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Biomedical subjects

H Soininen

Publications and source records attributed to H Soininen.

At least 37 records · Page 2Linked to original sources
PubMed2002

Midlife income, occupation, APOE status, and dementia: a population-based study.

OBJECTIVE: To examine the relationship between socioeconomic factors and APOE carrier status on the development of dementia. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1449 (73%) subjects aged 65 to 79 years were re-examined in 1998. The diagnosis of dementia among the nonparticipants was derived from patient records of the local hospitals and primary health care clinics. RESULTS: Low income level at old age was related to dementia, but low income level at midlife was not a risk factor for dementia. Dementia was also associated with decreasing income level, from midlife to old age 21 years later, when dementia was diagnosed. A sedentary occupation (office, service, or intellectual work) was associated with a decreased risk for dementia among participants; however, when the nonparticipants were included in the analysis, the associations were no longer significant. Low educational level and the APOE epsilon4 allele independently increased the risk for dementia. CONCLUSIONS: Reduction in income level during follow-up and low income level at old age might be the consequence of a dementing process rather than being associated with risk evolution of dementia.

Aged↗
PubMed2002

Seladin-1 transcription is linked to neuronal degeneration in Alzheimer's disease.

Seladin-1 is a gene recently shown to be down-regulated in brain regions selectively degenerated in Alzheimer's disease. The sequence of seladin-1 shares similarities with flavin-adenine-dinucleotide-dependent oxidoreductases and it has been found to protect cells from apoptotic cell death. In this work, we show that the transcription of seladin-1 is selectively down-regulated in the brain areas affected in Alzheimer's disease. The down-regulation in seladin-1 transcription was associated with hyperphosphorylated tau seen as linkage to immunohistochemically detected paired helical filament tau, neuritic plaques and neurofibrillary tangles. In contrast, no association was found between seladin-1 transcription and beta-amyloid deposition when analyzing human samples or tissue from transgenic animals. Furthermore, the relative transcription of seladin-1 was found to fluctuate during aging in the transgenic mouse model of Alzheimer's disease. The fluctuation was enhanced by Alzheimer's disease causing mutations in presenilin-1 and amyloid precursor protein genes. Finally, seladin-1 transcription was found to be up-regulated in mouse N2a cells induced to undergo apoptosis with okadaic acid. The results presented here indicate that seladin-1 transcription is selectively down-regulated in brain regions vulnerable to Alzheimer's disease and this down-regulation is associated with the hyperphosphorylation of tau protein.

Aged↗
PubMed2002

Auditory adaptation is differentially impaired in familial and sporadic Alzheimer's disease.

Neurophysiologic measures are particularly sensitive to alterations in attention and arousal. The purpose of this study was to evaluate the auditory adaptation of normal and mildly demented elderly people. We compared the automatic behavior of an auditory evoked potential (N100) in three age-matched groups of elderly subjects, one with familial Alzheimer's disease (AD), one with sporadic AD and one healthy group. All AD subjects corresponded clinically and neuropsychologically with the early stage of dementia. The dynamic range of auditory adaptation is known to be related to age, and normal auditory adaptation for the age was observed in our healthy aged and sporadic AD subjects, whereas the familial AD subjects lacked normal adaptation. The familial AD subjects also showed statistically significantly smaller peak amplitudes and shorter latencies of the N100 throughout the habituation test. This persistent difference in automatic habituation of sensory responses supports the view that different subtypes of AD are differentially affected. The observed differences give an objective measure of the impaired involuntary adaptive functions of neuronal networks involved in auditory processing in subtypes of AD. Since habituation reflects the most primitive stage of learning and short-term memory, altered habituation may predict faster deterioration of clinical status in the familial group of AD subjects.

Adaptation, Physiological↗
PubMed2002

Prevalence of mild cognitive impairment: a population-based study in elderly subjects.

OBJECTIVES: Mild cognitive impairment (MCI) has been suggested as a term for a boundary area between normal aging and dementia, especially Alzheimer's disease (AD). In follow-up studies, more than 50% of MCI subjects have been converted to dementia in 3-4 years. However, the epidemiology of MCI is not well known. This study was designed to determine the prevalence of MCI in an elderly population. METHODS: A total of 806 subjects (60-76 years of age) from a population-based random sample of 1150 subjects living in the city of Kuopio in eastern Finland were evaluated. Neuropsychological tests and a structured interview including the modified Clinical Dementia Rating (CDR) were used to apply the diagnostic criteria of MCI as proposed by Mayo Clinic Alzheimer's Disease Research Centre. Thus, subjects having a test score more than 1.5 SDs below the age appropriate mean in memory tests and a CDR score of 0.5 but no dementia, were diagnosed as having MCI. RESULTS: A total of 43 subjects, 5.3%, met the MCI criteria. MCI was more prevalent in older and less-educated subjects, but no difference was found between men and women. The CDR appeared to be the most important part of the criteria. The memory tests had less impact on prevalence variables. CONCLUSIONS: The low prevalence of MCI indicate that in a population-based study design its criteria may identify a more homogeneous group of subjects at the lower end of the cognitive continuum as contrasted with various other criteria of cognitive impairment in the elderly population. This is compatible with follow-up studies showing a high probability of dementia in the MCI group. Thus, probable candidates for trials of preventive intervention for dementia can be screened from the elderly population using these diagnostic criteria.

