Psychoeducation for bipolar disorder and risk of recurrence and hospitalization - a within-individual analysis using registry data.

BACKGROUND: The efficacy of psychoeducation for bipolar disorder has been demonstrated in clinical trials, but it is not known if the results translate into effectiveness in routine clinical practice. The aim was to determine the effectiveness of psychoeducation for bipolar disorder in a routine clinical setting. METHOD: We identified 2819 patients with at least three registrations in the Swedish Quality Assurance Register for Bipolar Disorder. Among those, 402 had not been exposed to psychoeducation at the first visit, but received psychoeducation during any of the following registrations. Using within-individual analyses, the risk of recurrence after having received psychoeducation was compared with the risk prior to psychoeducation. RESULTS: In adjusted within-individuals comparisons, periods after psychoeducation was associated with decreased risks of any recurrence [odds ratio (OR) 0.57, 95% CI 0.42-0.78], (hypo-)manic or mixed episodes (OR 0.54, 95% CI 0.39-0.76), depressive episodes (OR 0.63, 95% CI 0.47-0.86), and inpatient care (OR 0.54, 95% CI 0.33-0.86) relative to periods prior to psychoeducation. There was no association with rates of involuntary sectioning or suicide attempts. CONCLUSIONS: The results suggest that psychoeducation for bipolar disorder reduces the risk of mood episodes and inpatient care also when implemented in routine clinical practice.

Is the prevalence of psychosis in the very old decreasing? A comparison of 85-year-olds born 22 years apart.

OBJECTIVE: To elucidate whether there is a decrease of psychotic symptoms in 85-years-olds without dementia and if factors associated with psychotic symptoms have changed, we studied two birth cohorts of 85-year-olds born 22 years apart. METHODS: Every second, 85-year-olds in Gothenburg, Sweden was invited to neuropsychiatric examinations in 1986 to 1987 (participation 63.1%, N = 494) and in 2008 to 2010 (60.5%, N = 571). A close informant was interviewed by a psychiatrist or a research psychologist. RESULTS: The prevalence of psychotic symptoms in 85-years-olds without dementia decreased from 10.1% in 1986 to 1987 to 3.2% in 2008 to 2010 (P < .001). Disability in daily life (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.1-4.5), depressed mood (OR, 3.9; 95% CI, 2.1-7.1), irritability (OR, 3.6; 95% CI, 1.2-10.5), and suicidal ideation (OR, 4.1; 95% CI, 2.1-8.0) were associated with psychotic symptoms in both cohorts. Mean mini-mental state examination (MMSE) score was lower in those with psychotic symptom compared with those with no psychotic symptoms (Cohort 1986-1987, 26.4 vs 27.8, Cohort 2008-2009, 26.1 vs 27.7, t value -4.24, Pr > t < 0.001). CONCLUSION: The prevalence of psychotic symptoms decreased between 1986 to 1987 and 2008 to 2010 among 85-years-olds without dementia. These symptoms were associated with broad psychopathology, worse performance in cognitive testing, and with disability of daily life in both cohorts.

A 10-Year Follow-Up of Adiposity and Dementia in Swedish Adults Aged 70 Years and Older.

