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Jacobijn Gussekloo

Publications and source records attributed to Jacobijn Gussekloo.

33 records · Page 2Linked to original sources
PubMed2004

Temporal relation between depression and cognitive impairment in old age: prospective population based study.

OBJECTIVE: To examine the temporal relation between depression and cognitive impairment in old age. DESIGN: Prospective, population based study with four years of follow up. SETTING: City of Leiden, the Netherlands. PARTICIPANTS: 500 people aged 85 years at recruitment. MAIN OUTCOME MEASURES: Annual assessments of depressive symptoms (15 item geriatric depression scale), global cognitive function (mini-mental state examination), attention (Stroop test), processing speed (letter digit coding test), and immediate and delayed recall (12 word learning test). RESULTS: At 85 years old, participants' depressive symptoms and cognitive impairment were highly significantly correlated (P < 0.001). During follow up, an accelerated annual increase of depressive symptoms was associated with impaired attention (0.08 points (95% confidence interval 0.01 to 0.16)), immediate recall (0.17 points (0.09 to 0.25)), and delayed recall (0.10 points (0.02 to 0.18)) at baseline. In contrast, depressive symptoms at baseline were not related to an accelerated cognitive decline during follow up (P > 0.05). CONCLUSION: Caregivers should be aware of the development of depressive symptoms when cognitive impairment is present. However, the presence of depression only does not increase the risk of cognitive decline.

Aged↗
PubMed2004

Inflammation underlying cardiovascular mortality is a late consequence of evolutionary programming.

With the increase in life expectancy, death from cardiovascular disease has risen greatly. There is increasing evidence that inflammation plays an important role in cardiovascular disease. We postulate that the development of cardiovascular disease in old age is a late consequence of evolutionary programming for a pro-inflammatory response to resist infections in early age. In 311 women, aged 85 yr old, the production of the pro- and anti-inflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 was determined in lipopolysaccharide-stimulated whole blood samples and studied prospectively in association with cardiovascular mortality. High TNF-alpha was a risk factor for death from cardiovascular disease (relative risk [RR] = 1.56; 95% confidence interval [CI]: 1-2.40), whereas high IL-10 was protective (RR = 0.58; 95% CI: 0.40-0.85). A genetic variant of the IL-10 gene promoter, which is associated with lower IL-10 production, was found to predispose to a 2.8-fold higher cardiovascular mortality risk (95% CI: 1.17-6.60). Reproductive success, which was studied as a measure of evolutionary programming because it trades off with early survival by pro-inflammatory resistance genes, was negatively associated with an increasing production of TNF-alpha (RR = 0.77; 95% CI: 0.68-0.88), while a positive association with IL-10 was found (RR = 1.22; 95% CI: 1.05-1.41). We suggest that cardiovascular mortality is a late consequence of evolutionary programming for a pro-inflammatory response.

Adult↗
PubMed2004

The 15-item Geriatric Depression Scale (GDS-15) detects changes in depressive symptoms after a major negative life event. The Leiden 85-plus Study.

BACKGROUND: The 15-item Geriatric Depression Scale (GDS-15) is a widely used screening instrument for depressive symptoms in the elderly, but its ability to detect alterations in depressive symptoms over time has not been established. OBJECTIVE: To assess the change of the GDS-15 score after a major negative life event. METHODS: Within the Leiden 85-plus Study, we prospectively followed a population-based cohort of 599 subjects from 85 years onwards. The GDS-15 was applied annually to participants with a Mini-Mental State Examination (MMSE) score above 18 points. The change in GDS-15 score of 32 subjects who had lost their partner during follow-up was compared with a control group of 32 subjects who had not lost their partner, matched for age, sex, and initial GDS-15 score. RESULTS: At baseline, 241 subjects lived together with a partner. During a mean follow-up of 3.2 years, 55 participants (23%) lost their partner. Of those, 32 subjects completed the GDS-15 before and after the loss of their partner. All subjects reported the bereavement to be a major negative life event. The mean increase of the GDS-15 score after the death of a partner was 1.2 points (paired t-test, p = 0.013). This was significantly higher than the mean change of -0.06 points in the matched control group (independent t-test, p = 0.032), and independent of sex, level of education, pre-bereavement GDS-15 score, and time period since the loss of a partner. CONCLUSION: This study shows that the GDS-15 detects change in depressive symptoms after loss of a partner, a negative life event that is the most important risk factor for depression in the elderly. Therefore, it may be concluded that the GDS-15 has the ability to measure longitudinal alterations in depressive symptomatology.

