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Matti Viitanen

Publications and source records attributed to Matti Viitanen.

At least 19 recordsLinked to original sources
PubMed2006

Arterioles of the lenticular nucleus in CADASIL.

BACKGROUND AND PURPOSE: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) the arteriopathy leads to recurrent infarcts in cerebral white matter (WM) and deep gray matter (GM), whereas cortex is spared. To assess the pathogenesis of deep GM infarcts, we analyzed structural changes in arterioles of the lenticular nucleus (LN) in 6 CADASIL patients. METHODS: Five elderly and one 32-year-old deceased CADASIL patients were studied. Seven elderly and 4 young deceased persons without cerebrovascular diseases served as controls. In addition to immunohistochemical analysis the external and luminal diameters of arterioles in the LN, cerebral cortex and WM were measured. The thickness of arteriolar wall and sclerotic index were calculated. RESULTS: In CADASIL patients, LN arterioles were immunoreactive for the extracellular domain of Notch3 and collagen I, whereas alpha-smooth muscle actin staining was irregular or negative. No major leakage of plasma fibrinogen or fibronectin was observed. Although in patients the walls of LN arterioles were significantly thicker than in controls, definite stenosis was not observed. Arteriolar lumina in the LN were not only significantly larger than in the WM, where most lacunar infarcts in CADASIL occur, but also larger than in cortical GM, where infarcts virtually never exist. CONCLUSIONS: Fibrotic thickening of the arteriolar walls without consequent stenosis occurs in the LN of CADASIL patients. The pathogenesis of lacunar infarcts in the WM and LN seem to be different, stenosis in the former and probably hemodynamic disturbances in the latter.

Adult↗
PubMed2006

Mitochondrial DNA sequence variation and mutation rate in patients with CADASIL.

Mutations in the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is clinically characterised by recurrent ischemic strokes, migraine with aura, psychiatric symptoms, cognitive decline and dementia. We have previously described a patient with CADASIL caused by a R133C mutation in the NOTCH3 gene and with a concomitant myopathy caused by a 5650G>A mutation in the MTTA gene in mitochondrial DNA (mtDNA). We assume that the co-occurrence of the two mutations is not coincidental and that mutations in the NOTCH3 gene may predispose the mtDNA to mutations. We therefore examined the nucleotide variation in the mtDNA coding region sequences in 20 CADASIL pedigrees with 77 affected patients by conformation-sensitive gel electrophoresis and sequencing. The sequence variation in mtDNA was then compared with that among 192 healthy Finns. A total of 180 mtDNA coding region sequence differences were found relative to the revised Cambridge reference sequence, including five novel synonymous substitutions, two novel nonsynonymous substitutions and one novel tRNA substitution. We found that maternal relatives in two pedigrees differed from each other in their mtDNA. Furthermore, the average number of pairwise differences in sequences from the 41 unrelated maternal lineages with CADASIL was higher than that expected among haplogroup-matched controls. The numbers of polymorphic sites and polymorphisms that were present in only one sequence were also higher among the CADASIL sequences than among the control sequences. Our results show that mtDNA sequence variation is increased within CADASIL pedigrees. These findings suggest a relationship between NOTCH3 and mtDNA.

Adult↗
PubMed2006

Ophthalmologic findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a cross-sectional study.

