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Folate deficiency in dementia patients
Poster Presentations: P1 in nasal smears from individuals were measurable using this method. The mean concentration of Aß smears was 2.0 pg/ml and 12.3 pg/g protein. Conclusions: This study provides a simple and accurate method to measure trace Aß levels in biological samples.
P1-040
FOLATE DEFICIENCY IN DEMENTIA PATIENTS
Akihiko Ozaki1, Sadayuki Matsumoto2, 1Department of Neurology, The Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan; 2 The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan. Background: Folate deficiency and vitamin B12 deficiency could worsen dementia. The clinical character of folate deficiency was investigated serially in our department. Methods: The patients with dementia were assessed by mini-mental state examination (MMSE), category fluency, serum folate, vitamin B12, and homocysteine. Cut-off value was 3.1ng/ml for folate deficiency. 180pg/ml for vitamin B12 deficiency, 14.1nmol/ml for hyperhomocysteinemia. They were also assessed with brain MRI or CT. The degree of atrophy in hippocampus was measured by voxel-based analysis. These parameters were compared between patients with folate deficiency and those with normal serum folate. Results: 90 patients were assessed, 35 men and 55 women. The average age was 78.5. Median duration between first symptom and assessment, was 2 years and 2 months. Median score of MMSE was 21.0. 54% of the patients were clinically diagnosed as Alzheimer’s disease, 15% as vascular dementia. 16 patients (18%) had folate deficiency. 9 patients (10%) had vitamin B12 deficiency. 30 patients (33%) had hyperhomocysteinemia. Inverted correlation was found in serum folate and homocysteine. Patients with folate deficiency showd no differences in score of MMSE, category fluency, and degree of atrophy in hippocampus, compared with patients with normal serum folate. Conclusions: Folate deficiency was sometimes detected in dementia patients. It might influence cognitive function independently.
P1-041
CONTRIBUTION OF ALZHEIMER’S BIOMARKERS IN THE DIAGNOSIS OF ALZHEIMER’S DISEASE IN NONAMNESTIC PRESENTATIONS
Catherine Belin1, Didier Maillet2, Marie-Christine Nizzi2, Adama Sacko2, Antoine Carpentier2, 1CHU Avicenne APHP France, Bobigny, France; 2UF Memoire et Maladies Neurodegeneratives, Bobigny, France. Background: Amnestic presentations are the most common clinical forms of Alzheimer’s disease (AD). However, other non-amnestic presentations are not rare (language, visuospatial or executive dysfunction presentations). Executive dysfunction forms, when not associated with deficits in other cognitive domains, are difficult to diagnostic and can be confounded with Fronto-Temporal Dementia (FTD).AD biomarker tests include CSF biomarkers (Aß42 Amyloid and tau proteins) and FDG-PET scan which reflects neuronal injury and can help to the diagnosis of AD in atypical (non-amnestic) cases. Methods: We studied four patients with dysexecutive syndrome. Three patients had behavioral signs (2 with apathy, 1 with disinhibition). The neuropsychological assessment did not evidence other cognitive deficits. No predominant hippocampal atrophy was visible on brain MRI.The clinical diagnosis of these four patients was FTD. However, ECD-SPECT was not in favor of FTD and a lumbar puncture with AD biomarker assay were performed in each patient. Results: CSF analysis found a decreased Aß42 amyloid peptide level associated with increased protein Tau (total-tau and phosphorylated tau) level, which is characteristic of AD. The evolution of these patients was marked by a change in the neuropsychological profile with appearance of memory disorders and temporo-parietal hypometabolism in FDG-PET. Conclusions: Executive dysfunction can be the early signs of AD dementia. As in other nontypical cases, biomarkers tests are useful for the diagnosis of AD.
