'Big Five' personality characteristics are associated with loneliness but not with social network size in older adults, irrespective of depression.

OBJECTIVE: Loneliness and social isolation have negative health consequences and are associated with depression. Personality characteristics are important when studying persons at risk for loneliness and social isolation. The objective of this study was to clarify the association between personality factors, loneliness and social network, taking into account diagnosis of depression, partner status and gender. DESIGN: Cross-sectional data of an ongoing prospective cohort study, the Netherlands Study of Depression in Older Persons (NESDO), were used. SETTING AND PARTICIPANTS: 474 participants were recruited from mental health care institutions and general practitioners in five different regions in the Netherlands. MEASUREMENTS: NEO-Five Factor Inventory (NEO-FFI) personality factors and loneliness and social network were measured as well as possible confounders. Multinominal logistic regression analyses were performed to analyse the associations between NEO-FFI factors and loneliness and social network. Interaction terms were investigated for depression, partner status and gender. RESULTS: Higher neuroticism and lower extraversion in women and lower agreeableness in both men and women were associated with loneliness but not with social network size irrespective of the presence of depression. In the non-depressed group only, lower openness was associated with loneliness. Interaction terms with partner status were not significant. CONCLUSIONS: Personality factors are associated with loneliness especially in women. In men lower agreeableness contributes to higher loneliness. In non-depressed men and women, lower openness is associated with loneliness. Personality factors are not associated with social network size.

Age dependency of risk factors for cognitive decline.

BACKGROUND: Risk factors for cognitive decline might depend on chronological age. The aim of the study was to explore the age dependency of risk factors for cognitive decline in cognitively healthy subjects aged 55-85 years at baseline. METHODS: We included 2527 cognitively healthy subjects from the Longitudinal Aging Study Amsterdam (LASA). Median follow-up was 9.1 (IQR: 3.2-19.0) years. The association of genetic and cardiovascular risk factors, depressive symptoms, inflammation markers and lifestyle risk factors with decline in MMSE and memory function was tested using spline regression analyses. RESULTS: Subjects were on average 70.1 (SD 8.8) years old at baseline. Based on a spline regression model, we divided our sample in three age groups: ≤70 years (young-old), > 70-80 years (old) and > 80 years (oldest-old). The association of LDL cholesterol, homocysteine, hypertension, history of stroke, depressive symptoms, interleukin-6, a1-antichymotrypsin, alcohol use and smoking with cognitive decline significantly differed between the age groups. In general, the presence of these risk factors was associated with less cognitive decline in the oldest-old group compared to the young-old and old group. CONCLUSIONS: The negative effect of various risk factors on cognitive decline decreases with higher age. A combination of epidemiological factors, such as the selection towards healthier subjects during follow-up, but also risk factor specific features, for example ensuring the cerebral blood flow in case of hypertension, explain this diminished association at higher age. It is important to take these age differences into account when applying preventive strategies to avert cognitive decline.

The association between singing and/or playing a musical instrument and cognitive functions in older adults.

OBJECTIVES: Cognitive decline happens to everyone when aging, but to some more than others. Studies with children, adults, and professional musicians suggest that making music could be associated with better cognitive functioning. In older adults however, this association is less well investigated, which is therefore the aim of this study. METHODS: In this cross-sectional study data from 1101 participants aged 64 and older from the Longitudinal Aging Study Amsterdam were used. Multivariable linear regression analyses were performed to test the association between making music and cognitive functioning and time spent making music and cognitive functioning. ANCOVA analyses were performed to differentiate between participants who made no music, only sang, only played an instrument or both sang and played an instrument in terms of cognitive functioning. RESULTS: Making music was significantly positively associated with letter fluency, learning and attention/short-term memory. Time spent making music yielded no significant results. The ANCOVA analyses showed higher scores for participants who only played an instrument compared to participants who made no music on learning, working memory and processing speed. For processing speed the instrument only group also had a higher score than participants who only sang. DISCUSSION: Making music at least once every two weeks and especially playing a musical instrument, is associated with better attention, episodic memory and executive functions. The results suggest that making music might be a potential protective factor for cognitive decline; however, to support this notion a longitudinal study design is needed.

