The development of Alzheimer's disease in Down's syndrome assessed by auditory event-related potentials

ABSTRACT. Several studies have reported changes in auditory event-related potentials in patients with Alzheimer's type dementia, These include an increase in latency and a reduction in amplitude of the P300 (P3) response, a late positive component generated about 300 ms after an unexpected stimulus. Alzheimer's type dementia is an almost invariable acompaniment of ageing in Down's syndrome. This study was designed to assess the usefulness of the auditory P300 response as a measure of the onset of dementia in Down's subjects, who because of poor language development may be difficult to assess by psychological tests. Auditory event-related potentials were recorded from 89 Down's subjects, aged 16–66 years. A control group of 29 mentally retarded subjects with fragile-X syndrome and 83 normal volunteer controls were also tesled. Clinical psychological testing found evidence of dementia in 16 Down's subjects and none with fragile-X. Furthermore, in the Down's population but not the fragile-X or control groups, there was a marked increase in P300 latency with age starting around 37 years. In controls, the effect of age on P300 latency became significant some 17 years later around the age of 54 years. The premature effect of age on P300 in Down's syndrome was due to the prolonged P300 latency in the 16 subjects showing signs of dementia. It was confirmed that P300 latency increase reflects the development of Alzheimer's dementia in Down's subjects.     

Self-reported depression and anti-depressant medication use in essential tremor: cross-sectional and prospective analyses in a population-based study

There are few data on the co-morbidity of essential tremor (ET) with depression. To assess the associations of ET with self-reported depression and antidepressant medication use. In a population-based study in central Spain, participants were evaluated at baseline (1994–1995) and 3 years later. Self-reported depression and use of antidepressant medications were evaluated at each assessment. In cross-sectional analyses, prevalent ET cases were twice more probably than controls to report depression [103 (43.8%) of 235 cases versus 1137 (26.0%) of 4379 controls; adjusted odds ratio (OR) 2.20, 95% confidence interval (CI) 1.66–2.93, P  < 0.001] and three times more probably to be taking antidepressant medications [16 (6.8%) cases versus 113 (2.6%) controls; adjusted OR 3.33, 95% CI 1.91–5.82, P  = 0.001]. In prospective analyses, baseline self-reported depression (adjusted RR 1.78, 95% CI 1.11–2.89, P  = 0.018) and, perhaps, baseline use of antidepressant medication (adjusted RR 1.90, 95% CI 0.59–6.05, P  = 0.28) were associated with incident ET. Rather than being totally benign, ET seems to be associated with a mood disorder. Furthermore, as well as being a secondary response to disease manifestations, this mood disorder may be a primary feature of the underlying disease.     

Irritable bowel syndrome is more frequent in patients hospitalized for ischaemic colitis: results of a case–control study

Abstract  It has been suspected that there is an epidemiological link between irritable bowel syndrome (IBS) and ischaemic colitis (IC). We performed a retrospective case–control study to compare the frequency of IBS in patients hospitalized for IC compared with that of patients with peptic ulcer bleeding. Cases were patients with a first episode of IC and controls were patients with a first episode of peptic ulcer bleeding, matched to cases for sex and 10-year age-class. Diagnosis of IBS was based on medical information extracted from hospital medical files and a standard self-questionnaire. The association between IBS and IC was tested using Mc Nemar's paired odds ratio (OR); confidence interval at 95% (CI 95%) was calculated; Mantel–Haenzel's Chi² was applied. A total of 113 cases and 113 matched controls were studied. There were 37 males and 76 females and the mean age was 69 ± 15 years in each group. The prevalence of IBS in cases was 16.9% vs 1.8% in controls. The risk of IBS was 11.05 times higher among cases than in controls ( P  < 0.001); CI 95%: (2.45–49.74). A total of 87 pairs with complete data were used for OR calculation. The risk of IBS was 7.5 times higher in cases than in controls ( P  = 0.002); CI 95%: (1.72–32.80). This case–control study shows that IBS is more frequent in IC patients than in controls.     