P1-042
P121 Ab OLIGOMERS IN CSF ARE A BIOMARKER FOR ALZHEIMER’S DISEASE
Lei Wang-Dietrich1, Susanne Funke1, Kun Wang1, Oliver Bannach2, Eva Birkmann1, Dieter Willbold1, 1Forschungszentrum Juelich, Juelich, Germany; 2Heinrich-Heine-Universitaet Duesseldorf, Duesseldorf, Germany. Background: Alzheimer’s disease (AD) is a fatal neurodegenerative and progressive disorder. Currently, no reliable biomarkers for pre-symptomatic diagnosis or therapy monitoring are available. Recent studies indicate that especially soluble amyloid beta peptide (Ab) oligomers are the major toxic species during development and progression of AD. Therefore, we suggest that the number of Ab oligomers in body fluids can be used as the most relevant and direct biomarker for AD. Methods: Here we present decisive improvements of the surface fluorescence intensity distribution analysis (sFIDA) assay to be used as a tool for quantification of Ab oligomers with single particle sensitivity. We show that the optimized assay allows for counting Ab oligomers in human cerebrospinal fluid (CSF). Results: We challenged the assay with CSF samples from 14 AD patients and 12 age-matched control subjects. The Ab oligomer count revealed a surprisingly clear distinction between both groups. All samples of the control group showed homogenously low numbers of Ab oligomers, while the samples of the AD group exhibited significantly higher levels of Ab oligomers with high variability. The Ab oligomer levels clearly correlated with the patients’ mini-mental state examination (MMSE) scores. Conclusions: Our results support the idea that Ab oligomers play a crucial role in AD pathology and in turn can be used as a diagnostic biomarker. The sFIDA assay is able to reliably quantify the Ab oligomers in human CSF. In addition, the correlation between MMSE scores and Ab oligomer counts suggests that the quantity of Ab oligomers in CSF even reflects the severity of the disease. Further studies will reveal whether anti-Ab targeted therapies can be evaluated and monitored based on the Ab oligomer counts in treated individuals.
P1-043
REMISSION OF PRE-MILD COGNITIVE IMPAIRMENT (MCI), SUBJECTIVE COGNITIVE IMPAIRMENT (SCI): A TWO-YEAR PROSPECTIVE STUDY OF DEMOGRAPHIC AND BEHAVIORAL MARKERS
Barry Reisberg, Ricardo Osorio, Asif Khan, Carol Torossian, Kamalika Roy, Istvan Boksay, Ohnmar Thwin, Naveen Khanzada, Pawan Kumar, Melanie Shulman, Iryna Lobach, New York University School of Medicine, New York, New York, United States. Background: Pre-MCI, Subjective Cognitive Impairment (SCI) has been associated with worsening to MCI and AD (Jessen et al., Arch Gen Psychiatry, 2010). In our study (Reisberg, et al., Alzheimer’s & ~ greater risk of deDementia, 2010 1), persons with SCI had a 4.5 A— cline to MCI or dementia over 7-years, than subjects with no-cognitive impairment (NCI). There have apparently been no studies of SCI remission. Such studies might be of great relevance for AD prevention. Methods: Subjects from our published 7-year outcome study 1 were selected if they had: (1) SCI at baseline; (2) a follow-up (F/U) conducted from 1.5-3.0 years post baseline; and (3) no significant comorbidities. From 166 SCI subjects at baseline, 98 fulfilled the criteria (for sociodemographics see Table). Outcome was defined dichotomously as: remission (NCI status at F/U) or non-remission (SCI, MCI or dementia at F/U). Sociodemographic, clinical-behavioral, mental status, and psychometric predictors of outcome at baseline, were examined using the Wilcoxon procedure. Results: 8 subjects, 12.25%, remitted to an NCI status at F/U; 87.75% did not remit. Of the latter, at F/U, 68 subjects manifested SCI, 20 MCI, and 2 mild dementia. At baseline, subjects who remitted were younger (57.4 6 8.2 years) than non-remitters (68.0 6 8.3 years) (P<0.01). No baseline differences in outcome were noted for gender or education. Baseline Brief Cognitive Rating
P1-040
FOLATE DEFICIENCY IN DEMENTIA PATIENTS
Akihiko Ozaki1, Sadayuki Matsumoto2, 1Department of Neurology, The Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan; 2 The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan. Background: Folate deficiency and vitamin B12 deficiency could worsen dementia. The clinical character of folate deficiency was investigated serially in our department. Methods: The patients with dementia were assessed by mini-mental state examination (MMSE), category fluency, serum folate, vitamin B12, and homocysteine. Cut-off value was 3.1ng/ml for folate deficiency. 180pg/ml for vitamin B12 deficiency, 14.1nmol/ml for hyperhomocysteinemia. They were also assessed with brain MRI or CT. The degree of atrophy in hippocampus was measured by voxel-based analysis. These parameters were compared between patients with folate deficiency and those with normal serum folate. Results: 90 patients were assessed, 35 men and 55 women. The average age was 78.5. Median duration between first symptom and assessment, was 2 years and 2 months. Median score of MMSE was 21.0. 54% of the patients were clinically diagnosed as Alzheimer’s disease, 15% as vascular dementia. 16 patients (18%) had folate deficiency. 9 patients (10%) had vitamin B12 deficiency. 30 patients (33%) had hyperhomocysteinemia. Inverted correlation was found in serum folate and homocysteine. Patients with folate deficiency showd no differences in score of MMSE, category fluency, and degree of atrophy in hippocampus, compared with patients with normal serum folate. Conclusions: Folate deficiency was sometimes detected in dementia patients. It might influence cognitive function independently.
