Svante Östling

High total cholesterol levels in late life associated with a reduced risk of dementia

Objective: To examine the longitudinal association between plasma total cholesterol and triglyceride levels and incident dementia. Methods: Neuropsychiatric, anthropometric, laboratory, and other assessments were conducted for 392 participants of a 1901 to 1902 birth cohort first examined at age 70. Follow-up examinations were at ages 75, 79, 81, 83, 85, and 88. Information on those lost to follow-up was collected from case records, hospital linkage system, and death certificates. Cox proportional hazards regression examined lipid levels at ages 70, 75, and 79 and incident dementia between ages 70 and 88. Results: Increasing cholesterol levels (per mmol/L) at ages 70 (hazard ratio [HR] 0.77, 95% CI: 0.61 to 0.96, p = 0.02), 75 (HR 0.70, CI: 0.52 to 0.93, p = 0.01), and 79 (HR 0.73, CI: 0.55 to 0.98, p = 0.04) were associated with a reduced risk of dementia between ages 79 and 88. Examination of cholesterol levels in quartiles showed that the risk reduction was apparent only among the highest quartile at ages 70 (8.03 to 11.44 mmol/L [311 to 442 mg/dL]; HR 0.31, CI: 0.11 to 0.85, p = 0.03), 75 (7.03 to 9.29 mmol/L [272 to 359 mg/dL]; HR 0.20, CI: 0.05 to 0.75, p = 0.02), and 79 (6.82 to 9.10 mmol/L [264 to 352 mg/dL]; HR 0.45, CI: 0.17 to 1.23, p = 0.12). Triglyceride levels were not associated with dementia. Conclusions: High cholesterol in late life was associated with decreased dementia risk, which is in contrast to previous studies suggesting high cholesterol in mid-life is a risk factor for later dementia. The conflicting results may be explained by the timing of the cholesterol measurements in relationship to age and the clinical onset of dementia.

Midlife psychological stress and risk of dementia: a 35-year longitudinal population study

The number of people with dementia has increased dramatically with global ageing. Nevertheless, the pathogeneses of these diseases are not sufficiently understood. The present study aims to analyse the relationship between psychological stress in midlife and the development of dementia in late-life. A representative sample of females (n = 1462) aged 38-60 years were examined in 1968-69 and re-examined in 1974-75, 1980-81, 1992-93 and 2000-03. Psychological stress was rated according to a standardized question in 1968, 1974 and 1980. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders criteria based on information from neuropsychiatric examinations, informant interviews, hospital records and registry data. During the 35-year follow-up, 161 females developed dementia (105 Alzheimers disease, 40 vascular dementia and 16 other dementias). We found that the risk of dementia (hazard ratios, 95% confidence intervals) was increased in females reporting frequent/constant stress in 1968 (1.60, 1.10-2.34), in 1974 (1.65, 1.12-2.41) and in 1980 (1.60, 1.01-2.52). Frequent/constant stress reported in 1968 and 1974 was associated with Alzheimers disease. Reporting stress at one, two or three examinations was related to a sequentially higher dementia risk. Compared to females reporting no stress, hazard ratios (95% confidence intervals) for incident dementia were 1.10 (0.71-1.71) for females reporting frequent/constant stress at one examination, 1.73 (1.01-2.95) for those reporting stress at two examinations and 2.51 (1.33-4.77) at three examinations. To conclude, we found an association between psychological stress in middle-aged women and development of dementia, especially Alzheimers disease. More studies are needed to confirm our findings and to study potential neurobiological mechanisms of these associations.

The incidence of first-onset depression in a population followed from the age of 70 to 85.

BACKGROUND Due to the limited data available, it is not clear whether the incidence of first-onset depression varies with age in the elderly. METHODS A representative sample of individuals born 1901-2 (N = 392) was examined at the ages of 70, 75, 79, 81, 83 and 85 years by psychiatrists using a semi-structured schedule. Information on depressive episodes was also collected from self-report and examination of case records. Depression was diagnosed according to the DSM-III-R criteria. RESULTS The incidence of depression was 12 per 1,000 person-years in men and 30 per 1,000 person-years in women between the ages of 70 and 85 (sex difference P = 0.001). The incidence increased from 17 per 1,000 person-years (men 8.7, women 23.2, P = 0.007) between the ages of 70 and 79 to 44 per 1,000 person years (men 27.0, women 52.8, P = 0.166) between 79 and 85 (age difference: RR 2.6, P < 0.001; men RR 3.1, P = 0.036; women RR 2.3, P = 0.003). A diagnosis of depression was associated with increased mortality and refusal rate during the 15-year follow-up. Previous episodes of depression were associated with an increased risk of further episodes. The prevalence of depression increased from 5.6% at the age of 70 to 13.0% at the age of 85. The lifetime prevalence of depression was 23% in men and 45% in women. CONCLUSIONS Both the incidence and prevalence of depression increased with age in this longitudinally followed birth cohort, and the incidence was higher in women than in men.