Onset of dementia is associated with age at menopause in women with Down's syndrome

Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community-based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system. Information from cognitive assessments, medical record review, neurological evaluation, and caregiver interviews was used to establish ages for onset of menopause and dementia. We used survival and multivariate regression analyses to determine the relation of age at menopause to age at onset of Alzheimer's disease, adjusting for age, level of mental retardation, body mass index, and history of hypothyroidism or depression. Women with early onset of menopause (46 years or younger) had earlier onset and increased risk of Alzheimer's disease (AD) compared with women with onset of menopause after 46 years (rate ratio, 2.7; 95% confidence interval [CI], 1.2-5.9). Demented women had higher mean serum sex hormone binding globulin levels than nondemented women (86.4 vs 56.6 nmol/L, p = 0.02), but similar levels of total estradiol, suggesting that bioavailable estradiol, rather than total estradiol, is associated with dementia. Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD.     

Risk factors in Alzheimer's disease: a clinicopathologic study.

We investigated potential risk factors for Alzheimer's disease (AD) in a clinicopathologic study of 407 patients with definite AD, 100 non-Alzheimer dementia patients, and 50 normal subjects. The AD patients had more first-degree relatives with dementia than the non-AD dementia group (odds ratio of 1.85, 95% confidence interval of 1.07-3.20) or the normal elderly (odds ratio of 3.60, 95% confidence interval of 1.50-8.64) but did not have significantly more head injuries, medical and psychiatric illnesses, or relatives with Down's syndrome. The AD patients with a family history of dementia had their dementia at a later age than those without an affected relative. These findings indicate a familial risk for AD that is greater than for other dementing illnesses and has age-related penetrance. This study does not support other putative risk factors for AD such as head trauma and familial Down's syndrome.     

Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihypertensive medication use.

OBJECTIVE: To examine whether antihypertensive medication use can affect the occurrence and progression of dementia. SUBJECTS AND METHODS: In a community cohort of 1810 persons aged 75 years and older, 225 prevalent cases of dementia were detected. Among the 1301 persons without dementia, 224 incident cases of dementia were identified during an average period of 3 years. Among the 225 prevalent cases of dementia, 79 were suitable for the analysis of cognitive decline. Information on drug use was collected for the 2 weeks preceding the baseline interview. RESULTS: Subjects taking antihypertensive medication (n = 651, 83.9% of whom took diuretics) had a lower prevalence of dementia than those not taking antihypertensive medication (P<.001). Subjects without dementia who were taking antihypertensive medication at baseline (n = 584) had a reduced incidence of dementia (adjusted relative risk, 0.7; 95% confidence interval, 0.6-1.0; P = .03). Furthermore, subjects taking diuretics (n = 484) had an adjusted relative risk of 0.7 (95% confidence interval, 0.5-1.0; P = .02) for all dementia, and subjects taking diuretic monotherapy (n = 345) had an adjusted relative risk of 0.6 (95% confidence interval, 0.4-0.9; P = .006). The use of other antihypertensive medication (calcium antagonists or beta-blockers), however, was related to a reduced risk of Alzheimer disease (adjusted relative risk, 0.6; 95% confidence interval, 0.3-1.2) only in the subpopulation with a higher baseline blood pressure (n = 458). Patients with dementia at baseline who were not taking diuretics had a 2-fold faster rate of decline in the score on the Mini-Mental State Examination than those taking diuretics. CONCLUSION: The use of diuretics may protect against dementia in elderly persons.     

