Qt dispersion and mortality in the elderly.

BACKGROUND: The prognostic value of QT interval dispersion measured from a standard 12-lead electrocardiogram (ECG) in the general population is not well established. The purpose of the present study was primarily to assess the value of QT interval dispersion obtained from 12-lead ECG in the prediction of total, cardiac, stroke, and cancer mortality in the elderly. METHODS: A random population sample of community-living elderly people (n = 330, age > or = 65 years, mean 74 +/- 6 years) underwent a comprehensive clinical evaluation, laboratory tests, and 12-lead ECG recordings. RESULTS: By the end of the 10-year follow-up, 180 subjects (55%) had died and 150 (45%) were still alive. Heart rate corrected QT (QTc) dispersion had been longer in those who had died than in the survivors (75 +/- 32 ms vs 63 +/- 35 ms, P = 0.01). After adjustment for age and sex in the Cox proportional hazards model, prolonged QTc dispersion (> or = 70 msec) predicted all-cause mortality (relative risk [RR] 1.38, 95% confidence interval [CI] 1.02-1.86) and particularly stroke mortality (RR 2.7, 95% CI 1.29-5.73), but not cardiac (RR 1.38, 95% CI 0.87-2.18) or cancer (RR 1.51, 95% CI 0.91-2.50) mortality. After adjustment for age, sex, body mass index, blood pressure, blood glucose and cholesterol concentrations, functional class, history of cerebrovascular disease, diabetes, smoking, previous myocardial infarction, angina pectoris, congestive heart failure, medication, left ventricular hypertrophy on ECG, presence of atrial fibrillation and R-R interval, increased QTc dispersion still predicted stroke mortality (RR 3.21, 95% CI 1.09-9.47), but not total mortality or mortality from other causes. The combination of increased QTc dispersion and left ventricular hypertrophy on ECG was a powerful independent predictor of stroke mortality in the present elderly population (RR 16.52, 95% CI 3.37-80.89). QTcmin (the shortest QTc interval among the 12 leads of ECG) independently predicted total mortality (RR 1.0082, 95% CI 1.0028-1.0136, P = 0.003), cardiac mortality (RR 1.0191, 95% CI 1.0102-1.0281, P < 0.0001) and cancer mortality (RR 1.0162, 95% CI 1.0049-1.0277, P = 0.005). CONCLUSIONS: Increased QTc dispersion yields independent information on the risk of dying from stroke among the elderly and its component, QTcmin, from the other causes of death.

Prediction of sudden cardiac death by fractal analysis of heart rate variability in elderly subjects.

OBJECTIVES: The aim of this study was to test the hypothesis that abnormal scaling characteristics of heart rate (HR) predict sudden cardiac death in a random population of elderly subjects. BACKGROUND: An abnormality in the short-term fractal scaling properties of HR has been observed to be related to a risk of life-threatening arrhythmias among patients with advanced heart diseases. The predictive power of altered short-term scaling properties of HR in general populations is unknown. METHODS: A random sample of 325 subjects, age 65 years or older, who had a comprehensive risk profiling from clinical evaluation, laboratory tests and 24-h Holter recordings were followed up for 10 years. Heart rate dynamics, including conventional and fractal scaling measures of HR variability, were analyzed. RESULTS: At 10 years of follow-up, 164 subjects had died. Seventy-one subjects had died of a cardiac cause, and 29 deaths were defined as sudden cardiac deaths. By univariate analysis, a reduced short-term fractal scaling exponent predicted the occurrence of cardiac death (relative risk [RR] 2.5, 95% confidence interval [CI], 1.9 to 3.2, p < 0.001) and provided even stronger prediction of sudden cardiac death (RR 4.1, 95% CI, 2.5 to 6.6, p < 0.001). After adjusting for other predictive variables in a multivariate analysis, reduced exponent value remained as an independent predictor of sudden cardiac death (RR 4.3, 95% CI, 2.0 to 9.2, p < 0.001). CONCLUSIONS: Altered short-term fractal scaling properties of HR indicate an increased risk for cardiac mortality, particularly sudden cardiac death, in the random population of elderly subjects.

Cardiac interbeat interval dynamics from childhood to senescence : comparison of conventional and new measures based on fractals and chaos theory.

