Sten Landahl

A population study of apoE genotype at the age of 85: relation to dementia, cerebrovascular disease, and mortality

OBJECTIVES To study the association of apoE genotypes with dementia and cerebrovascular disorders in a population based sample of 85 year old people. METHODS A representative sample of 85 year old people (303 non-demented, 109 demented) were given a neuropsychiatric and a medical examination and head CT. The apoE isoforms were determined. Dementia was diagnosed according to DSM-III-R. RESULTS At the age of 85, carriers of the apoE ε4 allele had an increased odds ratio (OR) for dementia (1.9; p<0.01) and its subtypes Alzheimer’s disease (1.9; p<0.05) and vascular dementia (2.0; p<0.05). Among those categorised as having vascular dementia, the apoE ε4 allele was associated with mixed Alzheimer’s disease-multi-infarct dementia (OR 6.5; p<0.05), but not with pure multi-infarct dementia (OR 1.5; NS). Only carriers of the apoE ε4 allele who also had ischaemic white matter lesions on CT of the head had an increased OR for dementia (OR 6.1; p=0.00003), and its main subtypes Alzheimer’s disease (OR 6.8; p=0.002) and vascular dementia (OR 5.6; p=0.0007), whereas carriers of the apoE ε4 allele without white matter lesions had an OR for dementia of 1.0 (OR for Alzheimer’s disease 1.8; NS and for vascular dementia 0.6; NS) and non-carriers of the apoE ε4 allele with white matter lesions had an OR for dementia of 2.2; NS (OR for Alzheimer’s disease 2.7; NS and for vascular dementia 1.6; NS). The apoE allele variants were not related to mortality or incidence of dementia between the ages of 85 and 88. The ε2 allele was related to a higher prevalence of stroke or transient ischaemic attack at the age of 85 (OR 2.1; p<0.05) and a higher incidence of multi-infarct dementia during the follow up (OR 2.9; p<0.05). CONCLUSIONS Neither the apoE ε4 allele nor white matter lesions are sufficient risk factors by themselves for dementia at very old ages, whereas possession of both these entities increases the risk for Alzheimer’s disease and vascular dementia substantially.

Blood haemoglobin declines in the elderly: implications for reference intervals fromage 70 to 88

Abstract: The objective was to determine whether Hb declines in healthy elderly men and women and if this influences health‐related reference intervals. A representative population sample, comprising 30% of all 70‐yr‐old subjects in a Swedish city with 420,000 inhabitants (n=1148, participation rate 85%), was followed at 1–5‐yr intervals for 18 yr within a longitudinal population study. Age‐related changes in Hb were calculated after exclusion of non‐healthy probands and by multivariate analyses in the total study group. Mean Hb declined between age 70 and 88 from 149 to 138 g/L in men (annual decline 0.69 g/L, p=0.000), and from 139 to 135 g/L in women (annual decline 0.06 g/L, n.s.). Healthy men declined from 152 to 141 g/L (annual decline 0.53 g/L, p=0.038), for women from 140 to 138 g/L (annual decline 0.05 g/L, n.s.). Age and body mass index correlated, in multivariate analysis, independently to Hb in both men and women, as did variables indicating a non‐healthy state. Epidemiological decision limits for anaemia declined for men from 128 to 116 g/L, for women from 118 to 114 g/L. Anaemia, thus defined, occurred in 3.2 to 9.7% of the subjects, whereas 28.3% of the 88‐yr‐old men had anaemia according to the WHO definition. In conclusion, there is a significant age‐related decline in Hb from age 70 to 88 among healthy men, and a less pronounced decline among women. This justifies the use of lower epidemiological decision limits for anaemia of about 115 g/L for both men and women from age 80–82.

Mental disorders and the use of psychotropic drugs in an 85-year-old urban population.