Age-related variability in the presentation of symptoms of major depressive disorder.

BACKGROUND: The heterogeneous aetiology of major depressive disorder (MDD) might affect the presentation of depressive symptoms across the lifespan. We examined to what extent a range of mood, cognitive, and somatic/vegetative depressive symptoms were differentially present depending on patient's age. METHOD: Data came from 1404 participants with current MDD (aged 18-88 years) from two cohort studies: the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Study of Depression in Older Persons (NESDO). Associations between age (per 10 years) and 30 depressive symptoms as well as three symptom clusters (mood, cognitive, somatic/vegetative) were assessed using logistic and linear regression analyses. RESULTS: Depression severity was found to be stable with increasing age. Nevertheless, 20 (67%) out of 30 symptoms were associated with age. Most clearly, with ageing there was more often early morning awakening [odds ratio (OR) 1.47, 95% confidence interval (CI) 1.36-1.60], reduced interest in sex (OR 1.42, 95% CI 1.31-1.53), and problems sleeping during the night (OR 1.33, 95% CI 1.24-1.43), whereas symptoms most strongly associated with younger age were interpersonal sensitivity (OR 0.72, 95% CI 0.66-0.79), feeling irritable (OR 0.73, 95% CI 0.67-0.79), and sleeping too much (OR 0.75, 95% CI 0.68-0.83). The sum score of somatic/vegetative symptoms was associated with older age (B = 0.23, p < 0.001), whereas the mood and cognitive sum scores were associated with younger age (B = -0.20, p < 0.001; B = -0.04, p = 0.004). CONCLUSIONS: Depression severity was found to be stable across the lifespan, yet depressive symptoms tend to shift with age from being predominantly mood-related to being more somatic/vegetative. Due to the increasing somatic presentation of depression with age, diagnoses may be missed.

Metabolic dysregulation and late-life depression: a prospective study.

BACKGROUND: Depression is associated with the metabolic syndrome (MS). We examined whether metabolic dysregulation predicted the 2-year course of clinical depression. METHOD: A total of 285 older persons (⩾60 years) suffering from depressive disorder according to DSM-IV-TR criteria was followed up for 2 years. Severity of depression was assessed with the Inventory of Depressive Symptomatology (IDS) at 6-month intervals. Metabolic syndrome was defined according the National Cholesterol Education Programme (NCEP-ATP III). We applied logistic regression and linear mixed models adjusted for age, sex, years of education, smoking, alcohol use, physical activity, somatic co-morbidity, cognitive functioning and drug use (antidepressants, anti-inflammatory drugs) and severity of depression at baseline. RESULTS: MS predicted non-remission at 2 years (odds ratioper component = 1.26, 95% confidence interval 1.00-1.58), p = 0.047), which was driven by the waist circumference and HDL cholesterol. MS was not associated with IDS sum score. Subsequent analyses on its subscales, however, identified an association with the somatic symptom subscale score over time (interaction time × somatic subscale, p = 0.005), driven by higher waist circumference and elevated fasting glucose level. CONCLUSIONS: Metabolic dysregulation predicts a poor course of late-life depression. This finding supports the concept of 'metabolic depression', recently proposed on population-based findings of a protracted course of depressive symptoms in the presence of metabolic dysregulation. Our findings seem to be driven by abdominal obesity (as indicated by the waist circumference) and HDL cholesterol dysregulation.

Longitudinal associations between late-life depression dimensions and cognitive functioning: a cross-domain latent growth curve analysis.