BACKGROUND: New methods of R-R interval variability based on fractal scaling and nonlinear dynamics ("chaos theory") may give new insights into heart rate dynamics. The aims of this study were to (1) systematically characterize and quantify the effects of aging from early childhood to advanced age on 24-hour heart rate dynamics in healthy subjects; (2) compare age-related changes in conventional time- and frequency-domain measures with changes in newly derived measures based on fractal scaling and complexity (chaos) theory; and (3) further test the hypothesis that there is loss of complexity and altered fractal scaling of heart rate dynamics with advanced age. METHODS AND RESULTS: The relationship between age and cardiac interbeat (R-R) interval dynamics from childhood to senescence was studied in 114 healthy subjects (age range, 1 to 82 years) by measurement of the slope, beta, of the power-law regression line (log power-log frequency) of R-R interval variability (10(-4) to 10(-2) Hz), approximate entropy (ApEn), short-term (alpha(1)) and intermediate-term (alpha(2)) fractal scaling exponents obtained by detrended fluctuation analysis, and traditional time- and frequency-domain measures from 24-hour ECG recordings. Compared with young adults (<40 years old, n=29), children (<15 years old, n=27) showed similar complexity (ApEn) and fractal correlation properties (alpha(1), alpha(2), beta) of R-R interval dynamics despite lower spectral and time-domain measures. Progressive loss of complexity (decreased ApEn, r=-0.69, P<0.001) and alterations of long-term fractal-like heart rate behavior (increased alpha(2), r=0.63, decreased beta, r=-0.60, P<0.001 for both) were observed thereafter from middle age (40 to 60 years, n=29) to old age (>60 years, n=29). CONCLUSIONS: Cardiac interbeat interval dynamics change markedly from childhood to old age in healthy subjects. Children show complexity and fractal correlation properties of R-R interval time series comparable to those of young adults, despite lower overall heart rate variability. Healthy aging is associated with R-R interval dynamics showing higher regularity and altered fractal scaling consistent with a loss of complex variability.

Blood vitamins, mineral elements and inflammation markers as risk factors of vascular and non-vascular disease mortality in an elderly population.

BACKGROUND: The need for protecting agents against degenerative processes of the body has been proposed to be especially high in elderly people. In order to evaluate the prognostic value of various biochemical factors in ageing the associations of blood concentrations of several vitamins, mineral elements and some other suggested risk factors with vascular and non-vascular mortality were studied in an elderly population. METHODS: A large health survey with complete clinical evaluation was carried out in the City of Turku in 1982-1983. A random sample of 344 community-living elderly individuals aged 65 years or older, stratified into four age groups, was studied. During the 13 years follow-up 225 subjects had died. Calcium, magnesium, copper, ceruloplasmin, zinc, selenium, iron, ferritin, transferrin, alpha-tocopherol, retinol, folate, vitamin B12, malondialdehyde, orosomucoid and insulin levels were analysed from the blood specimens. The relations between the compounds measured and relative mortality risks during the 13-year follow-up were analysed by Cox proportional hazards model adjusting for other known risk factors. RESULTS AND CONCLUSIONS: High concentrations of serum copper, orosomucoid and insulin were associated with increased risk of vascular mortality. The relative risks within the subjects of the highest tertile of serum concentrations were 2.2 for copper, 1.8 for orosomucoid, and 1.8 for insulin when adjusted for many confounding risk factors. Low serum vitamin B12 concentrations appeared to be significantly (P = 0.01) associated with increased vascular mortality. The associations were essentially not more significant when adjusted only for age. Contrary to earlier observations concentrations of serum magnesium, selenium, alpha-tocopherol, iron and its binding proteins or plasma and erythrocyte folate were not associated with increased mortality risk when adjusted for confounding risk factors. The authors suggest that in elderly subjects these elements and compounds are at the most weak, and probably non-independent risk factors for vascular mortality.

Environmental differences in twin pairs discordant for Alzheimer's disease.