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PubMed2004

Does depression in old age increase only cardiovascular mortality? The Leiden 85-plus Study.

BACKGROUND: Depression in old age is associated with an increased mortality risk of cardiovascular disease but the mortality risk from non-cardiovascular causes is disputed. OBJECTIVE: To investigate the effect of depression on cardiovascular and non-cardiovascular mortality in old age. METHODS: We prospectively followed 500 subjects from age 85 years onwards within the population-based Leiden 85-plus Study. Depressive symptoms were assessed annually with the 15-item Geriatric Depression Scale (GDS-15). Mortality risks were estimated in a Cox proportional-hazards model with the annual assessment of depression (GDS-15> or =4 points) as a time-dependent covariate. RESULTS: During 1654 person-years of follow-up (mean per person, 3.2 years), depression was associated with a two-fold increase of all cause mortality [Relative Risk (RR), 1.83; 95% Confidence Interval (CI), 1.24-2.69] that was not explained by comorbid conditions. Both cardiovascular mortality and non-cardiovascular mortality contributed equally to the excess mortality (RR 1.95 and 1.75 respectively). CONCLUSION: Depression in old age contributes to an increase of both cardiovascular and non-cardiovascular mortality. Motivational depletion may play an important role in the increased mortality in elderly with depression.

Aged↗
PubMed2004

Impaired innate immunity predicts frailty in old age. The Leiden 85-plus study.

Aging is associated with an impaired capacity of the immune system to respond properly to danger signals, such as infection and cancer. Here, we provide evidence that an impaired innate immune response, as measured by a low production capacity of pro- and anti-inflammatory cytokines upon ex vivo standardized danger signalling with bacterial LPS, is predictive for frailty in elderly people: participants who at age 85-year produced low levels of LPS-induced IL-1beta, IL-6, TNF-alpha and IL-1Ra and IL-10, were found to have a more than 2-fold elevated overall mortality risk, independent of chronic illnesses (relative risk is 2.21, 95% confidence interval 1.27-3.82, P = 0.005), compared to peers with a higher production of any of the pro- and/or anti-inflammatory cytokines. A significant genetic association with the IL-10 promoter gene was found, indicating that people who are genetically predisposed low cytokine producers are at a higher risk of losing the capacity to respond properly to danger signals with aging. We conclude that a malfunctioning innate immune response predicts frailty in old age and is under specific (immuno-) genetic control.

Aged↗
PubMed2003

High-density vs low-density lipoprotein cholesterol as the risk factor for coronary artery disease and stroke in old age.

BACKGROUND: A high total serum cholesterol level does not carry a risk of cardiovascular mortality among people 85 years and older and is related to decreased all-cause mortality. At this old age, there are few data on fractionated lipoprotein levels in the determination of cardiovascular disease risk. The aim of this study was to evaluate the relationships between low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels and mortality from specific causes among people in the oldest age categories. METHODS: Between September 1, 1997, and September 1, 1999, a total of 705 inhabitants in the community of Leiden, the Netherlands, reached the age of 85 years. Among these old people, we initiated a prospective follow-up study to investigate determinants of successful aging. A total of 599 subjects participated (response rate, 87%) and all were followed up to September 2001. Serum levels of total, LDL, and HDL cholesterol were assessed at baseline along with detailed information on comorbid conditions. The main outcome measure was all-cause and specific mortality risk. RESULTS: During 4 years of follow-up, 152 subjects died. The leading cause of death was cardiovascular disease, with similar mortality risks in all tertiles of LDL cholesterol level. In contrast, low HDL cholesterol level was associated with a 2.0-fold higher risk of fatal cardiovascular disease (95% confidence interval [CI], 1.2-3.2). The mortality risk of coronary artery disease was 2.0 (95% CI, 1.0-3.9) and for stroke it was 2.6 (95% CI, 1.0-6.6). Both low LDL cholesterol and low HDL cholesterol concentrations were associated with an increased mortality risk of infection: 2.7 (95% CI, 1.2-6.2) and 2.4 (95% CI, 1.1-5.6), respectively. The risks were unaffected by comorbidity. CONCLUSION: In contrast to high LDL cholesterol level, low HDL cholesterol level is a risk factor for mortality from coronary artery disease and stroke in old age.