BACKGROUND: Cognitive impairment and depression often co-occur in older adults, but it is not clear whether depression is a risk factor for cognitive decline, a psychological reaction to cognitive decline, or whether changes in depressive symptoms correlate with changes in cognitive performance over time. The co-morbid manifestation of depression and cognitive impairment may reflect either a causal effect or a common cause, depending on the specific symptoms experienced and the cognitive functions affected. METHOD: The study sample comprised 1506 community-dwelling older adults aged ⩾65 years from the Longitudinal Aging Study Amsterdam (LASA). We conducted cross-domain latent growth curve analyses to examine longitudinal associations between late-life depression dimensions (i.e. depressed affect, positive affect, and somatic symptoms) and specific domains of cognitive functioning (i.e. processing speed, inductive reasoning, immediate recall, and delayed recall). RESULTS: Poorer delayed recall performance at baseline predicted a steeper increase in depressed affect over time. Steeper decline in processing speed correlated with a steeper increase in somatic symptoms of depression over time. CONCLUSIONS: Our findings suggest a prospective association between memory function and depressed affect, whereby older adults may experience an increase in depressed affect in reaction to poor memory function. Somatic symptoms of depression increased concurrently with declining processing speed, which may reflect common neurodegenerative processes. Our findings do not support the hypothesis that depression symptoms may be a risk factor for cognitive decline in the general population. These findings have potential implications for the treatment of late-life depression and for the prognosis of cognitive outcomes.

Big Five personality characteristics are associated with depression subtypes and symptom dimensions of depression in older adults.

OBJECTIVE: This study examined the associations of personality characteristics with both subtypes and symptom dimensions of depression in older adults. METHODS: Three hundred and seventy-eight depressed older adults participated in the Netherlands Study of Depression in Older Persons. Personality characteristics were assessed by the NEO-Five Factor Inventory. Subtypes and symptom dimensions of depression were determined using the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology (IDS). Multinomial logistic regression analyses were performed to examine the associations between personality and atypical, melancholic, and unspecified subtypes of major depression. Linear regression analyses examined the associations between personality and the IDS mood, somatic, and motivation symptom dimensions. The analyses were adjusted for confounders and additionally adjusted for depression severity. RESULTS: Neuroticism, Extraversion, Conscientiousness, and Agreeableness were associated with specified (atypical or melancholic) major depression compared with unspecified major depression in the bivariate analyses but lost their significance after adjustments for functional limitations and severity of depression. Neuroticism was positively associated with the IDS mood and motivation symptom dimensions, also in the adjusted models. Further, Extraversion and Agreeableness were negatively associated with the IDS mood symptom dimension, and Extraversion and Conscientiousness were negatively associated with the IDS motivation symptom dimension. None was associated with the IDS somatic symptom dimension. CONCLUSIONS: This study demonstrated the association of personality characteristics with mood and motivational symptoms of late-life depression. The lacking ability of personality to differentiate between melancholic and atypical depression seems to be largely explained by severity of depressive symptoms. Copyright © 2017 John Wiley & Sons, Ltd.

The long-term outcome of subthreshold depression in later life.

BACKGROUND: Subthreshold depression (SUBD) in later life is common and important as prodromal state and prominent risk factor in the development of major depressive disorder (MDD). Indicated prevention can reduce the incidence of MDD among people with SUBD substantially, but needs to be targeted to those that are truly at risk of developing MDD. METHOD: N = 341 eligible participants with SUBD were included from the first (1992/1993), second (1995/1996) and third (1998/1999) cycle from the Longitudinal Aging Study Amsterdam (LASA) by using a two-stage screening design. LASA is an ongoing prospective cohort study in The Netherlands among the older population (55-85 years). At baseline (1992/1993) N = 3107 participants were interviewed and follow-up cycles were conducted every 3 years until 2008/2009, resulting in maximal 17 years of observational period. The proportion of people that developed MDD, remained SUBD, or recovered from SUBD was measured and Cox proportional regression analyses were performed to investigate 29 putative predictors of MDD and recovery from SUBD. RESULTS: N = 153 (44.9%) recovered from SUBD, N = 138 (40.5%) remained chronically SUBD, and N = 50 (14.7%) developed MDD (incidence rate 15.1/1000 person-years). Women, high neuroticism, more chronic diseases, high body mass index, smoking and less social support predicted conversion to MDD. Men, low neuroticism and absence of pain predicted recovery from SUBD. CONCLUSIONS: Although older people with SUBD are clearly at risk of developing MDD, the majority did not, even after a long and thorough follow-up. Given the risk factors that were uncovered, targeting and prevention of MDD in those at very high risk is feasible.

