan, Mon, Karen, and Karenni regions collaborated on a pilot project between 2005 and 2008 to examine the feasibility of an innovative three-tiered network of community-based providers for delivery of maternal health interventions in the complex emergency setting of eastern Burma. Two-stage cluster-sampling surveys among ever-married women of reproductive age (15–45 y) conducted before and after program implementation enabled evaluation of changes in coverage of essential antenatal care interventions, attendance at birth by those trained to manage complications, postnatal care, and family planning services.

Results

Among 2,889 and 2,442 women of reproductive age in 2006 and 2008, respectively, population characteristics (age, marital status, ethnic distribution, literacy) were similar. Compared to baseline, women whose most recent pregnancy occurred during the implementation period were substantially more likely to receive antenatal care (71.8% versus 39.3%, prevalence rate ratio [PRR] = 1.83 [95% confidence interval (CI) 1.64–2.04]) and specific interventions such as urine testing (42.4% versus 15.7%, PRR = 2.69 [95% CI 2.69–3.54]), malaria screening (55.9% versus 21.9%, PRR = 2.88 [95% CI 2.15–3.85]), and deworming (58.2% versus 4.1%, PRR = 14.18 [95% CI 10.76–18.71]. Postnatal care visits within 7 d doubled. Use of modern methods to avoid pregnancy increased from 23.9% to 45.0% (PRR = 1.88 [95% CI 1.63–2.17]), and unmet need for contraception was reduced from 61.7% to 40.5%, a relative reduction of 35% (95% CI 28%–40%). Attendance at birth by those trained to deliver elements of emergency obstetric care increased almost 10-fold, from 5.1% to 48.7% (PRR = 9.55 [95% CI 7.21–12.64]).

Conclusions

Coverage of maternal health interventions and higher-level care at birth was substantially higher during the project period. The MOM Project''s focus on task-shifting, capacity building, and empowerment at the community level might serve as a model approach for similarly constrained settings. Please see later in the article for the Editors'' Summary     

超声系统筛查在孕早期胎儿中枢神经系统先天畸形诊断的价值分析

目的:探讨超声系统筛查在孕早期胎儿中枢神经系统先天畸形诊断的价值分析。方法:选取2014年3月~2017年4月来我院超声科行孕早期胎儿颈部透明层(Nuchal translucency,NT)筛查的孕妇2084例,胎儿共2135例。采用超声测量胎儿头臀长(Croen rump length,CRL)和颈部透明层(Nuchal translucency,NT)值,通过头胸部正中矢状断面、侧脑室水平横断面、小脑及后颅窝池断面、脊柱长轴断面等4个超声影像标准断面对孕早期胎儿的中枢神经系统解剖结构进行系统检查,统计各组在上述4个超声标准断面的检查显示情况及NT值,同时分析NT值、标准断面显示率与孕龄的关系,统计分析孕早期应用超声影像标准断面检查对中枢神经系统畸形的检出率、诊断敏感度、特异度、阳性预测值、阴性预测值。结果:孕早期胎儿采用超声检查,结果显示头胸部正中矢状断面、侧脑室水平横断面、小脑及后颅窝池断面、脊柱长轴断面的超声影像学显示率分别为98.17%、99.44%、98.78%和98.97%,不同孕龄组间超声断面显示率差异对比,x~2检验值分别为0.25、1.65、0.62、0.13,差异无统计学意义(P0.05);孕早期超声诊断胎儿中枢神经系统畸形的敏感度为90.91%,特异度为100%,阳性预测值为100%,阴性预测值为99.48%;正常胎儿的NT值与其孕龄呈正相关(r=0.153)。结论:超声检查对孕早期胎儿中枢神经系统结构畸形的显示率较高,且不受胎儿孕龄影响。     

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