Aged↗
PubMed2002

Usefulness of repeated presentation of Mini-Mental State Examination as a diagnostic procedure--a population-based study.

MATERIAL AND METHODS: The 280 subjects who achieved 24 points or less in the Mini-Mental State Examination (MMSE) in the first survey of 1449 subjects were invited for a comprehensive diagnostic examination for dementia including medical history, thorough neurological and cardiovascular examinations and detailed neuropsychological evaluation, magnetic resonance imaging (MRI)-study, cerebrospinal fluid (CSF)-analysis, electrocardiogram (ECG), chest radiograph and blood tests after the first assessment. The MMSE was presented again. RESULTS: Out of 240 persons, 57 subjects were diagnosed as having dementia. When the cut-off point of 24 or less in the second MMSE was used, the sensitivity of the second MMSE was 82% and the specificity was 64%. The positive predictive value of the second MMSE was 42% and negative predictive value 92%. The non-demented subjects improved their MMSE score at the second examination. In contrast, the demented subjects maintained their low MMSE score at the second examination.

Aged↗
PubMed2002

Detection of grey matter loss in mild Alzheimer's disease with voxel based morphometry.

OBJECTIVES: To test the applicability of an automated method of magnetic resonance image analysis (voxel based morphometry) to detect presence and severity of regional grey matter density reduction-a proxy of atrophy-in Alzheimer's disease. METHODS: Twenty nine probable Alzheimer's patients and 26 non-demented controls (mini-mental state examinations mean (SD) 21 (4) and 29 (1)) underwent high resolution 3D brain magnetic resonance imaging. Spatial normalisation to a stereotactic template, segmentation into grey matter, white matter, and cerebrospinal fluid, and smoothing of the grey matter were carried out based on statistical parametric mapping (SPM99) algorithms. Analyses were carried out: (a) contrasting all Alzheimer's patients with all controls (p<0.05 corrected for multiple comparisons); (b) contrasting the three Alzheimer's patients with mini-mental state of 26 and higher with all controls (p<0.0001 uncorrected); and (c) correlating grey matter density with mini-mental state score within the Alzheimer's group (p<0.0001 uncorrected). RESULTS: When all Alzheimer's patients were compared with controls, the largest atrophic regions corresponded to the right and left hippocampal/amygdalar complex. All parts of the hippocampus (head, body, and tail) were affected. More localised atrophic regions were in the temporal and cingulate gyri, precuneus, insular cortex, caudate nucleus, and frontal cortex. When the mildest Alzheimer's patients were contrasted with controls, the hippocampal/amygdalar complex were again found significantly atrophic bilaterally. The mini-mental state score correlated with grey matter density reduction in the temporal and posterior cingulate gyri, and precuneus, mainly to the right. CONCLUSIONS: Voxel based morphometry with statistical parametric mapping is sensitive to regional grey matter density reduction in mild Alzheimer's disease.

Aged↗
PubMed2001

Genome-wide linkage disequilibrium mapping of late-onset Alzheimer's disease in Finland.

BACKGROUND: AD is a complex neurodegenerative disorder comprising several disease-associated chromosome loci. To find novel susceptibility genes for late-onset AD, a population-based genome-wide search using linkage disequilibrium (LD) mapping approach has been performed. METHOD: Forty-seven patients with late-onset AD and 51 age-matched control subjects were carefully chosen from the same geographic area in eastern Finland, where the population is descended mainly from a small group of original founders. These subjects were initially genotyped with 366 polymorphic microsatellite markers, and a follow-up analysis was performed with additional microsatellite markers for those chromosome loci found to be associated with AD. RESULTS: Initial genome-wide screening revealed 21 chromosomal loci significantly associated with AD in addition to the 13q12 locus described previously. Subsequent comparison of single-allele frequencies of the microsatellite markers in the AD and control groups indicated the presence both of possible risk alleles (odds ratio [OR] > 1) and of possible protective alleles (OR < 1). Screening of the LD regions with additional microsatellite markers revealed seven chromosomal loci where more than one microsatellite marker was associated with AD (1p36.12, 2p22.2, 3q28, 4p13, 10p13, 18q12.1, and 19p13.3) in addition to the 13q12 locus. CONCLUSIONS: These genome-wide LD screening data suggest that several AD-associated chromosomal loci exist, which may encompass novel susceptibility genes for late-onset AD. Therefore, extensive screening of the genes located in the vicinity of these LD regions is necessary to elucidate their role in AD.