Cross-sectional and longitudinal associations between serum 25-hydroxyvitamin D and cognitive functioning.

BACKGROUND: Vitamin D deficiency is common in older persons. The objectives of this study were: To examine the cross-sectional and longitudinal association between serum 25-hydroxyvitamin D (25(OH)D) and cognitive functioning in older persons; and to explore the optimal cut-off for serum 25(OH)D. METHODS: Data of the Longitudinal Aging Study Amsterdam (LASA) were used. Serum 25(OH)D was determined using a competitive protein binding assay in 1995/6 (n = 1,320). Cognitive functioning was assessed in 1995/6 and 1998/9 using the Mini-Mental State Examination (MMSE, general cognitive functioning), Raven's Colored Progressive Matrices (RCPM, ability of nonverbal and abstract reasoning), the Coding Task (CT, information processing speed), and the 15 Words Test (15WT, immediate memory and delayed recall). The data were analyzed using linear regression analyses and restricted cubic spline functions. The MMSE was normalized using ln(31-MMSE). RESULTS: Mean serum 25(OH)D was 53.7 nmol/L. After adjustment for confounding, patients with serum 25(OH)D levels below 30 nmol/L had significantly lower general cognitive functioning (beta of ln(31-MMSE) = 0.122; p = 0.046) and slower information processing speed (beta = -2.177, p = 0.001) as compared with patients having serum 25(OH)D levels ≥ 75 nmol/L in the cross-sectional analyses. For both outcomes, the optimal cut-off was about 60 nmol/L. No other significant associations were observed. CONCLUSIONS: A lower serum 25(OH)D was significantly associated with lower general cognitive functioning and slower information processing speed, but not with a faster rate of cognitive decline.

Cerebrovascular involvement and clinical presentation of late-life depression, findings from the NESDO study.

OBJECTIVES: The vascular depression hypothesis, which supposes a causal relation of vascular risk factors and vascular disease with depression, has not been definitively accepted. Inconsistent findings may be due to different clinical presentations of depression in older people with and without a clear history of stroke. We therefore aimed to investigate the association between vascular pathology, with and without previous stroke, and different symptom domains of depression. METHOD: For our study, we used baseline data of 378 people aged 60 years and older with a current depression who participated in the Netherlands Study of Depression in Older persons (NESDO), an observational (multicentre) cohort study. Using all information on vascular pathology and risk factors, three classes were operationalized: a first class of depressed older people with previous stroke; a second class of depressed older people with cardiovascular and peripheral arterial diseases, but without stroke; and a third class of depressed older people with no vascular disease. RESULTS: The depressed older people with previous stroke were characterized by more 'motivational' symptoms, which distinguished them from other depressed older people. Inclusion in this stroke group was also associated with having increased prevalence of hypertension, smoking more cigarettes, and lower alcohol consumption. CONCLUSIONS: Our findings suggest that the 'vascular depression' connotation should be reserved for depressed (older) patients with vascular pathology and evident cerebral involvement.

[Screening for metabolic syndrome in older patients with severe mental illness]. / Metabole screening bij oudere patiënten met een ernstige psychiatrische aandoening1.

BACKGROUND: Diabetes, cardiovascular disease and metabolic syndrome are more prevalent in older patients with severe mental illness (smi) than in healthy older persons in the same age-group as the smi patients. Compared to the general population, smi patients are often in a poorer state of (physical) health and have a shorter life expectancy.
AIM: To assess the value of screening older smi patients (≥ 60) for metabolic syndrome.
METHOD: We performed a prospective evaluation of the metabolic screening outcome data relating to 100 older smi patients and 124 healthy older patients and compared the results.
RESULTS: In our smi patients (average age 69 years; 52% bipolar disorder, 48% schizophrenia) the frequency of metabolic syndrome (43%) was no higher than in healthy older persons (39.5%, p = 0.60). However, in 51% of the smi sample, metabolic screening detected at least one metabolic abnormality in a patient with no previous history for that specific parameter.
CONCLUSION: By making routine metabolic screening available to a greater number of older smi patients, we should be able to identify substantial numbers of metabolic abnormalities that have been previously overlooked.

