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We examined the associations between extracerebral markers of cholesterol homeostasis and cognitive decline over 6 years of follow-up, and studied the modifying effect of apolipoprotein E (ApoE) e4. Data were collected in the Longitudinal Aging Study Amsterdam (n = 967, with longitudinal data on cognition, ages ≥ 65 years) and analyzed using linear mixed models. General cognition (Mini-Mental State Examination; MMSE), memory (Auditory Verbal Learning Test), and information processing speed (Coding task) were measured. The results show that ApoE e4 was a significant effect modifier. Significant associations were found only in ApoE e4 noncarriers (n = 718). We found a nonlinear negative association between the ratio of lanosterol to cholesterol (≤ 189.96 ng/mg), a marker for cholesterol synthesis, and general cognition. Lower cholesterol absorption, i.e., lower ratios of campesterol and sitosterol to cholesterol, as well as a higher rate of cholesterol synthesis relative to absorption were associated with lower information processing speed. In ApoE e4 carriers, the negative association between the ratio of campesterol to cholesterol and memory reached borderline significance. Future research should focus on the interaction between (disturbed) cholesterol homeostasis and ApoE e4 status with respect to dementia., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The aim of this study was to examine the associations between high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, and cognition and focus on the modifying effect of inflammation. Data were collected in the population-based Longitudinal Aging Study Amsterdam and analyzed with mixed linear models. The sample comprised 1003 persons ≥ 65 years with cognitive data on at least 2 occasions over 6 years of follow-up. Cognition was measured with the Mini-Mental State Examination (general cognition), Auditory Verbal Learning Test (memory), and Coding Task (information processing speed). We found an independent association between high HDL cholesterol and better memory performance. In addition, low LDL cholesterol was predictive of worse general cognitive performance and faster decline on information processing speed. Furthermore, a significant modifying effect of inflammation (C-reactive protein, α-antichymotrypsin) was found. A negative additive effect of low LDL cholesterol and high inflammation was found on general cognition and memory performance. Also, high triglycerides were associated with lower memory performance in those with high inflammation. Thus, a combination of these factors may be used as markers of prolonged lower cognitive functioning., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The aim of the current study was to examine the association between homocysteine and 6-year cognitive decline, and the modifying role of the inflammatory markers Interleukin-6 (IL-6), C-reactive protein (CRP) and alpha-1-antichymotrypsin (ACT). Data were collected within the Longitudinal Aging Study Amsterdam (ages >or=65 years) and analyzed using multiple longitudinal regression models (N=1257 of whom N=1076 had longitudinal data). Cognition was measured with the Mini-Mental State Examination (general cognition), Auditory Verbal Learning Test (memory), Coding Task (information processing speed) and Raven Coloured Progressive Matrices (fluid intelligence). Higher homocysteine at baseline was negatively associated with prolonged lower cognitive functioning and a faster rate of decline in information processing speed and fluid intelligence. The negative association between higher homocysteine and immediate recall was strongest in persons with a high level of IL-6. Only in the highest tertile of CRP, higher homocysteine was negatively associated with retention. In the middle tertile of ACT, higher homocysteine was associated with lower information processing speed and faster decline. Both in the lower and middle tertile of CRP, higher homocysteine was associated with a faster rate of decline in information processing speed. The results implicate that a combination of both risk factors may be used as a marker for cognitive impairment., ((c) 2008 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to demonstrate the involvement of the inflammatory proteins IL-6, ACT and CRP early in the pathology process of AD in patients with mild cognitive impairment (MCI) and AD., Methods: IL-6, ACT, CRP, Abeta42, phospho-tau (p-tau) and total tau concentrations in serum and CSF of 145 patients with probable AD and 67 patients with MCI were measured by sandwich ELISA. MCI patients were characterized as high- respectively low-risk MCI according to their Abeta42/tau risk profile., Results: CSF and serum CRP levels were significantly higher in MCI compared to AD patients after adjustment for age, ApoE epsilon4 genotype and cardiovascular diseases (p<0.01). This difference remained present in patients with a low-risk biomarker profile for AD after adjustment for abovementioned covariates. CSF IL-6 levels were also significantly higher in MCI patients with a low-risk CSF profile., Conclusions: These findings suggest that inflammatory processes might be involved in early stages of AD, even before Abeta and tau changes are present in CSF of MCI patients.