BACKGROUND: Adiposity measured in mid- or late-life and estimated using anthropometric measures such as body mass index (BMI) and waist-to-hip ratio (WHR), or metabolic markers such as blood leptin and adiponectin levels, is associated with late-onset dementia risk. However, during later life, this association may reverse and aging- and dementia-related processes may differentially affect adiposity measures. OBJECTIVE: We explored associations of concurrent BMI, WHR, and blood leptin and high molecular weight adiponectin levels with dementia occurrence. METHODS: 924 Swedish community-dwelling elderly without dementia, aged 70 years and older, systematically-sampled by birth day and birth year population-based in the Gothenburg city region of Sweden. The Gothenburg Birth Cohort Studies are designed for evaluating risk and protective factors for dementia. All dementias diagnosed after age 70 for 10 years were identified. Multivariable logistic regression models were used to predict dementia occurrence between 2000-2005, 2005-2010, and 2000-2010 after excluding prevalent baseline (year 2000) dementias. Baseline levels of BMI, WHR, leptin, and adiponectin were used. RESULTS: Within 5 years of baseline, low BMI (<20 kg/m2) was associated with higher odds of dementia compared to those in the healthy BMI category (≥ 20-24.9 kg/m2). Compared to the lowest quartile, leptin levels in the second quartile were associated with lower odds of dementia in women (p < 0.05). CONCLUSION: In late-life, anthropometric and metabolic adiposity measures appear to be differentially associated with dementia risk. While BMI and leptin levels are highly positively correlated, our results show that their association with dementia at age ≥70 years, is asynchronous. These data suggest that with aging, the complexity of the adiposity exposure may increase and suggests metabolic dysregulation. Additional studies are needed to better understand this complexity.

Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium.

Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence.

A Longitudinal Study of the Mini-Mental State Examination in Late Nonagenarians and Its Relationship with Dementia, Mortality, and Education.

OBJECTIVES: To examine level of and change in cognitive status using the Mini-Mental State Examination (MMSE) in relation to dementia, mortality, education, and sex in late nonagenarians. DESIGN: Three-year longitudinal study with examinations at ages 97, 99, and 100. SETTING: Trained psychiatric research nurses examined participants at their place of living. PARTICIPANTS: A representative population-based sample of 97-year-old Swedes (N = 591; 107 men, 484 women) living in Gothenburg, Sweden. MEASUREMENTS: A Swedish version of the MMSE was used to measure cognitive status. Geriatric psychiatrists diagnosed dementia according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Mixed models were fitted to the data to model the longitudinal relationship between MMSE score and explanatory variables. RESULTS: Individuals with dementia between age 97 and 100 had lower mean MMSE scores than those without dementia. Those who died during the 3-year follow-up had lower MMSE scores than those who survived. MMSE scores at baseline did not differ between those without dementia and those who developed dementia during the 3-year follow-up. Participants with more education had higher MMSE scores, but there was no association between education and linear change. CONCLUSION: MMSE score is associated with dementia and subsequent mortality even in very old individuals, although the preclinical phase of dementia may be short in older age. Level of education is positively associated with MMSE score but not rate of decline in individuals approaching age 100.

Changes in the Lethality of Frailty Over 30 Years: Evidence From Two Cohorts of 70-Year-Olds in Gothenburg Sweden.

BACKGROUND: With aging, health deficits accumulate: people with few deficits for their age are fit, and those with more are frail. Despite recent reports of improved health in old age, how deficit accumulation is changing is not clear. Our objectives were to evaluate changes over 30 years in the degree of deficit accumulation and in the relationship between frailty and mortality in older adults. METHODS: We analyzed data from two population based, prospective longitudinal cohorts, assembled in 1971-1972 and 2000-2001, respectively. Residents of Gothenburg Sweden, systematically drawn from the Swedish population registry. The 1901-1902 cohort (N = 973) had a response rate of 84.8%; the 1930 cohort (N = 500) had a response rate of 65.1%. A frailty index using 36 deficits was calculated using data from physical examinations, assessments of physical activity, daily, sensory and social function, and laboratory tests. We evaluated mortality over 12.5 years in relation to the frailty index. RESULTS: Mean frailty levels were the same (x¯ = 0.20, p = .37) in the 1901-1902 cohort as in the 1930 cohort. Although the frailty index was linked to the risk of death in both cohorts, the hazards ratio decreased from 1.67 per 0.1 increment in the frailty index for the first cohort to 1.32 for the second cohort (interaction term p = .005). DISCUSSION: Although frailty was as common at age 70 as before, its lethality appears to be less. Just why this is so should be explored further.