全髋关节置换与人工股骨头置换治疗高龄患者股骨颈骨折有效性与安全性的Meta分析

目的：通过Meta分析方法在较大样本量的前提下,比较国内全髋关节置换与人工股骨头置换治疗高龄患者股骨颈骨折的临床疗效和安全性。 方法：计算机检索中国生物医学文献数据库CBM (2010-04)、中国期刊全文数据库CNKI (2010-04)、维普中文科技期刊数据库VIP (2010-04)及所有关于全髋关节置换与人工股骨头置换治疗高龄患者股骨颈骨折临床随机对照试验。采用Meta分析方法对假体关节功能、手术时间、术中出血量、出现并发症、髋关节残余疼痛进行综合分析。 结果：纳入7个临床对照研究,共624例高龄患者(>60岁)。其中行全髋关节置换实验组329例,人工股骨头置换对照组295例。Meta分析发现：①全髋关节置换组在疗效上优于人工股骨头置换组[OR=2.88和95%可信区间为(1.84, 4.49),P < 0.05]。②实验组手术时间上长于对照组[WMD=43.35和95%可信区间为(23.96,62.74),P < 0.05]。③实验组术中出血量多于对照组[WMD=336.36和95%可信区间为(196.34,476.37),P < 0.05]。④两组术后出现并发症无明显统计学差异[OR=0.54和95%可信区间为(0.29,1.02),P > 0.05]。⑤实验组髋关节残余痛少于对照组[OR=0.30和95%可信区间为(0.18, 0.50),P < 0.05]。 结论：全髋关节置换治疗高龄股骨颈骨折较人工股骨头置换具有更好的远期临床效果,尤其适用于原发髋关节疾病和较强活动能力者。但全髋关节置换手术持续时间与术中出血量明显高于人工股骨头置换,因此在临床工作中对于治疗方法的选择应该谨慎。由于纳入研究数量少且质量不高,论证强度较弱,尚需开展和设计大样本随机对照研究做进一步验证。     

Prevalence of overweight and obesity in Down's syndrome and other mentally handicapped adults living in the community

ABSTRACT. To find out the prevalence of overweight and obesity in the mentally handicapped, 183 subjects living in the community were studied; 58 of whom had Down's syndrome. It was found that 70–58% of males and 95–83% of females with Down's syndrome, and 49–29% males and 62–96% females from other mentally handicapped subjects, were categorized as overweight and obese, compared with 40% of males and 32% females in that category from normal population.     

A common NURR1 polymorphism associated with Parkinson disease and diffuse Lewy body disease

BACKGROUND: NURR1 plays a key role in mesencephalic dopaminergic neuron development and survival. A homozygous NURR1 polymorphism (a single base-pair insertion in intron 6) (NI6P) has been reported to be associated with Parkinson disease (PD). OBJECTIVE: To assess the association of the NI6P with PD and diffuse Lewy body disease. DESIGN: Case-control study. SETTING: Movement disorders clinic and tissue provided by brain banks. PATIENTS: Patients with pathologically proven PD (n = 37) or diffuse Lewy body disease (n = 35), neuropathologically normal control subjects (n = 59), those clinically diagnosed as having PD (n = 66), and spousal controls (n = 29). METHODS: Determining the frequency of heterozygotes and homozygotes for the NI6P by DNA sequencing and restriction endonuclease analyses. RESULTS: Overall, 41 (39.8%) of the 103 patients with PD were heterozygotes compared with 22 (25.0%) of the 88 controls (P =.03), with a relative risk (estimated from the odds ratio) for PD of 2.03 (95% confidence interval, 1.08-3.81) for heterozygotes vs wild type subjects. Heterozygotes were more frequent in the subgroup of patients with pathologically confirmed PD (18 [48.6%] of 37) vs controls (14 [23.7%] of 59) (P =.01), with a relative risk for PD of 2.84 (95% confidence interval, 1.17-6.88) for heterozygotes vs wild type subjects. In patients clinically diagnosed as having PD, heterozygotes were more frequent in early-onset cases (onset at < or =45 years) (10 [55.6%] of 18) compared with late-onset cases (onset at >45 years) (10 [23.8%] of 42) (P =.02) or spousal controls (8 [27.6%] of 29) (P =.06), with a relative risk for early-onset PD of 4.17 (95% confidence interval, 1.13-15.33) for heterozygotes vs subjects with 2 wild type alleles. The homozygous NI6P was not associated with PD, but was present in 6 (17.1%) of the 35 patients with diffuse Lewy body disease compared with 3 (5.1%) of the 59 controls (P =.06). CONCLUSIONS: The common heterozygous NI6P is associated with an increased risk of PD. An association of borderline significance was found for the homozygous NI6P and diffuse Lewy body disease.     