Comorbid anxiety disorders in late-life depression: results of a cohort study.

BACKGROUND: Comorbid anxiety disorders are common in late-life depression and negatively impact treatment outcome. This study aimed to examine personality characteristics as well as early and recent life-events as possible determinants of comorbid anxiety disorders in late-life depression, taking previously examined determinants into account. METHODS: Using the Composite International Diagnostic Interview (CIDI 2.0), we established comorbid anxiety disorders (social phobia (SP), panic disorder (PD), generalized anxiety disorder (GAD), and agoraphobia (AGO)) in 350 patients (aged ≥60 years) suffering from a major depressive disorder according to DSM-IV-TR criteria within the past six months. Adjusted for age, sex, and level of education, we first examined previously identified determinants of anxious depression: depression severity, suicidality, partner status, loneliness, chronic diseases, and gait speed in multiple logistic regression models. Subsequently, associations were explored with the big five personality characteristics as well as early and recent life-events. First, multiple logistic regression analyses were conducted with the presence of any anxiety disorder (yes/no) as dependent variable, where after analyses were repeated for each anxiety disorder, separately. RESULTS: In our sample, the prevalence rate of comorbid anxiety disorders in late-life depression was 38.6%. Determinants of comorbid anxiety disorders were a lower age, female sex, less education, higher depression severity, early traumatization, neuroticism, extraversion, and conscientiousness. Nonetheless, determinants differed across the specific anxiety disorders and lumping all anxiety disorder together masked some determinants (education, personality). CONCLUSIONS: Our findings stress the need to examine determinants of comorbid anxiety disorder for specific anxiety disorders separately, enabling the development of targeted interventions within subgroups of depressed patients.

No lower cognitive functioning in older adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Research illustrates cognitive deficits in children and younger adults with attention-deficit/hyperactivity disorder (ADHD). Few studies have focused on the cognitive functioning in older adults. This study investigates the association between ADHD and cognitive functioning in older adults. METHODS: Data were collected in a cross-sectional side study of the Longitudinal Aging Study Amsterdam (LASA). A diagnostic interview to diagnose ADHD was administered among a subsample (N = 231, age 60-94). ADHD symptoms and diagnosis were assessed with the Diagnostic Interview for ADHD in Adults (DIVA) 2.0. Cognitive functioning was assessed with tests in the domains of executive functioning, information processing speed, memory, and attention/working memory. RESULTS: Regression analyses indicate that ADHD diagnosis and ADHD severity were only negatively associated with cognitive functioning in the attention/working memory domain. When adjusting for depression, these associations were no longer significant. CONCLUSION: The study shows that ADHD in older adults is associated with lower cognitive functioning in the attention/working memory domain. However, this was partly explained by depressive symptoms.

In depressed older persons higher blood pressure is associated with symptoms of apathy. The NESDO study.

