Om de verschillende betekenissen van ‘succesvol oud’ nader uit te diepen, onderzocht de Leiden 85-plus Studie ten eerste: hoeveel 85-jarige deelnemers succesvol oud zijn, gedefinieerd als een toestand van optimaal functioneren en welbevinden (kwantitatief), en ten tweede: wat succesvol oud voor oudste ouderen betekent (kwalitatief). De Leiden 85-plus Studie is een longitudinaal bevolkingsonderzoek naar de gezondheid, het functioneren en het welbevinden van de oudste ouderen. In totaal namen 599 mensen deel aan de basismeting (respons 87%).

Dit boek bevat wat de basisarts moet weten over veroudering. Het behandelt eerst de belangrijkste aspecten van normale veroudering (Gerontologie), daarna de geneeskunde bij ouderen (Geriatrie) voor zover die anders is dan bij jongeren. Veroudering is het optreden van ogenschijnlijk spontane, irreversibele veranderingen met de tijd. Deze veranderingen zijn haast altijd universeel en toenemend. De definitie omvat dus naast biologische ook fysische zoals metaalmoeheid en het uitdijen van het heelal, chemische zoals colloidveroudering, en culturele veroudering zoals mode. Groei en differentiatie vallen er ook onder, immers bij de ontwikkeling van bevruchte eicel via kind naar volwassene treden voortdurend spontane, irreversibele veranderingen op. Met de lichamelijke groei nemen de kracht en andere vermogens van het organisme toe. Veroudering hoeft dan ook geen functionele achteruitgang in te houden of ongunstig te zijn. Na het volwassen worden blijven de veranderingen optreden, waarbij al snel de prestatietop lager wordt: bij veel takken van sport is men na het dertigste jaar al te oud om kampioen te worden. In de geneeskunde beperken we het begrip veroudering vaak tot de blijvende veranderingen bij volwassenen en deze gaan op den duur vaak, maar niet altijd, met functionele achteruitgang gepaard. Biologische veroudering loopt uit op sterven en maakt dit onontkoombaar. Zonder eeuwige jeugd zou onsterfelijkheid ook geen pretje zijn.

Successful aging; 'the Leiden 85-plus Study' Objective. To determine how many 85-year-old persons in the population were aging successfully, according to the definition 'optimal functioning and well-being' (quantitative approach) and according to themselves (qualitative approach). Design. Cross-sectional study. Method. All inhabitants of Leiden, the Netherlands, who were born during the period 1 September 1912-31 August 1914 were asked, shortly after their 85th birthday, to participate in the study. The number of participants was 599 (87%): 397 women and 202 men. During a home visit, they were assisted in completing questionnaires and, in a representative group of 27 participants, an in-depth interview was carried out about their experiences when aging and as an elderly person. Results. Of the 599 participants, 267 (45%) had optimal scores for well-being, 367 (45%) had optimal scores for functioning and 58 (10%) had optimal scores for both successful aging criteria. Of the 27 interviewees, 22 (81%) described themselves as satisfied with their life and as having aged successfully. Participants found optimum functioning to be important in being able to be old successfully, but considered having social contacts as the most important prerequisite for wellbeing. The ability to be able to adjust to limitations was essential to remain satisfied and thus successfully old.

In dit hoofdstuk wordt eerst besproken wat gerontologie is en welke subdisciplines er zijn. Er zijn verschillende manieren om veroudering bij de mens te bestuderen: via transversaal, longitudinaal en time-lag onderzoek (met verstorende invloeden daarop van leeftijd-, cohort- en periode-effecten) en via onderzoek naar mortaliteit en morbiditeit. Een keurkorps van ‘senieurs’ bewijst dat bij sommige ouderen functies tot op zeer hoge leeftijd intact blijven.

We tested the hypothesis that an additional effort to increase the response rate would diminish selection bias in a community-based cohort study. In the Leiden 85-plus Study, all subjects of the town of Leiden who had reached their 85th birthday were informed of the study by mail and then asked to participate by telephone. In an additional recruitment stage, those subjects who did not participate directly were visited and personally asked to participate. When these subjects refused, some nonresponse questions were asked. In this way we collected data on the whole source population. Of 691 eligible elderly subjects, 511 subjects (74%) participated directly. Of those who did not participate directly, 88 subjects participated after the additional effort. The response rate increased from 74% to 87%. Compared to the 511 subjects who directly participated, the 88 subjects who entered the study after the additional effort had poorer health and lower survival. The subjects who refused were more healthy and had poorer mood. The direct sample did not differ from the source population with respect to socio-demographics, health, and mortality. In conclusion, we showed that given a moderately high direct response the additional effort was effective in increasing the response rate, but was also selective and was not necessary to prevent selection bias.

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.

