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Biomedical subjects

Jacobijn Gussekloo

Publications and source records attributed to Jacobijn Gussekloo.

At least 19 recordsLinked to original sources

Prospective study of the effect of blood pressure on renal function in old age: the Leiden 85-Plus Study.

High BP is associated with decline of renal function. Whether this is true for very old people largely is unknown. Therefore, this study assessed the effect of BP on creatinine clearance over time in very old participants. A total of 550 inhabitants (34% men) of Leiden, The Netherlands, were enrolled in a population-based study at their 85th birthday and followed until death or age 90. BP was measured twice at baseline and at age 90 yr. Creatinine clearance was estimated annually (Cockcroft-Gault formula). The mean creatinine clearance at baseline was 45.4 ml/min (SD 11.5). Systolic BP was not associated with changes in creatinine clearance during follow-up. Those with diastolic BP (DBP) <70 mmHg had an accelerated decline of creatinine clearance (1.63 ml/min per yr) compared with those with DBP between 70 and 79 mmHg (1.21 ml/min per yr; P = 0.01), 80 to 89 mmHg (1.26 ml/min per yr; P = 0.03), and >89 mmHg (1.38 ml/min per yr; P = 0.32). Participants with a decline in systolic BP during follow-up had an accelerated decline of creatinine clearance compared with those with stable BP (1.54 [SE 0.09] versus 0.98 ml/min per yr [SE 0.09]; P < 0.001). Similar results were found for a decline in DBP (1.54 [SE 0.10] versus 1.06 ml/min per yr [SE 0.08]; P < 0.001). In the oldest individual, high BP is not associated with renal function. In contrast, low DBP is associated with an accelerated decline of renal function. The clinical implications of these findings have to be studied.

Aged, 80 and over↗

Randomised controlled trial of unsolicited occupational therapy in community-dwelling elderly people: the LOTIS trial.

OBJECTIVE: The objective of this trial, the Leiden 85-Plus Occupational Therapy Intervention Study (LOTIS), was to assess whether unsolicited occupational therapy, as compared to no therapy, can decelerate the increase in disability in high-risk elderly people. DESIGN: This was a randomised controlled trial with 2-y follow-up. SETTING: The study took place in the municipality of Leiden in the Netherlands. PARTICIPANTS: The participants were 402 community-dwelling 85-y-old people, with a Mini-Mental State Examination score of >18 points at baseline. INTERVENTIONS: Participants in the intervention group were visited by an occupational therapist who provided training and education about assistive devices that were already present and who gave recommendations and information about procedures, possibilities, and costs of assistive devices and community-based services. Control participants were not visited by an occupational therapist. OUTCOME MEASURES: The primary outcome measure was the score achieved on the Groningen Activity Restriction Scale. Secondary outcome measures included self-evaluations of well-being and feelings of loneliness. RESULTS: THE PARTICIPANTS WERE EVENLY DIVIDED BETWEEN THE TWO GROUPS: 202 participants were allocated to the intervention group and 200 participants to the control group. Of the 202 participants randomised to occupational therapy, 55 participants declined the proposed intervention. An occupational therapist indicated that of the remaining 147 participants, 66 (45%) needed an occupational therapy intervention. A total of 44 new assistive devices and five community-based services were implemented. During follow-up there was a progressive increase in disability in the intervention group (mean annual increase, 2.0 points; SE 0.2; p < 0.001) and control group (mean annual increase, 2.1 points; SE 0.2; p < 0.001). The increase in disability was not significantly different between study groups (0.08 points; 95% CI, -1.1-1.2; p = 0.75). There was also no difference between study groups for any of the secondary outcome measures. CONCLUSION: Unsolicited occupational therapy in high-risk elderly participants does not decelerate the increase in disability over time.

Journal Article↗

Markers of autonomic tone on a standard ECG are predictive of mortality in old age.

BACKGROUND: To investigate markers of autonomic tone on a standard electrocardiogram in relation to mortality in old age. METHODS: A total of 599 inhabitants of Leiden, the Netherlands, were enrolled in a population-based follow-up study at their 85th birthday. Electrocardiograms (ECGs) were taken on entry and annually thereafter. ECGs were analysed automatically to determine four markers of autonomic tone, i.e. heart rate, the occurrence of ventricular extrasystoles and two time domain measures of heart rate variability. All participants were followed up for mortality. RESULTS: Participants with a heart rate in the highest quartile had a 1.8-fold increased total mortality risk (95% confidence interval (CI) 1.0-3.4), but not an increased cardiovascular mortality risk. The occurrence of at least one ventricular extrasystole was related with a 2.3-fold increased total mortality risk (95% CI 1.3-3.9) and a 3.6-fold increased cardiovascular mortality (95% CI 1.6-8.2). In stratified analyses, the prognostic effect was confined to males. Both measures of heart rate variability were not related to mortality. CONCLUSION: High heart rate and the occurrence of a ventricular extrasystole, both markers of sympathetic dominance, were predictive of mortality in old age. Two short-term measures of heart rate variability as measured on a standard 10-s ECG were not related to mortality, and hence may not reflect autonomic tone in old age.