37 Years of Body Mass Index and Dementia: Effect Modification by the APOE Genotype: Observations from the Prospective Population Study of Women in Gothenburg, Sweden.

BACKGROUND: Overweight and obesity in mid- and late-life may increase risk for dementia, whereas a decline in body weight or body mass index (BMI) and underweight in years preceding a clinical dementia diagnosis are also associated with dementia. Little is known about the modifying effect of the APOE genotype, a major susceptibility gene for Alzheimer's disease (AD), on the BMI-dementia adult life course trajectory. OBJECTIVE: We evaluated the exposure, BMI, in relationship to the outcome, clinical dementia, over 37 years, considering the effect modification of the APOE ɛ4 allele. METHODS: The Prospective Population Study of Women (PPSW) in Sweden is a systematic sample of 1462 women born 1908, 1914, 1918, 1922, and 1930 and aged 38-60 years at baseline. Examinations occurred in 1968, 1974, 1980, 1992, 2000, and 2005; 559 women had information on dementia, BMI, and APOE ɛ4 allele status, in addition to covariates. Statistical analyses were conducted using mixed effects regression models. RESULTS: Trajectories of BMI over 37 years differed by APOE ɛ4 allele status. While women gained BMI similarly from mid-life to age 70 years, women with at least one APOE ɛ4 allele experienced BMI decline more quickly after age 70 years compared to women without an APOE ɛ4 allele. However, upon stratifying the sample by dementia occurrence, it appeared that dementia drove the overall BMI-trajectory. There was a main effect of age, interactions of age by APOE ɛ4 allele status, and age by presence versus absence of dementia. CONCLUSIONS: Women with similar average BMI at mid-life exhibited different BMI trajectories in relation to dementia occurrence. In addition, the pattern of BMI decline in late-life differed on the basis of APOE ɛ4 allele possession. Thus, these data suggest roles for both dementia- and APOE-associated changes in BMI during the adult life course.

Functional disability and death wishes in older Europeans: results from the EURODEP concerted action.

PURPOSE: Physical illness has been shown to be a risk factor for suicidal behaviour in older adults. The association between functional disability and suicidal behaviour in older adults is less clear. The aim of this study was to examine the relationship between functional disability and death wishes in late life. METHODS: Data from 11 population studies on depression in persons aged 65 and above were pooled, yielding a total of 15,890 respondents. Level of functional disability was trichotomised (no, intermediate, high). A person was considered to have death wishes if the death wish/suicidal ideation item of the EURO-D scale was endorsed. Odds ratios for death wishes associated with functional disability were calculated in a multilevel logistic regression model. RESULTS: In total, 5 % of the men and 7 % of the women reported death wishes. Both intermediate (OR 1.89, 95 % CI 1.42; 2.52) and high functional disability (OR 3.22, 95 % CI 2.34; 4.42) were associated with death wishes. No sex differences could be shown. Results remained after adding depressive symptoms to the model. CONCLUSIONS: Functional disability was independently associated with death wishes in older adults. Results can help inform clinicians who care for older persons with functional impairment.

Prevalence of obsessive-compulsive disorder in relation to depression and cognition in an elderly population.