Adiposity indicators and dementia over 32 years in Sweden

Background: High midlife and late-life adiposity may increase risk for dementia. Late-life decrease in body mass index (BMI) or body weight within several years of a dementia diagnosis has also been reported. Differences in study designs and analyses may provide different pictures of this relationship. Methods: Thirty-two years of longitudinal body weight, BMI, waist circumference, and waist-to-hip ratio (WHR) data, from the Prospective Population Study of Women in Sweden, were related to dementia. A representative sample of 1,462 nondemented women was followed from 1968 at ages 38-60 years, and subsequently in 1974, 1980, 1992, and 2000, using neuropsychiatric, anthropometric, clinical, and other measurements. Cox proportional hazards regression models estimated incident dementia risk by baseline factors. Logistic regression models including measures at each examination were related to dementia among surviving participants 32 years later. Results: While Cox models showed no association between baseline anthropometric factors and dementia risk, logistic models showed that a midlife WHR greater than 0.80 increased risk for dementia approximately twofold (odds ratio 2.22, 95% confidence interval 1.00-4.94, p = 0.049) among surviving participants. Evidence for reverse causality was observed for body weight, BMI, and waist circumference in years preceding dementia diagnosis. Conclusions: Among survivors to age 70, high midlife waist-to-hip ratio may increase odds of dementia. Traditional Cox models do not evidence this relationship. Changing anthropometric parameters in years preceding dementia onset indicate the dynamic nature of this seemingly simple relationship. There are midlife and late-life implications for dementia prevention, and analytical considerations related to identifying risk factors for dementia. ADCVD = AD with cerebrovascular disease; BMI = body mass index; DBP = diastolic blood pressure; DSM-III-R = Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised; HAAS = Honolulu Asia Aging Study; PPSW = Prospective Population Study of Women; SBP = systolic blood pressure; SES = socioeconomic status; VaD = vascular dementia; WHR = waist-to-hip ratio.

Attempted suicide in the elderly: characteristics of suicide attempters 70 years and older and a general population comparison group

OBJECTIVE To identify factors associated with attempted suicide in the elderly. DESIGN Social, psychological, and psychiatric characteristics were compared in suicide attempters (70 years and older) and a representative population sample. SETTINGS Emergency departments at five hospitals in western Sweden and a representative sample of the elderly population. PARTICIPANTS Persons with Mini Mental State Examination (MMSE) score <15 were excluded. One hundred forty persons who sought hospital treatment after a suicide attempt were eligible and 103 participated (57 women, 46 men, and mean age 80 years). Comparison subjects matched for gender and age group (N = 408) were randomly selected among participants in our general population studies. MEASUREMENTS Symptoms were rated with identical instruments in cases and comparison subjects. The examination included the MMSE and tests of short- and long-term memory, abstract thinking, aphasia, apraxia, and agnosia. Depressive symptomatology was measured using the Montgomery-Asberg Depression Rating Scale, and major and minor depressions were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, using symptom algorithms. RESULTS Factors associated with attempted suicide included being unmarried, living alone, low education level, history of psychiatric treatment, and previous suicide attempt. There was no association with dementia. Odds ratios were increased for both major (odds ratio [OR]: 47.4, 95% confidence interval [CI]: 19.1-117.7) and minor (OR: 2.6, 95% CI: 1.5-4.7) depressions. An association was observed between perceived loneliness and attempted suicide; this relationship was independent of depression (OR: 2.8, 95% CI: 1.3-6.1). CONCLUSIONS Observed associations mirrored those previously shown for completed suicide. Results may help to inform clinical decisions regarding suicide risk evaluation in this vulnerable and growing age group.

