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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. [ABSTRACT FROM AUTHOR]

Background/Aims: Psychological stress has previously been associated with higher risk of developing late-life dementia, especially Alzheimer’s disease (AD). This study tested whether longstanding midlife stress is related to cerebrospinal fluid (CSF) biomarkers of late-life AD, such as tau protein and amyloid beta (Aβ). Methods: The study included 79 nondemented females from the Prospective Population Study of Women in Gothenburg, Sweden, who responded to a standardized stress question at baseline (mean age 49 years) and underwent a lumbar puncture at follow-up 25 years later. Multiple linear regression models analyzed the relationships between midlife psychological stress and late-life CSF measures of total tau (t-tau), phosphorylated tau (p-tau), Aβ40, and Aβ42. Results: Longstanding stress in midlife was associated with higher levels of CSF t-tau (β = 0.64, p = 0.01) and Aβ40 (β = 0.60, p = 0.02) in late life. No associations were found between midlife stress and levels of p-tau or Aβ42. Conclusion: The findings suggest that longstanding stress stimulates unspecific neurodegenerative processes, but not the core processes of AD, at least not in the early phase of the disease. The association with higher concentration of CSF t-tau may reflect neural degeneration and the association with higher Aβ40 may be an early sign of Aβ overproduction or cerebrovascular processes in the brain. [ABSTRACT FROM AUTHOR]

Aim: To investigate validity of widely recommended anthropometric and total fat percentage cut-off points in screening for cardiovascular risk factors in women of different ages. Methods: A population-based sample of 1002 Swedish women aged 38, 50, 75 (younger, middle-aged and elderly, respectively) underwent anthropometry, health examinations and blood tests. Total fat was estimated (bioimpedance) in 670 women. Sensitivity, specificity of body mass index (BMI; ≥25 and ≥30), waist circumference (WC; ≥80 cm and ≥88 cm) and total fat percentage (TF; ≥35%) cut-off points for cardiovascular risk factors (dyslipidaemias, hypertension and hyperglycaemia) were calculated for each age. Cut-off points yielding high sensitivity together with modest specificity were considered valid. Women reporting hospital admission for cardiovascular disease were excluded. Results: The sensitivity of WC ≥80 cm for one or more risk factors was ~60% in younger and middle-aged women, and 80% in elderly women. The specificity of WC ≥80 cm for one or more risk factors was 69%, 57% and 40% at the three ages (p < .05 for age trends). WC ≥80 cm yielded ~80% sensitivity for two or more risk factors across all ages. However, specificity decreased with increasing age (p < .0001), being 33% in elderly. WC ≥88 cm provided better specificity in elderly women. BMI and TF % cut-off points were not better than WC. Conclusions:Validity of recommended anthropometric cut-off points in screening asymptomatic women varies with age. In younger and middle-age, WC ≥80 cm yielded high sensitivity and modest specificity for two or more risk factors, however, sensitivity for one or more risk factor was less than optimal. WC ≥88 cm showed better validity than WC ≥80 cm in elderly. Our results support age-specific screening cut-off points for women. [ABSTRACT FROM PUBLISHER]

Purpose: To investigate possible association between mental stress and psychosomatic symptoms, socioeconomic status, lifestyle, as well as incident mortality in a middle-aged female population followed over 37 years. Methods: A prospective observational study initiated in 1968-1969, including 1462 women aged 60, 54, 50, 46, and 38 years, with follow-ups in 1974-1975, 1980-1981, and 2000-2001, was performed. Measures included self-reported mental stress as well as psychosomatic symptoms and smoking, physical activity, total cholesterol, S-triglycerides, body mass index, waist-hip ratio, blood pressure, socioeconomic status and mortality. Results: Smoking, not being single, and not working outside home were strongly associated with reported mental stress at baseline. Women who reported high mental stress in 1968-1969 were more likely to report presence of abdominal symptoms (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.39-2.46), headache/migraine (OR = 2.04, 95% CI: 1.53-2.72), frequent infections (OR = 1.75, 95% CI: 1.14-2.70), and musculoskeletal symptoms (OR = 1.70, 95% CI: 1.30-2.23) than women who did not report mental stress. Women without these symptoms at baseline 1968-1969, but with perceived mental stress were more likely to subsequently report incident abdominal symptoms (OR = 2.15, 95% CI: 1.39-3.34), headache/migraine (OR = 2.27, 95% CI: 1.48-3.48) and frequent infections (OR = 2.21, 95% CI: 1.12-4.36) in 1974-1975 than women without mental stress in 1968-1969. There was no association between perceived mental stress at baseline and mortality over 37 years of follow-up. Conclusion: Women reporting mental stress had a higher frequency of psychosomatic symptoms than women who did not report these symptoms. Not working outside home and smoking rather than low socioeconomic status per se was associated with higher stress levels. Perception of high mental stress was not associated with increased mortality. [ABSTRACT FROM AUTHOR]