Objectives: High-cortisol levels in depressed persons could possibly give rise to the metabolic syndrome. This study investigated cross-sectionally whether depression and high-cortisol levels increased the odds of metabolic syndrome in an older community-based sample., Methods: In 1,212 participants, aged > or =65 years, enrolled in the Longitudinal Aging Study Amsterdam, depression (major [1-month diagnosis] or subthreshold [no 1-month diagnosis, but symptoms]), metabolic syndrome (modified Adult Treatment Panel III criteria), and free cortisol index (total serum cortisol/cortisol binding globulin) were assessed., Results: Major depression was not associated with the metabolic syndrome (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 0.54-2.49), but subthreshold depression was associated with a decreased odds (OR = 0.55, 95% CI = 0.37-0.82). Persons with higher levels of free cortisol index showed a higher odds of metabolic syndrome (OR per standard deviation increase = 1.21, 95% CI = 1.06-1.39)., Conclusions: As persons with high-cortisol levels more often had metabolic syndrome, hypercortisolemia within depressed persons may increase the risk of metabolic syndrome.

In this prospective study we examined whether total cholesterol and the oxysterols 24S- and 27-hydroxycholesterol were related to cognitive performance and rate of cognitive decline in elderly, and whether these associations were modified by ApoE epsilon 4. Data were collected during 6 years of follow-up as part of the Longitudinal Aging Study Amsterdam (N=1181, age >or=65 years), and analyzed using generalized estimating equations. Cognitive performance was measured with the mini-mental state examination (general cognition), the auditory verbal learning test (memory) and the coding task (information processing speed). Lower cholesterol at baseline was negatively associated with both general cognition (p=.012) and information processing speed (p=.045). ApoE modified the association between cholesterol and cognitive decline, and the association between the ratio of 27-hydroxycholesterol to cholesterol and cognitive functioning. In ApoE epsilon 4 carriers, lower cholesterol was related to a higher rate of decline on information processing speed (p=.006), and a higher ratio of 27-hydroxycholesterol to cholesterol was related to a lower level of general performance (p=.002) and memory functioning (p=.045). The results implicate that lower total cholesterol may be considered as a frailty marker, predictive of lower cognitive functioning in elderly.

The influence of seven highly prevalent somatic chronic diseases on changes in cognitive functioning is investigated in older persons in a prospective design covering a 6-year follow-up period. The data were collected as part of the Longitudinal Aging Study Amsterdam (LASA). The associations between chronic diseases and cognitive functioning during 6 years of follow-up were analyzed among 1358 respondents (age 62-85) using generalized estimated equations (GEE). Cognitive tests were used to assess: general cognitive functioning, fluid intelligence, information processing speed and memory performance. In the fully adjusted models diabetes mellitus, stroke and peripheral artherosclerosis were associated with cognitive decline during a 6-year follow-up period in older persons. In the unadjusted models cardiac disease was negatively associated with memory function. However, after the correction for possible confounders this association became positive. Cancer was also associated with better memory function. A faster decline in especially memory function was found for diabetes mellitus, stroke, cancer, and peripheral artherosclerosis. The study shows that in older persons specific chronic diseases (diabetes mellitus, stroke, cancer, and peripheral artherosclerosis) are associated with decline in one or more domains of cognitive functioning during a 6-year follow-up period. These findings further stress that careful clinical evaluation of cognitive functioning in older persons with these diseases is required in order to provide adequate care.

Aim: To evaluate previously developed classification models to make implementation in primary care possible and aid early identification of persons at risk for dementia., Methods: Data were drawn from the OCTO-Twin study. At baseline, 521 persons >or= 80 years of age were nondemented, and for 387 a blood sample was available. Predictors of dementia were collected and analyzed in initially nondemented persons using generalized estimating equations and Cox survival analyses., Results: In the basic model using predictors already known or easily obtained (basic set), the mean 2-year predictive value increased from 6.9 to 28.8% in persons with memory complaints and an MMSE score

Background and Objective: Many patients who suffer from an acute stroke, will need long-term nursing home care. We are poorly informed about the demographic and clinical characteristics and about the care problems and received care of these patients. This study aims to provide a first description of these characteristics in this group of patients., Methods: Data on demographic and health-related characteristics, social participation and received care were collected with the Minimum Data Set of the Resident Assessment Instrument, from january 2004-march 2007, in patients who needed long-term nursing home care. Data were collected in eight nursing homes at admission and six months after admission., Results: Many patients were functionally impaired, suffered from depressive symptoms and pain, and were cognitively impaired. In addition, decisional capacity was frequently diminished. The majority of patients were residing at somatic wards, even when severe cognitive impairment was present, such as dementia. Several forms of restraints were frequently used, also at somatic wards. About 40% of the patients, mostly residing at somatic wards, received paramedical treatment. Social engagement was low and was correlated with functional impairment., Conclusions: Stroke patients who need long-term nursing home care suffer from problems in several domains. The high prevalence of cognitive impairment in stroke patients residing at somatic wards, combined with the ample use of restraints on these wards, raises questions about the appropriateness of the currently delivered care to these patients, considering the problems they have.

