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0760 Frontal lobe dysfunction associated with glucose hypometabolism in aceruloplasminemia
$294
Poster Abstracts
Wednesday, November 9, 2005
Background: Observational studies suggest that high plasma homo-
cysteine concentrations are inversely related to cognitive function in older people. The objective was to test the hypothesis that lowering plasma homocysteine concentration affects cogtfffive function in older people. Method: Two year randomised controlled trial of 276 healthy participants, 65 y or older, with plasma homocysteine concentrations greater than 13 Imaol/L. Homo cysteine-lowering treatment was a daily supplement containing folate (1 rag, L-Mefolinic acid), vitarnins B12 (1500 pg) and B6 (50 mg). Tests of cogtfftion were conducted at baseline, one, and two years of treatment. Treatment effects were adjusted for age, sex, and education. Results: Plasma homocysteine concentration was decreased in the vitamin supplement group by 38% (P - 0.000) relative to the placebo group. Cogtfffive function as assessed by scores on the Weschler Paragraphs, the Rey Auditory Verbal Learning Test and Reitan Trail Making Test Part B were significantly lower in the treated than placebo group at two years. Performance on the Trail Making test scores was 8% (2-14%; p < 0.001) poorer in the group with lowered homocysteine concentrations. Conclusion: Our results suggest a deleterious effect of high dose vitamin supplements and homocysteine lowering on cognitive function in health older people. These results need to be confirmed in other randomised controlled trials. 0760
Frontal Lobe Dysfunction Associated With Glucose Hypometabolism In Aceruloplasminemia Miyajima, H l, Takahashi, Y~, Kono, S ~, Suzuki, H l, Shirakawa, K 1, Hishida, A ~. 1Harnamatsu University School of Medicine,
Hamamatsu, Japan Background: Aceruloplasminemia is slowly progressive neurodegenera-
University Sehool of Ivledieine, Yonago, Tottori, Japan; 3Brain Research Institute, Niigata University, Niigata, Japan; 4Geriatrics Research Institute and Hospital, Maebashi, Gunma, Japan; Slnstitute for [Vfolecular and Cellular Regulation, Gunma University, ]~faebashi, Japan Background: Nestin, a type 6 intermediate filament protein, was
originally detected in the neuroectoderm during early development of the central nervous system. We have reported the findings of two cases o f Creutzfeldt-Jakob disease (CJD) that Purkinje cells in the cerebellum are inmmnoreactive for nestin. However, the detailed examination of nestin expression has not been performed. Therefore, we examined another CJD cerebellums to observe the nestin immunoreactivity of Purkinje cells in addition to those of non-C.JD cases. Method: The samples from patients with 19 C.JD cases and those with 30 non-CJD cases consisting of seven amyotrophic lateral sclerosis, five multiple system atrophy, three Alzheimer's disease, one myasthenia gravis, one Huntington's disease, one Krabbe's disease, and twelve other diseases were examined, using the anti-nestin antibody. Results: Purkinje cells were immunohistochernically positive for nestin in almost all C.JD cases. The intensity of nestin remained strong until these cells became dark and shrunken on H-E staining. Interestingly, there were several different types of nestin inmmnoreactivity in Purkinje cells in CJD cases, indicated by fine granule-like, dot-like, and inclusion-like inmmnostairdngs witlffn the cells as well as dot-like staining outside of the cells. Furthermore, six of 30 non-C.JD cases showed nestin immunoreactivity to a lesser extent. Conclusion: Although the mechanism o f nestin immunoreactivity is not yet understood, nestin-positive Purkinje cells are more common in CJD cerebellmn. We speculate that such nestin-positive Purkinje cells would be reactivated to survive the cell death. 0762 Do stafines intluence tile progression of dementia?
tion that mainly affects the subcortical and cerebellar territories in association with iron accumulation. Neurological symptoms, including atm,~ia, involuntary movement, and parkinsonism, usually appear after the fourth decade. Various cognitive intpaimtents appear from the early stage of tiffs disease. Methods: We clinically characterized two Japanese patients with cognitive dysfunction who had different truncation mutations in their ceruloplasrnin genes. Regional analysis of their cerebral glucose metabolisms was made by positron emission tomography (PET). Results: A 59-year-old man suffered bradykinesia and gait ataxia for two years. His Mird Mental State Examination (MMSE) score was 23. In the Nelson modification of the Wisconsin card sorting test, he achieved two sorting categories only. Twenty per cent of errors were perseverative. A 56-year-old man had had blepharospasm, scanning speech and forgetfulness from age 54. The MMSE score was 19. On the card sorting test he could complete only one sorting category, and 80% of errors were perseverative. The patients presented with personality change and showed inertia, lack of concern, forgetfulness, and economic speech without aphasia. PET studies showed selective reduction in uptake in the anterior cerebral hemisphere as well as the basal ganglia. Conclusion: Mental features of the patients may be attributable to frontal lobe dysfunction. Loss of several subcortical afferents from the basal ganglia to the frontal cortex may be partially responsible for this frontal cortical hypometabolism. Metabolic alteration in the frontal lobe may appear early in the course of the disease.