Ample evidence supports a role for tumour necrosis factor α (TNFα) in the development of type 2 diabetes and cardiovascular disease. TNFα expression was found to be influenced by a −308G/A polymorphism in the promoter of the gene encoding TNFα (TNF). We investigated the contribution of this polymorphism to diabetes and cardiovascular mortality in a population-based cohort of 664 subjects aged 85 years and over (Leiden 85-plus Study). The −308G/A TNF promoter polymorphism was associated with the prevalence of diabetes in old age (P = 0.006). The risk of diabetes among subjects homozygous for the A-allele was estimated to be 4.6-fold (95% CI, 1.6–13.3) higher than among subjects homozygous for the common G-allele. The promoter polymorphism did not, however, predict mortality from all causes, cardiovascular diseases, cancer or infectious diseases during a 10-year follow-up period. In addition to the promoter polymorphism, TNFa and TNFc microsatellite genotypes were determined but these polymorphisms were not associated with morbidity or mortality. In conclusion, the −308G/A polymorphism in the TNF promoter is strongly associated with the risk of diabetes but not cardiovascular mortality in old age.

Responses to influenza vaccination are poor in frail elderly subjects who suffer the greatest morbidity and mortality due to infection. Therefore, a randomized clinical trial was performed to determine the effect of a double dose and booster vaccination on antibody responses after influenza vaccination. A total of 815 patients (median age 83 years, median disability score 8, median disease categories 2 and median number of medications 4) residing in 14 nursing homes in the Netherlands were vaccinated during the influenza season 1997-98. The first vaccine dose (15 or 30 mug) was given on Day 0 followed by a booster dose (placebo or 15 mug) on Day 84. Blood samples were taken before and 25 days after vaccination. There were four treatment groups: (i) 15 mug and placebo, (ii) 15 mug and 15 mug booster, (iii) 30 mug and placebo and (iv) 30 mug and 15 mug booster. Geometric mean antibody titers of those receiving the double vaccine dose was 15% (95% CI, 6% to 24%, P = 0.001) higher as compared to the standard 15 mug dose. A booster dose, given 84 days after the first vaccination, yielded postvaccination titters that were 14% (95% CI, 9% to 19%, P = 0.001) higher as compared to placebo. !jubgroup analysis did not reveal patient groups that had a proportionally greater benefit from adapted vaccination strategies. It is concluded that higher antibody responses can be achieved in frail elderly people by a double vaccine dose or a booster vaccination. (C) 2001 Wiley-Liss, Inc.

BACKGROUND Successful aging is a worldwide aim, but it is less clear which indicators characterize elderly persons as successfully aged. We explored the meaning of successful aging from 2 perspectives. METHODS Analysis of data from the first cross-sectional part of the longitudinal Leiden 85-plus Study, conducted in Leiden, the Netherlands. All inhabitants of Leiden aged 85 years were eligible. Data were obtained from 599 participants (response rate, 87%). Successful aging from a public health perspective was defined as a state of being. All participants were classified as successful or not successful based on optimal scores for physical, social, and psychocognitive functioning and on feelings of well-being, using validated quantitative instruments. Qualitative indepth interviews on the perspectives of elderly persons were held with a representative group of 27 participants. RESULTS Although 45% (267/599) of the participants had optimal scores for well-being, only 13% (79/599) had optimal scores for overall functioning. In total, 10% (58/599) of the participants satisfied all the criteria and could be classified as successfully aged. The qualitative interviews showed that most elderly persons viewed success as a process of adaptation rather than a state of being. They recognized the various domains of successful aging, but valued well-being and social functioning more than physical and psychocognitive functioning. CONCLUSIONS If successful aging is defined as an optimal state of overall functioning and well-being, only a happy few meet the criteria. However, elderly persons view successful aging as a process of adaptation. Using this perspective, many more persons could be considered to be successfully aged.

OBJECTIVE: To investigate the discrepancies between outcomes for competence (can do) and actual performance (do do) in activities of daily living (ADLs).DESIGN: Baseline measurements of a population-based follow-up study.SETTING: Leiden 85-Plus Study, the Netherlands.PARTICIPANTS: Five hundred and ninety-nine persons, age 85. The response rate was 86%.MEASUREMENTS: Face-to-face interviews. Measurements of competence and actual performance were based on the Groningen Activity Restriction Scale. Help received was assessed for several domains. Prevalence rates for disability were assessed according to the concepts of both competence and actual performance. Analysis was performed separately for basic activities of daily living (BADLs) and instrumental activities of daily living (IADLs).RESULTS: Seventy-seven percent of the oldest old were competent to perform all the BADLs and performed them regularly. Fifteen percent were not competent to perform certain BADLs independently but performed them regularly with help from others. The prevalence of disability defined as inability in one or more BADLs was 22% for women and 10% for men. The prevalence of disability defined as inactivity in one or more BADLs was 16% for women and 17% for men. Only 5% of the oldest old were competent to perform all IADLs and performed them regularly. In spite of being competent, 70% did not perform certain IADLs regularly. The prevalence of disability defined as inability in one or more IADLs was 64% for women and 55% for men. The prevalence of disability defined as inactivity in one or more IADLs was 92% for women and 98 % for men.CONCLUSION: The structural discrepancies between the outcomes of competence and actual performance have important consequences when estimating disability in old people. Promoting actual performance in IADLs may reduce disability.