Objective: To develop two classification models for use in primary care to aid early identification of persons at risk for persistent cognitive decline., Methods: Data were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing populationbased study. The study sample consisted of 2,021 non-demented men and women aged 58-88 years. Data on relevant predictors of persistent cognitive decline were collected at baseline., Results: The incidence of persistent cognitive decline after three years of follow-up was 4.0 %. In the first model, in which predictors already known or otherwise easily assessed (first set) were included, age was the strongest predictor of persistent cognitive decline, with an increased risk for persons > 75. In addition, having memory problems, low education, and a MMSE score of < or = 24, resulted in a predictive value for persistent cognitive decline of 43.5 %. In the second classification model, in addition to the first set, predictors requiring additional measurement (e.g. markers determined in blood) were included in the analyses. Age was again the strongest predictor of persistent cognitive decline. In persons > 75 years, having a low total cholesterol level (< 5.0 mmol/L) and a MMSE score of < or = 24 resulted in a predictive value of 30.0 %., Conclusions: Both models lead to a substantial increase of the predictive value for persistent cognitive decline, that is from 4.0 % to 43.5 % and 30.0 %, and may identify to a large extent a different subsample of persons who are at risk for persistent cognitive decline. The developed classification trees could be useful for case-finding of persons at risk for future persistent cognitive decline who are therefore at risk for dementia, in a feasible and cost-effective manner.

Context: Depression has incidentally been related to altered levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH), but this relation has never been studied systematically., Objective: To determine in a large population-based cohort whether there is an association between depression and altered 25(OH)D and PTH levels., Design: Population-based cohort study (Longitudinal Aging Study Amsterdam)., Participants: One thousand two hundred eighty-two community residents aged 65 to 95 years., Setting: The Netherlands., Main Outcome Measure: Depression was measured using self-reports (Center for Epidemiologic Studies-Depression scale) and diagnostic interviews (Diagnostic Interview Schedule). Levels of 25(OH)D and PTH were assessed. Potentially confounding factors (ie, age, sex, smoking status, body mass index, number of chronic conditions, and serum creatinine concentration) and explanatory factors (ie, season of data acquisition, level of urbanization, and physical activity) were also measured., Results: Levels of 25(OH)D were 14% lower in 169 persons with minor depression and 14% lower in 26 persons with major depressive disorder compared with levels in 1087 control individuals (P < .001). Levels of PTH were 5% and 33% higher, respectively (P = .003). Depression severity (Center for Epidemiologic Studies Depression Scale) was significantly associated with decreased serum 25(OH)D levels (P = .03) and increased serum PTH levels (P = .008)., Conclusion: The results of this large population-based study show an association of depression status and severity with decreased serum 25(OH)D levels and increased serum PTH levels in older individuals.

Background: Previous studies have reported conflicting results concerning the association between several inflammatory markers and depression. The association between inflammation and depression may depend on the presence of specific chronic diseases or be relevant in specific sub-groups of depressed patients only., Objective: To assess associations between inflammatory markers and depression in older people, taking account of confounding and effect-modifying factors., Method: Population-based study of 1285 participants of the Longitudinal Aging Study Amsterdam, aged 65 and over. Plasma concentrations of Interleukin-6 (IL-6) and C-reactive protein (CRP) were measured. Major depression (first- or recurrent episode) and sub-threshold depression were assessed. Associations were adjusted for confounding variables. Associations with inflammatory markers were further studied with regard to severity and duration of depression, and with regard to specific depressive symptoms., Results: High levels of IL-6 (above 5 pg/mL) were associated with major depression (odds ratio 2.49 (1.07-5.80), both in recurrent and first episodes. No significant effect of either one of the markers on specific symptom dimensions of depression was found. Mildly elevated plasma levels of CRP (above 3.2 mg/L) were associated with higher CES-D scores, but not after correction for the confounding effect of age and chronic diseases., Limitations: The cross-sectional design limits conclusions regarding causality., Conclusions: A high plasma level of IL-6, but not CRP, is associated with an increased prevalence of major depression in older people, independent of age, chronic diseases, cognitive functioning and anti-depressants. Present results suggest new directions for clinical research into the prevention of physical consequences of depression.

