Midlife improvements in financial situation are associated with a reduced dementia risk later in life: the CAIDE 30-year study.

OBJECTIVES: Perceived financial strain is associated with various health conditions, but it is unknown whether it is associated with an increased risk for dementia. The goal is to examine the associations between midlife perceptions of financial situation and dementia risk later in life. METHODS: Participants were derived from the Cardiovascular Risk Factors, Aging, and Dementia population-based cohort study (n = 2000) (between 1972 and 1987, baseline mean age 50 years) in Finland. Participants returned for two re-examinations in late life (in 1998 and 2005-2008, mean age 71 and 78 years). In this study, 1442 subjects that participated in at least one re-examination (mean total follow-up 25 years) were included in analyses. Financial strain was measured using two questions in midlife on perceptions of financial situation and perceptions of changes in financial situation. For each question, participants were categorized into three groups reporting improvement, worsening, or stability, with the latter set as the reference group. Analyses were adjusted for potential confounding factors. RESULTS: The group reporting better financial situation had a reduced risk for dementia (fully adjusted model: odds ratio (OR): 0.53, 95% confidence interval (CI): 0.33-0.86). In contrast, the group reporting worse financial situation did not have an increased risk for dementia (OR: 1.04, 95% CI: 0.53-2.02). Analyses on perceptions of current financial situation showed that the groups reporting satisfaction or dissatisfaction with financial situation did not differ in risk for dementia. CONCLUSION: This study is the first to show that midlife improvements in financial situation are associated with a reduced dementia risk later in life. Potential pathways related to stress reduction, improved lifestyle, and potential biological mechanisms are discussed.

Quejas cognitivas subjetivas: hacia una identificación precoz de la enfermedad de Alzheimer / Subjective cognitive impairment: Towards early identification of Alzheimer disease

Introducción: La neurodegeneración en enfermedad de Alzheimer (EA) empieza décadas antes que la demencia y algunos pacientes con deterioro cognitivo leve presentan una importante carga lesional. La ausencia de información sobre la fisiopatología temprana de la enfermedad dificulta la búsqueda de estrategias terapéuticas. La queja cognitiva subjetiva (QCS) agrupa a sujetos con quejas mnésicas sin déficits significativos en test neuropsicológicos. Es un síndrome heterogéneo sobre el que no existe consenso, pero algunos de estos pacientes podrían representar el estadio más precoz de EA. Método: Realizamos una revisión bibliográfica para resumir el estado del conocimiento actual sobre quejas cognitivas subjetivas. Resultados: Aunque a nivel individual no presenten enfermedad objetivable, a nivel de grupo los pacientes con QCS rinden peor en test neuropsicológicos que la población general y tienen mayor incidencia de declive cognitivo futuro. La depresión y la comorbilidad psiquiátrica desempeñan un papel pero no son la única causa de quejas cognitivas. Estudios con resonancia magnética muestran un patrón de atrofia hipocampal similar al del deterioro cognitivo leve amnésico y en resonancia funcional hay aumento de activación en tareas cognitivas que podrían representar una compensación ante pérdida de función. Los pacientes con QCS presentan un patrón tipo EA de marcadores betaamiloide (A 42) y tau con mayor frecuencia que la población general. Conclusiones: Las quejas mnésicas son un síntoma relevante y podrían predecir EA. La heterogeneidad de los pacientes y de los ensayos clínicos ha dificultado la definición del síndrome. En el futuro, una definición estandarizada y estudios longitudinales con un seguimiento suficiente, y centrados en variables cuantificables, podrían clarificar aspectos tempranos de la EA

Introduction: Neurodegeneration in Alzheimer disease (AD) begins decades before dementia and patients with mild cognitive impairment (MCI) already demonstrate significant lesion loads. Lack of information about the early pathophysiology in AD complicates the search for therapeutic strategies. Subjective cognitive impairment is the description given to subjects who have memory-related complaints without pathological results on neuropsychological tests. There is no consensus regarding this heterogeneous syndrome, but at least some of these patients may represent the earliest stage in AD. Method: We reviewed available literature in order to summarise current knowledge on subjective cognitive impairment. Results: Although they may not present detectable signs of disease, SCI patients as a group score lower on neuropsychological tests than the general population does, and they also have a higher incidence of future cognitive decline. Depression and psychiatric co-morbidity play a role but cannot account for all cognitive complaints. Magnetic resonance imaging studies in these patients reveal a pattern of hippocampal atrophy similar to that of amnestic mild cognitive impairment and functional MRI shows increased activation during cognitive tasks which might indicate compensation for loss of function. Prevalence of an AD-like pattern of beta-amyloid (A 42) and tau proteins in cerebrospinal fluid is higher in SCI patients than in the general population. Conclusions: Memory complaints are relevant symptoms and may predict AD. Interpatient variability and methodological differences between clinical studies make it difficult to assign a definition to this syndrome. In the future, having a standard definition and longitudinal studies with sufficient follow-up times and an emphasis on quantifiable variables may clarify aspects of early AD

