Auli Verkkoniemi

Apolipoprotein E, Dementia, and Cortical Deposition of β-Amyloid Protein

BACKGROUNDnThe epsilon 4 allele of apolipoprotein E has been associated with an increased risk of late-onset Alzheimers disease. In a cohort of elderly subjects we prospectively investigated the relation between the apolipoprotein E genotype, dementia, and the accumulation of beta-amyloid protein in the cerebral cortex.nnnMETHODSnAutopsy involving neuropathological analysis and DNA analysis of frozen blood samples were performed in 92 of 271 persons who were at least 85 years of age, who had been living in Vantaa, Finland, on April 1, 1991, and who had died between that time and the end of 1993. All subjects had been tested for dementia. Apolipoprotein E genotyping was done with a solid-phase minisequencing technique. The percentage of the cortex occupied by methenamine silver-stained plaques was used as an estimate of the extent of beta-amyloid protein deposition.nnnRESULTSnThe frequency of the epsilon 4 allele was significantly higher in the subjects with Alzheimers disease than in the subjects without dementia (30 percent vs. 8 percent, P < 0.001). There was a greater accumulation of beta-amyloid protein in the brain and more neurofibrillary tangles in the subjects with the epsilon 4 allele than in those without it (P < 0.001). The deposition of beta-amyloid protein varied according to the genotype in both the subjects with dementia and those without dementia: it was lowest in those with the epsilon 2/epsilon 3 genotype, intermediate in those with the epsilon 3/epsilon 3 genotype, and highest in those with the epsilon 3/epsilon 4 genotype. A single subject had the epsilon 4/epsilon 4 genotype and had dementia.nnnCONCLUSIONSnThe epsilon 4 allele of apolipoprotein E is significantly associated with Alzheimers disease. Even in elderly subjects without dementia, the apolipoprotein E genotype is related to the degree of deposition of beta-amyloid protein in the cerebral cortex.

Atrial Fibrillation, Stroke, and Cognition A Longitudinal Population-Based Study of People Aged 85 and Older

Background and Purpose— The aim of this study was to investigate the association between atrial fibrillation (AF), stroke, dementia, and their correlation with brain pathology in subjects aged 85 years or older. Methods— This is a prospective 9-year follow-up population based study in Vantaa, a town in Southern Finland; 553 subjects (92% of the total population) aged 85 years or older were clinically examined by a neurologist. The presence of AF was collected from the medical records or examined by ECG or ambulatory ECG. Neuropathological examination was conducted in more than half of the clinically examined subjects. Results— AF was significantly associated with stroke at baseline; 32% of patients with AF had clinical evidence of stroke compared with 16.7% of those without such evidence (P<0.001). Dementia at baseline was significantly associated with age, clinical stroke, and the presence of apolipoprotein E ϵ4 allele, but not with sex, education, or vascular risk factors. Multiple regression analysis including neuropathological results showed that dementia was significantly associated with education (OR, 0.89; 95% CI, 0.80 to 0.98; P=0.019), the β-amyloid load in the brain (OR, 1.26; 95% CI, 1.13 to 1.39; P<0.001) and with the vascular pathology (OR, 2.03; 95% CI, 1.14 to 3.62; P=0.016), but not with sex, age at death, apolipoprotein E ϵ4 allele, or vascular risk factors. Conclusions— AF is a significant and preventable risk factor for stroke but not for dementia in the very old. The etiology of dementia syndrome in the very old is multifactorial. Both Alzheimer disease pathology and vascular pathology, particularly multiple small infarcts, contribute to cognitive decline.

The prevalence and associates of depressive disorders in the oldest-old Finns.

Aim: To describe the prevalence and associates of major depression and minor depression among the Finnish non-demented population aged 85 years and older (nu2009=u2009339). Methods: DSM-III-R criteria were used in diagnosing major depression and dementia. Minor depression was diagnosed by the physician in those who did not fulfil the DSM-III-R criteria for major depression, but had still at least two depressive symptoms. In the first phase, cross-tabulation was used to determine relative risks (RR) and their 95% confidential intervals (95% CI). An additive logistic regression model was then used to find the independent associates of depressive disorders. Results: The prevalence of major depression was 8.1% in men and 4.9% in women, and that of minor depression 18.9% in men and 18.5% in women. In men major depression was associated independently with poor physical health and in women with rare contact with family or friends and poor physical health. Minor depression was associated independently with poor physical health and previous myocardial infarction in men and with poor physical health, a poor ability to walk, and smoking in women. Conclusions: The prevalence of depressive disorders is quite high among the oldest-old Finns. The factors associated with major and minor depression are largely similar. Although the results suggest that psychosocial stress factors affect the development of both major and minor depression in the oldest-old, no conclusions about causality can be made.

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.

APOE alleles in Alzheimer's disease and vascular dementia in a population aged 85+

Apolipoprotein E genotyping was carried out in a stratified random sample of 52 patients with Alzheimers disease, 48 patients with vascular or mixed dementia, and 49 nondemented controls in a population-based study of people aged 85 and older (the Vantaa 85+ Study). Our results indicate that the apolipoprotein E epsilon 4 allele is associated with approximately a twofold increase in clinically diagnosed Alzheimers disease in this very old general population aged 85+. When combined with previous studies, our data also suggest that the association is decreasing with age. In contrast, there appears to be no relation between apolipoprotein E alleles and clinically diagnosed vascular dementia.

Depression measured by the Zung Depression Status Inventory is very rare in a Finnish population aged 85 years and over.

The purpose of this study was to obtain information about the prevalence of depressive symptoms in a representative sample of elderly subjects aged 85 years and over. The study was carried out as a population-based interview study in the City of Vantaa in Finland. The Zung Depression Status Inventory (DSI) was used to evaluate various depressive symptoms in this study population. The DSI scores range from 20 to 80; the higher the score, the more severe the disturbance. In subjects interviewed (n = 467, 362 women, 105 men), the prevalence estimates of depression with cutoff scores used in earlier studies (40 and 48) were very low: 5.2% and 1.1%. Also, the mean DSI score (SD) was very low, 27.9 (6.4). The scores tended to decrease with age, although the differences were not statistically significant. The DSI means were 28.0 (6.1) for women and 27.3 (7.2) for men (p = .0349). Women had a greater risk of being classified as depressed on the DSI (odds ratio: 1.60, 95% confidence interval: 1.00-2.57, p = .049). Feelings of emptiness, personal devaluation, and depressive mood were the most common depressive symptoms. In conclusion, the present population-based study shows that subjective experience of depression is very rare in Finnish people aged 85+. Our results suggest that optimistic mood might give some protection against death.