Functional foods with supplementation of plant sterols are already used by millions of people. However, at the same time it is current scientific thinking that elevation of plant sterols in the circulation causes coronary heart disease. Therefore, this study aimed to define the risk for coronary heart disease associated with moderately high plant sterol plasma levels in a cohort of elderly. In this study, we evaluated the association between plant sterols and coronary heart disease in a cohort of 1242 subjects older than 65 years, participating at the Longitudinal Aging Study Amsterdam (LASA). Concentrations of sitosterol, campesterol, brassicasterol and stigmasterol were assessed using highly sensitive and specific gas chromatography-mass spectrometry-selected ion-monitoring. Plant sterol concentrations (and their ratios to cholesterol) were slightly, however, significantly lower in patients with coronary heart disease. Moreover, high plasma concentrations of a marker plant sterol, sitosterol, were associated with a markedly reduced risk for coronary heart disease (OR 0.78, CI 0.62-0.98, p<0.05). In contrast neither plant stanols (sitostanol or campestanol) nor the cholesterol synthesis markers (lathosterol, lanosterol and desmosterol) nor their ratios to cholesterol were significantly different in the study groups. These data suggest that plant sterols could have neutral or even protective effects on development of coronary heart disease, which have to be confirmed in interventional trials.

Aim: To describe the distribution of apolipoprotein E (APOE) genotypes in a cohort of memory clinic patients., Methods: We included 749 memory clinic patients. Diagnoses were made in a multidisciplinary consensus meeting and the APOE genotype was determined. The community-based cohort of the Longitudinal Aging Study Amsterdam was used as control population (n = 2,233)., Results: In the memory clinic sample, there were 173 patients with subjective complaints, 125 patients with mild cognitive impairment (MCI), 251 patients with Alzheimer disease (AD), 107 patients with another type of dementia, and 93 patients with another neurologic or psychiatric diagnosis. The APOE allele distribution differed among groups. There was no difference in the prevalence of the epsilon2 allele, but there were differences in distribution of the epsilon3 and epsilon4 alleles. Compared with the control population (15%), the prevalence of APOE epsilon4 was increased among patients with subjective complaints (22%), MCI (36%), AD (42%) and other types of dementia (25%)., Conclusion: We observed an increased prevalence of APOE epsilon4 in patients with MCI and subjective complaints. This finding is of great clinical importance as nondemented patients positive for APOE epsilon4 could be identified as being at genetic risk of AD, and for that reason monitored more closely., ((c) 2008 S. Karger AG, Basel)

Objective: Recent evidence suggests that the metabolic syndrome and inflammation affect cognitive decline in old age and that they reinforce each other. However, it is not known what the roles of the individual components of the metabolic syndrome on cognition are., Research Design and Methods: The sample consisted of 1,183 participants in the Longitudinal Aging Study Amsterdam who were aged 65-88 years. Metabolic syndrome (U.S. National Cholesterol Education Program definition) and its individual components and the inflammatory markers C-reactive protein (CRP) and alpha1-antichymotrypsin (ACT) were assessed. Cognitive assessments included general cognition (Mini-Mental State Examination), memory (verbal learning test), fluid intelligence (Raven's Matrices), and information processing speed (coding task)., Results: Of the sample, 36.3% had metabolic syndrome. Metabolic syndrome was significantly associated with all cognitive measures (P < 0.05). Of the individual components, hyperglycemia was most strongly and significantly associated with cognitive function (multivariate adjusted models; B values, indicating differences in scores between both groups, ranging from -0.38 to -1.21). There was a significant interaction between metabolic syndrome and inflammation on cognition (P < 0.01-0.09). Metabolic syndrome was negatively associated with cognition in subjects with high inflammation (highest tertile for both CRP and ACT; B values ranging from -0.86 to -1.94, P < 0.05), whereas an association was absent in subjects with low inflammation (B values ranging from -0.10 to -0.70)., Conclusions: Subjects with metabolic syndrome showed poorer cognitive performance than subjects without metabolic syndrome, especially those with high levels of inflammation. Hyperglycemia was the main contributor of the association of metabolic syndrome with cognition.