Antidepressants and mortality risk in a dementia cohort: data from SveDem, the Swedish Dementia Registry.

BACKGROUND: The association between mortality risk and use of antidepressants in people with dementia is unknown. OBJECTIVE: To describe the use of antidepressants in people with different dementia diagnoses and to explore mortality risk associated with use of antidepressants 3 years before a dementia diagnosis. METHODS: Study population included 20 050 memory clinic patients from the Swedish Dementia Registry (SveDem) diagnosed with incident dementia. Data on antidepressants dispensed at the time of dementia diagnosis and during 3-year period before dementia diagnosis were obtained from the Swedish Prescribed Drug Register. Cox regression models were used. RESULTS: During a median follow-up of 2 years from dementia diagnosis, 25.8% of dementia patients died. A quarter (25.0%) of patients were on antidepressants at the time of dementia diagnosis, while 21.6% used antidepressants at some point during a 3-year period before a dementia diagnosis. Use of antidepressant treatment for 3 consecutive years before a dementia diagnosis was associated with a lower mortality risk for all dementia disorders and in Alzheimer's disease. CONCLUSION: Antidepressant treatment is common among patients with dementia. Use of antidepressants during prodromal stages may reduce mortality in dementia and specifically in Alzheimer's disease.

Subjective cognitive impairment: Towards early identification of Alzheimer disease. / Quejas cognitivas subjetivas: hacia una identificación precoz de la enfermedad de Alzheimer.

INTRODUCTION: Neurodegeneration in Alzheimer disease (AD) begins decades before dementia and patients with mild cognitive impairment (MCI) already demonstrate significant lesion loads. Lack of information about the early pathophysiology in AD complicates the search for therapeutic strategies.Subjective cognitive impairment is the description given to subjects who have memory-related complaints without pathological results on neuropsychological tests. There is no consensus regarding this heterogeneous syndrome, but at least some of these patients may represent the earliest stage in AD. METHOD: We reviewed available literature in order to summarise current knowledge on subjective cognitive impairment. RESULTS: Although they may not present detectable signs of disease, SCI patients as a group score lower on neuropsychological tests than the general population does, and they also have a higher incidence of future cognitive decline. Depression and psychiatric co-morbidity play a role but cannot account for all cognitive complaints. Magnetic resonance imaging studies in these patients reveal a pattern of hippocampal atrophy similar to that of amnestic mild cognitive impairment and functional MRI shows increased activation during cognitive tasks which might indicate compensation for loss of function. Prevalence of an AD-like pattern of beta-amyloid (Aß42) and tau proteins in cerebrospinal fluid is higher in SCI patients than in the general population. CONCLUSIONS: Memory complaints are relevant symptoms and may predict AD. Interpatient variability and methodological differences between clinical studies make it difficult to assign a definition to this syndrome. In the future, having a standard definition and longitudinal studies with sufficient follow-up times and an emphasis on quantifiable variables may clarify aspects of early AD.

Association between mid- to late life physical fitness and dementia: evidence from the CAIDE study.