Hypertension and the risk of mild cognitive impairment

OBJECTIVE: To explore whether hypertension is associated with the risk of mild cognitive impairment (MCI), an intermediate stage of dementia, because there are conflicting data relating hypertension to the risk of Alzheimer disease. DESIGN AND SETTING: Prospective community-based cohort study conducted in northern Manhattan. Multivariate proportional hazards regression analyses were used, relating hypertension to incident all-cause MCI, amnestic MCI, and nonamnestic MCI in 918 persons without prevalent MCI at baseline followed up for a mean of 4.7 years. RESULTS: There were 334 cases of incident MCI, 160 cases of amnestic MCI, and 174 cases of nonamnestic MCI during 4337 person-years of follow-up. Hypertension was associated with an increased risk of all-cause MCI (hazard ratio, 1.40; 95% confidence interval, 1.06-1.77; P = .02) and nonamnestic MCI (hazard ratio, 1.70; 95% confidence interval, 1.13-2.42; P = .009) after adjusting for age and sex. Both associations were slightly attenuated in models additionally adjusting for stroke and other vascular risk factors. There was no association between hypertension and the risk of amnestic MCI (hazard ratio, 1.10; 95% confidence interval, 0.79-1.63; P = .49). Consistent with this association, hypertension was related with the slope of change in an executive ability score, but not with memory or language score. There was no effect modification of the association between hypertension and MCI by APOEepsilon4 genotype or use of antihypertensive medication. CONCLUSIONS: A history of hypertension is related to a higher risk of MCI. The association seems to be stronger with the nonamnestic than the amnestic type of MCI in the elderly. These findings suggest that prevention and treatment of hypertension may have an important impact in lowering the risk of cognitive impairment.     

Regurgitant reflux, vs non-regurgitant reflux, is preceded by rectus abdominis contraction in infants

Abstract Infants commonly regurgitate during some, but not all, gastro-oesophageal reflux episodes. As several different mechanisms for reflux episodes have been identified, it was hypothesized that the mechanisms for regurgitant and non-regurgitant reflux differ. To test whether regurgitant episodes are associated with, and perhaps propelled by, rectus abdominis contraction, ten infants, aged 9–30 weeks (median 16.5 weeks), with regurgitant reflux and no other cause for their regurgitation, were studied with concurrent distal oesophageal pH probe monitoring and surface electromyography of the rectus abdominis muscles. Reflux episodes with material emanating from the mouth (regurgitant reflux) were distinguished from those without visible regurgitation, and were characterized as being, or not being, temporally associated with rectus abdominis activity.
During 80 h of monitoring of the ten infants, 279 reflux episodes were identified. Electromyographic activity was observed with 58% of 24 regurgitant reflux episodes compared to only 32% of 255 non-regurgitant reflux episodes (Mantel Haenzel P = 0.006, common odds ratio = 4.1, 95% confidence interval = 1.5–11.3). Among the 95 reflux episodes that were positive for rectus abdominis activity (whether regurgitant or not), 25% of those in the first 42 min following feeding were regurgitant, whereas only 6% of those occurring beyond 42 min were regurgitant (Mantel Haenzel P = 0.03, common odds ratio = 4.48, 95% confidence interval = 1.14–17.6). It was concluded that rectus abdominis contraction is one of the propulsive mechanisms that contribute to regurgitant reflux. Further, rectus abdominis contraction is more likely to result in regurgitation in the early period after a meal, suggesting that intragastric volume is a factor which influences whether reflux will be regurgitant.     