The aim of this study was to examine the contribution of environmental factors to the pathogenesis of Alzheimer's disease by comparing environmental differences in twin pairs discordant for Alzheimer's disease. Seventy four twin pairs discordant for Alzheimer's disease were found by linking the Finnish twin cohort and the Hospital Discharge Register from years 1972-91. In 50 pairs (25 monozygotic and 25 dizygotic pairs), both co-twins had responded to a questionnaire survey in 1975. Exposure differences were compared between these pairs. A reduced risk of Alzheimer's disease was significantly associated with a higher level of schooling (relative risk 0.3; 95% confidence interval 0.1-0.9, p=0.029). In addition, a reduced risk was suggestively associated with ambidextrousness or left handedness (p=0.083) and an increased risk with marriage (p=0.052), widowhood (p=0.074), and a history of cholelithiasis (p=0.071). In conclusion, a reduced risk of Alzheimer's disease was associated with a higher level of schooling.

Power-law relationship of heart rate variability as a predictor of mortality in the elderly.

BACKGROUND: The prognostic role of heart rate (HR) variability analyzed from 24-hour ECG recordings in the general population is not well known. We studied whether analysis of 24-hour HR behavior is able to predict mortality in a random population of elderly subjects. METHODS AND RESULTS: A random sample of 347 subjects of > or =65 years of age (mean, 73+/-6 years) underwent a comprehensive clinical evaluation, laboratory tests, and 24-hour ECG recordings and were subsequently followed up for 10 years. Various spectral and nonspectral measures of HR variability were analyzed from the baseline 24-hour ECG recordings. Risk factors for all-cause, cardiac, cerebrovascular, cancer, and other causes of death were assessed. By the end of 10-year follow-up, 184 subjects (53%) had died and 163 (47%) were still alive. Seventy-four subjects (21%) had died of cardiac disease, 37 of cancer (11%), 25 of cerebrovascular disease (7%), and 48 (14%) of various other causes. Among all analyzed variables, a steep slope of the power-law regression line of HR variability (< -1.50) was the best univariate predictor of all-cause mortality (odds ratio, 7.9; 95% confidence interval [CI], 3.7 to 17.0; P<.0001). After adjusting for age and sex and including all univariate predictors of mortality in the proportional hazards analysis, ie, measures of HR variability, history of heart disease, functional class, smoking, medication, and blood cholesterol and glucose concentrations, all-cause mortality was predicted only by the slope of HR variability (adjusted relative risk, 1.74; 95% CI, 1.42 to 2.13; P<.0001) and a history of congestive heart failure (adjusted relative risk, 1.70; P=.0002). The slope of HR variability predicted both cardiac (adjusted relative risk, 2.05; P=.0002) and cerebrovascular death (adjusted relative risk, 2.84; P=.0001) but not cancer or other causes of death. CONCLUSIONS: Power-law relationship of 24-hour HR variability is a more powerful predictor of death than the traditional risk markers in elderly subjects. Altered long-term behavior of HR implies an increased risk of vascular causes of death rather than being a marker of any disease or frailty leading to death.

Lifestyle, stress, and genes in peptic ulcer disease: a nationwide twin cohort study.