OBJECTIVES: This study investigated the association between perceived physical fitness at midlife, changes in perceived fitness during the three decades from mid- to late life and dementia risk. DESIGN: Prospective cohort study. SETTING: Cardiovascular risk factors, ageing and incidence of dementia (CAIDE) study. SUBJECTS: Subjects were selected from four independent, random samples of population-based cardiovascular surveys and were first examined in 1972, 1977, 1982 or 1987, when they were on average 50 years old. The CAIDE target population included 3559 individuals. A random sample of 2000 individuals still alive in 1997 was drawn for re-examinations (performed in 1998 and 2005-2008) that consisted of cognitive assessments, with 1511 subjects participating in at least one re-examination. Dementia diagnoses were also confirmed from national registers for the entire target population. MAIN OUTCOME MEASURE: All-cause dementia. RESULTS: Poor physical fitness at midlife was associated with increased dementia risk in the entire target population [hazard ratio (HR), 1.5; 95% confidence interval (CI), 1.1-2.0]. In participants, odds ratio (OR) was 2.0 (95% CI, 0.9-4.0). This association was significant in apolipoprotein E ε4 allele (APOEε4) noncarriers (OR, 4.3; 95% CI, 1.4-13.3), men (HR, 1.8; 95% CI, 1.1-3.0) and people with chronic conditions (HR, 2.9; 95% CI, 1.3-6.6). A decline in fitness after midlife was also associated with dementia (OR, 3.0; 95% CI, 1.7-5.1), which was significant amongst both men and women and more pronounced in APOEε4 carriers (OR, 4.4; 95% CI, 2.1-9.1). CONCLUSIONS: Perceived poor physical fitness reflects a combination of biological and lifestyle-related factors that can increase dementia risk. A simple question about perceived physical fitness may reveal at-risk individuals who could benefit from preventive interventions.

Differences in brain cholesterol metabolism and insulin in two subgroups of patients with different CSF biomarkers but similar white matter lesions suggest different pathogenic mechanisms.

Investigate possible associations of white matter hyperintensities (WMHs) with the metabolism of cholesterol and insulin in two subgroups of patients with memory complaints and different CSF Aß42 and CSF tau levels. 59 patients from the memory clinic at Karolinska Hospital were included. Degree of WMHs was rated using the ARWMC scale and the following biomarkers were measured in CSF and plasma: insulin, cholesterol, lanosterol, lathosterol, and oxidized cholesterol metabolites. The WMHs in CSF control-like group correlated with increased brain cholesterol synthesis and reduced efflux of oxysterols and insulin in CSF. In the CSF AD-like group, the WMHs correlated with increased peripheral cholesterol metabolism. Despite having similar appearance on FLAIR images, the pathogenic mechanisms of WMHS are likely to be different in the two groups investigated.

Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly: a longitudinal study.

OBJECTIVES: To examine the associations between serum homocysteine (tHcy), holotranscobalamin (holoTC, the biologically active fraction of vitamin B12) and folate and cognitive functioning in a longitudinal population-based study of Finnish elderly subjects. SUBJECTS AND DESIGN: tHcy, holoTC and folate were measured at baseline in 274 dementia-free subjects aged 65-79years from the Cardiovascular Risk Factors, Aging and Dementia study. Subjects were re-examined 7years later, and global cognition, episodic memory, executive functioning, verbal expression and psychomotor speed were assessed. RESULTS: Higher baseline tHcy levels were associated with poorer performance in global cognition, relative difference: 0.90 [95% confidence interval (CI) 0.81-0.99]; episodic memory: 0.87 (95% CI 0.77-0.99); executive functions: 0.86 (95% CI 0.75-0.98); and verbal expression: 0.89 (95% CI 0.81-0.97) at follow-up. Increased holoTC levels were related to better performance on global cognition: 1.09 (95% CI 1.00-1.19); executive functions: 1.11 (95% CI 1.01-1.21); and psychomotor speed: 1.13 (95% CI 1.01-1.26). After excluding 20 cases of incident dementia, increased tHcy remained associated with poorer performance in episodic memory, execution functions and verbal expression. Higher holoTC levels tended to be related to better performance in executive functions and psychomotor speed, while elevated serum folate concentrations were significantly related to higher scores in global cognition and verbal expression tests. CONCLUSIONS: tHcy, holoTC and folate levels are related to cognitive performance 7years later even in nondemented elderly subjects. Randomized trials are needed to determine the impact of vitamin B12 and folate supplementation on preventing cognitive decline in the elderly.

Homocysteine and holotranscobalamin and the risk of Alzheimer disease: a longitudinal study.

