Ismo Räihä

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.

Alzheimer's disease in Finnish twins

BACKGROUND The genetics of Alzheimers disease (AD) are obscure. Although most cases are sporadic half the patients with sporadic AD have a positive family history. The mode of genetic transmission and the role of environmental factors are unknown. The purpose of this study was to examine the contribution of genetic factors to the pathogenesis of AD in a twin cohort. METHODS The Finnish Twin Cohort consists of all Finnish same-sexed twin pairs born before 1958 with both co-twins alive in 1975. The total number of twin pairs is 13 888, of whom 4307 are monozygotic (MZ) and 9581 ar dizygotic (DZ). These data were linked with the Hospital Discharge Register from 1972 to 1991 to identify twins who had dementia or related disease as a discharge diagnosis. The linkage of the registries yielded a total of 285 twin individuals. The medical records of these twins and their co-twins were reviewed to confirm and classify dementia (AD, vascular dementia, mixed dementia, and other dementia). The incidence, concordance, and age at onset of AD were examined. FINDINGS The incidence of AD was significantly higher in MZ than in DZ twin individuals, with and adjusted MZ/DZ incidence ratio of 1.8 (95% confidence intervals 1.2 to 2.7). In contrast, the incidence of vascular or mixed dementia did not differ between MZ and DZ individuals (MZ/DZ ratio 0.6 [0.3 to 1.2]) for vascular and 1.0 [0.5 to 2.1] for mixed dementia). The pairwise concordance for AD was 18.6% in MZ pairs and 4.7% in DZ pairs and the corresponding probandwise concordance rates were 31.3% and 9.3%. The pairwise concordance for vascular dementia was 18.2% in MZ pairs and 6.7% in DZ pairs with corresponding probandwise rates of 30.8% and 12.5%. The onset age of AD concordant MZ pairs was identical in two pairs and diverged by up to 15 years. INTERPRETATION The higher incidence of AD in MZ individuals than in DZ individuals may provide a clue to the aetiology of AD. The higher concordance rate of MZ pairs confirms the contribution of the major genetic component while indicating the need to identify environmental triggers.

Characteristics of two telephone screens for cognitive impairment

We studied 56 subjects, 30 patients with a clinical diagnosis of Alzheimer’s disease (AD) and 26 healthy controls, using two telephone screens for cognitive impairment, a self-report interview referred to as the TELE and the Telephone Interview for Cognitive Status (TICS). The sensitivity and specificity of the TELE to differentiate AD patients from healthy controls was 90.0 and 88.5% and those of the TICS were 86.7 and 88.5%, respectively. When receiver operator characteristic curves were constructed, the area under the curve for the TELE was 96.0% (SE 2.4%) and for the TICS 90.3% (SE 4.2%). Pearson’s correlation between the TELE and the Mini-Mental State Examination (MMSE) was 0.87 (p < 0.0001) and between the TICS and the MMSE 0.86 (p < 0.0001). The correlation between the TELE and the sum of the boxes of the Clinical Dementia Rating scale (CDR-SB) was –0.71 (p < 0.0001) and –0.75 between the TICS and the CDR-SB (p < 0.0001). These results indicate that both screens are sensitive and specific instruments for differentiating AD patients from healthy controls and have a strong correlation with face-to-face measures of cognitive function.

Binge Drinking in Midlife and Dementia Risk

Background: Studies examining the long-term effects of alcohol consumption on cognitive functioning have produced conflicting results. Our goal was to determine whether a long follow-up period combined with information about drinking patterns, in addition to total alcohol consumption, would provide new insights about the relationship of alcohol use with dementia risk. Methods: A population-based cohort of 554 Finnish twins, who had provided data on alcohol consumption in questionnaires in 1975 and 1981, was followed for 25 years. Subjects were age 65 years or older at the time of dementia assessment in 1999–2001. Dementia risk was analyzed with respect to varying patterns of alcohol use by log-linear modeling, adjusted for age, sex, and education. Results: By the end of follow-up, 103 participants had developed dementia. Binge drinking (ie, alcohol exceeding the amount of 5 bottles of beer or a bottle of wine on 1 occasion at least monthly), as reported in 1975, was associated with a relative risk of 3.2 (95% confidence interval = 1.2–8.6) for dementia. Passing out at least twice as a result of excessive alcohol use during the previous year, as reported in 1981, was associated with a relative risk of 10.5 (2.4–46) for dementia in drinkers. Conclusions: Binge drinking in midlife is associated with an increased risk of dementia.