BACKGROUND: The familial accumulation of peptic ulcer disease observed in several studies may be attributable to genetic effects, aggregation of environmental exposure (shared environment), or both. The intrafamilial spread of Helicobacter pylori infection has raised the question whether shared environment could explain the familial aggregation of peptic ulcer disease rather than genetic similarity of family members. OBJECTIVE: To examine the contribution of genetic and environmental factors to the pathogenesis of peptic ulcer disease in a nationwide population-based cohort of adult twins. METHODS: The Finnish Twin Cohort consists of all same-sexed twin pairs born before 1958 with both twins alive in 1975. The total number of twin pairs is 13888, of whom 4307 are monozygotic (MZ) and 9581 are dizygotic (DZ) twins. Questionnaire surveys of twins were carried out in 1975, 1981, and 1990, including medical and psychosocial questions. One question asked whether a physician had ever made a diagnosis of gastric or duodenal ulcer. In addition, hospital discharge data from 1972 to 1991 were linked with the twin cohort to obtain those twin individuals who had been treated for gastric or duodenal ulcer. The prevalence of and concordance for peptic ulcer disease were examined in MZ and DZ twins. Model-fitting analysis was used to specify the relative roles of genetic and environmental factors. The contribution of lifestyle factors and stress was examined prospectively in an incidence study and by comparison of discordant pairs. RESULTS: The prevalence of peptic ulcer disease was 6.2% in men and 2.8% in women in 1975. There were 63 MZ and 86 DZ pairs concordant for peptic ulcer disease. Concordance for disease was significantly higher in MZ than in DZ twin pairs; the probandwise concordance rate was 23.6% (95% confidence interval [CI], 20.9%-26.3%) in MZ twins and 14.8% (95% CI, 13.3%-16.3%) in DZ twins. In the model-fitting analysis, a model with both additive genetic and unshared environmental effects had the best goodness-of-fit. Thirty-nine percent (95% CI, 32%-47%) of the liability to peptic ulcer disease was explained by genetic factors and 61% (95% CI, 53%-68%) by individual environmental factors. In the incidence study (logistic regression analysis of the entire cohort initially free of peptic ulcer disease, with subjects diagnosed as having peptic ulcer after 1975 as cases), current smoking (relative risk, 2.2; 95% CI, 1.5-3.2) and high stress levels (relative risk, 3.2; 95% CI, 1.4-7.6) in men and regular use of analgesics (relative risk, 3.3; 95% CI, 1.3-8.1) in women predicted peptic ulcer disease during the follow-up from 1976 to 1991. In the analysis of discordant pairs, smoking in men and regular use of analgesics in both sexes were predictors of peptic ulcer disease. CONCLUSIONS: The questionnaire and hospital usage data on peptic ulcer disease in the population-based twin cohort suggest that the familial aggregation of the disease is modest, and attributable almost solely to genetic factors. Environmental effects not shared by family members were significant predictors of disease, and they were attributable to smoking and stress in men and the use of analgesics in women. The minor effects of shared environment to disease liability do not support the concept that the clustering of risk factors, such as H pylori infection, would explain the familial accumulation of peptic ulcer disease.

Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease: a community based follow up study.

OBJECTIVES: Biochemical markers for Alzheimer's disease would be of great value, especially to help in diagnosis early in the course of the disease. A pronounced increase in CSF tau protein (CSF-tau) is found in most patients with Alzheimer's disease. However, the specificity has to be further studied, as an increase in CSF-tau has also been found in other dementias, especially in vascular dementia. As most previous CSF studies have been based on selected inpatients, it was considered of special interest to examine the diagnostic potential of CSF-tau in a community population based sample of consecutive patients with dementia. Such patient material has been examined at the Piteå River Valley Hospital in Northern Sweden since 1986, and includes all those with memory disturbances in the community. The aim was also to study if an increase in CSF-tau is found early in the disease process, and whether CSF-tau changes during the progression of disease. PARTICIPANTS: Community population based sample of 75 demented patients (43 with Alzheimer's disease, 21 with vascular dementia, and 11 with mixed Alzheimer's disease/vascular dementia), 18 healthy subjects, and 18 neurological controls. A follow up investigation (including analysis of a new CSF sample) was performed in all patients after about one year. MAIN OUTCOME MEASURES: Concentrations of total (both normal tau and PHF-tau) tau in CSF, clinical measures (duration and severity of dementia), and apoE polymorphism. RESULTS: CSF-tau was markedly increased in Alzheimer's disease, 41/43 (95%) patients had values above the cut off level (mean+2 SD) in controls (306 pg/ml). High CSF-tau concentrations were also found in most patients with vascular dementia, preferentially in patients with vascular dementia without progressive leukoaraiosis on CT, whereas patients with vascular dementia with progressive leukoaraiosis had normal CSF-tau. Concentrations of CSF-tau were stable at one year follow up in both patients with Alzheimer's disease and patients with vascular dementia, and there was no correlation between CSF-tau and either duration or severity of dementia. CONCLUSIONS: The findings confirm the high sensitivity of CSF-tau for the diagnosis of Alzheimer's disease, but high CSF-tau was also found in vascular dementia, resulting in a lower specificity. However, high CSF-tau is preferentially found in patients with vascular dementia without progressive leukoaraiosis, which may constitute a group with concomitant Alzheimer's disease pathology. High CSF-tau may be present during the whole course of the disease in Alzheimer's disease. Possibly, therefore, the same high CSF-tau concentrations may be present before the onset of clinical dementia. Follow up studies on such patients will tell whether analysis of CSF-tau is useful as a biochemical marker for early Alzheimer's disease.