Female reproductive factors and risk of seizure or epilepsy: data from the Nurses' Health Study II

Reproductive factors are associated with seizures in women with epilepsy. We prospectively examined the association between reproductive factors and the risk of adult-onset isolated seizure, epilepsy, or any unprovoked seizure (defined as single unprovoked seizure or epilepsy) among 114,847 Nurses' Health Study II participants followed from 1989 to 2005. Validated seizure questionnaires and medical records were used to confirm incident cases of isolated seizure (n = 95) or epilepsy (n = 151). Overall, there were no significant associations between any reproductive factor and risk of any unprovoked seizure (n = 196). However, menstrual irregularity at ages 18-22 years was specifically associated with an increased risk of epilepsy [relative risk (RR) 1.67, 95% confidence interval (CI) 1.12-2.51]. Menstrual irregularity during follow-up (RR 2.21, 95% CI 1.16-4.20) and early age at menarche (<12 years vs. 12-13 years; RR 1.76, 95% CI 1.10-2.81) increased the risk of isolated seizure. Oral contraceptive use and parity were not associated with isolated seizure or epilepsy. Therefore, menstrual factors were associated with risk of seizure and epilepsy.     

Risk factors for isolated periventricular leukomalacia

Periventricular leukomalacia, a major cause of neurologic disabilities in preterm infants, can be isolated or associated with intraventricular and periventricular hemorrhage. To determine the risk factors for isolated periventricular leukomalacia, we retrospectively studied the characteristics of all very low birth weight infants affected by isolated periventricular leukomalacia who were delivered over a 5-year period and compared them with a control group of very low birth weight infants, matched within 2 weeks for gestational age, with no central nervous system pathology, and born during the same period. In total, 20 affected infants were compared with 98 control infants. Neonatal sepsis caused by coagulase-negative Staphylococcus (P = 0.014) and neonatal seizure (P = 0.026) were associated with isolated periventricular leukomalacia only on univariate analysis. Three variables demonstrated statistically significant associations with isolated periventricular leukomalacia on both univariate and multivariate logistic regression analysis as independent risk factors: birth weight (odds ratio, 4.31; 95% confidence interval, 1.54-12.06; P = 0.005), early neonatal hypotension requiring combined inotropic therapy (odds ratio, 4.90; 95% confidence interval; 1.22-19.68, P = 0.025), and delayed surgical closure of hemodynamically significant patent ductus arteriosus beyond age 7 days (odds ratio, 1.20; 95% confidence interval, 1.06-1.35; P = 0.003).     

Association of intronic variants of the KCNAB1 gene with lateral temporal epilepsy

The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequencies of 14 KCNAB1 intronic SNPs were determined in 142 Italian LTE patients and 104 healthy controls and statistically evaluated. Single SNP analysis revealed one SNP (rs992353) located near the 3'end of KCNAB1 slightly associated with LTE after multiple testing correction (odds ratio=2.25; 95% confidence interval 1.26-4.04; P=0.0058). Haplotype analysis revealed two haplotypes with frequencies higher in cases than in controls, and these differences were statistically significant after permutation tests (Psim=0.047 and 0.034). One of these haplotypes was shown to confer a high risk for the syndrome (odds ratio=12.24; 95% confidence interval 1.32-113.05) by logistic regression analysis. These results support KCNAB1 as a susceptibility gene for LTE, in agreement with previous studies showing that this gene may alter susceptibility to focal epilepsy.     

Relation of medial temporal lobe volumes to age and memory function in nondemented adults with Down's syndrome: implications for the prodromal phase of Alzheimer's disease.