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.

Fractures as predictors of excess mortality in the aged—A population-based study with a 12-year follow-up

Introduction and objective The association between fractures and excess mortality in old age is ambiguous. The objective of this study was to analyze the long-term gender-specific association between fractures and mortality among older persons by controlling several survival related confounders. Methods A population-based prospective cohort study in the municipality of Lieto, south-western Finland. Data on health, health behaviour, fractures, and mortality in 482 men and 695 women aged 65 or older was collected from 1991 until 2002. The Cox Proportional Hazards regression model with fractures as time-dependent variables was used in the analyses. Results During the 12-year follow-up, 295 (25%) persons sustained at least one fracture. Sustaining any kind of fracture was related to excess mortality both in men (age-adjusted Hazards Ratio, HR 2.2, 95% confidence intervals, CI 1.6–3.1) and in women (HR 1.6, 95% CI 1.3–2.1). In the multivariate analyses, hip fractures in men (HR 8.1, 95% CI 4.4–14.9) and in women (HR 3.0, 95% CI 1.9–4.9), and proximal humerus fractures in men (HR 5.4, 95% CI 1.6–17.7) were related to increased mortality. Conclusion A hip fracture was a powerful independent predictor of long-term excess mortality in both genders but the risk in men was more than 2-fold compared to women. Proximal humerus fractures were associated with increased mortality in men. Actions to improve prevention, acute care and rehabilitation of fractures are needed in order to reduce excess mortality in older people.

Coffee drinking in middle age is not associated with cognitive performance in old age

BACKGROUND The lack of effective disease-modifying treatments highlights the need for research on the prevention of dementia. It has been suggested that coffee has a protective effect on cognitive performance in old age, but only some of the previous studies have shown this association. OBJECTIVE The aim of our study was to analyze the potential association between coffee drinking in middle age and cognitive performance in old age in a large sample of Finnish twins. DESIGN Coffee consumption and other baseline variables of 2606 middle-aged Finnish twins were assessed in 1975 and 1981 by postal questionnaires. After the median follow-up of 28 y, their cognitive status was measured by using a validated telephone interview questionnaire. RESULTS Coffee consumption was high and associated with educational level and several other baseline variables. After adjustment for these variables, linear regression analysis showed that coffee consumption was not an independent predictor of cognitive performance in old age (beta = -0.12 test score units per coffee cup; 95% CI: -0.27, 0.04). No consistent differences in coffee consumption and cognitive score were observed within discordant twin pairs. Also, coffee drinking did not affect the risk of mild cognitive impairment or dementia. CONCLUSIONS Coffee drinking is associated with many sociodemographic and health variables, but our results do not support an independent role of coffee in the pathogenesis of cognitive decline and dementia.

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.

Midlife sleep characteristics associated with late life cognitive function.

STUDY OBJECTIVES Previous studies with limited follow-up times have suggested that sleep-related traits are associated with an increased risk of incident dementia or cognitive decline. We investigated the association between midlife sleep characteristics and late life cognitive function. DESIGN A follow-up study with a median follow-up time of 22.5 (range 15.8-25.7) years assessing the association between midlife sleep characteristics and later cognitive function. SETTING Questionnaire data from 1981 were used in the assessment of sleep characteristics, use of hypnotics, and covariates at baseline. Between 1999 and 2007, participants were assigned a linear cognitive score with a maximum score of 51 based on a telephone interview (mean score 38.3, SD 6.1). Linear regression analyses were controlled for age, sex, education, ApoE genotype, and follow-up time. PARTICIPANTS 2,336 members of the Finnish Twin cohort who were at least 65 years of age. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Baseline short (< 7 h/day) and long (> 8 h/day) sleepers had lower cognitive scores than participants sleeping 7-8 h/ day (β = -0.84, P = 0.014 and β = -1.66, P < 0.001, respectively). As compared to good sleep quality, poor or rather poor sleep quality was associated with a lower cognitive score (β = -1.00, P = 0.011). Also, the use of hypnotics ≥ 60 days per year was associated with poorer cognitive function (β = -1.92, P = 0.002). CONCLUSIONS This is the first study indicating that midlife sleep length, sleep quality, and use of hypnotics are associated with late life cognitive function. Further confirmation is needed, but sleep-related characteristics may emerge as new risk factors for cognitive impairment.

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.