| 1. |
- Hooshmand, Babak, et al.
(författare)
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Plasma homocysteine, Alzheimer and cerebrovascular pathology : a population-based autopsy study
- 2013
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 136, s. 2707-2716
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Tidskriftsartikel (refereegranskat)abstract
- Elevated plasma total homocysteine is associated with increased risk of dementia/Alzheimer's disease, but underlying pathophysiological mechanisms are not fully understood. This study investigated possible links between baseline homocysteine, and post-mortem neuropathological and magnetic resonance imaging findings up to 10 years later in the Vantaa 85+ population including people aged epsilon 85 years. Two hundred and sixty-five individuals had homocysteine and autopsy data, of which 103 had post-mortem brain magnetic resonance imaging scans. Methenamine silver staining was used for amyloid-beta and modified Bielschowsky method for neurofibrillary tangles and neuritic plaques. Macroscopic infarcts were identified from cerebral hemispheres, brainstem and cerebellum slices. Standardized methods were used to determine microscopic infarcts, cerebral amyoloid angiopathy, and alpha-synuclein pathology. Magnetic resonance imaging was used for visual ratings of the degree of medial temporal lobe atrophy, and periventricular and deep white matter hyperintensities. Elevated baseline homocysteine was associated with increased neurofibrillary tangles count at the time of death: for the highest homocysteine quartile, odds ratio (95% confidence interval) was 2.60 (1.28-5.28). The association was observed particularly in people with dementia, in the presence of cerebral infarcts, and with longer time between the baseline homocysteine assessment and death. Also, elevated homocysteine tended to relate to amyloid-beta accumulation, but this was seen only with longer baseline-death interval: odds ratio (95% confidence interval) was 2.52 (0.88-7.19) for the highest homocysteine quartile. On post-mortem magnetic resonance imaging, for the highest homocysteine quartile odds ratio (95% confidence interval) was 3.78 (1.12-12.79) for more severe medial temporal atrophy and 4.69 (1.14-19.33) for more severe periventricular white matter hyperintensities. All associations were independent of several potential confounders, including common vascular risk factors. No relationships between homocysteine and cerebral macro- or microinfarcts, cerebral amyoloid angiopathy or alpha-synuclein pathology were detected. These results suggest that elevated homocysteine in adults aged epsilon 85 years may contribute to increased Alzheimer-type pathology, particularly neurofibrillary tangles burden. This effect seems to be more pronounced in the presence of cerebrovascular pathology. Randomized controlled trials are needed to determine the impact of homocysteine-lowering treatments on dementia-related pathology.
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| 2. |
- Peuralinna, Terhi, et al.
(författare)
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Neurofibrillary tau pathology modulated by genetic variation of alpha-synuclein
- 2008
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 64:3, s. 348-352
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed whether genetic variation of alpha-synuclein modulates the extent of neuropathological changes in a population-based autopsied sample of 272 elderly Finns. None of the 11 markers was associated with the extent of neocortical beta-amyloid pathology. The intron 4 marker rs2572324 was associated with the extent of neurofibrillary pathology (p = 0.0006, permuted p = 0.004; Braak stages IV-VI vs 0-II). The same variant also showed a trend for association with neocortical Lewy-related pathology. These results suggest for the first time that variation of alpha-synuclein modulates neurofibrillary tau pathology and support the recent observations of an interaction of alpha-synuclein and tau in neurodegeneration.
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| 3. |
- Ylikoski, Ari, et al.