Cardiovascular and cancer morbidity and mortality and sudden cardiac death in postmenopausal women on oestrogen replacement therapy (ERT)

BACKGROUND: Advantages and disadvantages of postmenopausal oestrogen replacement therapy (ERT) are still not clear. We aimed to analyse the relation between postmenopausal oestrogen replacement therapy (ERT), cardiovascular disease, and cancer. METHODS: We examined 7944 women born between 1923 and 1930, who participated in a mammography screening for breast cancer, and who were followed up from 1987 to 1995. The follow-up consisted of 53,305 person-years. 988 women were current users and 757 were former users of ERT. Information about hormone use and health events was obtained through biennial questionnaires and recording and linking information from the hospital discharge registers of the region, the national cancer register, the social insurance reimbursement register, and the national death register. We used proportional-hazards models to calculate risk ratios and 95% CIs, adjusted for eight confounding variables. FINDINGS: Current ERT was associated with decreased cardiovascular mortality and a decrease in sudden cardiac death. Adjusted risk ratio (RR) for cardiovascular mortality in current users was 0.21 (95% CI 0.08-0.59) and in former users 0.75 (0.41-1.37). Absolute risk per 1000 person-years for deaths from acute myocardial infarction (AMI) was 1.1 in never users, 1.2 in former users, and 0.45 in current users (p=0.197). Corresponding absolute risk for other coronary-artery-disease (CAD) deaths was 1.0, 0.81, and 0 (p=0.009), and for deaths from stroke 1.2, 1.0, and 0.15 (p=0.012). Absolute risk for sudden cardiac death was 1.6 in never users, 1.0 in former users, and 0 in current users (p<0.001). Cardiovascular morbidity was not decreased by ERT: the RR for current use was 1.07 (0.86-1.32) and for former use 1.11 (0.89-1.39). Incidence of cardiovascular disease per 1000 person-years was 24.9 in never users, 23.4 in former users, and 20.9 in current users (p=0.153). Breast-cancer morbidity did not increase with current ERT--the RR was 0.57 (0.27-1.20). Incidence of breast cancer was 1.8, 1.6, and 1.0 in never, former, and current users (p=0.242). Endometrial cancer increased with current ERT--the RR was 5.06 (2.47-10.41). Incidence of endometrial cancer was 0.52 in never users, 0.51 in former users, and 2.1 in current users (p<0.001). INTERPRETATION: Current ERT reduced primarily sudden cardiac death and predicted reduced cardiovascular mortality, but did not reduce morbidity. ERT did not increase the risk of breast cancer, but was associated with increased risk of endometrial cancer.

Characteristics of Helicobacter pylori-negative and -positive peptic ulcer disease.

OBJECTIVE: To examine histological and other features of patients with Helicobacter pylori-positive (HP+) and -negative (HP-) peptic ulcers and characterize typical features of peptic ulcer in elderly patients. METHODS: 137 consecutive patients with peptic ulcer and 70 patients with dyspepsia were studied over 24 months. Endoscopy and a structured personal interview were carried out in all patients. Three histological specimens were obtained from the antral mucosa. RESULTS: The mean age of ulcer patients was 62.4 (SD 15.7) years and that of dyspepsia patients was 56.9 (SD 18.1) years (P=0.026). Of patients with HP- ulcers, 80.6% were aged 65 years or over; the corresponding proportion of patients with HP+ ulcer was 33.7% (P=0.0001). The use of non-steroidal anti-inflammatory analgesics was more common among those whose ulcer was HP- (69.4% vs 33%, P=0.0002). The occurrence of antral inflammation, atrophy and intestinal metaplasia did not differ between those with HP- and HP+ ulcers, but activity of gastritis was more common in HP+ than in HP- patients (94.9% vs 47.1%, P=0.0001). In the logistic regression analysis, HP- peptic ulcer disease was independently associated with older age, bile reflux, the use of non-steroidal anti-inflammatory analgesics and intestinal metaplasia, while HP+ ulcer disease was associated with active inflammation of the antral mucosa and tendency to ulcer recurrence. CONCLUSION: HP+ and HP- peptic ulcers have well-defined characteristics which probably reflect their different pathogenesis. Peptic ulcer disease of elderly people is mostly HP-.