Background: several studies have found that lung function correlates with survival in older people. We examined secular trends in lung function and its relation to survival in Swedish 75 year olds.Method: representative samples from the general population in Gothenburg, Sweden, were examined at the age of 75 in 1976–77 (n = 743) and 2005–06 (n = 765) with comprehensive somatic and psychiatric examinations. Lung function was measured as peak expiratory flow (PEF).Results: the mean PEF was higher in 75 year olds examined 2005–06 compared with those examined 1976–77 both among women (339 versus 307 l/min; P < 0.001) and men (490 versus 400 l/min, P < 0.001). The birth cohort effect was still significant after adjusting for a number of confounders. PEF correlated with survival between age 75 and 78 years among those examined in 1976–77 both in women (OR per 10 l/min increase in PEF = 1.112, 95% CI: 1.047–1.182) and in men (OR = 1.040, 95% CI: 1.015–1.066), but not in those examined 2005–06 (women: OR = 1.071, 95% CI: 0.965–1.188; men: OR = 1.000, 95% CI: 0.957–1.046).Conclusion: we found better lung function in the later-born cohort of 75 year olds, which was only partially explained by changes in smoking, height and weight, physical activity, socio-economic/educational factors and pulmonary/cardiovascular morbidity. The association between better lung function and short-term survival was strong in 1976–77, but had disappeared in 2005–06. More studies are needed to elucidate the role of lung function for long-term survival and identify other factors that explain the secular trends in lung function. [ABSTRACT FROM PUBLISHER]

Background: the number of nonagenarians increases dramatically worldwide.Objectives: to examine the prevalence of stroke/transient ischaemic attack (TIA) and dementia, their inter-relationship and their relation to 2-year mortality and institutionalisation in 97 year olds.Methods: a population-based sample of 97 year olds (n = 591) was examined. Information on stroke/TIA was obtained from self-reports, key informants and hospital discharge registers. Dementia was diagnosed according to DSM-III-R criteria.Results: the response rate was 65%. The prevalence of dementia was 32.7% in men and 59.3% in women (P < 0.001). The prevalence of stroke/TIA was 21.5% (17.8% in men, 22.3% in women). Stroke/TIA was related to dementia in women (odds ratio = 1.9, 95% CI: 1.2–3.0), but not in men. Dementia, but not stroke/TIA, was related to 2-year mortality and institutionalisation in logistic regression models.Conclusion: dementia was very common in this age group, and related to mortality and institutionalisation. Stroke/TIA in 97 year olds showed less association with dementia, mortality and institutionalisation than reported in studies of younger elderly populations. The finding that stroke was not associated with dementia in men needs to be taken cautiously due to the small number of men. The findings also emphasise that more studies are needed to scrutinise the aetiology of dementia in nonagenarians. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase. (JINS, 2011, 17, 000–000) [ABSTRACT FROM AUTHOR]

Studies the relationships between motor performance and age, anthropometric characteristics, and serum lipids in a population-based sample of women in Goteborg, Sweden. Analysis of the relationship between the postural-locomotion-manual (PLM) test results and age; Relation of the PLM test to anthropometric characteristics, serum lipids and vascular diseases; Factors of PLM variables.