Background and Aims: This study aimed at examining the association between unhealthy lifestyle in young age, midlife and/or old age and physical decline in old age, and between chronic exposure to an unhealthy lifestyle throughout life and physical decline in old age., Methods: The study sample included 1297 respondents of the Longitudinal Aging Study Amsterdam (LASA). Lifestyle in old age (55-85 y) was assessed at baseline, whereas lifestyle in young age (around 25 y) and midlife (around 40 y) were assessed retrospectively. Lifestyle factors included physical activity, body mass index (BMI), number of alcohol drinks per week and smoking. Physical decline was calculated as a change in physical performance score between baseline and six-year followup., Results: Of the lifestyle factors present in old age, a BMI of 25-29 vs BMI < 25 kg/m2 (OR=1.6; 95% CI: 1.1-2.2) and a BMI of > or = 30 vs BMI < 25 kg/m2 (OR=1.8; 95% CI: 1.2-2.7) were associated with physical decline in old age. Being physically inactive in old age was not significantly associated with an increased risk of physical decline, although, being physically inactive in both midlife and old age increased the odds of physical decline in old age to 1.6 (95% CI: 1.1-2.4), compared with respondents who were physically inactive in midlife and physically active in old age. Being overweight in both age periods was associated with an OR of 1.5 (95% CI: 1.1-2.2)., Conclusions: These data suggest that overweight in old age, and chronic exposure to physical inactivity or overweight throughout life, increases the risk of physical decline in old age. Therefore, physical activity and prevention of excessive weight at all ages should be stimulated, to prevent physical decline in old age.

This study aimed to examine the association between unhealthy lifestyle in young age, midlife and/or old age and physical decline in old age, and to examine the association between chronic exposure to an unhealthy lifestyle throughout life and physical decline in old age. The study sample included 1297 respondents of the Longitudinal Aging Study Amsterdam (LASA). Lifestyle in old age (55-85 y) was assessed at baseline, while lifestyle in young age (around 25 y) and midlife (around 40 y) were assessed retrospectively. Lifestyle factors included physical activity, body mass index (BMI), number of alcohol drinks per week and smoking. Physical decline was calculated as change in physical performance score between baseline and six-year follow-up. Of the lifestyle factors present in old age, a BMI of 25-29 vs. BMI <25 kg/m2 (odds ratio (OR) 1.6; 95% confidence interval (CI) 1.1-2.2) and a BMI of > or =30 vs. BMI <25 kg/m2 (OR 1.8; 95% CI 1.2-2.7) were associated with physical decline in old age. Being physically inactive in old age was not significantly associated with an increased risk of physical decline, however, being physically inactive both in midlife and in old age increased the odds of physical decline in old age to 1.6 (95% CI 1.1-2.4) as compared to respondents who were physically inactive in midlife and physically active in old age. Being overweight in both age periods was associated with an OR of 1.5 (95% CI 1.1-2.2). These data suggest that overweight in old age, and chronic exposure to physical inactivity or overweight throughout life increases the risk of physical decline in old age. Therefore, physical activity and prevention of overweight at all ages should be stimulated to prevent physical decline in old age.

In order to identify persons who are at risk for dementia in an early phase, two classification trees were developed. Data were used from the Longitudinal Aging Study Amsterdam (LASA). The prevalence of dementia in the whole sample was 4.0%. In the first tree age seemed to be the strongest predictor, with an increased risk for persons older than 75. In this group the positive predictive value reached a maximum of 33.3% when the persons had memory complaints and a score on the Mini Mental State Examination (MMSE) <24. In a second classification tree, age was excluded as a predictor because of high association with the other potential predictors. In this tree functional limitations seemed the strongest predictor. In the group of persons with at least one functional limitations, the positive predictive value reached a maximum of 28.8% when the persons had memory complaints and a score <24 on the MMSE. In persons without memory complaints, persons with cardiovascular diseases or diabetes were at increased risk of dementia. Further research is necessary before these classification trees can be implemented in general health care.

Background: The apolipoprotein E (ApoE) e4 polymorphism is linked to increased mortality rates, Alzheimer's disease, and cardiovascular disease in older people, but previous studies have largely failed to detect an effect on self-reported mobility disability. We hypothesized that poor performance on mobility-related tests may provide a better measure of effects, and we aimed to estimate the extent to which the ApoE e4 allele increases risks of poor performance on measured mobility and self-reported mobility disability compared to e3/3, in a medium-sized population cohort., Methods: Data were from 1262 people at baseline older than 65 years from the Longitudinal Aging Study Amsterdam (LASA), followed up for 6 years. Age- and sex-adjusted logistic regression models were used to explore associations., Results: At baseline, those individuals with an e4 allele had an odds ratio of 2.26 (95% confidence interval, 1.31-3.90) for poor performance on gait speed testing (<0.4 m/s) and 1.94 (95% confidence interval, 1.19-3.16) for five chair stands (> or =20 s), compared to those with e3/3 status. At follow-up, associations between e4 status and incident poor performance on the chair stand test was significant. Associations with self-reported inability or need for help walking for 5 minutes or for climbing 15 steps were nonsignificant throughout., Conclusions: The ApoE e4 polymorphism is associated with a substantial excess of mobility limitation. The impact is detectable by performance testing, but not by self-reports. Poor results on mobility performance tests may provide a phenotype of ageing.