OBJECTIVE: To determine the ophthalmologic findings, especially the nature of retinal vascular changes, and their clinical significance in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a disease that causes migraine, recurrent strokes, and finally subcortical vascular dementia. DESIGN: Cross-sectional study. PARTICIPANTS: Thirty-eight CADASIL patients (19 to 61 years old; 20 in a prestroke group, 15 in a stroke group, and 3 in a dementia group), all with the R133C NOTCH3 mutation and including one homozygous patient, underwent a detailed ophthalmologic examination. METHODS: Common cardiovascular risk factors were evaluated. Ophthalmologic examination included best-corrected visual acuity, anterior- and posterior-segment biomicroscopy, and measurement of intraocular pressure. In 33 patients and 16 healthy controls (20-64 years old), retinal fundus photographs were taken. Diameters of all arterioles and venules located in the area from 0.5 to 1.0 disc diameters from the optic disc margin were measured with a computer-based program and arteriole-to-venule (A/V) ratios were calculated from digitized photographs. RESULTS: General arterial narrowing and arteriovenous nickings were common. Straightening of the retinal arterioles and a marked wall reflex (n = 6) occurred. The A/V ratio of CADASIL patients was significantly (P< 0.001) lower than that of controls. One patient had one retinal microinfarct and hemorrhages. The homozygous patient had a chorioretinal scar as a sign of circulatory deficiency. Anterior-segment changes included mild iris atrophy (n = 5) and various degrees of lens opacities. Visual acuity was normal in all but 2 patients, who had cataract and amblyopia. CONCLUSIONS: The generalized arteriopathy of CADASIL causes a wide variety of changes in retinal arterioles but only minimal functional disturbances. These findings are consistent with alterations in arterioles in the cerebral cortex with which the retina and its arterioles are analogous, but contrast with the severe damage of cerebral white matter arterioles.

Adult↗
PubMed2006

Periodontal disease in the oldest-old living in Kungsholmen, Sweden: findings from the KEOHS project.

AIMS: The Kungsholmen Elders Oral Health Study evaluated the oral health status of generally healthy, community-dwelling persons aged 80 years and over living in Stockholm, Sweden. This paper reports periodontal disease findings and evaluates the distribution by sociodemographic factors. METHODS: Eligible persons were identified through the Kungsholmen Project, an ongoing, longitudinal, population-based study of older adults. A total of 121 study subjects received a periodontal examination. RESULTS: The mean pocket probing depth was 2.6 mm and the mean clinical attachment loss was 3.7 mm. Gingival bleeding was common. Over half of all study participants met the criteria used for "serious periodontitis" (SP). In the best fit adjusted odds ratio (OR) model, males were 3.1 times more likely than females to have "SP" (OR=3.1, 95% CI 1.2, 8.0), a statistically significant observation. A sub-analysis of the differences in proportion of participants with SP revealed that the difference by sex also increased by age. CONCLUSIONS: These findings document the substantial and ongoing impact of periodontal disease in a sample of generally healthy, community dwelling older adults and underscore the importance of continued periodontal disease prevention and treatment in the oldest-old.

Age Factors↗
PubMed2006

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Journal Article↗
PubMed2006

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Journal Article↗
PubMed2006

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Journal Article↗
PubMed2005

What causes increased stroke mortality in patients with prestroke dementia?

BACKGROUND AND PURPOSE: In patients with dementia, the incidence of stroke is higher and strokes are more severe and lethal. The purpose of this population-based study was to describe in what way previous dementia affects mortality in stroke patients. METHODS: Subjects were all persons > or =65 years old who had a first-ever stroke during 1 year (n = 327). The prestroke dementia (PSD) diagnosis was made at the time of the stroke diagnosis using data from next of kin and from patient records. Patients were followed prospectively and causes of death were evaluated. RESULTS: The 28-day case fatality was 44% for PSD patients and 15% for non-PSD patients. Corresponding ratios at 1 year were 71 and 36%, respectively. Twenty-eight percent of the PSD patients had a new stroke during the first year, compared to 8% of the non-PSD patients. More patients in the PSD group died as a direct or indirect consequence of their stroke. Multivariate analysis showed that PSD, in addition to age, atrial fibrillation and stroke severity, was an independent predictor of mortality. CONCLUSIONS: The PSD patients more often had a stroke-related death, even when we adjusted for a number of other factors. The cause for this is most likely multifactorial, including an increased tendency to contract complications in the acute phase, and iatrogenic causes. The brain of the PSD patients may also be frailer and more susceptible to ischemic or hemorrhagic damage than the nondemented brain.

Aged↗
PubMed2005

Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease.