Moiler, W ~, Gotz, D ~, Voss, A 1, Kropp, P~. 1HG-Creutzfeldt Institute;
0761 Different types of nes~tin immunoreac~vity of Purkinje cells in Crentzfeldt-Jakob disease
Molle~, W 1, Kropp, p2, Gotz, D 1. ~HG-Creutzfeldt Institute;
Mizuno, y1, Ohama, E 2, Hirato, J~, Nakazato, Y~, Takahaslff, H 3, Takatama, M 4, Takeuchi, T s, Okamoto, K 1. ~Gunrna University
vascular dementia (VD) often report problems in attention. Methods: In a screening, 1428 patients were identified with minimal cognitive dysfunction, especially in attention. Attentional functions of
Graduate School of Medicine, Maebashi, Gunma, Japan; :Tottori
~Institute of Medical Psychology, University of Kiel, Germany Introduction: Long-term treatment with statines lower lffgh choles-
terolemia especially in elderly patients. There are few reports that mild hypercholesterolemia seems to be a risk factor for the development of Alzheimer amyolid pathology (Pappolla et al., Neurology 2003, Menge et al., 2005). What's about the incidence of dementia (vascular dementia, VD or dementia of Alzheimer's type, DAT) in persons with a long history of statine treatment o f high cho lesterolemia? Methods: 268 patients (1148 female, median age 58 years, and 120 male, median age 59 years) were examined neuropsychologically to exclude VD or DAT. Severity of dementia was scored by Mini-Mental State Examination (Folstein, 1990) and classified into "no dementia", "mild", "moderate" and "severe". All patients received long-term treatment with statines for a mean of 28 months. Results: Two of 268 patients had mild DAT (0,75%), two patients had mild VD (0,75%). Discussion: The inddence o f DAT or VD in the observed group with long-term treatment with statines is lower than in the general population (about 2%). We propose that treatment with statines to lower tfigh cholesterolenffa may protect for VD or DAT. This should be confirmed by controlled studies. 0763 Problems of attention - indicators of an incoming dementia?
~Institute of Medical Psychology, University of Kiel, Germany Introduction: Patients with dementia of Alzheimer's type (DAT) or
Poster Abstracts
Wednesday, November 9, 2005
Background: Observational studies suggest that high plasma homo-
cysteine concentrations are inversely related to cognitive function in older people. The objective was to test the hypothesis that lowering plasma homocysteine concentration affects cogtfffive function in older people. Method: Two year randomised controlled trial of 276 healthy participants, 65 y or older, with plasma homocysteine concentrations greater than 13 Imaol/L. Homo cysteine-lowering treatment was a daily supplement containing folate (1 rag, L-Mefolinic acid), vitarnins B12 (1500 pg) and B6 (50 mg). Tests of cogtfftion were conducted at baseline, one, and two years of treatment. Treatment effects were adjusted for age, sex, and education. Results: Plasma homocysteine concentration was decreased in the vitamin supplement group by 38% (P - 0.000) relative to the placebo group. Cogtfffive function as assessed by scores on the Weschler Paragraphs, the Rey Auditory Verbal Learning Test and Reitan Trail Making Test Part B were significantly lower in the treated than placebo group at two years. Performance on the Trail Making test scores was 8% (2-14%; p < 0.001) poorer in the group with lowered homocysteine concentrations. Conclusion: Our results suggest a deleterious effect of high dose vitamin supplements and homocysteine lowering on cognitive function in health older people. These results need to be confirmed in other randomised controlled trials. 0760
Frontal Lobe Dysfunction Associated With Glucose Hypometabolism In Aceruloplasminemia Miyajima, H l, Takahashi, Y~, Kono, S ~, Suzuki, H l, Shirakawa, K 1, Hishida, A ~. 1Harnamatsu University School of Medicine,
Hamamatsu, Japan Background: Aceruloplasminemia is slowly progressive neurodegenera-
University Sehool of Ivledieine, Yonago, Tottori, Japan; 3Brain Research Institute, Niigata University, Niigata, Japan; 4Geriatrics Research Institute and Hospital, Maebashi, Gunma, Japan; Slnstitute for [Vfolecular and Cellular Regulation, Gunma University, ]~faebashi, Japan Background: Nestin, a type 6 intermediate filament protein, was
originally detected in the neuroectoderm during early development of the central nervous system. We have reported the findings of two cases o f Creutzfeldt-Jakob disease (CJD) that Purkinje cells in the cerebellum are inmmnoreactive for nestin. However, the detailed examination of nestin expression has not been performed. Therefore, we examined another CJD cerebellums to observe the nestin immunoreactivity of Purkinje cells in addition to those of non-C.JD cases. Method: The samples from patients with 19 C.JD cases and those with 30 non-CJD cases consisting of seven amyotrophic lateral sclerosis, five multiple system atrophy, three Alzheimer's disease, one myasthenia gravis, one Huntington's disease, one Krabbe's disease, and twelve other diseases were examined, using the anti-nestin antibody. Results: Purkinje cells were immunohistochernically positive for nestin in almost all C.JD cases. The intensity of nestin remained strong until these cells became dark and shrunken on H-E staining. Interestingly, there were several different types of nestin inmmnoreactivity in Purkinje cells in CJD cases, indicated by fine granule-like, dot-like, and inclusion-like inmmnostairdngs witlffn the cells as well as dot-like staining outside of the cells. Furthermore, six of 30 non-C.JD cases showed nestin immunoreactivity to a lesser extent. Conclusion: Although the mechanism o f nestin immunoreactivity is not yet understood, nestin-positive Purkinje cells are more common in CJD cerebellmn. We speculate that such nestin-positive Purkinje cells would be reactivated to survive the cell death. 0762 Do stafines intluence tile progression of dementia?
