Irma-Leena Notkola

Serum Total Cholesterol, Apolipoprotein E {FC12}e4 Allele, and Alzheimer’s Disease

The σ4 allele of the apolipoprotein E (apoE) is associated with Alzheimer’s disease (AD) and also with elevated serum total cholesterol and low-density lipoprotein levels. However, the interrelationships between apoE genotype, plasma cholesterol levels and AD risk have been studied very little. We examined the possible role of serum total cholesterol in the pathogenesis of AD in a population-based sample of 444 men, aged 70–89 years, who were survivors of the Finnish cohorts of the Seven Countries Study. Previous high serum cholesterol level (mean level ≥6.5 mmol/l) was a significant predictor of the prevalence of AD (odds ratio = 3.1; 95% confidence interval = 1.2, 8.5) after controlling for age and the presence of apoE σ4 allele. In men who subsequently developed AD the cholesterol level decreased before the clinical manifestations of AD. We conclude that high serum total cholesterol may be an independent risk factor for AD and some of the effect of the apoE σ4 allele on risk of AD might be mediated through high serum cholesterol.

Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study.

Background. Senile systemic amyloidosis (SSA) is characterized by deposition of wild‐type transthyretin (TTR)‐based amyloid in parenchymal organs in elderly individuals. Previously, no population‐based studies have been performed on SSA. Methods. Here we have studied the prevalence and risk factors for SSA in a Finnish autopsied population aged 85 or over, as part of the population‐based Vantaa 85+ Autopsy Study (n = 256). The diagnosis of SSA was based on histological examination of myocardial samples stained with Congo red and anti‐TTR immunohistochemistry. The genotype frequencies of 20 polymorphisms in 9 genes in subjects with and without SSA were compared. Results. The prevalence of SSA was 25%. SSA was associated with age, myocardial infarctions, the G/G (Val/Val) genotype of the exon 24 polymorphism in the alpha2‐macroglobulin (α2M), and the H2 haplotype of the tau gene (P‐values 0.002, 0.004, 0.042, and 0.016). Conclusion. This population‐based study shows that SSA is very common in old individuals, affecting one‐quarter of people aged over 85 years. Myocardial infarctions and variation in the genes for α2M and tau may be associated with SSA.

Effects of supporting community-living demented patients and their caregivers: a randomized trial.

To determine whether community care of demented patients can be prolonged by means of a 2‐year support program based on nurse case management.

Tracking of systolic blood pressure during childhood: a 15-year follow-up population-based family study in eastern Finland.

Objectives To investigate the tracking of systolic arterial blood pressure (SBP) during childhood. Design and setting All children born during 1981–82 in a rural community of eastern Finland were followed at the ages of 6 months, 7 and 15 years (SBP-6m, SBP-7y, SBP-15y). One hundred and thirty-eight out of 205 children completed the full follow-up period, of which 100 (45 girls) were included in the analysis with complete data. Main outcome measures SBP (mmHg). Results SBP-6m was associated with SBP-7y (r = 0.715;P < 0.001) and with SBP-15y (r = 0.238;P = 0.017) and SBP-7y was associated with SBP-15y (r = 0.348;P < 0.001). Adjustment for confounders did not change these results. Children at the highest tertile of SBP-6m had a higher probability of being at the highest tertile of SBP-7y [relative risk (RR) = 4.3; 95% confidence interval (CI), (2.4–7.6)] and SBP-15y [RR = 1.9; 95% CI, (1.1–3.3)]. Children at the highest tertile of SBP-7y had a higher probability of being at the highest tertile of SBP-15y [RR = 2.6 (1.5–4.6)]. The regression analysis showed a significant main effect on SBP-15y for birth weight (negative association), male gender, current body mass index (BMI), change of BMI between the ages of 7 years and 15 years, SBP–6m, SBP-7y and the mean SBP between the ages of 6 months and 7 years (all with positive association). Children with family history of hypertension appear to have a higher SBP during childhood; however, this association did not reach a significant level. Conclusions The study confirmed the tracking of SBP during childhood. Birth weight was inversely associated with SBP-15y. Family history of hypertension was not significantly associated with SBP during childhood.

