D.L. Knook

A high response is not essential to prevent selection bias: Results from the Leiden 85-plus study

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.

Mortality risk in men is associated with a common mutation in the methylene-tetrahydrofolate reductase gene (MTHFR).

An elevated level of homocysteine in plasma is associated with the occurrence of cardiovascular disease. A common ala-to-val mutation in the methylenetetrahydrofolate reductase gene (MTHFR) is associated with an elevated level of plasma homocysteine. We studied the possible detrimental effects of the MTHFR mutation on mortality. Within a population-based study in the city of Leiden, the Netherlands, we first compared the MTHFR genotype distribution among 365 elderly subjects aged 85xa0years and over born in Leiden, and 250 young subjects aged 18 to 40xa0years whose families originated from the same geographical region. Second, the complete cohort of 666 subjects aged 85xa0years and over was followed over a period of 10xa0years for all-cause and cause-specific mortality and stratified according to MTHFR genotype. The frequency of the MTHFR mutation was significantly lower in the elderly than in the young (0.30 and 0.36, respectively; Pxa0=xa00.03). The difference in genotype distribution was only present in men. The estimated mortality risk up to 85xa0years in men carrying the val/val genotype was 3.7 (95% confidence interval (CI), 1.3–10.9). Over the age of 85, mortality in men with the val/val genotype was increased 2.0-fold (95% CI, 1.1–3.9) and appeared to be attributable to cancer rather than cardiovascular causes of death. Among women aged 85xa0years and over, no deleterious effect of the MTHFR mutation was observed. In conclusion, the MTHFR mutation is associated with increased mortality in men in middle and old age, but not in women.

Disability in the oldest old: "can do" or "do do"?

OBJECTIVE: To investigate the discrepancies between outcomes for competence (can do) and actual performance (do do) in activities of daily living (ADLs).

Thermolabile methylenetetrahydrofolate reductase gene and the risk of cognitive impairment in those over 85

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.

Angiotensin I-converting enzyme and plasminogen activator inhibitor-1 gene variants : Risk of mortality and fatal cardiovascular disease in an elderly population-based cohort

OBJECTIVESnWe 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.nnnBACKGROUNDnThe 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.nnnMETHODSnThe ACE and PAI-1 genotypes were determined in 648 subjects > or =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.nnnRESULTSnIn 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.nnnCONCLUSIONSnThe 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.

Succesvol oud in maat en getal en volgens ouderen zelf

SamenvattingOm 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%).Wanneer ‘succesvol oud’ wordt gedefinieerd als een toestand van optimaal functioneren en welbevinden, voldeden slechts 58 deelnemers (10%) aan de gestelde criteria op het meetmoment. In diepte-interviews met 27 deelnemers bespraken wij de ervaringen van de ouderen zelf gedurende het oud worden en oud zijn. Van de 27 geïnterviewde deelnemers omschreven 22 (81%) zichzelf als tevreden met hun leven en als succesvol oud. De deelnemers vinden optimaal functioneren belangrijk om succesvol oud te kunnen zijn, maar beschouwen het hebben van sociale contacten als de belangrijkste voorwaarde voor welbevinden en dus voor succesvol oud worden. Als het functioneren niet optimaal is, kan aanpassing aan deze lichamelijke beperkingen toch leiden tot het gevoel van succesvol oud zijn; de betrokken persoon is dan tevreden met het huidige leven.Voor zowel artsen, onderzoekers en beleidsmakers is het belangrijk zich te realiseren dat optimaal functioneren voor ouderen niet zaligmakend is om succesvol oud te zijn. Het vermogen van ouderen om zich te kunnen aanpassen aan de hindernissen die het ouder worden opwerpt, lijkt van minstens even groot belang.hoogbejaardensuccesvol oudkwaliteit van levenwelbevindenoptimaal functionerenpatiëntenperspectief

Cognitive function in the oldest old: Women perform better than men

It is possible that gender differences in cognitive function in aged persons can be explained by limited formal education, which is more common in women than in men. This study measured cognitive speed and memory in 85-year-old men and women in Leiden, The Netherlands, to confirm whether sex influences cognition and whether differences in formal education are relevant. A total of 599 individuals, 87% of Leiden residents 85 years of age, were visited at their residences and completed the Mini-Mental State Examination (MMSE). Cognitive speed and memory were estimated by neuropsychological tests when the MMSE score exceeded 18 points. Cognitive speed was measured using the abbreviated 40-item Stroop test of attention and the letter-digit coding test of processing speed. Memory function was estimated with the 12-word learning test of immediate and delayed recall. Significantly more women than men had had no schooling or primary school education only (70 vs. 53%). Nevertheless, women had better scores for both cognitive speed and memory than did men. After adjusting for educational differences and depressive symptoms, the odds ratio for women having higher cognitive speed was 1.7, and for better memory, 1.8. Women recalled more words than men on the immediate word learning test but had similar test scores on the delayed word learning measure. Those with more education had significantly higher test scores for cognitive speed. Men and women lacking depressive symptoms scored significantly better on all tests. The effects of educational level and depression on cognitive function were similar in women and men. Despite a lower educational level, women aged 85 years in this study exhibited better overall cognitive function than did men of the same age. Rather than education being the controlling factor, better cognitive function in women is likelier to represent some biological factor, such as atherosclerotic disease.