Age Factors↗

In a population-based prospective study, no association between high blood pressure and mortality after age 85 years.

OBJECTIVE: To study the impact of a history of hypertension and current blood pressure on mortality in the oldest old. DESIGN: An observational population-based cohort study. SETTING: Community city of Leiden, The Netherlands. PARTICIPANTS: Five hundred and ninety-nine inhabitants of the birth-cohort 1912-1914 were enrolled on their 85th birthday. There were no selection criteria related to health or demographic characteristics. INTERVENTIONS: The mean follow-up was 4.2 years. Medical histories were obtained from general practitioners. Medication histories were obtained from the participant's pharmacist. Blood pressure was measured twice at baseline. MAIN OUTCOME MEASURES: All cause and cardiovascular mortality. RESULTS: Five hundred and seventy-one participants were included, 39.2% had a history of hypertension. During follow-up 290 participants died, 119 due to cardiovascular causes. Compared to participants without a history of hypertension, those with a history of hypertension had increased mortality from cardiovascular causes [relative risk (RR) 1.60, confidence interval (CI) 1.06-2.40] but equal mortality from all causes (RR 1.19, CI 0.91-1.55). High blood pressure at baseline (age 85) was not a risk factor for mortality. Baseline blood pressure values below 140/70 mmHg (n = 48) were associated with excess mortality, predominantly in participants with a history of hypertension. CONCLUSION: In the oldest old, high blood pressure is not a risk factor for mortality, irrespective of a history of hypertension. Blood pressure values below 140/70 mmHg are associated with excess mortality.

Aged↗

Natural history of depression in the oldest old: population-based prospective study.

BACKGROUND: Despite its negative consequences, little is known about the natural history of depression in the oldest old. AIMS: To study the incidence, course and predictors of depression in the general population of the oldest old. METHOD: The Leiden 85-plus Study is a prospective population-based study of 500 people from their 85th to their 89th birthdays. Depressive symptoms were annually assessed with the 15-item Geriatric Depression Scale, using a cut-off of 4 points. RESULTS: During a mean follow-up of 3.9 years, the annual risk for the emergence of depression was 6.8%. Poor daily functioning and institutionalisation predicted depression. Among the 77 participants with depression at baseline (prevalence 15%) the annual remission rate was ony 14%. In more than half of the participants with a remission of depression, we observed a relapse of depression during follow-up. No predictors of remission could be identified. CONCLUSIONS: Among the oldest old, depression is frequent and highly persistent. More active case-finding and treatment would be potentially rewarding.

Aged, 80 and over↗

Association between chronic diseases and disability in elderly subjects with low and high income: the Leiden 85-plus Study.

BACKGROUND: Disability in activities of daily living (ADL) might be more prevalent among elderly with low income due to higher prevalence of chronic diseases and impairments, as well as stronger associations of these factors with ADL-disability. METHODS: In the Leiden 85-plus Study, we defined disability as being unable to perform one or more basic ADL activities. Presence of chronic diseases was obtained from medical records, impairments were assessed with performance-tests. RESULTS: Elderly with low income had higher prevalence of ADL-disability (23% versus 12%; odds ratio 2.0; 95% confidence interval 1.3-3.2), higher prevalence of impairments and equal prevalence of chronic diseases, except for dementia and co-morbidity. Associations of these factors with ADL-disability were not stronger. CONCLUSIONS: We conclude that ADL-disability is more prevalent in elderly with low income. Neither prevalence of chronic diseases nor the association with disability could explain this.

Activities of Daily Living↗

Late-onset dementia: structural brain damage and total cerebral blood flow.