BACKGROUND: Vascular risk factors play a role in the development of dementia, including Alzheimer disease (AD). However, little is known about the effect of body mass index and clustering of vascular risk factors on the development of dementia. OBJECTIVE: To investigate the relation between midlife body mass index and clustering of vascular risk factors and subsequent dementia and AD. DESIGN AND SETTING: Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1449 individuals (73%) aged 65 to 79 years participated in the reexamination in 1998. MAIN OUTCOME MEASURES: Dementia and AD. RESULTS: Obesity at midlife (body mass index>30 kg/m2) was associated with the risk of dementia and AD even after adjusting for sociodemographic variables (odds ratio [OR], 2.4 [95% confidence interval (CI), 1.2-5.1]). The association was somewhat modified by further adjusting for midlife blood pressure, total cholesterol level, and smoking (OR, 2.1 [95% CI, 1.0-4.6]) and also for apolipoprotein E genotype and history of vascular disorders (OR, 1.9 [95% CI, 0.8-4.6]). Midlife obesity, high total cholesterol level, and high systolic blood pressure were all significant risk factors for dementia with ORs of around 2 for each factor, and they increased the risk additively (OR, 6.2 for the combination). CONCLUSIONS: Obesity at midlife is associated with an increased risk of dementia and AD later in life. Clustering of vascular risk factors increases the risk in an additive manner. The role of weight reduction for the prevention of dementia needs to be further investigated.

Age Factors↗
PubMed2005

Mice carrying a R142C Notch 3 knock-in mutation do not develop a CADASIL-like phenotype.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, MIM 125310) is a genetic vascular dementia disease that is linked to missense mutations, small in-frame deletions, and splice site mutations in the human Notch 3 gene. Here we describe the generation of a mouse knockin model for one of the most prevalent CADASIL mutations, an arginine to cysteine transition at position 141, R141C, which corresponds to mutation R142C in mouse NOTCH 3. CADASIL(R142C) mice show no apparent CADASIL-like phenotype after histological and MRI analysis. The NOTCH 3 (R142C) receptor is processed normally and does not appear to accumulate the ectodomain, which has been observed in CADASIL patients. We discuss possible reasons for the different outcomes of the same germline CADASIL mutation in mice and humans.

Amino Acid Substitution↗
PubMed2005

Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease.

BACKGROUND: Physical activity may help maintain cognitive function and decrease dementia risk, but epidemiological findings remain controversial. The aim of our study was to investigate the association between leisure-time physical activity at midlife and the subsequent development of dementia and Alzheimer's disease (AD). METHODS: Participants were randomly selected from the survivors of a population-based cohort previously surveyed in 1972, 1977, 1982, or 1987. 1449 persons (72.5%) age 65-79 years participated in the re-examination in 1998 (mean follow-up, 21 years). 117 persons had dementia and 76 had AD. Multiple logistic regression methods were used to analyse the association between leisure-time physical activity and dementia or AD. FINDINGS: Leisure-time physical activity at midlife at least twice a week was associated with a reduced risk of dementia and AD (odds ratio [OR] 0.48 [95% CI 0.25-0.91] and 0.38 [0.17-0.85], respectively), even after adjustments for age, sex, education, follow-up time, locomotor disorders, APOE genotype, vascular disorders, smoking, and alcohol drinking. The associations were more pronounced among the APOE epsilon4 carriers. INTERPRETATION: Leisure-time physical activity at midlife is associated with a decreased risk of dementia and AD later in life. Regular physical activity may reduce the risk or delay the onset of dementia and AD, especially among genetically susceptible individuals.

Aged↗
PubMed2005

Dental caries, periodontal disease, and cardiac arrhythmias in community-dwelling older persons aged 80 and older: is there a link?