The prevalence of mental disorders was studied in a representative sample of 85-year-olds living in Gothenburg, Sweden, (n = 494). All subjects were examined by a psychiatrist, whose diagnoses were defined according to the DSM-III-R criteria. In the sample, the prevalence of dementia was 29.8%, and of any other mental disorder was 24.3%. Psychotic disorders were present in 4.7%, depressive disorders in 12.6%, and anxiety disorders in 10.5%. Anxiety disorders were more common in women than in men. Of all subjects, 42.5% used a psychotropic drug (men 30.1%, women 47.6%, p < 0.001), 34.2% used anxiolytic-sedatives, 14.0% used antidepressants, and 5.7% used neuroleptics. Women used significantly more anxiolytic-sedatives and antidepressants than did men. Of those with no mental disorders, 29.1% used a psychotropic drug. Although the prescription of psychotropic drugs was high, only one fifth of those with depressive disorders received antidepressant drug therapy and one tenth of those with psychotic disorders received neuroleptics.

Low serum cobalamin levels in a population study of 70- and 75-year-old subjects. Gastrointestinal causes and hematological effects.

We examined causes and hematological consequences of low serum cobalamin (vitamin B12)concentration in two representative population samples of 70- year-old (N=293) and 75- year- old subjects (N=486). Subjects with values below 130 pmol/liter (4.8% and 5.6%, respectively) were investigated with Schilling test, upper gastrointestinal endoscopy, determination of serum gastrin and group I pepsinogens, and bone marrow examination. Gastrointestinal abnormalities of etiologic significance were found in 26 of the 32 examined subjects: atrophy of the gastric body mucosa (N=16, with pernicious anemia in six), partial gastrectomy (N=6), and intestinal malabsorption (N=4). Megaloblastic hematopoiesis was found in 10 individuals, four of whom had macrocytic anemia. Our results indicate that low serum cobalamin concentration in the elderly is usually a consequence of disease rather than of high age per se and that gastric mucosal atrophy is a major etiologic factor.

Pharmacokinetics of metoprolol and its metabolite α-OH-metoprolol in healthy, non-smoking, elderly individuals

SummaryThe absorption and disposition of metoprolol have been evaluated in 10 healthy, non-smoking, elderly individuals (mean age 73.1 years) by simultaneous determination of [3H]-metoprolol and unlabelled metoprolol. The labelled drug was given as an intravenous tracer dose, immediately followed by oral metoprolol 25 mg. The experiment was preceded by administration of metoprolol 25 mg b.i.d. for 3 days. The volume of distribution, elimination half-life and total body clearance were almost the same as previously observed in healthy, young subjects. The mean systemic availability was about 39% in the elderly, which is lower than the mean of 55% observed in a control group of young volunteers who received 50 mg b.i.d. In the elderly, the mean plasma concentration of α-OH-metoprolol was about twice as high as that of the parent drug, whereas the opposite was true of the control group. The results indicate that age-related physiological changes have a negligible effect on the pharmacokinetics of metoprolol.

Health-promoting interventions for persons aged 80 and older are successful in the short term-results from the randomized and three-armed Elderly Persons in the Risk Zone study

To examine the outcomes of the Elderly Persons in the Risk Zone study, which was designed to evaluate whether it is possible to delay deterioration if a health‐promoting intervention is made when an older adult (≥80) is at risk of becoming frail and whether a multiprofessional group intervention is more effective in delaying deterioration than a single preventive home visit with regard to frailty, self‐rated health, and activities of daily living (ADLs) at 3‐month follow‐up.

Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients. A comparison with young healthy subjects.

SummaryThe pharmacokinetics and antihypertensive effects of felodipine, a new dihydropyridine calcium channel blocker, were studied in elderly hypertensive patients, 67 to 79 years of age and in young healthy subjects, 20 to 34 years of age following oral administration of 5mg twice daily to steady-state. A single intravenous dose of 3H-felodipine (0.04mg) was given together with the oral dose on the study day.Cmax (17 nmol/L), Cmin (5 nmol/L) and AUC (82 nmol/L • h) were 3 times higher in the elderly than in the young subjects. Systemic availability was about 15% in both groups. Plasma clearance (CL) was reduced from 56.1 L/h in the young to 25.4 L/h in the elderly. There was no effect of age on the volume of distribution at steady-state (Vss). Reduced hepatic blood flow and enzyme activity or increased gut wall metabolism are possible reasons for the altered pharmacokinetics in the elderly.Blood pressure was reduced in the elderly from 190/99 to 177/91mm Hg 12 hours after 5mg felodipine during twice daily dosage. The effect on blood pressure correlated with plasma concentrations of felodipine.