Serum pepsinogen I and gastrin in peptic ulcer patients using nonsteroidal anti-inflammatory drugs.

BACKGROUND/AIMS: The inhibition of prostaglandin synthesis induced by nonsteroidal anti-inflammatory drugs (NSAIDs) have very complex effects on the gastric mucosa. They, for instance, inhibit mucosal cell proliferation in gastric ulcer patients. The aim of this study was to investigate whether these effects manifest as changes in pepsinogen I and gastrin concentrations. METHODOLOGY: Fasting serum pepsinogen I and gastrin samples were collected from 53 consecutive Helicobacter pylori (HP) positive peptic ulcer patients. Ulcer was diagnosed by endoscopy. The presence of HP was determined from the histological specimen taken from the antral mucosa. Histological changes in the gastric mucosa were evaluated according to the Sydney system. A structured personal interview was carried out with all patients at endoscopy, including detailed questions on the daily use of NSAIDs. Patients were divided into two groups according to their use of NSAIDs. RESULTS: The age-adjusted mean pepsinogen I concentration was significantly lower in patients who used NSAIDs compared to those who did not (91 vs 127 ng/l, p = 0.0035). There was no difference in the mean gastrin concentration between these two groups (91 vs 86 micrograms/l, p = 0.74). CONCLUSIONS: Serum pepsinogen I concentration was lower in HP positive peptic ulcer patients who used NSAIDs compared to those who did not.

Effect of serum lipids, lipoproteins, and apolipoproteins on vascular and nonvascular mortality in the elderly.

The purpose of this study was to determine the effect of serum lipids, lipoprotein fractions, and apolipoprotein (apo) A-1, B and E on mortality from vascular and nonvascular causes in an unselected elderly population. The random sample of 347 community-living individuals aged 65 years or older was obtained in 1982. Serum total cholesterol, LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglyceride, and apo A-1, B and E were determined at baseline. After the 11-year follow-up, 199 of the participants had died, and 148 were still alive. Mortality data from vascular and nonvascular causes by the end of 1993 were obtained from official registers. In the univariate analysis, a low total cholesterol level was associated with death due to both vascular and nonvascular causes (P value for trend, .021 and .0027, respectively). After the adjustment for other risk factors, the inverse association between total cholesterol and vascular mortality disappeared, but low total cholesterol was still a significant predictor of death due to nonvascular causes. Adjusted relative risks (RRs) of death due to nonvascular causes for those with elevated total cholesterol (5.1 to 6.5, 6.6 to 8.0, and > 8.0 mmol/L) compared with the reference group (< or = 5.0 mmol/L) were 0.5 (95% confidence interval [CI], 0.2 to 1.2), 0.6 (0.2 to 1.0), and 0.2 (0 to 0.8), respectively. Neither concentrations of HDL-C, LDL-C, triglyceride, nor apo B were associated with vascular or nonvascular mortality. On the other hand, low concentration of apo A-1 predicted vascular death. The RR for the lowest tertile was 1.6 (1.1 to 2.5) compared with the highest tertile. Furthermore, the occurrence of the apo E e4 allele was associated with increased risk of vascular mortality (RR, 1.5; 95% CI, 1.0 to 2.2), but the risk was not related to the levels of lipids, lipoproteins, or other apolipoproteins at baseline. Nonvascular mortality also tended to be predicted by the presence of the e4 allele (RR, 1.5; 95% CI, 0.9 to 2.5). In an unselected elderly population, the allelic variation of apo E, i.e., the presence of the e4 allele, and a low concentration of apo A-1 were more accurate indicators of vascular mortality than total cholesterol or lipoprotein fractions. The risk associated with the apo E polymorphism is unrelated to dyslipidemia.

Gangliosides and sulfatide in cerebrospinal fluid in leukoaraiosis.