Aged↗
PubMed2003

Accuracy of the 15-item geriatric depression scale (GDS-15) in a community sample of the oldest old.

BACKGROUND: Cognitive impairment is common in the oldest old. This might influence the sensitivity and specificity of the 15-item Geriatric Depression Scale (GDS-15). Few studies, however, have included subjects older than 85 years to evaluate the GDS-15 as a screening instrument for depression. OBJECTIVE: To assess the sensitivity and specificity of the GDS-15 in a community sample of the oldest old. METHODS: Seventy-nine subjects aged 85 and over were enrolled in the study. The GDS-15 and the Mini-Mental State Examination (MMSE) were administered by a trained interviewer. Within two days the Geriatric Mental State (GMS)/AGECAT, was administered to obtain a clinical diagnosis of depression. RESULTS: Eight subjects (10%) were diagnosed with clinical depression. At a cut-off point of 3/4 the sensitivity and specificity of the GDS-15 were 88% and 76% respectively. In the group with MMSE scores of 28 and higher sensitivity was unaffected at all cut-off points while specificity increased. In the group with MMSE scores below 28 sensitivity was also unaffected at all cut-off points while specificity decreased. CONCLUSION: The GDS-15 is a suitable instrument to diagnose depression in the general population of the oldest old. The optimal cut-off point depends on its intended use. In subjects with cognitive impairment the accuracy should be investigated further.

Aged↗
PubMed2003

Walking and talking as predictors of falls in the general population: the Leiden 85-Plus Study.

OBJECTIVES: To compare the value of dual tasking in predicting falling in the general population of oldest old with that of easy-to-administer single tasks. DESIGN: Prospective population-based follow-up study. SETTING: Municipality of Leiden, the Netherlands. PARTICIPANTS: Representative cohort of 380 individuals, all aged 85 at baseline. MEASUREMENTS: During enrollment, walking time over a 12-meter distance was measured, as well as the verbal fluency to recite names of animals or professions during a 30-second period. In the dual task, performance was assessed when participants combined walking with reciting names. Incidence of falls and fractures was assessed by interviewing participants and checking their medical histories. RESULTS: After 1 year of follow-up, 42% of the participants reported one or more falls, and 4% suffered a fracture. Total walking time, number of steps, and verbal fluency were all strongly related to incident falls (P for trend for all <.01), but dual-task performance was not a better predictor for incident falls than single-task performance. CONCLUSION: The dual-task test in this study had no predictive value above that of a single-task test to predict falling. Dual tasks with more-sensitive measures of impaired dual-task execution might have better test characteristics. In this study, history of falls and performance on an easy-to-administer single walking task identified old persons at higher risk for falling who could benefit from fall preventive strategies.

Accidental Falls↗
PubMed2003

Auditory rehabilitation of older people from the general population--the Leiden 85-plus study.