PURPOSE: To prospectively compare indicators of structural brain damage and total cerebral blood flow in patients with late-onset dementia, subjects of the same age with optimal cognitive function, and young subjects. MATERIALS AND METHODS: The institutional ethics committee approved the studies, and all participants (or their guardians) gave informed consent. The test group included 17 patients older than 75 years (four men, 13 women; median age, 83 years) and with a diagnosis of dementia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The control group included 16 subjects (four men, 12 women; median age, 87 years) with optimal cognitive function, who were selected from among 599 elderly subjects enrolled in a population-based follow-up study, and 15 young healthy subjects (seven men, eight women; median age, 29 years). Measurements of intracranial and total brain volumes, structural brain damage, and cerebral blood flow were obtained with magnetic resonance imaging. Mean values were compared with the t test; medians, with the Mann-Whitney U test. RESULTS: Values for total brain volume were significantly smaller in elderly subjects (P < .001) but did not differ significantly between patients with dementia and subjects of the same age with optimal cognitive function (P = .69). Among the elderly, significantly higher scores for number and extent of white matter areas of signal hyperintensity (P = .028) and lower magnetization transfer ratios (P = .016) indicated greater structural brain damage in those with dementia. Cerebral blood flow was 246 mL/min lower (P < .001) in elderly subjects than in young subjects. In patients with dementia, cerebral blood flow was 108 mL/min lower than that in subjects of the same age with optimal cognitive function (551 vs 443 mL/min, P < .001). CONCLUSION: The combined observations of more structural brain damage and lower cerebral blood flow in demented elderly individuals than in subjects of the same age with optimal cognitive function support the hypothesis that vascular factors contribute to dementia in old age.

Aged↗

Meta-analysis of nonsteroidal antiinflammatory drug use and risk of dementia.

The authors performed a systematic review to summarize the epidemiologic evidence on the association between use of nonsteroidal antiinflammatory drugs (NSAIDs) and the risk of dementia. A total of 25 case-control and cohort studies that reported an odds ratio/relative risk were included. Study-specific log relative risks were weighted by the inverse of their variances to obtain pooled relative risks and 95% confidence intervals. The authors divided the reports into studies with prevalent dementia cases, studies with incident dementia cases, and studies where cognitive decline was used as the clinical endpoint. The pooled relative risks of the three groups of studies were 0.51 (95% confidence interval (CI): 0.37, 0.70), 0.79 (95% CI: 0.68, 0.92), and 1.23 (95% CI: 0.70, 2.31), respectively. Within these subgroups, heterogeneity was present only in the studies with prevalent cases (p = 0.001). Because the benefit of NSAIDs in preventing dementia or cognitive impairment was 50% in studies with prevalent dementia cases, declined to 20% in studies with incident dementia cases, and was absent in studies where cognitive decline was used as the endpoint, the authors conclude that most of the reported beneficial effects of NSAIDs may result from various forms of bias: recall bias, prescription bias, and publication bias.

Aged↗

Seasonal mood variation in the elderly: the Leiden 85-plus study.

BACKGROUND: The influence of seasonal changes on mood and behaviour is called seasonality. The prevalence of seasonality in elderly subjects is unknown. AIM: To investigate the seasonality pattern in mood and behaviour at old age. METHODS: All subjects from the Leiden 85-plus Study with an MMSE score of 19 or more were assessed for depressive feelings at age 85 and yearly thereafter. The influence of time of the year, duration of sunlight, daylight, and rain on the prevalence of depressive symptoms was assessed using linear mixed models for repeated measurements. RESULTS: There was no significant seasonal pattern in the data (p=0.44). Within each of the four years of observation (85, 86, 87 and 88 years) and all years combined, there was also no significant association between the one-month cumulation of duration of sunlight, daylight, or rain and the score on the GDS (all p-values >0.05). The results of either the one week or three-month accumulation of sunlight, daylight, or rain were comparable to the one-month results. CONCLUSIONS: Estimates of prevalence of seasonality reported in the literature might be overestimated or a remarkable difference between young and old subjects exists.

Affect↗

Evaluation of continuous summary physical performance scores (CSPPS) in an elderly cohort.

BACKGROUND AND AIMS: Physical performance is an important predictor of quality of life among the elderly. A valid and sensitive measure of physical performance is needed in order to evaluate possible interventions. The aim of this study was to examine the validity and reliability of the Continuous Summary Physical Performance Score (CSPPS) and its relationship to the Quartile Summary Physical Performance Score (QSPPS). METHODS: This cross-sectional study of an elderly cohort from 5 centers in the US and Europe included men and women (> age 65) reporting at least two domains of disability. Subjects completed assessments of mobility and ability to perform activities of daily living (ADLs), the physical component of the SF-36, and a self-rating of physical performance. Timed physical performance tests were used to calculate the CSPPS and QSPPS. RESULTS: 216 subjects took part (mean age = 81 years). The distribution of CSPPS scores was similar for men and women, with a mean of 59.2 (SD 17.8), median of 64.3, and range from 1.3 to 91. Subjects with older age, higher degree of disability, and lower self-rated physical performance had lower CSPPS scores. The CSPPS had good test-retest reliability (r = 0.92), and CSPPS and QSPPS are highly correlated (r = 0.94, p < 0.001). However, the QSPPS appears to lack the linearity, and the ranges of the CSPPS for each score of the QSPPS overlap substantially. CONCLUSIONS: In a cohort with moderate to severe disability, the CSPPS appears to be a valid, reproducible measure that can discriminate smaller yet clinically meaningful differences in physical function, as compared with the QSPPS.