OBJECTIVE: In Down's syndrome (trisomy 21), a dementia syndrome occurs that is phenotypically similar to Alzheimer's disease; the initial phase is characterized by memory loss. The authors used an in vivo structural technique in the predementia stage of Alzheimer's disease in adults with Down's syndrome to investigate whether atrophy of medial temporal lobe structures occurs in these subjects and whether volumes of these structures correlate specifically with performance on memory tests. METHOD: The subjects were 34 nondemented Down's syndrome adults (mean age=41.6 years, 17 women and 17 men) and 33 healthy comparison subjects (mean age=41.3, 15 women and 18 men). By using T(1)-weighted magnetic resonance imaging slices taken perpendicular to the Sylvian fissure, volumes of the hippocampus, amygdala, anterior and posterior parahippocampal gyrus, and temporal pole CSF were measured in both hemispheres. These data were normalized to the total intracranial volume. RESULTS: For Down's syndrome, smaller volumes of the right and left amygdala, hippocampus, and posterior parahippocampal gyrus were significantly associated with greater age; this association was not seen in the anterior parahippocampal gyrus. The amygdala and hippocampus volumes were positively correlated with memory measures. For the comparison group, there was no relationship between volume and age in any region. CONCLUSIONS: In the predementia phase of Down's syndrome, significant volume changes in medial temporal lobe structures occur with age and are related to memory. These structures are affected early in Alzheimer's disease in Down's syndrome, and their evaluation may help identify people in the preclinical stages of Alzheimer's disease.     

Hip displacement and scoliosis in Rett syndrome – screening is required

Aim  This study aimed to determine the prevalence of hip displacement and spinal deformity in a clinic population of females with Rett syndrome to define implications for screening and management.
Method  Age, MECP2 gene status, gross motor function, prevalence of hip displacement, as measured by migration percentage, and spinal deformity, determined by measurement of Cobb angle, were recorded.
Results  Thirty-one females with a mean age of 15 years 6 months (SD 5y 4mo) fulfilled a clinical diagnosis of Rett syndrome. Fifteen (48%, 95% confidence interval [CI] 30–67) of the cohort had a hip migration percentage of 30% of more. Eight of the 31 patients (95% CI 12–45) had undergone surgery for the prevention or treatment of hip displacement or dislocation. Twenty-seven of the 31 patients (95% CI 70–96) had a scoliosis, with a Cobb angle of less than 10°; 20 patients (95% CI 45–81) had a Cobb angle greater than 30°. Eleven (95% CI 19–55) patients have required spinal fusion surgery.
Interpretation  The prevalence of hip displacement and spinal deformity in a clinic cohort of females with Rett syndrome in Victoria, Australia, was very high. Early, repeated, and consistent clinical and radiological surveillance for hip displacement and spinal deformities is recommended in all young patients with Rett syndrome.     

Allergy, family history of autoimmune diseases, and the risk of multiple sclerosis

Objective – Previous reports suggested an association between allergy, autoimmunity, and risk of multiple sclerosis (MS), but results have been inconsistent. The present study assessed the association between history of allergy and autoimmune diseases, and the risk of MS.
Methods – We conducted a case–control study nested in the Nurses' Health Study (NHS) and NHS II cohorts. A total of 298 women with MS were matched with 1248 healthy controls and 248 women with history of breast cancer. A mailed questionnaire gathered information about history of allergic conditions and autoimmune disorders.
Results – History of allergy was not associated with MS risk [odds ratio (OR) 1.0, 95% confidence interval (CI) 0.8–1.4]. As expected, cases were more likely to have a positive family history of MS than controls (OR 9.7, 95% CI 6.1–15.3). A modest association was found between family history of other autoimmune diseases and MS risk (OR 1.4, 95% CI 1.0–1.8). We obtained similar results when we used women with breast cancer as comparison group.
Conclusion – Family history of other autoimmune diseases was associated with a higher MS risk, suggesting a common genetic background or shared environmental triggers. There was no clear association between personal history of allergy and risk of MS.     