tion that mainly affects the subcortical and cerebellar territories in association with iron accumulation. Neurological symptoms, including atm,~ia, involuntary movement, and parkinsonism, usually appear after the fourth decade. Various cognitive intpaimtents appear from the early stage of tiffs disease. Methods: We clinically characterized two Japanese patients with cognitive dysfunction who had different truncation mutations in their ceruloplasrnin genes. Regional analysis of their cerebral glucose metabolisms was made by positron emission tomography (PET). Results: A 59-year-old man suffered bradykinesia and gait ataxia for two years. His Mird Mental State Examination (MMSE) score was 23. In the Nelson modification of the Wisconsin card sorting test, he achieved two sorting categories only. Twenty per cent of errors were perseverative. A 56-year-old man had had blepharospasm, scanning speech and forgetfulness from age 54. The MMSE score was 19. On the card sorting test he could complete only one sorting category, and 80% of errors were perseverative. The patients presented with personality change and showed inertia, lack of concern, forgetfulness, and economic speech without aphasia. PET studies showed selective reduction in uptake in the anterior cerebral hemisphere as well as the basal ganglia. Conclusion: Mental features of the patients may be attributable to frontal lobe dysfunction. Loss of several subcortical afferents from the basal ganglia to the frontal cortex may be partially responsible for this frontal cortical hypometabolism. Metabolic alteration in the frontal lobe may appear early in the course of the disease.
Moiler, W ~, Gotz, D ~, Voss, A 1, Kropp, P~. 1HG-Creutzfeldt Institute;
0761 Different types of nes~tin immunoreac~vity of Purkinje cells in Crentzfeldt-Jakob disease
Molle~, W 1, Kropp, p2, Gotz, D 1. ~HG-Creutzfeldt Institute;
Mizuno, y1, Ohama, E 2, Hirato, J~, Nakazato, Y~, Takahaslff, H 3, Takatama, M 4, Takeuchi, T s, Okamoto, K 1. ~Gunrna University
vascular dementia (VD) often report problems in attention. Methods: In a screening, 1428 patients were identified with minimal cognitive dysfunction, especially in attention. Attentional functions of
Graduate School of Medicine, Maebashi, Gunma, Japan; :Tottori
~Institute of Medical Psychology, University of Kiel, Germany Introduction: Long-term treatment with statines lower lffgh choles-
terolemia especially in elderly patients. There are few reports that mild hypercholesterolemia seems to be a risk factor for the development of Alzheimer amyolid pathology (Pappolla et al., Neurology 2003, Menge et al., 2005). What's about the incidence of dementia (vascular dementia, VD or dementia of Alzheimer's type, DAT) in persons with a long history of statine treatment o f high cho lesterolemia? Methods: 268 patients (1148 female, median age 58 years, and 120 male, median age 59 years) were examined neuropsychologically to exclude VD or DAT. Severity of dementia was scored by Mini-Mental State Examination (Folstein, 1990) and classified into "no dementia", "mild", "moderate" and "severe". All patients received long-term treatment with statines for a mean of 28 months. Results: Two of 268 patients had mild DAT (0,75%), two patients had mild VD (0,75%). Discussion: The inddence o f DAT or VD in the observed group with long-term treatment with statines is lower than in the general population (about 2%). We propose that treatment with statines to lower tfigh cholesterolenffa may protect for VD or DAT. This should be confirmed by controlled studies. 0763 Problems of attention - indicators of an incoming dementia?
~Institute of Medical Psychology, University of Kiel, Germany Introduction: Patients with dementia of Alzheimer's type (DAT) or