Recent studies indicate that the enzyme paraoxonase may be an important modulator of cardiovascular disease risk because of its ability to protect LDL from oxidation. We tested for association between two functional variants of the paraoxonase gene (Met-55/Leu and Gln-192/Arg) and both all-cause mortality and fatal cardiovascular disease. This was done within a population-based study among subjects aged 85 years and over in a cross-sectional and a prospective design. In the cross-sectional analysis, the distribution of both paraoxonase genotypes was found to be similar in the subset of 364 elderly subjects who were born in Leiden, The Netherlands, as compared with 250 young subjects whose families originated from the same geographical region. The polymorphisms were in strong linkage disequilibrium (P<0.00001) and the frequency of the haplotype carrying both risk alleles was not lower in the elderly than in the young (0.313 vs. 0.284). The complete cohort of 666 elderly subjects was followed over 10 years. The risk of all-cause and cardiovascular mortality was not increased in elderly subjects with the paraoxonase Leu/Leu (RR, 1.1 [95% CI, 0.9-1.5] and 1.3 [95% CI, 0.8-2.0], respectively) or the Arg/Arg genotype (RR, 0. 9 [95% CI, 0.7-1.2] and 0.7 [95% CI, 0.4-1.3], respectively). In a subset of patients with diabetes, the all-cause mortality risk was elevated in Arg/Arg carriers (RR, 2.1 [95% CI, 0.8-5.8]) but this did not reach statistical significance. Analysis of genotype combinations did not yield significant associations with mortality. The paraoxonase gene variants, previously associated with coronary artery disease, are thus not likely to have a major effect on the risk of fatal cardiovascular disease in the population at large. Adverse effects of the gene variants might be observed in subjects exposed to factors that enhance oxidative stress such as diabetes.

OBJECTIVES We studied the contribution of putative risk genotypes at the angiotensin I-converting enzyme inhibitor (ACE D/D) and plasminogen activator inhibitor-1 (PAI-1 4G/4G) loci to all-cause and cardiovascular mortality in a population-based cohort.BACKGROUND The ACE D/D and PAI-1 4G/4G genotypes have been consistently associated with elevated plasma activities of the gene products. Their role in cardiovascular disease, although explored intensively, is still equivocal.METHODS The ACE and PAI-1 genotypes were determined in 648 subjects greater than or equal to 85 years old. In a cross-sectional analysis, the genotype distributions in a subset of 356 elderly subjects who were born in Leiden, The Netherlands, were compared with those in 250 young subjects whose families originated from the same geographic region. In addition, the complete cohort of elderly subjects was followed over 10 years for all-cause and cardiovascular mortality and was stratified according to genotype.RESULTS In the cross-sectional analysis, the ACE and PAI-1 genotype distributions were similar in elderly and young subjects. In the prospective follow-up study, however, the age-adjusted risk of fatal ischemic heart disease was increased threefold (95% confidence interval [CI] 1.2 to 7.6) in elderly men carrying the PAI-1 4G/4G genotype. The risk of all-cause mortality was not increased among elderly subjects carrying the PAI-1 4G/4G (relative risk [RR] 0.9, 95% CI 0.7 to 1.1) or the ACE D/D genotype (RR 0.9, 95% CI 0.7 to 1.1), nor did we observe elevated risks of death from all cardiovascular diseases combined. There was no interaction between the genotypes.CONCLUSIONS The PAI 4G/4G genotype may be a risk factor for fatal ischemic heart disease in elderly men. The impact of moderately increased ACE and PAI-1 activities associated with the ACE D/D and PAI-1 4G/4G genotypes is too small to affect mortality in the general population. (J Am Coll Cardiol 1999;34:1176-83) (C) 1999 by the American College of Cardiology.

OBJECTIVES Previous reports have shown raised plasma concentrations of homocysteine in older persons with cognitive impairment. This may be caused by environmental and genetic factors. The relation between cognitive function and a commonala/val mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was studied in those over 85. Homozygous carriers of this mutation are characterised by a lifelong exposure to moderately raised plasma concentrations of homocysteine. METHODS In the Leiden 85-plus Study, a population based study of persons aged 85 years and over, the score on the mini mental state examination (MMSE) and the presence of dementia dependent on the MTHFR genotypes were compared in 641 participants (456 women, 185 men) at baseline. In addition, the association between the MTHFR genotype and cognitive decline was studied by re-examining cognitive function of 172 participants without dementia at baseline after a median follow up of 4.0 years. RESULTS At baseline, carriers of the ala/ala genotype had a median MMSE score of 27 points (interquartile range (IQR) 21.5–29), for the ala/val genotype it was 26 points (IQR 20–29), and for the val/val genotype it was 27 points (IQR 20–28.3) (p=0.3). The prevalence of dementia was also not significantly different for the various genotypes (ala/ala 22%,ala/val 28%,val/val 27%; p=0.4). None of the carriers of the val/val genotype without cognitive impairment at baseline developed dementia during the follow up. CONCLUSIONS Although previous studies have shown that older persons with cognitive impairment have raised plasma concentrations of homocysteine, homozygosity for the ala toval mutation in the MTHFR gene is not a genetic risk factor for cognitive impairment in persons aged 85 years and over.