OBJECTIVES: We examined the 1-month prevalence of obsessive-compulsive disorder (OCD) and obsessive-compulsive symptoms (OCS) not fulfilling OCD criteria in relation to sex, age, social and mental function, comorbid depression, and cognitive functioning in an elderly nondemented population. SETTINGS AND PARTICIPANTS: Population-based sample (N = 900), stratified into two age groups: 70-year-olds (335 women and 224 men) and those aged 78 and above (341 women). MEASUREMENTS: Semi-structured interviews. Psychiatric symptoms were assessed with the Comprehensive Psychopathological Rating Scale and Mini-International Neuropsychiatric Interview, mental and social function with the GAF-scale, memory function with the Word Recall Task and general cognition with MMSE. OCD and Depression were diagnosed according to DSM-IV. RESULTS: The one-month prevalence of OCD was 2.9%; a further 21% had OCS. Among 70-year-olds, the prevalence of OCD was 1.3% in men and 4.5% in women. Depression was more common among those with OCD (34.6%) than among those with (12.7%) and without (8.0%) OCS. GAF-score was lower among those with OCD (74.8) and OCS (82.9) compared with individuals without obsessions and compulsions (88.2). The association between OCD and GAF-score remained after adjustment for age, sex, and depression. The OCD subgroup with checking behavior had more memory and concentration problems and did worse on Word Recall Task than other groups in our sample. CONCLUSIONS: We found that OCD and OCS are common among the elderly. Both conditions are related to depression and poorer mental and social functioning. Physicians who meet elderly patients need to be aware of OCD as it is potentially treatable.

Paranoid symptoms and hallucinations among the older people in Western Europe.

OBJECTIVE: It is not clear whether the prevalence of psychosis increases with age. We studied the age-specific prevalence of psychotic symptoms in older people in Western Europe. METHODS: Older people without dementia (age 65-104 years, N = 8762) from the western part of Europe in the EURODEP concerted action took part in psychiatric examinations. RESULTS: In total, 2.4% of the men and 2.9% of the women had psychotic symptoms. Using a multilevel logistic regression model that included gender and age as a continuous variable, we found that a 5-year increase in age increased the prevalence of psychotic symptoms (odds ratio 1.2 95% confidence interval 1.06-1.3, p = 0.001). A second multilevel regression model showed that wishing to be dead, depressed mood, functional disability, not being married and cognitive impairment measured with Mini mental state examination were all associated with psychotic symptoms whereas gender was not. CONCLUSION: The prevalence of psychotic symptoms in non-demented older people increases with age, and these symptoms are associated with other psychopathology, social isolation and problems with daily living.

Leptin and dementia over 32 years-The Prospective Population Study of Women.

BACKGROUND: We have shown that high mid-life central adiposity may increase the risk for dementia after 32 years. Leptin, an adipose tissue hormone, is correlated with adiposity measures and may contribute to a better etiological understanding of the relationship between high adiposity and dementia. We explored the relationship between serum leptin in mid-life and dementia, which is a late-life outcome. METHODS: A longitudinal cohort study, the Prospective Population Study of Women, in Gothenburg, Sweden, includes a representative sample of 1462 women followed from mid-life ages of 38 to 60 years to late-life ages of 70 to 92 years. Women were examined in 1968, 1974, 1980, 1992, and 2000 using neuropsychiatric, anthropometric, clinical, and other measurements. Serum leptin was measured on samples collected at the 1968 baseline examination, after storage at -20°C for 29 years. Cox proportional hazards regression models estimated incident dementia risk by baseline leptin. Logistic regression models related leptin levels to dementia among surviving participants 32 years later. All models were adjusted for multiple potential confounders. RESULTS: Mid-life leptin was not related to dementia risk using Cox or logistic regression models. This was observed despite positive baseline correlations between leptin and adiposity measures, and given our previous report of high mid-life waist-to-hip ratio being related to a twofold higher dementia risk. CONCLUSIONS: Leptin is not a mid-life marker of late-life dementia risk in this population sample of Swedish women born between 1908 and 1930.

Blood pressure trajectories from midlife to late life in relation to dementia in women followed for 37 years.