Age of Onset↗
PubMed2001

A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD.

OBJECTIVE: To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD. METHODS: Patients (n = 286; mean age, 72.5 years) with possible or probable AD from five Northern European countries were randomized to receive either donepezil (n = 142; 5 mg/day for 28 days, followed by 10 mg/day) or placebo (n = 144) for 1 year. RESULTS: The study was completed by 66.9% of the donepezil- and 67.4% of the placebo-treated patients. The benefit of donepezil over placebo was demonstrated by the Gottfries-Bråne-Steen (a global assessment for rating dementia symptoms) total score at weeks 24, 36, and 52 (p < 0.05) and at the study end point (week 52, last observation carried forward; p = 0.054). Advantages of donepezil over placebo were also observed in cognition and activities of daily living (ADL) assessed by the Mini-Mental State Examination at weeks 24, 36, and 52, and the end point (p < 0.02) and by the Progressive Deterioration Scale at week 52 and the end point (p < 0.05). Adverse events (AE) were recorded for 81.7% of donepezil- and 75.7% of placebo-treated patients, with 7% of donepezil- and 6.3% of placebo-treated patients discontinuing because of AE. Treatment response to donepezil was not predicted by APOE genotype or sex in this population. CONCLUSION: As the first 1-year, multinational, double-blinded, placebo-controlled study of a cholinesterase inhibitor in AD, these data support donepezil as a well tolerated and effective long-term treatment for patients with AD, with benefits over placebo on global assessment, cognition, and ADL.

Aged↗
PubMed2001

Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study.

OBJECTIVE: To evaluate the impact of midlife elevated serum cholesterol levels and blood pressure on the subsequent development of mild cognitive impairment (MCI) and to investigate the prevalence of MCI in elderly Finnish population, applying the MCI criteria devised by the Mayo Clinic Alzheimer's Disease Research Center. BACKGROUND: MCI has been considered as a predictor of AD. Vascular risk factors may be important in the development of cognitive impairment and AD. However, the role of vascular risk factors in MCI and the prevalence of MCI still remain virtually unknown. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1,449 subjects aged 65 to 79 years were reexamined in 1998. RESULTS: Eighty-two subjects, 6.1% of the population (average age, 72 years) met the criteria for MCI. Midlife elevated serum cholesterol level (> or =6.5 mmol/L) was a significant risk factor for MCI (OR, 1.9; 95% CI, 1.2 to 3.0, adjusted for age and body mass index); the effect of systolic blood pressure approached significance. CONCLUSION: Data point to a role for midlife vascular risk factors in the development of MCI in late life.

Aged↗
PubMed2001

Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study.

OBJECTIVE: To examine the relation of midlife raised blood pressure and serum cholesterol concentrations to Alzheimer's disease in later life. DESIGN: Prospective, population based study. SETTING: Populations of Kuopio and Joensuu, eastern Finland. PARTICIPANTS: Participants were derived from random, population based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average of 21 years' follow up, a total of 1449 (73%) participants aged 65-79 took part in the re-examination in 1998. MAIN OUTCOME MEASURES: Midlife blood pressure and cholesterol concentrations and development of Alzheimer's disease in later life. RESULTS: People with raised systolic blood pressure (>/=160 mm Hg) or high serum cholesterol concentration (>/=6.5 mmol/l) in midlife had a significantly higher risk of Alzheimer's disease in later life, even after adjustment for age, body mass index, education, vascular events, smoking status, and alcohol consumption, than those with normal systolic blood pressure (odds ratio 2.3, 95% confidence interval 1.0 to 5.5) or serum cholesterol (odds ratio 2.1, 1.0 to 4.4). Participants with both of these risk factors in midlife had a significantly higher risk of developing Alzheimer's disease than those with either of the risk factors alone (odds ratio 3.5, 1.6 to 7.9). Diastolic blood pressure in midlife had no significant effect on the risk of Alzheimer's disease. CONCLUSION: Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increase the risk of Alzheimer's disease in later life.

Adult↗
PubMed2001

APOE-epsilon4 is associated with weight loss in women with AD: a population-based study.

