Role of lipoproteins and inflammation in cognitive decline: do they interact?

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.

The role of extracerebral cholesterol homeostasis and ApoE e4 in cognitive decline.

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.

Late-life depression, cortisol, and the metabolic syndrome.

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.

Classification models for early identification of persons at risk for dementia in primary care: an evaluation in a sample aged 80 years and older.

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

Somatic chronic diseases and 6-year change in cognitive functioning among older persons.

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.

Inflammatory markers in AD and MCI patients with different biomarker profiles.

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.

Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults.

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.

Moderately elevated plant sterol levels are associated with reduced cardiovascular risk--the LASA study.

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.

Contribution of metabolic syndrome components to cognition in older individuals.

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.

Unhealthy lifestyles during the life course: association with physical decline in late life.

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.

The impact of change in cognitive functioning and cognitive decline on disability, well-being, and the use of healthcare services in older persons. Results of Longitudinal Aging Study Amsterdam.

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 decline in older persons: results from the longitudinal aging study amsterdam.

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.

Insulin-like growth factor I (IGF-I) and cognitive decline in older persons.

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.