Activities of Daily Living↗

In an observational study elderly patients had an increased risk of falling due to home hazards.

OBJECTIVE: The objective of this study was to explore the relationship between home hazards and the incidence of falls in the oldest old population. STUDY DESIGN AND SETTING: The Leiden 85-plus Study is a population-based study of all 85-year-old inhabitants of Leiden in the birth-cohort 1912-1914. Participants and general practitioners were interviewed at baseline and annually there after. We analyzed the incidence of falling in the first year dependent on the presence of home hazards at baseline. There were no exclusion criteria other than the inability to walk alone. RESULTS: During the 1-year follow-up, 44% of the participants experienced one or more falls. Participants without preceding falls (n=246) had a 4-fold risk for falls in the presence of six or seven home hazards (relative risk 3.58, 95% confidence interval 1.75-5.05) compared with those without home hazards. Participants with preceding falls (n=234) had no increased risk of falls with increasing numbers of home hazards, although they had a higher risk to fall. The data confirmed the known increased risk for falls in participants with physical impairments. CONCLUSION: We conclude that participants without a history of preceding falls have an increased risk of falling due to the presence of home hazards.

Accidental Falls↗

Homocysteine, vitamin B-12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study.

BACKGROUND: High concentrations of homocysteine and low concentrations of vitamin B-12 and folic acid are frequently observed in subjects with dementia. OBJECTIVE: We assessed whether serum concentrations of homocysteine, vitamin B-12, or folic acid predict cognitive decline in old age. DESIGN: This was a prospective, population-based, longitudinal study of 599 subjects (Leiden 85-Plus Study, Netherlands). The subjects were administered a battery of cognitive tests (including the Mini Mental State Examination, the Stroop test, a letter digit coding test, and a word recall test) at 85 y of age and yearly thereafter until 89 y of age. Serum concentrations of homocysteine, vitamin B-12, and folic acid were measured at 85 and 89 y of age. Cross-sectional associations between serum concentrations and cognition were assessed at 85 and 89 y of age. The association between baseline serum concentrations and subsequent longitudinal cognitive decline was assessed with the use of mixed linear models. RESULTS: In the cross-sectional analyses, serum concentrations of homocysteine and folic acid were significantly associated with cognitive performance, but serum concentrations of vitamin B-12 were not. In the longitudinal analyses, there were no significant associations of serum concentrations of homocysteine, vitamin B-12, or folic acid with rate of cognitive decline. CONCLUSIONS: Elevated serum concentrations of homocysteine and reduced folic acid are associated with cognitive impairment in elderly persons but do not predict an increased rate of cognitive decline. The association of high serum concentrations of homocysteine and low folic acid with cognitive impairment in old age is likely to be a consequence of disease and not a contributory cause.

Aged↗

Telomere length in white blood cells is not associated with morbidity or mortality in the oldest old: a population-based study.

Cross-sectional studies have repeatedly suggested peripheral blood monocyte telomere length as a biomarker of aging. To test this suggestion in a large population-based follow-up study of the oldest old, we measured telomere length at baseline in 598 participants of the Leiden 85-plus Study (mean age at baseline 89.8 years). We also obtained second telomere measurements from 81 participants after an average time span of between 3.9 and 12.9 years. Telomere length at baseline was not predictive for mortality (P > 0.40 for all-cause, cardiovascular causes, cancer or infectious diseases, Cox regression for gender-adjusted tertiles of telomere length) or for the incidence of dementia (P = 0.78). Longitudinally, telomere length was highly unstable in a large fraction of participants. We conclude that blood monocyte telomere length is not a predictive indicator for age-related morbidity and mortality at ages over 85 years, possibly because of a high degree of telomere length instability in this group.

Aged, 80 and over↗

Sensory impairment and cognitive functioning in oldest-old subjects: the Leiden 85+ Study.