OBJECTIVES: To examine whether caries or periodontitis is associated with cardiac arrhythmias in community-dwelling people aged 80 and older. SETTING: Urban, community-based population in Stockholm, Sweden. DESIGN: Cross-sectional. PARTICIPANTS: Eligible persons were identified through the Kungsholmen Project, which is an ongoing, longitudinal, population-based study of the oldest old. The present study included 125 dentate individuals. MEASUREMENTS: Data from interviews, a medical examination, and an oral examination. The assessment of cardiac arrhythmia was based on a clinical examination by a physician or the Stockholm Inpatient Register. Active root caries, active coronal caries, and periodontitis were assessed using previously defined National Institute of Dental and Craniofacial Research diagnostic criteria. RESULTS: The primary finding of the multivariate logistic regression analysis was that persons with three or more active root caries lesions had more than twice the odds of cardiac arrhythmias than persons without active root caries. The results did not notably change after adjusting for age, medications that reduce saliva, and number of teeth. Persons with one to two active coronal caries lesions had 2.8 times higher odds (95% confidence interval=1.1-7.0) of arrhythmia than persons without active coronal caries, but there was no greater risk for persons with three or more coronal caries lesions. There was no association between periodontal disease and arrhythmia. CONCLUSION: The findings indicate that there may be a link between active root caries and cardiac arrhythmias in the oldest old. Nevertheless, although a biological pathway is not obvious, it is plausible that both are simply markers of declining general health. The results suggest the need for further study of these relationships.

Aged↗
PubMed2005

The strength of two indicators of social position on oral health among persons over the age of 80 years.

OBJECTIVE: The objective of the present study is to analyze how two dimensions of social position, education and social class, are associated with oral health among generally healthy, community-dwelling persons over the age of 80 years. METHODS: The present investigation is based on a sample of 157 community-dwelling individuals from The Kungsholmen Elders Oral Health Study (KEOHS) and included data from interviews and oral examinations. Social position was measured by education and social class. Oral health was measured by active coronal caries, active root caries, edentulism and use of dental services. RESULTS: The primary findings of the adjusted multivariate logistic regression analysis were that, compared to persons who had been in higher positions, persons who had been blue-collar/ white-collar workers had significantly greater odds of having coronal caries and high, but nonsignificant odds of being edentulous. Further, persons with elementary/ medium education tended to forego regular dental services more than persons with high education. CONCLUSION: The study identified social inequalities in oral health even in a population of independently living, generally healthy very old Swedes and in a country where the public health policies have tried to minimize these inequalities.

Age Factors↗
PubMed2004

Scanning laser Doppler flowmetry shows reduced retinal capillary blood flow in CADASIL.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a progressive systemic nonatherosclerotic angiopathy which causes ischemic strokes and vascular subcortical dementia. A cross-sectional study was performed to examine the retinal vascular caliber and blood flow in CADASIL. METHODS: Scanning laser Doppler flowmetry was used in a case-control study (11 patients and controls) of peripapillary retinal circulation. Automated full-field perfusion image analysis was used to analyze the flow data. Retinal vessel calibers were measured from retinal images acquired with scanning laser ophthalmoscopy. The caliber of the superior and inferior temporal retinal artery and vein were measured 1 and 2 mm from the disc rim, and the mean values were used for analysis. RESULTS: Retinal capillary peak systolic flow (mean, 249 versus 311 arbitrary unit [AU]; P=0.072) was lower, and mean capillary flow (mean, 184 versus 224 AU; P=0.12) and minimum diastolic flow (mean, 105 versus 132 AU; P=0.16) tended to be lower in patients than in controls. No significant difference in the calibers of proximal retinal arteries (mean, 104 versus 108 microm) and veins (mean, 150 versus 145 microm) was found between the patients and controls. CONCLUSIONS: Retinal capillary blood flow is mild to moderately reduced in CADASIL but that does not appear to cause major ischemic injury. Such reduction is analogous to that in the cerebral cortex in CADASIL patients with which retina appears to share its relative sparing from severe arterial ischemic tissue damage.

Adult↗
PubMed2004

Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: a prospective population based study.