Serum cobalamins in the elderly: A longitudinal study of a representative population sample from age 70 to 81

Abstract: In a representative population sample (n = 973) born 1901–1902 and examined at the ages of 70, 75, 79, and 81, the change in serum cobalamins with increasing age was studied by trend analysis using values obtained in single individuals at all four examinations. In subsamples without definable disorders, the mean annual decline was: among men 3.4 pmol/l (p < 0.05), among women 3.2 pmol/l (n.s.). The decline was possibly more pronounced among individuals with low and intermediate concentrations. The health‐related lower reference limits (the 2.5 percentile values of subsamples without definable disorders) did not differ significantly between sexes and age groups, but low concentrations or ongoing cobalamin medication became more common with advancing age. The results indicate a slight fall in serum cobalamins between age 70 and 81 but do not call for age‐related lower reference limits.

Decline of blood haemoglobin in the aged: a longitudinal study of an urban Swedish Population from age 70 to 81

Summary Blood haemoglobin (Hb) and telated components were determined in a representative sample (n=973, 449 men and 524 women) of a 70‐yar‐old population. reinvestigated at age 75. 79 and 81. At age 81. 145 men and 259 wonem remained in the study. Longitudinal analysis demonstrated a significant decline in Hb concentration with advancing age, in the total study groups as well as in subsamples remaining after exclusions due to disease. The mean annual decline from age 70 to 81 in a subsample without definable disorders was in men 0.063 g/g/dl. in women 0.035 g/dl. There was a similar decline among subjects with high, intermediate or low Hb concentrations during the study. Only part of the observed intrainadividual variations could be explainedbny factors other than age.

Association between Multi-Dose Drug Dispensing and Quality of Drug Treatment - A Register-Based Study

Background In the elderly in Scandinavia, multi-dose drug dispensing (MDD) is a common alternative to ordinary prescriptions (OP). MDD patients receive their drugs in unit bags, one for each dose occasion. The prescribing procedure differs between MDD and OP. The aim of the present study was to investigate the association between MDD and quality of drug treatment (QDT). Methodology/Principal Findings A cross-sectional study was performed of all inhabitants in Region Västra Götaland alive on December 31st 2007, aged ≥65 years, with ≥1 prescribed drug and ≥2 health care visits for ≥2 diagnoses for obstructive pulmonary disease, diabetes mellitus, and/or cardiovascular disease in 2005–2007 (n = 24,146). For each patient, drug treatment on December 31st 2007 was estimated from drugs registered in the Swedish Prescribed Drug Register. QDT was evaluated according to established quality indicators (≥10 drugs, Long-acting benzodiazepines, Drugs with anticholinergic action, ≥3 psychotropics, and Drugs combinations that should be avoided). Logistic regression, with adjustments for age, sex, burden of disease, and residence, was performed to investigate the association between MDD and QDT. Mean age was 77 years, 51% were females, and 20% used MDD. For all quality indicators, the proportion of patients with poor QDT was greater in patients with MDD than in patients with OP (all P<0.0001). Unadjusted and adjusted odds ratios (95% confidence intervals) for poor QDT (MDD patients vs. OP patients) ranged from 1.47 (1.30–1.65) to 7.08 (6.30–7.96) and from 1.36 (1.18–1.57) to 5.48 (4.76–6.30), respectively. Conclusions/Significance Patients with MDD have poorer QDT than patients with OP. This cannot be explained by differences in age, sex, burden of disease, or residence. These findings must be taken into account when designing alternative prescribing systems. Further research is needed to evaluate causative factors and if the findings also apply to other dose dispensing systems.