OBJECTIVE: To examine the relation between serum levels of homocysteine (tHcy) and holotranscobalamin (holoTC), the active fraction of vitamin B12, and risk of incident Alzheimer disease (AD) in a sample of Finnish community-dwelling elderly. METHODS: A dementia-free sample of 271 subjects aged 65-79 years derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed up for 7 years to detect incident AD. The association between serum tHcy and holoTC with AD was analyzed with multiple logistic regression after adjusting for several potential confounders, including common vascular risk factors. RESULTS: The odds ratios (ORs) (95% confidence interval [CI]) for AD were 1.16 (1.04-1.31) per increase of 1 µmol/L of tHcy at baseline and 0.980 (0.965-0.995) for each increase of 1 pmol/L baseline holoTC. Adjustment for several potential confounders including age, sex, education, APOE ε4 allele, body mass index, Mini-Mental State Examination, smoking, stroke, and blood pressure did not alter the associations: ORs (95% CI) for AD became 1.19 (1.01-1.39) for tHcy and 0.977 (0.958-0.997) for holoTC. Adjusting for holoTC attenuated the tHcy-AD link (OR changed from 1.16 to 1.10, 95% CI 0.96-1.25). The holoTC-AD relationship was less influenced by controlling for tHcy (OR changed from 0.980 to 0.984, 95% CI 0.968-1.000). Addition of folate did not change any of the results. CONCLUSIONS: This study suggests that both tHcy and holoTC may be involved in the development of AD. The tHcy-AD link may be partly explained by serum holoTC. The role of holoTC in AD should be further investigated.

Personality and lifestyle in relation to dementia incidence.

OBJECTIVE: High neuroticism has been associated with a greater risk of dementia, and an active/socially integrated lifestyle with a lower risk of dementia. The aim of the current study was to explore the separate and combined effects of neuroticism and extraversion on the risk of dementia, and to examine whether lifestyle factors may modify this association. METHODS: A population-based cohort of 506 older people with no dementia from the Kungsholmen Project, Stockholm, Sweden, was followed up for an average of 6 years. Personality traits were assessed using the Eysenck Personality Inventory. Dementia was diagnosed by specialists according to DSM-III-R criteria. RESULTS: Neither high neuroticism nor low extraversion alone was related to significantly higher incidence of dementia. However, among people with an inactive or socially isolated lifestyle, low neuroticism was associated with a decreased dementia risk (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.27-0.96). When compared to persons with high neuroticism and high extraversion, a decreased risk of dementia was detected in individuals with low neuroticism and high extraversion (HR = 0.51, 95% CI = 0.28-0.94), but not among persons with low neuroticism and low extraversion (HR = 0.95, 95% CI = 0.57-1.60), nor high neuroticism and low extraversion (HR = 0.97 95% CI = 0.57-1.65). Stratified analysis by lifestyle showed that the inverse association of low neuroticism and high extraversion in combination was present only among the inactive or socially isolated persons. CONCLUSION: Low neuroticism in combination with high extraversion is the personality trait associated with the lowest dementia risk; however, among socially isolated individuals even low neuroticism alone seems to decrease dementia risk.

Serum total cholesterol, statins and cognition in non-demented elderly.

BACKGROUND: The association between serum total cholesterol (TC), lipid-lowering drugs and cognition in the elderly is currently controversial. OBJECTIVE: To investigate the relationship between TC, lipid-lowering drugs and cognitive functions in non-demented elderly. DESIGN AND SETTING: Participants of the Cardiovascular risk factors, aging and dementia (CAIDE) study were derived from random, population-based samples previously studied in 1972, 1977, 1982 or 1987. Analyses are based on 1382 non-demented participants re-examined in 1998 after an average follow-up of 21 years. RESULTS: High midlife TC was associated with poorer late-life episodic memory and category fluency. TC decreased in most individuals over time. A more pronounced decrease was related to poorer late-life episodic memory and psychomotor speed, but not if subjects used statins. CONCLUSIONS: The TC-cognition relationship seems bidirectional. High midlife TC is associated with poorer late-life cognition, but decreasing TC after midlife may reflect poorer cognitive status. Statins may be beneficial for cognition in non-demented elderly.

Serum cholesterol changes after midlife and late-life cognition: twenty-one-year follow-up study.