OBJECTIVE: To evaluate the relation between midlife alcohol consumption and mild cognitive impairment and dementia in old age, and the possible modification of this relation by apolipoprotein E. DESIGN: Prospective, population based study. SETTING: Populations of Kuopio and Joensuu, eastern Finland. PARTICIPANTS: Of 1464 men and women aged 65-79 years randomly selected from population based samples studied in 1972 or 1977, 1018 (70%) were re-examined in 1998 (after an average follow up of 23 years). MAIN OUTCOME MEASURES: Mild cognitive impairment and dementia in old age. RESULTS: Participants who drank no alcohol at midlife and those who drank alcohol frequently were both twice as likely to have mild cognitive impairment in old age as those participants who drank alcohol infrequently. The risk of dementia related to alcohol drinking was modified by the presence of the apolipoprotein e4 allele. The carriers of apolipoprotein e4 had an increased risk of dementia with increasing alcohol consumption: compared with non-carriers who never drank, the odds ratio for carriers who never drank was 0.6, for infrequent drinkers it was 2.3, and for frequent drinkers was 3.6 (the overall interaction term "drinking frequency(*)apolipoprotein e4" was significant (P = 0.04), as were the interactions "infrequent drinking(*)apolipoprotein e4" (P = 0.02) and "frequent drinking(*)apolipoprotein e4" (P = 0.03)). Non-carriers of apolipoprotein e4 had similar odds ratios for dementia irrespective of alcohol consumption. CONCLUSION: Alcohol drinking in middle age showed a U shaped relation with risk of mild cognitive impairment in old age. Risk of dementia increased with increasing alcohol consumption only in those individuals carrying the apolipoprotein e4 allele.

Aged↗
PubMed2004

Insidious cognitive decline in CADASIL.

BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) causes repeated ischemic attacks leading to subcortical vascular dementia. The aim of this study was to characterize cognitive function in subjects with a C475T (R133C) mutation in the Notch3 gene, leading to CADASIL. METHODS: Prestroke (n=13) and poststroke (n=13) mutation carriers and mutation carriers with dementia (n=8) were compared with healthy noncarriers from the same families using a comprehensive set of neuropsychological tests. RESULTS: Changes in working memory and executive function were observed in the very early phase of the disease before transient ischemic attack (TIA) or stroke. Later, in the poststroke phase, the cognitive impairment concerned also mental speed and visuospatial ability. Finally, the subjects with dementia had multiple cognitive deficits, which engaged even verbal functions, verbal episodic memory, and motor speed. The 2 mutation carrier groups without dementia and the controls could be reliably distinguished using 3 tests that assessed working memory/attention, executive function, and mental speed. Episodic memory was relatively well-preserved late in the disease. CONCLUSIONS: A deterioration of working memory and executive function was already observed in the prestroke phase, which means that cognitive decline may start insidiously before the first onset of symptomatic ischemic episodes.

Adult↗
PubMed2004

Neuropsychological functions in variant Alzheimer's disease with spastic paraparesis.

Few data exist on the effects of specific Alzheimer's disease (AD)-related mutations on cognitive function. We present neuropsychological test results in eight members of a large kindred with variant Alzheimer's disease (VarAD) due to a deletion of the presenilin 1 (PS-1) gene, encompassing exon 9. The disease was neuropathologically characterized by the presence of large, unusual, "cotton wool" plaques (CWP). Four surviving patients were prospectively tested, and retrospective neuropsychological data were collected from additional four deceased patients. The neuropsychological evaluation was based on tests of verbal and visual memory, abstract thinking, and visuoconstructive and spatial functions. In addition, psychiatric symptoms were evaluated. In four patients, brain glucose metabolism was examined by positron emission tomography (PET). PET showed temporoparietal hypometabolism typical of AD. In addition, variable patterns of hypometabolism (hemispherical asymmetry and occipital accentuation) were related to individual deficits of cognitive performance. However, all these early-onset patients (age range 43-63 years) with a deletion mutation of PS-1 gene showed prominent memory impairment and deficits in visuoconstructive and intellectual functions.

Alzheimer Disease↗