The aim of the study was to evaluate gangliosides and sulfatide in cerebrospinal fluid (CSF) as markers for neuronal degeneration, gliosis, and demyelination in leukoaraiosis (LA). Lumbar CSF samples were taken from 37 elderly subjects with LA on computed tomography (CT). Patients with other pathology than LA or infarction on CT were excluded. In addition, CSF samples were collected from 16 elderly reference subjects without any neurological disease. Gangliosides GM1, GD1a, GD1b, GT1b, GD3, and sulfatide were determined. This concentration of the individual gangliosides and sulfatide showed no correlation with age. Gangliosides GD1b, GT1b, and GD3 were elevated in patients with mild LA compared to controls and patients with moderate or severe LA. GD1a was elevated in patients with mild LA compared to those with moderate LA. The concentration of sulfatide did not differ between the groups. When the patients were grouped in accordance to whether they had had cerebral infarction or not, differences between the groups were not found in the concentrations of any gangliosides and sulfatide. In conclusion, the analysis of CSF markers suggests that neuronal degeneration and gliosis predominate in the early stage of LA.

A marked increase in the incidence of colorectal cancer over two decades in southwest Finland.

The Finnish Cancer Registry's data on all colorectal cancer cases from 1971 to 1990 in southwest Finland, an area of mean population of 433,000, were analyzed. The age-adjusted incidence of colon cancer per 100,000 population increased in men from 8.5 in 1971-1980 to 13.5 in 1981-1990 and in women from 10.3 to 13.1. The incidence of male rectal cancer increased from 9.8 to 11.1 and in women from 6.4 to 7.1. The proportion of elderly patients clearly rose and, in 1981-1990, patients over 65 years of age had 68.4% of all colon cancers and 73.9% of all rectal cancers. There was a proximal shift in the site distribution of cancers: the proportion of rectal cancers decreased from 45.9% in 1971-1980 to 40.9% in 1981-1990. This change was most marked in men. There was no change in the spread and operability of colorectal cancers during the two decades. There was an increase in colon cancer mortality while the mortality of rectal cancer cancer slightly decreased.

Alzheimer's disease in twins.

Besides familial Alzheimer's disease (AD), the genetic susceptibility has also been found in sporadic cases of AD, mostly related to the apolipoprotein E polymorphism. The penetrance of AD is determined by age and probably by environmental exposure. Gene-environment interaction of a disease can be examined through studies of twins. The relative roles of genetic and environmental influences can be estimated by comparing the concordance rates between monozygotic (MZ) and dizygotic (DZ) twins. Genetic models can be used to specify contributions both from genetic as well as shared and unique environmental effects. The role of environmental factors can be investigated in the co-twin control study, either by comparing environmental exposure in MZ twins discordant for a disease or by comparing MZ twins discordant for an exposure suspected of causing a particular disease. The sampling of twin pairs AD can be carried out using voluntary recruitment, linkage of twin and hospital discharge registries or screening of twin registry population. Potential sources of biases in sampling are discussed. The majority of the published twin studies on AD are case reports or based on selected materials. In MZ pairs, the concordance rates for AD have varied between 31% and 83%. Only one co-twin control study in twins discordant for AD has been published. Published twin studies on AD are briefly reviewed.

Clinical presentation of peptic ulcer in the elderly.

The aim of this study was to determine the age-related characteristics of peptic-ulcer patients. A total of 125 consecutive patients (63 men and 62 women) with peptic ulcer were studied prospectively. The ulcers were diagnosed at endoscopy. The mean age of patients was 62 years (57 years in men and 68 in women). Patients were asked about their use of nonsteroidal anti-inflammatory drugs (NSAIDs). The main symptom, the duration of symptoms, the ulcer location and size, and the presence of Helicobacter pylori (HP) from the histologic specimen were recorded. Ulcer complications such as bleeding or perforation were also noted. These parameters were compared in two age groups: 65 years or under (n = 65) and over 65 years (n = 60). In the older age group, duodenal ulcer was less common (42 vs. 66%, p = 0.008) and typical epigastric pain was rare (35 vs. 91%, p < 0.001). Ulcer bleeding was present more commonly in the older age group (50 vs. 14%, p < 0.001). The duration of symptoms was shortest in patients who used NSAIDs, especially among older patients. Elderly patients also had an atypical location more often (39 vs. 15%, p = 0.003). After adjustment for use of NSAIDs, these characteristics remained among the elderly. The presence of HP was less common in the older age group (56 vs. 92%, p < 0.001). Furthermore, in the group of elderly patients who did not use NSAIDs, 35% were HP-negative. In conclusion, the presentation of peptic ulcer in the elderly has distinct characteristics, which are not entirely related to the use of NSAIDs.