Long-Term Survival of People with Unprovoked Seizures: A Population-Based Study

Summary: Purpose : Few population-based studies of longterm survival in people with seizures or epilepsy have been made.
Methods: Between January 1, 1960 and December 31, 1964, we identified 224 incidence cases of unprovoked seizures in Iceland and determined survivorship status and date of death for the cases as of January 1, 1996. We compared survivorship with that expected based on data from age-/sex-specific life tables from the country for 1961–1990 and calculated the standardized mortality ratio (SMR).
Results: By 30 years after diagnosis, there were 45 deaths among patients with unprovoked seizures as compared with an expected 28 deaths [standardized mortality ratio (SMR) 1.6; 95% confidence interval (CI) 1.2–2.21. Patients with unprovoked seizures of unknown etiology did not have a significant increase in mortality overall (SMR 1.3, 95% CI 0.8–1.9) or in any time interval. For patients with remote symptomatic un provoked seizures, mortality was increased (SMR 2.3, 95% CI 1.4–3.5). This increase was attributable to excess mortality for the first 15 years after diagnosis (SMR 4.1, 95% CI 2.4–6.6), and SMR was not different after that time.
Conclusions: Survivorship was decreased for the population of patients with unprovoked seizures. The increased mortality was primarily due to excess mortality in patients with remote symptomatic seizures, occurring in the first 15 years after diagnosis. Overall mortality for idiopathic unprovoked seizures was not significantly increased.     

Antihypertensive medication use and incident Alzheimer disease: the Cache County Study

BACKGROUND: Recent reports suggest that antihypertensive (AH) medications may reduce the risk of dementing illnesses. OBJECTIVES: To examine the relationship of AH medication use with incidence of Alzheimer disease (AD) among the elderly population (aged 65 years and older) of Cache County, Utah, and to examine whether the relationship varies with different classes of AH medications. METHODS: After an initial (wave 1) multistage assessment (1995 through 1997) to identify prevalent cases of dementia, we used similar methods 3 years later (wave 2) to identify 104 incident cases of AD among the 3308 survivors. At the baseline assessment, we obtained a detailed drug inventory from the study participants. We carried out discrete time survival analyses to examine the association between the use of AH medications (including angiotensin converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics) at baseline with subsequent risk of AD. RESULTS: Use of any AH medication at baseline was associated with lower incidence of AD (adjusted hazard ratio, 0.64; 95% confidence interval, 0.41-0.98). Examination of medication subclasses showed that use of diuretics (adjusted hazard ratio, 0.57; 95% confidence interval, 0.33-0.94), and specifically potassium-sparing diuretics (adjusted hazard ratio, 0.26; 95% confidence interval, 0.08-0.64), was associated with the greatest reduction in risk of AD. Corresponding analysis with a fully examined subsample controlling for blood pressure measurements did not substantially change our findings. CONCLUSIONS: These data suggest that AH medications, and specifically potassium-sparing diuretics, are associated with reduced incidence of AD. Because the latter association is a new finding, it requires confirmation in further study.     

Epidemiological and clinical characteristics of ALS in Belgrade, Yugoslavia

We present the results of the first epidemiological study of ALS in Belgrade. The distribution of 58 newly discovered cases in a 7-year survey period (1985–1991) showed that the average annual age-adjusted incidence rate was 0.42 per 100,000 population (95% confidence interval, 0.18–0.83). The rate for males was 1.5 times higher than the rate for females. The greatest age-specific average incidence rate was observed in patients between 60 and 64 (3.66 per 100,000 population; 95% confidence interval, 2.17–5.78). The actual age-adjusted prevalence rate on December 31, 1991 was 1.07 per 100,000 (95% confidence interval, 0.71–1.71). The mean age at onset of the disease was 56.2 ± 9.8 and it ranged from 24 to 74. We studied the natural course of the disease through the mean duration and cumulative probability of survival. The mean duration of the disease was 27.7 ± 18.2 months. The cumulative probability of survival was 27% for the whole population in a 5-year interval. Elderly patients and those with bulbar signs at onset had a poorer prognosis. Patients under 49 at onset and those with the spinal form of the disease survived longer.