Background It is well established that there is an association between the apolipoprotein E ( APOE ) ε4 allele ( APOE*E4 ) and Alzheimerʼs disease. It is less clear whether there is also an association with geriatric depression. We examined the relationship between APOE*E4 and 5-year incidence of depression in a Swedish population-based sample of older adults without dementia and excluding older adults who developed dementia within 4 years after the diagnosis of depression. Methods In 2000–2001, 839 women and men (age range, 70–92 years; mean age, 73.8 years) free from dementia and depression underwent neuropsychiatric and neuropsychological examinations and genotyping of the APOE*E4 allele. Follow-up evaluations were conducted in 2005 and 2009.The association between APOE*E4 allele and 5-year incidence of depression was examined, while avoiding possible confounding effects of clinical or preclinical dementia by excluding participants who had dementia at study entry, subsequently developed dementia during the 9-year follow-up period, or had a decline in Mini-Mental State Examination score of ≥5 points. Results Among subjects without depression at study entry and without dementia or significant cognitive decline during the subsequent 9 years, APOE*E4 was prospectively associated with more severe depressive symptoms ( b = 1.56, p = .007), incident minor depression (odds ratio = 1.99 [confidence interval = 1.11–3.55], p = .020), and any depression (odds ratio = 1.75 [confidence interval = 1.01–3.03], p = .048). Conclusions The presence of the APOE*E4 allele predicted future depression in this Swedish population study, even after excluding depressed individuals who later developed dementia, suggesting that the APOE*E4 allele could potentially identify people at high risk for clinically significant depression. [ABSTRACT FROM AUTHOR]

Objectives: To describe representativeness in the Gothenburg H70 1930 Birth Cohort Study., Design: Repeated cross-sectional examinations of a population-based study., Setting: Gothenburg, Sweden., Participants: All residents of Gothenburg, Sweden, born on specific birth dates in 1930 were invited to a comprehensive health examination at ages 70, 75, 79, 85 and 88. The number of participants at each examination was 524 at age 70, 767 at age 75, 580 at age 79, 416 at age 85, and 258 at age 88., Primary Outcome Measures: We compared register data on sociodemographic characteristics and hospital discharge diagnoses between participants and (1) refusals, (2) all same-aged individuals in Gothenburg and (3) all same-aged individuals in Sweden. We also compared mortality rates between participants and refusals., Results: Refusal rate increased with age. At two or more examination waves, participants compared with refusals had higher educational level, more often had osteoarthritis, had lower mortality rates, had lower prevalence of neuropsychiatric, alcohol-related and cardiovascular disorders, and were more often married. At two examination waves, participants compared with same-aged individuals in Gothenburg had higher education and were more often born in Sweden. At two examination waves or more, participants compared with same-aged individuals in Sweden had higher education, had higher average income, less often had ischaemic heart disease, were less often born in Sweden and were more often divorced., Conclusions: Participants were more similar to the target population in Gothenburg than to refusals and same-aged individuals in Sweden. Our study shows the importance of having different comparison groups when assessing representativeness of population studies, which is important in evaluating generalisability of results. The study also contributes unique and up-to-date knowledge about participation bias in these high age groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Blood pressure has decreased in the general population. We aimed to examine whether this is true also among the very old, and among persons with and without dementia. Further, we aimed to investigate how common undetected and untreated hypertension is in the very old, both among people with and without dementia., Method: Blood pressure was measured in representative population samples of 85-year-olds living in Gothenburg, Sweden, examined 1986-1987 (n = 484) and 2008-2010 (n = 571). Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, edition 3 revised, by the same medical doctor at both examinations., Results: Both systolic and diastolic blood pressure were lower in 85-year-olds examined 2008-2010 than in those examined 1986-1987, both among those with and without dementia. Participants with dementia had lower systolic blood pressure than those without dementia in both cohorts, and blood pressure levels related to dementia severity. Despite this, hypertension (≥140/90 mmHg) was found in almost half (46.5%) of those with dementia in 2008-2010., Conclusion: Our findings show that time-trends of lower blood pressure in western populations also applies to the very old, and that individuals with dementia continue to have lower blood pressure compared to the rest of the population. The latter finding suggests that the pathophysiological processes in dementia affect blood pressure regulating regions in the brain independent of time trends. Still, hypertension is common in dementia and needs to be detected and treated., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Dementia is the major predictor of death in old age. The aim of this paper was to determine whether 8-year mortality among 85-year olds with and without dementia, and if the contribution of dementia to mortality relative to other common diseases has changed. We used two population-based cohorts of 85-year-olds (N = 1065), born in 1901-02 and 1923-24, which were examined with identical methods in 1986-87 and 2008-2010 and followed for 8-year mortality according to data from the Swedish Tax Agency. Dementia was diagnosed according to DSM-III-R. Other diseases were diagnosed based on self-reports, close informant interviews, somatic examinations, and the Swedish National In-patient Register. Compared to cohort 1901-02, cohort 1923-24 had a lower 8-year mortality both among those with (HR 0.7; 95% CI 0.5-0.99) and without dementia (HR 0.7; 95% CI 0.5-0.9). Dementia was associated with increased mortality in both cohorts (cohort 1901-02, HR 2.6; 95% CI 2.0-3.2, cohort 1923-24, HR 2.8; 95% CI 2.3-3.5), and remained the major predictor of death, with a population attributable risk of 31.7% in 1986-87 and 27.7% in 2008-10. Dementia remained the most important predictor of death in both cohorts. The relative risk for mortality with dementia did not change between cohorts, despite a decreased mortality rate in the population.