OBJECTIVE: Because studies on the association of sensory impairment (both hearing and visual impairment) and cognitive functioning in elderly persons yielded conflicting results, the authors explored this association within the Leiden 85+ Study. METHODS: Within this population-based study of 459 participants aged 85+ years, hearing impairment was measured by audiometry and visual impairment by a visual acuity chart, both under standardized conditions. The Mini-Mental State Exam (MMSE) assessed global cognitive functioning. In participants with MMSE scores >18, the authors further assessed memory (Word-Learning Test, Immediate and Delayed Recall) and cognitive speed (by Stroop Test, Letter-Digit Coding test). RESULTS: Both hearing impairment (prevalence: 85%) and visual impairment (prevalence: 59%) were associated with lower scores on the MMSE. Increasing visual impairment was associated with poorer scores on memory and cognitive speed, as measured with visually presented cognitive tests. In contrast, there was no association between hearing impairment and memory and cognitive speed. CONCLUSIONS: In elderly people, cognitive functioning as assessed by visual cognitive tests relates to visual impairment but not to hearing impairment. The authors therefore assume that the association between sensory impairment and cognitive functioning is, at least partly, based on practical disadvantages of elderly persons with sensory impairment during cognitive assessments.

Aged, 80 and over↗

Is depression in old age fatal only when people feel lonely?

OBJECTIVE: The impact of depression and perceived loneliness in the oldest old is largely unknown. The authors studied the relationship between the presence of depressive symptoms and all-cause mortality in old age, especially the potential distorting effect of perceived loneliness. METHOD: Within a prospective population-based study of 85-year-olds, the 15-item Geriatric Depression Scale and the Loneliness Scale were annually applied in all 476 participants with a Mini-Mental State Examination score of 18 points or more. RESULTS: Depression was present in 23% and associated with marital state, institutionalization, and perceived loneliness. When depression and perceived loneliness were assessed during follow-up, neither depression nor perceived loneliness had a significant effect on mortality. However, those who suffered from both depression and feelings of loneliness had a 2.1 times higher mortality risk. CONCLUSIONS: The data suggest that the increased mortality risk attributable to depression in the presence of perceived loneliness may result from motivational depletion.

Aged↗

Thyroid status, disability and cognitive function, and survival in old age.

CONTEXT: Despite the equivocal outcomes of randomized controlled trials, general clinical opinion favors screening and treatment of elderly individuals with subclinical thyroid disorders. OBJECTIVES: To determine whether subclinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age. DESIGN, SETTING, AND PARTICIPANTS: A prospective, observational, population-based follow-up study within the Leiden 85-Plus Study of 87% of a 2-year birth cohort (1912-1914) in the municipality of Leiden, the Netherlands. A total of 599 participants were followed up from age 85 years through age 89 years (mean [SD] follow-up, 3.7 [1.4] years). MAIN OUTCOME MEASURES: Complete thyroid status at baseline; disability in daily life, depressive symptoms, cognitive function, and mortality from age 85 years through 89 years. RESULTS: Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life, depressive symptoms, and cognitive impairment at baseline or during follow-up. Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status. The hazard ratio (HR) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 (95% confidence interval [CI], 0.63-0.94; P = .009). The HR for mortality per SD increase of 0.21 ng/dL (2.67 pmol/L) of free thyroxine increased 1.16-fold (95% CI, 1.04-1.30; P = .009). CONCLUSIONS: In the general population of the oldest old, elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span. However, evidence for not treating elderly individuals can only come from a well-designed, randomized placebo-controlled clinical trial.

Activities of Daily Living↗

Phenotypic and functional characterization of CD4 T cells expressing killer Ig-like receptors.

Killer Ig-like receptors (KIR) are commonly found on human NK cells, gammadelta T cells, and CD8 T cells. Although KIR(+) CD4 T cells are found in certain patients, their prevalence in healthy donors is controversial. We now provide definitive proof that such cells are present in most individuals, and report on their frequency, surface phenotype, cytokine profile, and Ag specificity. The number of KIR(+) CD4 T cells detected in peripheral blood increased with age. In contrast with regular KIR(-) CD4 T cells, the majority of KIR(+) CD4 T cells lacked surface expression of CD27, CD28, CCR4, and CCR7, but did express CD57 and 2B4. In addition, KIR were detected on approximately one-tenth of CD28(-) and CD57(+) memory CD4 T cells. In line with the absence of the Th2 marker CCR4, the KIR(+) CD4 cells produced mainly IFN-gamma and little IL-4, IL-10, or IL-17 upon TCR triggering. Furthermore, the KIR(+) population contained cells that responded to recall Ags in an HLA class II-restricted fashion. Together, our data indicate that KIR-expressing CD4 T cells are predominantly HLA class II-restricted effector memory Th1 cells, and that a significant, previously unrecognized fraction of effector memory Th1 cells expresses KIR.

Adolescent↗