(författare)
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White matter hyperintensities on MRI in the neurologically non-diseased elderly : Analysis of cohorts of consecutive subjects aged 55 to 85 years living at home
- 1995
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 26:7, s. 1171-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: We undertook this study to evaluate the frequency and risk factors of white matter hyperintensities seen on T2-weighted MR imaging. We examined cohorts of neurologically nondiseased elderly subjects participating in a general-community study, the Helsinki (Finland) Aging Brain Study. Cohorts of consecutive subjects aged 55, 60, 65, 70, 75, 80, and 85 years (n = 20, 18, 20, 18, 19, 18, and 15, respectively; total, n = 128) were divided into a young-old (age < 75 years, n = 76) group and an old-old (age > or = 75 years, n = 52) group. METHODS: Frequency of hyperintensities seen on T2-weighted axial and coronal MR images (0.02 T) was rated using a four-point scale in periventricular and centrum semiovale areas. RESULTS: The majority of the subjects showed only mild white matter hyperintensities, which were more frequent in the periventricular areas. Age was the most important factor to explain the presence of hyperintensities. A logistic regression analysis related periventricular hyperintensities in the entire group to central atrophy (odds ratio [OR], 4.7; 95% confidence interval [CI], 1.7 to 12.9) and silent infarcts (OR, 5.6; 95% CI, 1.0 to 19.8); among the young-old, hyperintensities related to diabetes (OR, 17.0; 95% CI, 1.9 to 154.2) and central atrophy (OR, 14.7; 95% CI, 3.5 to 61.8). Centrum semiovale hyperintensities related in the entire group to cardiac arrhythmia (OR, 4.0; 95% CI, 1.0 to 15.5), central atrophy (OR, 3.9; 95% CI, 1.2 to 12.4), and silent infarcts (OR, 3.6; 95% CI, 1.0 to 12.5). CONCLUSIONS: These mild white matter hyperintensities in the neurologically nondiseased elderly related especially to age and also to concomitant silent infarcts, atrophy, and some vascular risk factors. The known factors, however, explained only part of the variation. The young-old and old-old groups showed different associations. In contrast to former assumptions, the presence of white matter hyperintensities among the aged is likely to be linked to other as yet unidentified age-related factors.
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| 4. |
- Ylikoski, Raija, et al.
(författare)
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Cardiovascular diseases, health status, brain imaging findings and neuropsychological functioning in neurologically healthy elderly individuals
- 2000
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Ingår i: Archives of gerontology and geriatrics (Print). - 0167-4943 .- 1872-6976. ; 30:2, s. 115-130
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Tidskriftsartikel (refereegranskat)abstract
- The aim of our study was to evaluate the relationship between health-related factors, brain imaging findings and cognitive functioning. We examined 113 neurologically healthy subjects from 55 to 85 years of age. Health-related variables included a clinical health evaluation, cardiovascular diseases, and other systemic diseases. The presence of white matter changes and cerebral and peripheral atrophy were obtained with magnetic resonance imaging. Neuropsychological tests measuring verbal memory, visual memory, intellectual and language functions, visuoconstructional functions, flexibility, and speed and attention were administered. Results showed that overall health status was not related to cognition. Subjects, who had both arterial hypertension and white matter changes had difficulties in flexibility. Cardiac failure and white matter changes were related to impairment in visuoconstructional functions, flexibility and attention. Significant speed and attention deficits were observed in subjects with cardiac failure and central atrophy. In conclusion, this study verifies the relationship between hypertension, white matter changes and cognitive functions. We found also specific patterns in relation with cardiac failure, brain imaging findings and cognitive functioning, the most vulnerable domains were visuoconstructional functions, flexibility and attention.
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| 5. |
- Ylikoski, Raija, et al.
(författare)
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Differences in neuropsychological functioning associated with age, education, neurological status and magnetic resonance imaging findings in neurologically healthy elderly individuals
- 1998
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Ingår i: Applied neuropsychology. - : Informa UK Limited. - 0908-4282 .- 1532-4826. ; 5:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- In a cross-sectional study, a sample of 113 individuals, 55 to 85 years old, without any neurological diseases was investigated. The study provides information on differences associated with age, education, and gender, and in relation to neurological status, magnetic resonance imaging, and cognitive functioning. Differences between age groups were shown in memory, constructional, and language functions, and especially in tests related to speed and attention. Education was related to most of the cognitive functions, but especially to verbal intellectual functions, visual and logical memory, language functions, and calculation. Gender differences were found in finger tapping, constructional functions, and verbal intellectual functions. Primitive reflexes showed a tendency to correlate with comprehension and memory of sentences. Extrapyramidal signs were related to psychomotor speed, and attention, verbal fluency, and set shifting together with intellectual functions and learning. Central atrophy on magnetic resonance imaging was related to memory functions in those 65 and 70 years of age, whereas in the oldest age groups immediate recall was associated with the severity of lesions.
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