Objective: To examine the 1-month prevalence of generalized anxiety disorder (GAD) according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), Diagnostic and Statistical Manual of Mental, Fifth Edition (DSM-V), and International Classification of Diseases, Tenth Revision (ICD-10), and the overlap between these criteria, in a population sample of 75-year-olds. We also aimed to examine comorbidity between GAD and other psychiatric diagnoses, such as depression., Method: During 2005-2006, a comprehensive semistructured psychiatric interview was conducted by trained nurses in a representative population sample of 75-year-olds without dementia in Gothenburg, Sweden (N = 777; 299 men and 478 women). All psychiatric diagnoses were made according to DSM-IV. GAD was also diagnosed according to ICD-10 and DSM-V., Results: The 1-month prevalence of GAD was 4.1% (N = 32) according to DSM-IV, 4.5% (N = 35) according to DSM-V, and 3.7% (N = 29) according to ICD-10. Only 46.9% of those with DSM-IV GAD fulfilled ICD-10 criteria, and only 51.7% and 44.8% of those with ICD-10 GAD fulfilled DSM-IV/V criteria. Instead, 84.4% and 74.3% of those with DSM-IV/V GAD and 89.7% of those with ICD-10 GAD had depression. Also other psychiatric diagnoses were common in those with ICD-10 and DSM-IV GAD. Only a small minority with GAD, irrespective of criteria, had no other comorbid psychiatric disorder. ICD-10 GAD was related to an increased mortality rate., Conclusions: While GAD was common in 75-year-olds, DSM-IV/V and ICD-10 captured different individuals. Current definitions of GAD may comprise two different expressions of the disease. There was greater congruence between GAD in either classification system and depression than between DSM-IV/V GAD and ICD-10 GAD, emphasizing the close link between these entities., (2012 American Association for Geriatric Psychiatry)

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., (Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

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.