Higher midlife blood pressure increases risk for dementia. To further understand the relation between blood pressure and dementia, it is necessary to examine evolution of blood pressure from midlife to late life. We examined blood pressure trajectories using linear mixed models in a representative sample of middle-aged women (N=1462) who were followed from 1968-1969 until 2005-2006 with comprehensive medical and neuropsychiatric examinations. Dementia was diagnosed according to established criteria. Among those not treated with antihypertensives, higher systolic blood pressure at baseline but not blood pressure trajectories from 1968 to 1992 was associated with dementia and Alzheimer disease. Those with history of antihypertensive treatment had higher baseline systolic blood pressure than those who were never treated. In this group, those who developed dementia and Alzheimer disease had lower baseline systolic blood pressure and steeper increase in systolic blood pressure from 1968 to 1992 than those who did not. A steeper decline in systolic blood pressure during the later part of the study was observed in those who developed dementia regardless of antihypertensive treatment. The latter association was attenuated or disappeared when adjusting for body mass index. The association between blood pressure and dementia is complex and influenced by antihypertensive treatment. The findings emphasize the importance of detecting increased blood pressure in midlife and controlling blood pressure in those treated. Whether the trajectory of blood pressure is a risk factor or part of the clinical course of dementia needs to be elucidated.

37 years of body mass index and dementia: observations from the prospective population study of women in Gothenburg, Sweden.

Level of adiposity is linked to dementia in epidemiological studies. Overweight and obesity in mid- and late-life may increase risk for dementia, whereas decline in body weight or body mass index (BMI) and underweight in years preceding and at the time of a dementia diagnosis may also relate to dementia. Longitudinal studies with sufficient follow-up are necessary to estimate trajectories that allow better understanding of the relationship between adiposity indices and dementia over the life course. We evaluated the natural history of BMI in relationship to clinical dementia over 37 years in the Prospective Population Study of Women (PPSW) in Sweden. PPSW is a systematic sample of 1462 women born 1908, 1914, 1918, 1922, and 1930 and aged 38-60 years at baseline. Examinations occurred in 1968, 1974, 1980, 1992, 2000, and 2005. Statistical analyses were conducted using mixed effects regression models. Trajectories of BMI over 37 years as a function of age differed between women who did versus did not develop dementia. Women developing dementia evidenced a lesser increase in BMI from age 38 to 70 years. After age 70, the BMI slope decreased similarly (no "accelerated decline") irrespective of dementia status. A lower BMI before and during dementia onset was observed. Women with similar BMI at mid-life exhibited a different pattern of BMI change as they approached late-life that was related to dementia onset. BMI may be a potential marker of dementia-related neuropathologies in the brain. Dementia is related to a common risk factor, BMI, from mid-to late-life.

Prematurely ended phase III trials in Sweden during the years 2002-2008.

PURPOSE: The aim of this study was to identify prematurely ended phase III clinical trials (CTs) and the proportion of such trials among all phase III CTs, review the reasons for the premature discontinuation of the CT, determine whether a data monitoring committee (DMC) was involved in this decision-making process, identify the data source on which the decision was based and review the consequences of the premature ending for product development. An additional aim was to identify risk factors for a premature ending. METHODS: Prematurely ended phase III CTs in Sweden between 2002 and 2008 were identified by database searches. Identified trials were reviewed for treatment tested, study design, reasons for the premature ending, data source on which the decision was based and existence of and recommendation from a DMC. Three randomly selected but not prematurely ended control trials were identified, starting 1 May 2004, that were matched on the basis of application year. RESULTS: A total of 84 phase III CT applications (8%) were prematurely ended during the study period. Most trials were ended due to safety and/or efficacy concerns. A DMC was more common among trials in which mortality was the primary endpoint and oncology trials. A recommendation from the DMC to terminate the trial was most likely in the case of combined safety- and efficacy-related issues arising from within the trial. Possible risk factors for a premature ending included mortality as an endpoint, obesity as an indication and a longer than planned study duration. Approximately 30% of prematurely ended trials with active substances that did not have a marketing authorization at the time of the clinical trial application resulted in the discontinuation of further development of the substance. CONCLUSIONS: The DMCs in the phase III CTs reviewed here were used in accordance with guidelines. The use of DMCs was associated with possible risk factors for a premature ending and numerically, but not significantly associated with a premature ending.