OBJECTIVE: To investigate whether the APOE-epsilon4 allele is associated with weight loss in patients with AD or in nondemented elderly subjects. BACKGROUND: Weight loss has been considered a typical feature of AD. APOE-epsilon4 is a risk factor for AD and was recently proposed to be associated with weight loss in elderly women. It is not known whether APOE-epsilon4 is associated with weight loss in patients with AD or in the general population. METHODS: Weight and BMI measurements at an average interval of 3.5 years and APOE phenotype determination were performed in an elderly population (n = 980), including 46 patients with AD and 911 control subjects at the end of the follow-up. RESULTS: On average, patients with AD with the epsilon4 allele lost 1.9 +/- 4.0 kg (BMI 0.8 +/- 1.8 kg/m2) whereas epsilon4 noncarriers gained 1.2 +/- 3.8 kg (BMI 0.4 +/- 1.5 kg/m2) (both p < 0.05), after controlling for diabetes and exercise. However, when men and women were analyzed separately, weight loss was observed only in those women with AD with the epsilon4 allele. Clinically significant weight loss, defined as loss of > or = 5% of body weight, occurred more frequently in both patients with AD (30% versus 6%; p < 0.05) and control subjects (28% versus 18%; p < 0.001) carrying the epsilon4 allele. CONCLUSIONS: The APOE-epsilon4 allele may contribute to the unexplained weight loss in AD, especially in women.

Aged↗
PubMed2001

The levels of cdk5 and p35 proteins and tau phosphorylation are reduced during neuronal apoptosis.

Cyclin-dependent kinase 5 (cdk5) is believed to be involved in the phosphorylation of tau protein. We studied the expression of the protein levels of cdk5 and the neuron-specific cdk5 activator p35 as well as cdk5 activity and tau phosphorylation during apoptosis in rat hippocampal neuronal cultures. We observed that in cells treated with etoposide, cyclosporin A, 4-hydroxynonenal (HNE), or okadaic acid, there was an early reduction in the protein levels of p35, and later also in cdk5 with all treatments except etoposide. The level of p25, a calpain cleavage product of p35 suggested to have increased ability to activate cdk5, was reduced paralleling the amount of p35. The changes in the p35 and p25 protein levels coincided with decreases in cdk5 activity and tau phosphorylation after treatment with HNE and etoposide. However, the relationship between the p35 and p25 levels and cdk5 activity was complex. We conclude that neuronal apoptosis is accompanied with a decrease in the levels of p35, p25, and cdk5, and tau phosphorylation. These changes may reinforce the neuronal damage.

Aldehydes↗
PubMed2001

Psychopathy and the posterior hippocampus.

Neurobiology of psychopathy is of interest, not only because neural underpinnings of psychopathy remain obscure, but also because psychopaths may provide a model to study violent behavior, neurology of morals and impaired decision-making. Medial temporal lobe pathology has been suggested to be a part of the neural systems dysfunction which manifests as violent and psychopathic behavior. Yet, so far no sound evidence of neuroanatomical correlates for psychopathic behavior has been found. In this study regional hippocampal volumes were measured using magnetic resonance imaging in 18 habitually violent offenders with antisocial personality disorder and type 2 alcoholism (derived from forensic psychiatric evaluation). The regional volumes along the anteroposterior axis of the hippocampus were correlated with the subjects' degree of psychopathy as evaluated by the Psychopathy Checklist-Revised. Strong negative correlations, up to -0.79, were observed, among the study subjects, between the psychopathy scores and the posterior half of the hippocampi bilaterally. These data are in accordance with experimental studies proposing that lesions of the dorsal hippocampus impair acquisition of conditioned fear, and with theories on psychopathology according to which one of the central features in the birth of psychopathy is a deficit in acquisition of conditioned fear.

Adult↗
PubMed2001

Beta-amyloid (1-42) affects MTT reduction in astrocytes: implications for vesicular trafficking and cell functionality.

Beta-amyloid (Abeta) peptide deposition in the brains of Alzheimer's disease patients results in reactive astrogliosis which may enhance neuronal cell death. Abeta has also been reported to impair important supportive astrocyte functions, such as glutamate uptake in vitro. We studied the effect of amyloid beta-peptide (Abeta) on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, cellular ATP content, lactate release, and proliferation using neonatal rat astrocyte cultures. Abeta(1-42) decreased MTT reduction potently in the absence of cell death, but did not affect cellular ATP levels or lactate release. Moreover, the cells displayed increased proliferation after incubation with Abeta(1-42), confirming that the decreased MTT reduction was not deleterious to cell viability. Abeta(1-42) enhanced transfer of MTT dye to the cell surface leading to cessation of MTT reduction and cell death. Bafilomycin A1, but not brefeldin A, prevented the enhanced trafficking of MTT, suggesting that lysosomes, but not Golgi apparatus, are involved. Our results show that the viability of astrocytes themselves is not diminished by beta-amyloid peptide. However, Abeta alters vesicular trafficking in astrocytes, which may disturb the supportive function of astrocytes in the brains of patients with Alzheimer's disease.

Amyloid beta-Peptides↗