Sari Rastas

Association between blood pressure and survival over 9 years in a general population aged 85 and older

OBJECTIVES: To investigate the association between blood pressure and mortality in people aged 85 and older.

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.

Vascular risk factors and dementia in the general population aged >85 years: prospective population-based study.

The aim of this study was to evaluate the association between dementia and common vascular risk factors including blood pressure, blood lipids, homocysteine and diabetes mellitus in a population of very old people. This study is a 9-year follow-up prospective population-based study monitoring 339 non-demented subjects aged 85 years or over in the city of Vantaa, Southern Finland. During the follow-up, those individuals with diabetes mellitus at the baseline and new incident stroke had a higher probability for developing dementia. History of hypertension or higher level of education were associated with a lower probability of dementia. It seems that the contribution of vascular risk factors to the risk of dementia may be age-dependent and their role in the very old subjects may be mediated through their influence on cerebrovascular morbidity. Thus, prevention of stroke and diabetes mellitus may reduce the risk of cognitive decline in the very old.

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.

Association of apolipoprotein E genotypes, blood pressure, blood lipids and ECG abnormalities in a general population aged 85+

BackgroundSeveral studies have linked apolipoprotein E (ApoE) ε4 allele with elevated cholesterol and blood pressure levels. Data on the association of APOE genotypes with blood pressure, lipids, atrial fibrillation and ECG abnormalities in individuals aged 85 years and over is sparse.MethodsThis cross sectional study consisted of all residents of the city of Vantaa (N = 601) aged 85 years or over of whom 505 participated in the study. Blood pressure was measured by using mercury sphygmomanometer. 12-Lead ECG, short ambulatory ECG, or both were taken from all study subjects to diagnose atrial fibrillation (AF). Ambulatory ECG was carried out home or in the institute. APOE genotyping was performed using a combination of the polymerase chain reaction (PCR) and solid-phase minisequencing technique. Statistical analysis was made by using Kruskall-Wallis-test (continuous data) and χ2-test (rates and proportions).ResultsIn these very elderly individuals, APOE 4 allele was significantly associated with elevated cholesterol and low-density lipoprotein (LDL) levels. Blood pressure or cardiac arrhythmias did not differ between APOE genotypes.ConclusionsThese observations suggest that the important role of APOE genotype still influences cardiovascular risk profile even among the very elderly people.

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.

Intracerebral Hemorrhage in the Oldest Old: A Population-Based Study (Vantaa 85+)

Aims: Very elderly subjects represent the fastest growing population in the world. Most of the recent studies on intracerebral hemorrhage (ICH) have been carried out on younger patients and/or preferably using novel radiological techniques. We investigated the prevalence, risk factors, and histopathological characteristics of the ICH in the oldest old. Materials and methods: The brains of 300 autopsied individuals (248 females, 52 males, mean age at death 92.4 ± 3.7 years) were investigated as part of the prospective population-based Vantaa 85+ study. After macroscopic investigation, the presence and extent of microscopic brain hemorrhages (MH) were analyzed by counting the number of iron containing macrophages (siderophages) by Prussian blue staining. Deposits with >5 siderophages were defined as MH+, forming a subgroup of MH. Genotyping of apolipoprotein E (APOE) and the analysis of microscopic (MI) or larger infarctions and cerebral amyloid angiopathy (CAA) were performed using standardized methods. Regression analysis was used to predict the presence of ICH, with and without co-localized CAA, and was adjusted for age at death and gender. Results: The prevalence of macroscopic ICH was 2.3% in total; consisting of 1% large lobar hemorrhage (LH), 1% deep hemorrhage (DH), and 0.3% of subarachnoid hemorrhage (SAH). 62% had MH and 15.3% MH+. All MH+ lesions were found to be >2 mm wide. 55.9% of subjects with MH and 81.2% of those with MH+ showed MH/MH+ and CAA in the same brain region (MHCAA and MH+CAA, respectively). MH was associated with none of the neuropathological or clinical conditions, nor with the APOE carrier status. The subjects with MH+, MHCAA or MH+CAA carried the APOE ε4 allele more frequently than controls (OR 3.681, 3.291, 7.522, respectively). Siderophages in MH+CAA co-localized with CAA and with two-thirds of the MI in the tissue sections. Conclusion: Macroscopic ICH was rare in the very elderly. MH was frequent and clinically insignificant. MH+ was rare but closely related with the APOE ε4 genotype and the presence of severe CAA and infarction.

Senile systemic amyloidosis, cerebral amyloid angiopathy, and dementia in a very old Finnish population

Senile systemic amyloidosis (SSA) and cerebral amyloid angiopathy (CAA) are amyloid disorders, which typically manifest with old age. The aim of our study was to examine the possible association of these disorders in very old Finns. We performed a prospective, population-based post mortem study and used histological and immunohistochemical staining methods to verify the presence of these types of amyloid. All 63 subjects (59% of the 107 individuals 95 years of age or more, who died during the 10-year follow-up study), 53 women and 10 men), had been neurologically examined. The prevalence of SSA and its association with CAA, dementia, and neuropathologically verified AD was analyzed. Overall SSA occurred in 23 (37%) and CAA in 28 (44%) of the 63 subjects. At clinical examination 41 individuals (65%) were demented; 24 (38%) had Alzheimers disease. SSA showed no association with the presence of CAA (P = 0.45), clinical dementia (P = 0.09), or Alzheimers disease (P = 0.21), or sex (P = 0.53). Our prospective population based study shows that SSA and CAA are frequent in very old Finns, but they do not associate.