Physical functioning in elderly Europeans: 10 year changes in the north and south: the HALE project

Objectives: To examine age related changes in physical functioning in elderly men and women. Design: Prospective, population based study. Setting: Population of 15 rural and urban centres in 10 European countries. Participants: Altogether 3496 men and women born between 1900 and 1920 who participated in the baseline survey of the HALE project in 1988–1991. The study population was examined again about five (in 1993–1995) and 10 (in 1999–2001) years after the baseline examination. Main outcome measures: Physical functioning was measured by means of a self administered questionnaire of activities of daily living (ADL). Dichotomised prevalence of disability and need for help in self care and mobility ADL were used as dependent variables in the analyses. Results: Prevalence of disability and need for help tended to be higher in women than in men and in mobility abilities than in self care activities. Disability and need for help increased with advancing age but ameliorated over time from one birth cohort to another. In longitudinal analyses this beneficial time trend was independent of the effect of age, study, and region in self care disability in men and women (OR 0.85, 95% CI 0.75 to 0.97 and OR 0.64, 95% CI 0.43 to 0.97, respectively) and self care need for help in men (OR 0.83, 95% CI 0.70 to 0.96). Mobility disability among men and self care disability among women decreased more in the south than in the north. Conclusion: While European populations are aging, the proportions of elderly people with disability are decreasing. These results suggest that dynamics of functioning may differ across cultures. Future studies are needed to clarify which potentially modifiable and culturally determined factors protect against functional decline.

Pulmonary function, smoking cessation and 30 year mortality in middle aged Finnish men

BACKGROUND Although it is well known that impaired pulmonary function is a strong predictor of mortality and that smoking decreases pulmonary function, little is known about the long term effect of smoking cessation on mortality at different levels of pulmonary function. We have studied the impact of smoking cessation on mortality over the entire range of baseline pulmonary function. METHODS The study subjects consisted of men aged 40–59 at entry who were the Finnish participants in the Seven Countries Study during 1959–89. RESULTS In all the participants (n = 1582) impaired forced expiratory volume in 0.75 seconds (FEV0.75) was significantly associated with increased all cause mortality. When those who gave up smoking during the follow up period were compared with continuous smokers (n = 860) all cause mortality was found to be decreased among those who quit. The relative adjusted hazard (HR) was 0.71 (95% confidence interval 0.50 to 1.00). The median survival time in those who stopped smoking compared with those who continued to smoke from 1969 onwards was 7.65, 7.59, and 6.30 years longer in the lowest, middle and highest tertiles of adjusted FEV0.75 distribution, respectively. In those who gave up smoking, mortality from cardiovascular causes was significantly lower (HR 0.60 (95% CI 0.37 to 0.98)). CONCLUSIONS These findings suggest that smokers across the entire range of pulmonary function may increase their expectation of lifespan by giving up smoking.

Neuropathologic Findings of Dementia with Lewy Bodies (DLB) in a Population-based Vantaa 85+ Study

The consortium on dementia with Lewy bodies has established consensus guidelines for the neuropathologic diagnosis of dementia with Lewy bodies (DLB) including the likelihood that the neuropathologic findings associate with the clinical syndrome. Nevertheless, clinico-pathological correlations remain controversial. We applied the consensus guidelines for determining Lewy-related pathology (LRP) and evaluated the clinical presentation in the prospective, population-based Vantaa 85+ study consisting of individuals at least 85 years of age. LRP was seen in 36% of 304 subjects and categorized as follows: 3% brainstem-predominant, 14% limbic, 15% diffuse neocortical type (4% could not be categorized). The likelihood that the neuropathology predicts the DLB clinical syndrome was low in 6%, intermediate in 13%, and high in 13% of all 304 subjects. In the latter two groups, 77% were demented, 35% had at least one extrapyramidal symptom, and 15% had visual hallucinations. Surprisingly, DLB clinical features associated better with high neurofibrillary stage than with diffuse neocortical LRP. Moreover, the neurofibrillary stage, substantia nigra neuron loss, and grade of Lewy neurites in hippocampal CA2-3 region, each showed a significant association with the extent of LRP. In conclusion, the neuropathologic DLB in this very elderly population was common, but the clinical symptoms tended to associate better with severe neurofibrillary pathology than with extensive LRP.