The 32-year relationship between cholesterol and dementia from midlife to late life

Background: Cellular and animal studies suggest that hypercholesterolemia contributes to Alzheimer disease (AD). However, the relationship between cholesterol and dementia at the population level is less clear and may vary over the lifespan. Methods: The Prospective Population Study of Women, consisting of 1,462 women without dementia aged 38–60 years, was initiated in 1968–1969 in Gothenburg, Sweden. Follow-ups were conducted in 1974–1975, 1980–1981, 1992–1993, and 2000–2001. All-cause dementia was diagnosed according to DSM-III-R criteria and AD according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimers Disease and Related Disorders Association criteria. Cox proportional hazards regression examined baseline, time-dependent, and change in cholesterol levels in relation to incident dementia and AD among all participants. Analyses were repeated among participants who survived to the age of 70 years or older and participated in the 2000–2001 examination. Results: Higher cholesterol level in 1968 was not associated with an increased risk of AD (highest vs lowest quartile: hazard ratio [HR] 2.82, 95% confidence interval [CI] 0.94–8.43) among those who survived to and participated in the 2000–2001 examination. While there was no association between cholesterol level and dementia when considering all participants over 32 years, a time-dependent decrease in cholesterol over the follow-up was associated with an increased risk of dementia (HR 2.35, 95% CI 1.22–4.58). Conclusion: These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia. Declining cholesterol levels from midlife to late life may better predict AD risk than levels obtained at one timepoint prior to dementia onset. Analytic strategies examining this and other risk factors across the lifespan may affect interpretation of results.

Alcoholic Beverages and Incidence of Dementia: 34-Year Follow-up of the Prospective Population Study of Women in Göteborg

The objective of this study was to assess the association between different types of alcoholic beverages and 34-year incidence of dementia. Among a random sample of 1,462 women aged 38-60 years and living in Göteborg, Sweden, in 1968-1969, 164 cases of dementia were diagnosed by 2002. At baseline as well as in 1974-1975, 1980-1981, and 1992-1993, the frequency of alcohol intake, as well as other lifestyle and health factors, was recorded and related to dementia with Cox proportional hazard regression, by use of both baseline and updated covariates. Wine was protective for dementia (hazard ratio (HR) = 0.6, 95% confidence interval (CI): 0.4, 0.8) in the updated model, and the association was strongest among women who consumed wine only (HR = 0.3, 95% CI: 0.1, 0.8). After stratification by smoking, the protective association of wine was stronger among smokers. In contrast, consumption of spirits at baseline was associated with slightly increased risk of dementia (HR = 1.5, 95% CI: 1.0, 2.2). Results show that wine and spirits displayed opposing associations with dementia. Because a protective effect was not seen for the other beverages, at least part of the association for wine may be explained by components other than ethanol.

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.

Midlife respiratory function and Incidence of Alzheimer's disease: a 29-year longitudinal study in women.

Normal cognitive function depends on sufficient supply and efficient utilization of oxygen in the brain. Prospective studies on respiratory function and dementia are lacking. This study investigated the relationship between midlife respiratory function and incidence of dementia in a population-based sample of 1291 women followed from 1974 to 2003. Respiratory function was measured by peak expiratory flow in 1974, and forced vital capacity and forced expiratory volume in 1980. Dementia diagnoses were based on information from neuropsychiatric examinations, informant interviews, hospital records and registry data. Better respiratory function in midlife was associated with a lower late-life risk of developing dementia and Alzheimers disease (AD). Per 1 standard deviation increase in peak expiratory flow, forced vital capacity and forced expiratory volume, hazard ratios (95% confidence intervals) for dementia were 0.77 (0.65-0.91), 0.72 (0.57-0.92) and 0.75 (0.59-0.95), respectively, and for AD 0.76 (0.62-0.94), 0.71 (0.54-0.95) and 0.74 (0.56-0.98), respectively, after adjustment for potential confounders. These data reinforce the advantages of maintaining good respiratory function in midlife, even though causation cannot be established.

Midlife homocysteine and late-life dementia in women. A prospective population study.

Elevated serum total homocysteine (tHcy) is an established risk factor for cardiovascular disease. Its role in dementia is still controversial, and no study has examined the role of midlife tHcy, or reports longer than 8 years of follow-up. We examined the relation between midlife tHcy and late-life dementia in women followed for 35 years. The Prospective Population Study of Women in Gothenburg began in 1968-1969, comprising a representative population of women aged 38-60 years. Four extensive follow-ups were conducted by 2003. Serum samples from 1968 to 1969 were analysed for tHcy in 1368 women. In total, 151 women developed dementia. The highest tHcy tertile was related to a hazard ratio of 1.7 (95% CI 1.1-2.6) for developing any dementia, 2.1 (95% CI 1.2-3.7, n=100) for AD and 2.4 (95% CI 1.3-4.7, n=68) for AD without cerebrovascular disease. Kaplan-Meier plots showed divergence with respect to dementia after 22 years of follow-up. In conclusion, high homocysteine in midlife is an independent risk factor for the development of late-life Alzheimer dementia in women.