BACKGROUND: Very few older people with severe hearing loss use hearing aids to reduce the negative consequences of reduced hearing in daily functioning. AIM: Assessment of a screening test and a standardised auditory rehabilitation programme for older people from the general population with untreated severe hearing loss. DESIGN OF STUDY: Intervention study and qualitative exploration. SETTING: Leiden 85-Plus Study, a prospective population-based study of 85-year-old inhabitants of Leiden, the Netherlands. METHOD: Hearing loss was measured by pure-tone audiometry in 454 subjects aged 85 years. Subjects with hearing loss above 35 dB at 1, 2, and 4 kHz who did not use hearing aids were invited to participate in a standardised programme for auditory rehabilitation. In-depth interviews were held with participants to explore arguments for participating in this programme. RESULTS: Of the 367 participants with severe hearing loss (prevalence = 81%), 66% (241/367) did not use a hearing aid. Three out of four of these participants (n = 185) declined participation in the auditory rehabilitation programme. The most common reason given for not participating was the subjects' feeling that their current hearing loss did not warrant the use of a hearing aid. Subjects who participated in the programme were found to suffer from more severe hearing loss and experienced more hearing disability. Those who did not participate in the programme felt they could cope with their disabilities and considered a hearing aid unnecessary. CONCLUSION: Untreated hearing loss is prevalent among older people from the general population. The majority of older people decline auditory rehabilitation. For these people the use of a hearing aid is not perceived as necessary in order to function on a daily basis. Older people who have expected benefits from a hearing aid have already obtained them, marginalising the benefits of a rehabilitation (and screening) programme.

Aged↗
PubMed2002

Association of APOE epsilon2/epsilon3/epsilon4 and promoter gene variants with dementia but not cardiovascular mortality in old age.

The common apolipoprotein E (APOE) alleles epsilon2, epsilon3, and epsilon4 are associated with the risk of dementia and cardiovascular disease. Recently, two functional variants (- 219G/T and -491A/T) were identified in the promoter of the APOE gene that enable a further characterization of the role of the APOE locus in disease. We investigated the contribution of these APOE gene variants to dementia and cardiovascular mortality in old age using a population-based cohort of 648 subjects aged 85 years and over (Leiden 85-Plus Study). Genotypes containing an APOE epsilon4 allele were associated with a 4.1-fold (95% CI, 2.2-7.7) increased risk of dementia as compared to the epsilon3/epsilon3 genotype in old subjects. Moreover, homozygosity for the -219T allele was found to be associated with a 2.4-fold (95% CI, 1.0-5.8) increased risk independently of epsilon2 and epsilon4; the -491A/T variant was not associated with dementia. Over a 10-year follow-up period, the risk of cardiovascular mortality was not increased among epsilon4 carriers (RR, 0.6; 95% CI, 0.4-1.0) or -219T homozygous subjects (RR, 1.1; 95% CI, 0.7-1.7), nor did it decrease among -491T homozygous subjects (RR, 1.4; 95% CI, 0.6-3.1). In conclusion, both the APOE epsilon2/epsilon3/epsilon4 and the -219G/T variant were identified as risk factors for dementia but not cardiovascular mortality in old age. Our results support the hypothesis that both the isoform and the amount of APOE may influence the risk of dementia. Furthermore, they emphasize that variation at the APOE locus has a higher impact on the risk of dementia than on the risk of cardiovascular disease in old age.

Age Factors↗
PubMed2002

Association between high-density lipoprotein and cognitive impairment in the oldest old.

Low high-density lipoprotein cholesterol is associated with an increased risk for cardiovascular disease and stroke. At the same time, cardiovascular disease and stroke are important risk factors for dementia. We assessed the association between total and fractionated cholesterol and cognitive impairment and explored whether observed associations were dependent on or independent of atherosclerotic disease. In a population-based study, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured in 561 subjects 85 years old and grouped in three equal strata representing decreasing serum concentrations. History of cardiovascular disease and stroke was determined. All subjects completed the Mini-Mental State Examination (MMSE), and the presence of dementia was determined. Median MMSE scores were significantly lower in subjects with low high-density lipoprotein cholesterol (25 points vs 27 points, p < 0.001). No differences in MMSE scores were found for other lipids and lipoproteins. MMSE scores in subjects with and without cardiovascular disease were 26 and 27 points (p = 0.007), respectively, and in subjects with and without stroke were 21 and 26 points (p < 0.001), respectively. The associations between low MMSE scores and low high-density lipoprotein cholesterol remained significant after subjects with cardiovascular disease or stroke were excluded. In a comparison of subjects with low high-density lipoprotein cholesterol with subjects with high high-density lipoprotein cholesterol, the odds ratio for dementia was 2.3 (95% confidence interval, 1.2-4.3), and in subjects without cardiovascular disease or stroke, it was 3.7 (95% confidence interval, 1.3-10.1). All odds ratios were unaffected by education, low-density lipoprotein cholesterol, triglycerides, and survival. Low high-density lipoprotein cholesterol is associated with cognitive impairment and dementia. At least part of the association between high-density lipoprotein cholesterol and cognitive function is independent of atherosclerotic disease.