Association of lipoprotein lipase Ser447Ter polymorphism with brain infarction: a population-based neuropathological study

BACKGROUND. Variants of the lipoprotein lipase (LPL) gene have been shown to influence serum lipid levels, risk of coronary heart disease and, as found recently, risk of clinical ischaemic cerebrovascular disease. Here we tested for an association between brain infarction and two common polymorphisms of the LPL gene, Ser447Ter and Asn291Ser. METHOD. To avoid ascertainment and selection bias involved in many association studies, we compared the distribution of these polymorphisms in neuropathologically verified patients (n = 119) vs controls (n = 133) derived from a prospective, population-based study (the Vantaa 85+ study). RESULTS. The LPL Ter447 variant was negatively associated with neuropathologically verified brain infarcts (P = 0.006), and even more strongly with small brain infarcts (P = 0.004). In addition, we found that the Ter447 variant was associated with higher serum HDL cholesterol (P = 0.004) and lower triglyceride levels (P = 0.003), and that it was negatively associated with pathologically verified severe coronary artery disease (P= 0.001) in the Vantaa 85+ study sample. The Asn291Ser polymorphism was not significantly associated with brain infarction. CONCLUSION. The Ter447 variant of LPL is associated with decreased risk of brain infarction and coronary artery disease in our very elderly population.

Incidence of Dementia in Very Elderly Individuals: A Clinical, Neuropathological and Molecular Genetic Study

Aims: To evaluate the effect of medical record use on figures for the incidence of dementia and the effect of apolipoprotein E (APOE) polymorphism on this incidence and neuropathologically defined Alzheimer’s disease (AD) in very elderly individuals. Methods: Cognitive functions were examined in a cohort of 328 (92% of the very elderly people of a town participated in this study) nondemented Finnish elderly individuals 85 years of age or more in 1991. The examination was repeated in survivors in 1994, 1996, 1999 and 2001. Medical notes and social work records were evaluated. All these individuals were genotyped for APOE. Neuropathological analysis of AD-type pathology was performed on 159 of 303 subjects who died during the follow-up. Results: Age group, gender or APOE did not significantly affect the incidence of dementia, which was over 20% higher (85 vs. 69 per 1,000 person-years) if the cognitive status at death was ascertained by medical and social work records than without this evaluation. The APOE υ4 allele was highly significantly (p = 0.002) and age almost significantly (p = 0.06) associated with neuropathological AD in nondemented individuals. Conclusions: Medical records should be analyzed in studies on the incidence of dementia in very elderly individuals. APOE polymorphism does not affect the incidence of dementia in this age group. However, clinical dementia diagnosis in very elderly individuals does not necessarily correlate well with the presence of neuropathological AD which, even in this age group, is significantly associated with the APOE υ4 allele.

Does apolipoprotein E influence learning and memory in the nondemented oldest old

The objective of this study was to analyze the relationship of the apolipoprotein E (apoE) epsilon4 and epsilon2 alleles to learning and memory performances in the nondemented oldest old. Forty-six nondemented persons aged 85 years or over from a randomly selected group of 128 subjects in Vantaa, Finland, were studied. ApoE genotyping was performed using the minisequencing technique. A structured clinical examination and interview were carried out. The test variables studied were learning and memory scores (from the Fuld Object-Memory Evaluation), verbal fluency, and conceptualization (the Similarities subtest of the WAIS-R). We compared apoE-epsilon4 carriers to noncarriers and apoE-epsilon2 carriers to noncarriers. No statistically significant differences were found in any of the test variables. The results failed to confirm the hypotheses that poor cognitive performance is associated with the apoE-epsilon4 allele and good performance with the apoE-epsilon2 allele in the oldest old. This suggests that the apoE alleles do not have a detectable relationship to learning and memory in nondemented very elderly people.