BACKGROUND: In older persons, a relationship between both higher and lower blood pressure and depression has inconsistently been reported. Blood pressure may be differentially associated with distinct symptom domains of depression. We examined the cross-sectional relation of current systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) with different depressive symptom domains among depressed older persons. METHODS: In the Netherlands Study of Depression in Older Persons (NESDO), 270 participants aged 60 years and above were diagnosed with depression in the past month. Using the three corresponding subscales of the Inventory of Depressive Symptoms-Self Report (IDS-SR), motivational, mood and somatic symptom domains were assessed. Additionally, symptoms of apathy were determined with the Apathy Scale. Multiple linear regression was used to examine the cross-sectional relationship between current SBP, DBP and MAP with both IDS-SR subscale and Apathy Scale scores. Unstandardized betas were calculated per 10 mmHg increase in blood pressure measures. RESULTS: Mean age of participants was 70.4 years (standard deviation 7.3). Higher SBP (Beta 0.33, t (254) = 2.01, p = 0.045), higher DBP (Beta 0.68, t (254) = 2.15, p = 0.03) and higher MAP (Beta 0.63, t (254) = 2.33, p = 0.02) were associated with higher Apathy Scale scores in the fully adjusted model. Furthermore, a higher SBP was associated with higher IDS-SR mood subscale scores (Beta 0.25, t (254) = 2.13, p = 0.03). CONCLUSIONS: Depressed older people with higher blood pressure measures had particularly more symptoms of apathy. To disentangle the relationship of blood pressure with late-life depression, it is important to pay attention to the role of apathy symptoms.

Theory of Mind differences in older patients with early-onset and late-onset paranoid schizophrenia.

OBJECTIVE: Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ between older patients with early-onset and late-onset schizophrenia. METHODS: Theory of Mind abilities were assessed using the Hinting Task in 15 older patients (age 60 years and older) with early-onset paranoid schizophrenia, 15 older patients with late-onset paranoid schizophrenia and 30 healthy controls. ANCOVA was performed to test differences between groups. Analyses were adjusted for level of education. Effect sizes, partial eta squared (ε(2) ), were computed as an indication of the clinical relevance of the findings. RESULTS: Patients with early-onset schizophrenia scored significantly lower on the Hinting Task (mean 16.1; SD 4.3) compared with patients with late-onset schizophrenia (mean 18.6; SD 1.5) and with healthy controls (mean 19.0; SD 1.4). The effect size of this difference was large (ε(2) = 0.2). CONCLUSIONS: These results suggest that ToM functioning may be a protective factor modulating the age at onset of psychosis. Further studies into the relationship between social cognition and onset age of psychosis are warranted.

[Alcohol consumption and depressive symptoms among older adults: results of the Longitudinal Aging Study Amsterdam]. / Alcoholgebruik en depressieve symptomen bij ouderen: Resultaten van de Longitudinal Aging Study Amsterdam.

The aim of this research is to investigate the often assumed relation between alcohol use and depressive symptoms among older men and women. For this study, a subsample of 2119 participants of the Longitudinal Aging Study Amsterdam, aged 65 to 85 years at baseline, was followed over time and visited in their homes in 1992, 1995, 1998 and 2002. Depressive symptoms are assessed with the Centre for Epidemiologic Studies Depression Scale (CES-D). Alcohol use is measured with questions about the frequency and quantities of alcohol use. A relation between depressive symptoms and alcohol use could not be demonstraded in a population based sample of older drinkers. Only older heavily drinking men with higher levels of depressive symptoms, higher levels of anxiety, and more chronic diseases at baseline significantly reduced the number of glasses consumed per week from 26 to 14 in the ten years of follow-up. Heavily drinking women do not reduce the level of alcohol intake during follow-up. Public prevention strategies are needed to make older heavy drinking women and men who are still in relatively good health aware of the potential risks of excessive alcohol use.

[Alcohol consumption among persons aged 55+ in The Netherlands]. / Alcoholgebruik onder 55-plussers in Nederland.

In The Netherlands no detailed information about alcohol consumption among older persons (55 years and older) is available. Therefore we investigated the prevalence and determinants of alcohol consumption with data from the Longitudinal Aging Study Amsterdam. The results show that 13.4% of persons of 55 years and older are heavy drinkers (male >3 glasses per day, female >2 glasses per day). Most heavy drinkers are younger than 75 years of age, and in this age group more female (22.2%) than male (14.8%) are heavy drinkers. 13% of all participants frequently drinks 6 or more glasses in a short period of time (binge drinking). In the age group of 55-65 years alcohol consumption has considerably increased over a period of ten years. This increase is stronger among females than among males. When people grow older alcohol consumption decreases, which seems associated with a decline in physical or psychological health and/or cognitive decline. Heavy and binge drinking is associated with younger age, higher education and income, and may be strongly related to their social lifes.