Aged↗
PubMed2002

Common chronic diseases and general impairments as determinants of walking disability in the oldest-old population.

OBJECTIVES: Walking disability affects older people's autonomy and well-being. We investigated the relative effect of common chronic diseases and general impairments on walking disability in the general oldest-old population. DESIGN: Population-based cohort study. SETTING: Leiden 85-plus Study, the Netherlands. PARTICIPANTS: Five hundred ninety-nine persons aged 85, response rate 87%. MEASUREMENTS: Walking disability was assessed using a 6-meter walking test. Persons with a walking time below the 25th percentile and those who were physically unable to perform the walking test were categorized as having a walking disability. Information on common chronic diseases was obtained from records of subjects' general practitioners and pharmacies. General impairments were assessed with functional tests and standardized questions during face-to-face interviews. We expressed the effect of common chronic diseases and general impairments as the population attributable risk (PAR), indicating how much disability can be prevented when the identified risk factor is eliminated from the population. RESULTS: One hundred ninety-two persons (33%) had a walking disability. This disability was highly associated with poor mobility in daily life, recurrent falls, and poor well-being (all P <.001). Of the common chronic diseases, stroke, angina pectoris, diabetes mellitus, and hip fracture but not arthritis contributed most (PARs from 6% to 15%) to walking disability in the population at large. General impairments had higher prevalence rates and higher PARs than common chronic diseases. Cognitive impairment, depressive symptoms, and dizziness upon rising contributed most (PARs between 22 to 27%) to walking disability. In multivariate regression analyses of all common chronic diseases and general impairments, associations remained significant. CONCLUSION: Within the general oldest-old population, general impairments contribute more substantially to walking disability than do common chronic diseases. The diagnosed diseases did not explain the impairments that led to walking disability. Especially in the oldest old, clinicians should focus not merely on common chronic diseases but particularly on general impairments as targets for diagnostic analysis and treatment to decrease walking disability.

Aged↗
PubMed2002

Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes : the Leiden 85-Plus Study.

It has been suggested that the metabolic syndrome and type 2 diabetes are manifestations of the inflammatory host response. This host response is orchestrated by the production of pro- and anti-inflammatory cytokines that are under genetic control. We therefore hypothesized that a low production capacity of interleukin-10 (IL-10), a centrally operating cytokine with strong anti-inflammatory properties, associates with the metabolic syndrome and type 2 diabetes in old age. In the current study, 599 inhabitants of the city of Leiden, age 85 years, were visited at their place of residence. The production capacity of the anti-inflammatory cytokine IL-10 was assessed in a whole-blood assay in which lipopolysaccharide was used as a stimulus. Serum concentrations of lipids, lipoproteins, glucose, and HbA(1c) were determined, and a history of type 2 diabetes was obtained. Serum concentrations of total cholesterol, LDL cholesterol, triglycerides, glucose, and HbA(1c) gradually decreased over strata representing higher IL-10 production capacity, whereas the concentration of HDL cholesterol gradually increased (all P < 0.01). The odds ratio for type 2 diabetes was 2.7 (95% confidence interval 1.5-4.9) when subjects with the lowest IL-10 production capacity were compared with those with the highest IL-10 production capacity. These findings showed that low IL-10 production capacity (i.e., a pro-inflammatory response) is associated with the metabolic syndrome and type 2 diabetes.

Aged↗