Objective: To assess whether serum levels of the inflammatory proteins alpha(1)-antichymotrypsin (ACT), C-reactive protein (CRP), interleukin-6 (IL-6), and albumin are associated with cognitive decline in older persons., Methods: The study sample consisted of 1,284 participants in the Longitudinal Aging Study Amsterdam, aged 62 to 85 years. Cognition was assessed on general cognition (Mini-Mental State Examination [MMSE]), memory (Auditory Verbal Learning Test), fluid intelligence (Raven's Colored Progressive Matrices), and information-processing speed (Coding Task) at baseline and at 3-year follow-up., Results: The highest tertile of ACT was associated with an increased risk of decline on the MMSE (age-, sex-, education-adjusted odds ratio [OR] 1.60; 95% CI: 1.05 to 2.43) but not on any other cognitive test score. CRP, IL-6, and albumin were not associated with cognitive decline on any cognitive test in our study., Conclusions: This population-based study showed that the serum inflammatory protein alpha1-antichymotrypsin is associated with cognitive decline in older persons, whereas C-reactive protein, interleukin-6, and albumin are not.

The study investigated the impact of change in cognitive functioning and cognitive decline on disability, well-being, and the use of healthcare services among older persons in the Longitudinal Aging Study Amsterdam (LASA). Data were collected from 1,349 subjects, aged 65-85 years, who had scores of 24 and higher on the Mini-Mental State Examination (MMSE) at baseline, over a period of 6 years in three waves. The results indicate that cognitive decline and changes in cognitive functioning in older persons who were either not impaired or only mildly cognitively impaired at baseline have an impact on disability, well-being, and the use of healthcare services. With the aging of the population, the number of persons with cognitive impairment is likely to increase, and appropriate services should be available to them.

The course of cognitive functioning in older persons was studied over a period of 6 years. The first aim was to distinguish cognitive decline as a temporary state from progressive cognitive decline. The second aim was to identify predictors which may be useful in discriminating persons with temporary cognitive decline from persons with progressive cognitive decline at an early stage. Data were derived from the Longitudinal Aging Study Amsterdam (LASA), a population-based study in the Netherlands. The results show that 18.2% of the sample of older persons showed cognitive decline over a period of 3 years. Of this group, 44% recovered from cognitive decline or stayed stable in the next 3 years. Especially older age, memory complaints and an increase of cardiovascular diseases at follow-up predict further deterioration., (Copyright 2004 S. Karger AG, Basel)

Insulin-like growth factor I (IGF-I) deficiency may be involved in cognitive deficits seen with aging, and in neurodegenerative diseases such as Alzheimer's disease. The objective of this study was to investigate whether IGF-I is associated with cognitive performance and 3-year cognitive decline in 1318 subjects, aged 65-88 years. Cross-sectionally, IGF-I was directly related to information processing speed, memory, fluid intelligence, and Mini-Mental State Examination (MMSE) score, but these associations did not remain significant after adjustment for age and other factors. Analysis in quintiles of IGF-I revealed a threshold effect of low IGF-I on information processing speed, with lower speed in subjects in the lowest quintile of IGF-I (<9.4 nmol/l)(1) versus those in the other four quintiles (fully adjusted B=-0.89; 95% CI, -1.72 to -0.05). This threshold of low IGF-I was also observed for 3-year decline in information processing speed (adjusted RR=1.78; 95% CI, 1.19-2.68). In summary, this study suggests that IGF-I levels below 9.4 nmol/l are negatively associated with both the level and decline of information processing speed.