Subjective quality of sleep and use of hypnotics in an elderly urban population.

To investigate the characteristics and subjective quality of sleep, the use of hypnotics and their correlates in an urban elderly population, a structured interview was administered to a stratified random sample of 600 elderly subjects in five age groups. Interrupted sleep and napping were common; nonetheless, 88% of the subjects considered their sleep at least satisfactory. According to specific criteria, 17% were good, 72% moderate and 11% poor sleepers. Habitual insomnia was reported by 12% of the subjects. Quality of sleep did not differ between age groups or genders. Hypnotics were habitually used by 8% of the men and 25% of the women. Consumption increased with age in both sexes, and 77% of the hypnotics were benzodiazepines. In multivariate regression analyses, insomnia and habitual use of hypnotics were associated with poor health, but only the latter with age and gender. As a conclusion, most of the subjects considered their sleep satisfactory, and aging itself did not seem to have an effect on the quality of sleep. The use of hypnotics was common, more prevalent in women and increased with age. Aging and poor health were independently associated with the use of hypnotics, but not with poor quality of sleep or insomnia.

Clinical presentation of bleeding peptic ulcer in the elderly.

The aim of this study was to evaluate the characteristics and risk factors of bleeding peptic ulcer in elderly people. The histories of 206 consecutive patients (110 men and 96 women) with peptic ulcer were examined from hospital records. The ulcer was confirmed by endoscopy, surgery or autopsy. Clinical parameters were compared in different age groups. The mean age of the patients with bleeding ulcer (N = 105) was 65.5 years compared to 57.1 years in those without bleeding (N = 101) (p = 0.0001). In the univariate analysis, the duration of symptoms was shorter than seven days in 84% of bleeders compared to 40% of non-bleeders (p = 0.0001). Ninety percent of the bleeding patients were painfree, compared to 23% of patients without bleeding (p = 0.0001). Even when patients using nonsteroidal anti-inflammatory drugs (NSAIDs) were excluded, short duration of symptoms as well as absence of epigastric pain were significantly associated with bleeding. The bleeders tended to use more NSAIDs than non-bleeders, but the difference was significantly only in patients who had used NSAIDs for 30 or fewer days. Atypically located as well as giant ulcers bled more often than typically situated ulcers or smaller ulcers. In the logistic regression analysis, advanced age, short duration of symptoms and absence of epigastric pain independently predicted bleeding of peptic ulcer. In conclusion, although bleeding is a complication of peptic ulcer, it can also be considered a variant type of ulcer with specific characteristics. Old age seems to be an independent risk factor for bleeding, but it has no effect on the clinical presentation of the disease.

Clinical features of leuko-araiosis.

OBJECTIVE: To study the clinical features of leuko-araiosis. METHODS: Age matched groups of patients with a CT finding of pure leukoaraiosis (n = 26) and a control group with a normal CT finding (n = 26) were formed (mean ages 78.6 (SD 3.3) v 76.5 (SD 4.6) years; NS). RESULTS: Dementia, vascular dementia, central brain atrophy on CT, disability in activities of daily living and instrumental activities of daily living, urinary incontinence, gait disorder (assistance needed), personality change, and night time confusion were found to be more commonly present in leuko-araiosis positive patients than in controls, whereas focal neurological symptoms and signs were not associated with leuko-araiosis. The occurrences of heart failure and systolic hypotension-but not hypertension-were higher in the leuko-araiosis positive group than in the controls. Leuko-araiosis was also found to be related to a less sudden onset of symptoms and a lower Hachinski score than true brain infarction(s). CONCLUSIONS: Leuko-araiosis on CT in these elderly patients seems to be a vascular disorder aetiologically different from brain infarction, with clinical manifestations of subtle onset and general disabling nature and no prominent focal neurological signs or symptoms.