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 Alzheimer's 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 Alzheimer's 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 Alzheimer's disease. More studies are needed to confirm our findings and to study potential neurobiological mechanisms of these associations.

Abstract-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 (Nϭ1462) 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. life-course perspective when evaluating risk and protective factors for dementia is essential. This may be especially important in relation to blood pressure (BP), which varies with age and in relation to dementia onset and progression. Several studies report that high midlife BP or hypertension increases risk for late-life dementia, 1-6 whereas studies on late-life BP have given mixed results. [7][8][9][10] The relation between BP and dementia is complex. BP decreases the years before dementia diagnosis 8,[11][12][13] and is lower in individuals with manifest dementia compared with those without. 14-17Studies on trajectories of BP in relation to dementia have typically been over short periods of time and encompassed late life. An exception is the Honolulu-Asia Aging Study (HAAS), where Japanese American men who developed dementia experienced a steeper increase in systolic BP (SBP) from midlife to late life, followed by a steeper decrease in late life, than those who did not develop dementia.18 An additional increase in midlife SBP 18 was only related to dementia in men not treated for hypertension. In addition, several studies report that antihypertensive drugs are associated with lower risk of dementia.19-21 Treatment may, thus, modify the association between BP and dementia. Another factor that may influence BP trajectories in relation to dementia is body mass index (BMI), wh...

Background: High midlife and late-life adiposity may increase risk for dementia. Late-life decrease

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.

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ObjectiveTo investigate whether cognitive and physical activities in midlife are associated with reduced risk of dementia and dementia subtypes in women followed for 44 years.MethodsA population-based sample of 800 women aged 38–54 years (mean age 47 years) was followed from 1968 to 2012. Cognitive (artistic, intellectual, manual, religious, and club) and physical activity were assessed at baseline. During follow-up, dementia (n = 194), Alzheimer disease (n = 102), vascular dementia (n = 27), mixed dementia (n = 41), and dementia with cerebrovascular disease (n = 81) were diagnosed according to established criteria based on information from neuropsychiatric examinations, informant interviews, hospital records, and registry data. Cox regression models were used with adjustment for age, education, socioeconomic status, hypertension, body mass index, cigarette smoking, diabetes mellitus, angina pectoris, stress, and major depression.ResultsWe found that cognitive activity in midlife was associated with a reduced risk of total dementia (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.49–0.89) and Alzheimer disease (HR 0.54; 95% CI 0.36–0.82) during follow-up. Physical activity in midlife was associated with a reduced risk of mixed dementia (HR 0.43; 95% CI 0.22–0.86) and dementia with cerebrovascular disease (HR 0.47; 95% CI 0.28–0.78). The results were similar after excluding those who developed dementia before 1990 (n = 21), except that physical activity was then also associated with reduced risk of total dementia (HR 0.67; 95% CI 0.46–0.99).ConclusionOur findings suggests that midlife cognitive and physical activities are independently associated with reduced risk of dementia and dementia subtypes. The results indicate that these midlife activities may have a role in preserving cognitive health in old age.

Our study suggests that midlife neuroticism is associated with increased risk of AD dementia, and that distress mediates this association. The results have clinical implications because a group of women at risk of AD dementia is identified.

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