Background: The objective is to investigate whether memory complaints in older persons without manifest cognitive decline are associated with depressive symptoms, anxiety symptoms, physical health and personality characteristics. Furthermore, it is investigated whether personality characteristics have a modifying effect on the association of memory complaints with depressive and anxiety symptoms and physical health., Methods: The study was carried out using the Longitudinal Aging Study Amsterdam (LASA). Participants were examined during three observation cycles covering a period of 6 years. They were asked about memory complaints, and were examined on cognitive functioning, physical health, depressive and anxiety symptoms, and the personality characteristics: mastery, perceived self-efficacy and neuroticism. The data were analysed by means of Generalised Estimating Equations (GEE)., Results: Memory complaints were associated with physical health problems, depressive and anxiety symptoms, low feelings of mastery, low perceived self-efficacy and high neuroticism. The associations between memory complaints and physical health problems, depressive and anxiety symptoms were significantly stronger in people with high mastery, high perceived self-efficacy and low neuroticism., Limitations: We used a conservative criterion for cognitive decline and therefore we might have included some people with cognitive decline during our follow-up. In order to minimise selection bias we included actual cognitive performance in our regression models., Conclusions: Our findings suggest that when older persons complain about their memory and do not show actual cognitive decline, one should be aware that these complaints might reflect psycho-affective or health problems.

The aim of this study was to examine whether the presence of apolipoprotein E epsilon4 (ApoE epsilon4) is associated with a lower bone mineral density (BMD), lower quantitative ultrasound (QUS) measurements, higher bone turnover and fracture risk, and whether these relations are modified by gender and age. A total of 1406 elderly men and women (> or =65 years) of the Longitudinal Aging Study Amsterdam (LASA) participated in this study. In all participants, QUS measurements were assessed, as well as serum osteocalcin (OC) and urine deoxypyridinolin (DPD/Cr urine). Follow-up of fractures was done each three months. In a subsample ( n = 604), total body bone mineral content (BMC) and BMD of the hip and lumbar spine were measured. In addition, prevalent vertebral deformities were identified on radiographs. In women, the presence of ApoE epsilon4 was associated with significantly lower femoral neck BMD (g/cm(2); mean +/- SEM; epsilon4+, 0.64 +/- 0.01 vs. epsilon4-, 0.67 +/- 0.01; p = 0.04), lower trochanter BMD (g/cm(2); mean +/- SEM; epsilon4+, 0.58 +/- 0.01 vs. epsilon4-, 0.61 +/- 0.01; p = 0.01) and lower total body BMC (g; mean +/- SEM; epsilon4+, 1787 +/- 40.0 vs. epsilon4-, 1863 +/- 23.8; p = 0.04). Women with ApoE epsilon4 also had a higher risk of severe vertebral deformities (OR=2.78; 95%CI: 1.21-6.34). In men, the associations between ApoE status and both hip BMD and QUS depended on age. Only among the younger men (65-69 years) was the presence of ApoE epsilon4 associated with lower BMD values. Bone markers and fractures were not associated with ApoE epsilon4 in either women, or men. In conclusion, this large community-based study confirms the importance of ApoE epsilon4 as a possible genetic risk factor related to BMD and vertebral deformities and demonstrates that its effect is gender related, and depends on age in men only.

Objective: To investigate to what extent subjective memory complaints and APOE-epsilon4 allele carriage predict future cognitive decline in cognitively intact elderly persons, by evaluating both their separate and combined effects., Methods: We selected 1,168 subjects from the population-based Longitudinal Aging Study Amsterdam who were 62 to 85 years of age and had no obvious cognitive impairment at baseline (Mini-Mental State Examination [MMSE] score, > or =27). Memory complaints and APOE phenotypes were assessed at baseline. MMSE, the Auditory Verbal Learning Test (memory: immediate recall and delayed recall), and the Alphabet Coding Task-15 (information processing speed) were used to study cognitive decline. Follow-up data were collected after 3 and 6 years. Data were analyzed with generalized estimating equations, adjusted for age, sex, education, and depression., Results: Baseline memory complaints were reported by 25.5% of the cognitively intact elderly persons. Overall, 25.3% of the subjects were carriers of at least one APOE-epsilon4 allele. Memory complaints were associated with a greater rate of decline in all cognitive measures, except immediate recall. In addition, APOE-epsilon4 allele carriers had a greater rate of cognitive decline shown by MMSE scores and slower information processing speeds after 6 years. The effects of both memory complaints and APOE-epsilon4 allele carriage were additive: subjects with both factors had a two times higher cognitive decline than did subjects without both factors., Conclusions: Both memory complaints and APOE-epsilon4 allele carriage predict cognitive decline at an early stage. This finding highlights the importance of subjective memory complaints, which are important even at an early stage when objective tests are still unable to detect cognitive deficits and are especially important for elderly carriers of the APOE-epsilon4 allele because they have an additional risk.