BACKGROUND: Longitudinal studies have shown that high serum total cholesterol (TC) at midlife is a risk factor for dementia/Alzheimer disease. The significance of TC later in life is unclear. OBJECTIVE: To investigate changes in serum TC from midlife to late life and their relationship with late-life cognition. METHODS: Participants of the Cardiovascular Risk Factors, Aging and Dementia study were derived from random, population-based samples previously studied in a survey in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1,449 individuals aged 65 to 79 were reexamined in 1998. RESULTS: Serum TC levels decreased in most individuals. High midlife TC represented a risk factor for more severe cognitive impairment later in life, and the values were significantly different between the control, mild cognitive impairment, and dementia groups. There were no significant differences in serum TC at reexamination. A moderate decrease in serum TC from midlife to late life (0.5 to 2 mmol/L) was significantly associated with the risk of a more impaired late-life cognitive status, even after adjusting for age, follow-up time, sex, years of formal education, midlife cholesterol, changes in body mass index, APOE epsilon4 genotype, history of myocardial infarction/stroke/diabetes, and lipid-lowering treatment. CONCLUSIONS: The relationship between serum total cholesterol (TC) and dementia seems to be bidirectional. High midlife serum TC is a risk factor for subsequent dementia/Alzheimer disease, but decreasing serum TC after midlife may reflect ongoing disease processes and may represent a risk marker for late-life cognitive impairment.

The amount of informal and formal care among non-demented and demented elderly persons-results from a Swedish population-based study.

BACKGROUND: Developed countries are experiencing a dramatic increase in the proportion of elderly persons, as well as a progressive aging of the elderly population itself. Knowledge regarding the amount of formal and informal care and its interaction at population-based level is limited. OBJECTIVES: To describe the amount of formal and informal care for non-demented and demented persons living at home in a population-based sample. METHODS: The population consisted of all inhabitants, 75 + years, living in a rural community (n = 740). They were clinically examined by physicians and interviewed by nurses. Dementia severity was measured according to Washington University Clinical Dementia Rating Scale (CDR). Informal and formal care was examined with the RUD (Resource Utilization in Dementia) instrument. RESULTS: The amount of informal care was much greater than formal care and also greater among demented than non-demented. There was a relationship between the severity of the cognitive decline and the amount of informal care while this pattern was weaker regarding formal care. Tobit regression analyses showed a clear association between the number of hours of informal and formal care and cognitive decline although this pattern was much stronger for informal than formal care. CONCLUSIONS: Informal care substitutes rather than compliments formal care and highlights the importance of future studies in order to truly estimate the amount of informal and formal care and the interaction between them. This knowledge will be of importance when planning the use of limited resources, and when supporting informal carers in their effort to care for their intimates.

The relationship between heart problems and mortality in different social classes.

The aim of this study is to analyze how relative mortality risk varies between persons with and without heart problems in different social classes. Cox proportional hazards regression was used to analyze relative mortality risk for the period 1968-1996 for a Swedish nationally representative sample of 4585 persons born between 1892 and 1942, and interviewed 1968. Survivors from the original sample were also interviewed in 1974, 1981 and 1991 or 1992. "Heart problems" is defined as the presence of three mild or one severe symptom associated with circulatory problems. Social class is based on occupation. The relative mortality risk varied significantly between social classes and between persons with and without heart problems, among both men and women. These differences were smaller among women than among men. The main results are that there are significant additive interactions between social class and heart problems among men. Men from lower social classes have a more elevated mortality risk than men from higher social classes when they have a heart problem. Among white-collar workers the coefficient of the difference between men with and without heart problems was 0.53. The corresponding difference was significantly larger among workers (1.59, P = 0.01), thus demonstrating an additive interaction. The difference was even greater (1.86) among "unclassifiable" men--those who could not report an occupation that could be coded into a social class, mainly because they were long-term unemployed or on early-retirement pensions. Among women, the mortality difference between white-collar workers with and without heart problems was 0.85. None of the mortality differences between those with and without heart problems in other social classes differed significantly from those of white-collar workers. The mortality difference between women with and without heart problems was, however, large (2.34) among the "unclassifiable". This difference is even larger than the corresponding difference among men.

Predictors of physical function among the oldest old: a comparison of three outcome variables in a 24-year follow-up.

This study has measured physical function in a nationally representative sample of persons aged 77 to 98 (N = 508) in 1992. Three measures of function are used: activities of daily living (ADL), an index of mobility, and performance tests. These are used as outcomes and analyzed in relation to variables gathered in a survey in 1968. Variables from 1968 include education, mobility, smoking, and an index of circulation problems. All four variables predict some limitations in physical function in old age. However, there are different patterns of predictors found for the three outcome measures. All three outcomes are associated with age, education, and previous circulation problems. ADL limitations are also associated with poor previous mobility and smoking; mobility limitations are also associated with sex and smoking; performance limitations are also associated with sex.