Objective: Long-standing psychological distress increases the risk of dementia, especially Alzheimer's disease. The present study examines the relationship between midlife psychological distress and late-life brain atrophy and white matter lesions (WMLs), which are common findings on neuroimaging in elderly subjects., Methods: A population-based sample of 1462 women, aged 38 to 60 years, was examined in 1968, with subsequent examinations in 1974, 1980, 1992, and 2000. Computed tomography (CT) of the brain was done in 379 survivors in 2000, and of those, 344 had responded to a standardized question about psychological distress in 1968, 1974, and 1980. WMLs, cortical atrophy, and central atrophy (ventricular sizes) were measured at CT scans., Results: Compared with women reporting no distress, those reporting frequent or constant distress at one examination or more (in 1968, 1974, and 1980) more often had moderate-to-severe WMLs (multiadjusted odds ratio = 2.39, 95% confidence interval = 1.16-4.92) and moderate-to-severe temporal lobe atrophy (multiadjusted odds ratio = 2.51, 95% confidence interval = 1.04-6.05) on brain CT in 2000. Frequent/constant distress was also associated with central brain atrophy, that is, higher bicaudate ratio, higher cella media ratio, and larger third-ventricle width., Conclusions: Long-standing psychological distress in midlife increases risks of cerebral atrophy and WMLs on CT in late life. More studies are needed to confirm these findings and to determine potential neurobiological mechanisms of these associations.

We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase.

This study aimed to examine the long-term effect of high blood pressure (systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure) on white matter lesions and to study changes in different blood pressure components in relation to white matter lesions. A representative population of women was examined in 1968 and re-examined in 1974, 1980, 1992, and 2000. The presence and severity of white matter lesions on computed tomography were rated by a visual rating scale in 1992 and 2000 in 539 women. Systolic and diastolic blood pressures were measured at all of the examinations. We found that presence and severity of white matter lesions in 1992/2000 were associated with higher diastolic blood pressure and mean arterial pressure at each examination but not with systolic blood pressure and pulse pressure. Odds ratios (95% CIs) for the presence of white matter lesions per 10-mm Hg increase in diastolic pressure were 1.4 (1.0 to 1.9) in 1968, 1.3 (1.0 to 1.8) in 1974, 1.4 (1.1 to 1.9) in 1980, and 1.3 (1.0 to 1.6) in 1992 after adjustment for confounders. The presence of white matter lesions was also associated with a 24-year increase in diastolic pressure (>10 mm Hg), systolic pressure (>40 mm Hg), pulse pressure (>24 mm Hg), and mean arterial pressure (>6 mm Hg; odds ratios [95% CIs]: 2.6 [1.3 to 5.1] for diastolic pressure; 2.0 [1.2 to 3.4] for systolic pressure; 1.8 [1.1 to 2.7] for pulse pressure; and 2.2 [1.4 to 3.4] for mean arterial pressure). Our findings suggest that lowering high diastolic blood pressure and preventing large increases in systolic and diastolic blood pressures may have a protective effect on white matter lesions.

Background: Few studies have examined whether cognitive symptom patterns differ by age and length of time before dementia onset. Our objective was to investigate whether different patterns of cognitive symptoms at ages 70, 75, and 79 years predict short-term (< or =5 years) and long-term (>5 years) dementia onset., Methods: A representative sample of 382 nondemented 70-year-olds from Gothenburg, Sweden was examined periodically up to age 90 years. Information on dementia in those lost to follow-up was obtained from medical records. Cognitive assessments at ages 70, 75, and 79 years included psychiatric and psychometric examinations. Four patterns of cognitive performance were examined in relation to dementia onset: (1) unimpaired cognition, (2) isolated low memory, (3) low non-memory, and (4) global low cognitive performance., Results: Short-term onset was predicted by global low performance at ages 70, 75, and 79 years and by low non-memory performance at ages 70 and 75. Isolated low memory was not a short-term predictor at any examination, but it predicted long-term onset at ages 70 and 75 years., Conclusions: A global pattern of low cognitive performance predicts short-term but not long-term onset of dementia, whereas isolated low memory performance predicts dementia only in the long-term. Our findings also suggest that preclinical symptoms of dementia might differ by age.