[The inter-rater reliability of the Dutch version of the core. A validation study conducted among depressed elderly in-patients]. / De interbeoordelaarsbetrouwbaarheid van de Nederlandse versie van de CORE; een studie bij opgenomen ouderen met een depressie.

BACKGROUND: Assessment of psychomotor symptoms may lead to better classification of depressive disorders. AIM: To test the inter-rater reliability of the Dutch version of CORE, an observational instrument for psychomotor symptoms. METHOD: The CORE was used with 37 depressed in-patients and was scored by 5 psychiatrists. Intra-class correlation (ICCagreement) was tested. RESULTS: ICCagreement of the total score (0.80), and the subscales non-interaction (0.74), retardation (0.70) and agitation (0.79) were sufficient. CONCLUSION: The Dutch version of the CORE is a reliable instrument.

[The immune system and Alzheimer's disease]. / Het immuunsysteem en de ziekte van Alzheimer.

BACKGROUND: It has still not been established unequivocally whether vascular risk factors and inflammatory reactions, determined by heredity, are a cause or a result of Alzheimer's disease AIM: If the offspring of parents with AD have more risk factors and more frequent and severe inflammatory reactions than the offspring of parents without AD , this argues strongly in favor of a causal relationship between vascular risk factors, a pro-inflammatory cytokine response and AD. AIM: To determine whether the offspring of parents with ad have more risk factors and more frequent and severe inflammatory reactions than the offspring of parents without ad. method Vascular risk-factors, pro-inflammatory cytokines and the apoe genotype were determined in 206 offspring of parents with ad and in 200 offspring of parents without AD. RESULTS: Offspring of parents with ad carried more apoe epsilon4 than offspring of parents without ad (47% vs 21%). Middle-aged offspring of parents with a history of ad also had higher blood pressure and a greater atherosclerotic burden than the offspring of parents without AD. Also their response to the pro-inflammatory cytokine was significantly higher. CONCLUSION: Hypertension and an inherited pro-inflammatory cytokine profile in middle age are early risk factors that contribute to the development of ad in old age. Offspring with a parental history of AD should therefore be offered screening and treatment for hypertension and have their blood pressure checked so that the development of AD in old age can be prevented.

Early and late life events and salivary cortisol in older persons.

BACKGROUND: It has been hypothesized that stressful life events are associated with changes in hypothalamic-pituitary-adrenal (HPA) axis regulation, which increases susceptibility to psychiatric disorders. We investigated the association of early and late life events with HPA axis regulation in older persons. METHOD: Within the Longitudinal Aging Study Amsterdam (LASA) 1055 participants (47% male), aged 63-93 years, collected saliva within 30 min after waking and late in the evening. Early and late life events were assessed during a home interview. The associations between life events and cortisol levels were examined using linear regression and analysis of covariance with adjustments for demographics, cardiovascular risk factors and depressive symptoms. RESULTS: Within our sample, the median morning and evening cortisol levels were 15.0 nmol/l [interdecile range (10-90%): 7.4-27.0 nmol/l] and 2.8 nmol/l (10-90%: 1.5-6.3 nmol/l), respectively. Persons who reported early life events showed lower levels of natural log-transformed morning cortisol [B=-0.10, 95% confidence interval (CI) -0.17 to -0.04] and flattened diurnal variability of cortisol (B=-1.06, 95% CI -2.05 to -0.08). Those reporting two or more late life events showed higher levels of natural log-transformed morning cortisol (B=0.10, 95% CI 0.02-0.18) and higher diurnal variability (B=1.19, 95% CI 0.05-2.33). No associations were found with evening cortisol. CONCLUSIONS: The results of this large population-based study of older persons suggest a differential association of early and late life events with HPA axis regulation; early life events were associated with a relative hypo-secretion of morning cortisol and flattened diurnal variability, while late life events were associated with elevated secretion of morning cortisol and high diurnal variability of cortisol.