The objective of this study was to investigate whether the association between Apolipoprotein E4 (ApoE4) and memory decline is modified by baseline general cognitive impairment and age in a population-based elderly sample. Subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). The study sample consisted of 1,243 subjects, 62-85 years old, with a Mini-Mental State Examination (MMSE) score between 21-30 and known ApoE phenotypes. Memory performance was measured with a short version of the Auditory Verbal Learning Test (AVLT) at baseline and repeated after three years (N = 854). Memory decline was defined as a decrease of at least one standard deviation from the mean change score on immediate recall, delayed recall and retention. ApoE4 was associated with memory decline in cognitively impaired subjects (MMSE 21-26), but not in cognitively normal subjects (MMSE 27-30). In particular cognitively impaired E4 carriers older than 75 years were at high risk of memory decline. Contrary to AD studies, our study suggests that the risk of ApoE4 on memory decline does not decrease with ageing.

Background and Purpose: Stroke and apolipoprotein E epsilon4 (ApoE epsilon4) are individually important risk factors for cognitive decline, including Alzheimer disease. It has been suggested that ApoE epsilon4 multiplies the risk for cognitive decline following stroke. In a population-based sample, using well-defined sensitive cognitive measures, this study investigates whether cognitive decline following stroke is worse for patients who carry the ApoE epsilon4 allele., Methods: Subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). The sample consisted of 1224 subjects, aged 62 to 85 years, who participated in the 3-year follow-up examination and for whom ApoE and stroke data were complete. We assessed cognitive decline using the Mini-Mental State Examination, the Auditory Verbal Learning Test (memory: immediate and delayed recall), and the Coding Task (information processing speed). The effects of stroke and ApoE epsilon4 on cognitive decline were evaluated with ANOVA and multiple logistic regression analysis, adjusted for age, sex, education, and baseline cognition., Results: A synergistic effect modification for stroke and ApoE epsilon4 on cognitive decline was not observed. Unexpectedly, instead, stroke patients carrying the epsilon4 allele demonstrated a nonsignificantly lowered risk for Mini-Mental State Examination decline (OR=0.3; 95% CI 0.1 to 1.1). ApoE epsilon4 was associated with declines in information processing speed (OR=1.5; 95% CI 1.1 to 2.1) and small declines for immediate and delayed recall., Conclusions: Stroke and ApoE epsilon4 may impair cognition through distinct nonsynergistic mechanisms. The slowing of information processing speed for ApoE epsilon4 carriers was more evident than impairment in memory.

Objective: To investigate whether the association between APOE-epsilon4 and memory decline is modified by baseline cognition and age in a population-based elderly sample., Methods: The study sample consisted of 1,243 subjects, 62 to 85 years old, with a Mini-Mental State Examination (MMSE) score between 21 and 30 and known APOE phenotypes. Memory performance was measured with an abbreviated Auditory Verbal Learning Test (AVLT) at baseline and repeated after 3 years (n = 854). Memory decline was defined as a decrease of at least 1 SD from the mean change score on immediate recall (IR), delayed recall (DR), and retention, based on the AVLT., Results: Multivariate logistic regression analyses showed that APOE-epsilon4 is associated with memory decline in cognitively impaired subjects (MMSE score, 21 to 26) (OR for decline on IR adjusted for age, sex, education, and baseline recall score, 3.8; 95% CI, 1.4 to 10.0; adjusted OR for decline on DR, 2.9; 95% CI, 1.2 to 7.0; adjusted OR for decline on retention, 3.3; 95% CI, 1.1 to 10. 1), but not in cognitively normal subjects (MMSE score, 27 to 30) (adjusted OR for decline on IR, 1.1; 95% CI, 0.6 to 2.0; adjusted OR for decline on DR, 1.0; 95% CI, 0.6 to 1.8; adjusted OR for decline on retention, 1.5; 95% CI, 0.7 to 3.0). In particular, cognitively impaired epsilon4 carriers older than 75 years were at high risk of memory decline (adjusted OR for decline on IR, 4.5; 95% CI, 1.4 to 13.8; adjusted OR for decline on DR, 3.6; 95% CI, 1.2 to 10.8; adjusted OR for decline on retention, 6.6; 95% CI, 1.5 to 29.7)., Conclusions: APOE-epsilon4 was associated with memory decline in subjects with cognitive impairment, but not in normally functioning subjects. Contrary to AD studies, our study suggests that the risk of APOE-epsilon4 on memory decline does not decrease at higher ages.