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

AbstractWe 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

Time Trend in Persistent Cognitive Decline: Results from the Longitudinal Aging Study Amsterdam

Objective To study time trends in the incidence of persistent cognitive decline (PCD), and whether an increase or decrease is explained by changes in well-known risk factors of dementia. Method Data from the Longitudinal Aging Study Amsterdam over a period of 20 years were used. Subsamples of 65-88 year-olds were selected at 7 waves, with numbers ranging from 1,800 to 1,165. Within-person change in cognitive functioning was used to determine PCD. In logistic generalized estimating equations (GEE), time (0, 3, 6, 9, 13, and 16 years) was the main predictor of 3-year PCD incidence. Explanatory variables were lagged one wave before incident PCD and included in separate models. Results PCD incidence was 2.5% at first, and 3.4% at last follow-up. GEE showed a positive time trend for PCD incidence [Exp(B) time = 1.042; p <.001]. None of the explanatory variables significantly changed the strength of the regression coefficient of linear time. Higher age, lower education, diabetes mellitus, smoking, lower body-mass index, and lower level of physical activity were associated with higher incidence of PCD. Conclusion An increase in PCD incidence over time was found. Although well-known risk factors were associated with incidence per se, they did not explain the increase in incidence of PCD

Prevalence and Incidence of Memory Complaints in Employed Compared to Non-Employed Aged 55–64 Years and the Role of Employment Characteristics

<div><p>Objectives</p><p>To examine the association of employment status and characteristics with prevalent and incident memory complaints (MC) in 55–64-year-olds.</p><p>Methods</p><p>Subjects were participants of the Longitudinal Aging Study Amsterdam (LASA). Respondents with baseline data were selected to examine the association of employment status (n = 1525) and employment characteristics (n = 1071) with prevalent MC (i.e., MC at baseline). Respondents without MC at baseline were selected to examine the association of employment (n = 526) and employment characteristics (n = 379; working hours, job prestige, job level, psychological job demands, iso-strain) with incident MC (i.e., no MC at baseline and MC at three-year follow-up). Associations were adjusted for relevant covariates (demographics, memory performance, physical health, mental health, personality traits). Logistic regression was applied. Data were weighed according to gender and age of the Dutch population.</p><p>Results</p><p>At baseline 20.5% reported MC. At three-year follow-up, 15.4% had incident MC. No associations were found between employment status and MC. Adjusted analysis revealed that individuals with high occupational cognitive demands were more likely to have prevalent MC.</p><p>Conclusions</p><p>Middle-aged workers are equally as likely to experience MC as non-working age-peers. Among workers, those with cognitively demanding work were more likely to experience MC, independent of memory performance. Memory decline due to ageing may be noticed sooner in 55–64-year-olds performing cognitively demanding work.</p></div

Associations of baseline employment characteristics with prevalent MC at baseline and incident MC at (3-year) follow-up.

<p>Associations of baseline employment characteristics with prevalent MC at baseline and incident MC at (3-year) follow-up.</p

Flow-chart of selected respondents at baseline (T1) and three-year follow-up (T2).

<p>Flow-chart of selected respondents at baseline (T1) and three-year follow-up (T2).</p

Weighed number of prevalent and incident MC in employed and unemployed individuals.

<p>Weighed number of prevalent and incident MC in employed and unemployed individuals.</p

Classification models for identification of at-risk groups for incident memory complaints

Background: Memory complaints in older adults may be a precursor of measurable cognitive decline. Causes for these complaints may vary across age groups. The goal of this study was to develop classification models for the early identification of persons at risk for memory complaints using a broad range of characteristics. Methods: Two age groups were studied, 55-65 years old (N = 1,416.8) and 65-75 years old (N = 471) using data from the Longitudinal Aging Study Amsterdam. Participants reporting memory complaints at baseline were excluded. Data on predictors of memory complaints were collected at baseline and analyzed using logistic regression analyses. Multiple imputation was applied to handle the missing data; missing data due to mortality were not imputed. Results: In persons aged 55-65 years, 14.4% reported memory complaints after three years of follow-up. Persons using medication, who were former smokers and had insufficient/poor hearing, were at the highest risk of developing memory complaints, i.e. a predictive value of 33.3%. In persons 65-75 years old, the incidence of memory complaints was 22.5%. Persons with a low sense of mastery, who reported having pain, were at the highest risk of memory complaints resulting in a final predictive value of 56.9%. In the subsample of persons without a low sense of mastery who (almost) never visited organizations and had a low level of memory performance, 46.8% reported memory complaints at follow-up. Conclusions: The classification models led to the identification of specific target groups at risk for memory complaints. Suggestions for person-tailored interventions may be based on these risk profiles

Associations of employment with prevalent MC at baseline and incident MC at (3-year) follow-up.

<p>Associations of employment with prevalent MC at baseline and incident MC at (3-year) follow-up.</p

Sample characteristics at baseline for those with and without memory complaints.

<p>Sample characteristics at baseline for those with and without memory complaints.</p