Objectives: To examine whether total serum homocysteine (tHcy) in a population-based sample of middle-aged women is an independent risk factor for presence of lacunar infarcts (LIs) 24 years later., Design: Prospective population study, follow-up time 24 years., Setting: Gothenburg, an urban area in western Sweden., Participants: Five hundred twenty-six women, 89.6% of the original study sample of the Population Study of Women in Gothenburg, aged 46 to 60 at baseline in 1968/69 and re-examined at age 70 to 84., Measurements: After 24 years of follow-up, all subjects underwent a psychiatric examination, and 277 computerized tomography (CT) scans of the brain were performed. Two radiologists assessed LIs and white matter lesions (WMLs). Baseline serum tHcy was analyzed from frozen stored serum samples. Logistic regression analyses were performed controlling for potential confounders such as age and selected cardiovascular risk factors., Results: Thirty-four subjects had LIs in 1992 (12.3%). In the full multivariate-adjusted stepwise model, LIs were associated with elevated tHcy (odds ratio (OR)=1.09, 95% confidence interval (CI)=1.01-1.17 per micromol/L of tHcy increment). Women with tHcy values in the highest tertile were almost three times as likely to have LIs (OR=2.82, 95% CI=1.34-5.93) as were those in the lowest tertile. tHcy was not related to WMLs. Subjects who did not undergo a CT scan did not differ from those who did regarding tHcy or any of the covariates studied., Conclusion: tHcy in middle-aged women is an independent risk factor for LIs, but not WMLs, as observed using CT later in life.

Background and Purpose: Increased evidence suggests that poor respiratory function increases risk of ischemic damage to the brain. Longitudinal studies on respiratory function and cerebral small-vessel disease are lacking. We examined midlife and late-life respiratory function in relation to small-vessel disease on computed tomography (CT) in women followed for 26 years., Methods: White matter lesions (WMLs) and lacunar infarcts were rated on brain CT scans in 2000 in 379 women 70 to 92 years of age from a longitudinal population study in Göteborg, Sweden. Respiratory function was measured by peak expiratory flow (PEF) in 1974 and 2000 and by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) in 1980 and 2000., Results: Lower FVC and FEV1 in 1980 and 2000 were associated with presence and severity of WMLs and lacunar infarcts in 2000. Per 1-SD decrease of FVC in 1980, odds ratios (95% CIs) were 1.49 (1.11 to 2.02) for presence of WMLs and 1.95 (1.34 to 2.84) for lacunar infarcts after adjustment for potential confounders. Per 1-SD decrease of FEV1 in 1980, adjusted odds ratios were 1.46 (1.06 to 2.00) for presence of WMLs and 1.42 (1.02 to 1.97) for lacunar infarcts. PEF in 1974 and 2000 was not associated with WMLs or lacunar infarcts., Conclusions: WMLs and lacunar infarcts in elderly women were related to lower midlife respiratory function. Although our data may not establish causation between lower respiratory function and small-vessel disease, they imply the importance of good respiratory function in midlife.

We described longitudinal changes of movement performance in a population-based sample of women followed from age 70 to 78. We also studied the cross-sectional relationships between medical conditions and movement performance at baseline, and longitudinal relationships between baseline medical conditions and changes of movement performance. Two hundred and thirty-four women aged 70 years participated in the baseline study, and 88 women participated in a follow-up study 8 years later. Movement performance was measured by an optoelectronic test, the postural-locomotor-manual (PLM) test, which objectively and precisely measures the subject's mobility of lower and upper extremities. Information on medical conditions including selected diseases and symptoms were obtained by self-report and/or by physical examination. Movement time (MT), an indicator of the overall movement performance of the PLM test, increased over 8 years. This change was mainly related to prolonged duration of the locomotor phase (walking forward), but not to the duration of the manual phase (goal-directed arm reaching). At baseline, poor PLM performance was related to hypertension, orthostatic hypotension, cerebrovascular diseases, chronic bronchitis, depression, arthritis, dizziness, chest pain, dyspnea, joint problems, leg pain, tiredness, number of diseases and number of symptoms at baseline. Increased MT during follow-up was associated with arthritis and dyspnea at baseline, and newly developed diseases during follow-up. Our study results indicated that 70-year-old women had a general slowing of their movement performance over 8 years. Age-related decrements of movement performance were more striking in the lower extremities than in the upper extremities. Arthritis and dyspnea at baseline, and incident diseases during follow-up were related to this age-related decline of movement performance.