P1-041
CONTRIBUTION OF ALZHEIMER’S BIOMARKERS IN THE DIAGNOSIS OF ALZHEIMER’S DISEASE IN NONAMNESTIC PRESENTATIONS
Catherine Belin1, Didier Maillet2, Marie-Christine Nizzi2, Adama Sacko2, Antoine Carpentier2, 1CHU Avicenne APHP France, Bobigny, France; 2UF Memoire et Maladies Neurodegeneratives, Bobigny, France. Background: Amnestic presentations are the most common clinical forms of Alzheimer’s disease (AD). However, other non-amnestic presentations are not rare (language, visuospatial or executive dysfunction presentations). Executive dysfunction forms, when not associated with deficits in other cognitive domains, are difficult to diagnostic and can be confounded with Fronto-Temporal Dementia (FTD).AD biomarker tests include CSF biomarkers (Aß42 Amyloid and tau proteins) and FDG-PET scan which reflects neuronal injury and can help to the diagnosis of AD in atypical (non-amnestic) cases. Methods: We studied four patients with dysexecutive syndrome. Three patients had behavioral signs (2 with apathy, 1 with disinhibition). The neuropsychological assessment did not evidence other cognitive deficits. No predominant hippocampal atrophy was visible on brain MRI.The clinical diagnosis of these four patients was FTD. However, ECD-SPECT was not in favor of FTD and a lumbar puncture with AD biomarker assay were performed in each patient. Results: CSF analysis found a decreased Aß42 amyloid peptide level associated with increased protein Tau (total-tau and phosphorylated tau) level, which is characteristic of AD. The evolution of these patients was marked by a change in the neuropsychological profile with appearance of memory disorders and temporo-parietal hypometabolism in FDG-PET. Conclusions: Executive dysfunction can be the early signs of AD dementia. As in other nontypical cases, biomarkers tests are useful for the diagnosis of AD.
P1-042
P121 Ab OLIGOMERS IN CSF ARE A BIOMARKER FOR ALZHEIMER’S DISEASE
Lei Wang-Dietrich1, Susanne Funke1, Kun Wang1, Oliver Bannach2, Eva Birkmann1, Dieter Willbold1, 1Forschungszentrum Juelich, Juelich, Germany; 2Heinrich-Heine-Universitaet Duesseldorf, Duesseldorf, Germany. Background: Alzheimer’s disease (AD) is a fatal neurodegenerative and progressive disorder. Currently, no reliable biomarkers for pre-symptomatic diagnosis or therapy monitoring are available. Recent studies indicate that especially soluble amyloid beta peptide (Ab) oligomers are the major toxic species during development and progression of AD. Therefore, we suggest that the number of Ab oligomers in body fluids can be used as the most relevant and direct biomarker for AD. Methods: Here we present decisive improvements of the surface fluorescence intensity distribution analysis (sFIDA) assay to be used as a tool for quantification of Ab oligomers with single particle sensitivity. We show that the optimized assay allows for counting Ab oligomers in human cerebrospinal fluid (CSF). Results: We challenged the assay with CSF samples from 14 AD patients and 12 age-matched control subjects. The Ab oligomer count revealed a surprisingly clear distinction between both groups. All samples of the control group showed homogenously low numbers of Ab oligomers, while the samples of the AD group exhibited significantly higher levels of Ab oligomers with high variability. The Ab oligomer levels clearly correlated with the patients’ mini-mental state examination (MMSE) scores. Conclusions: Our results support the idea that Ab oligomers play a crucial role in AD pathology and in turn can be used as a diagnostic biomarker. The sFIDA assay is able to reliably quantify the Ab oligomers in human CSF. In addition, the correlation between MMSE scores and Ab oligomer counts suggests that the quantity of Ab oligomers in CSF even reflects the severity of the disease. Further studies will reveal whether anti-Ab targeted therapies can be evaluated and monitored based on the Ab oligomer counts in treated individuals.
P1-043
REMISSION OF PRE-MILD COGNITIVE IMPAIRMENT (MCI), SUBJECTIVE COGNITIVE IMPAIRMENT (SCI): A TWO-YEAR PROSPECTIVE STUDY OF DEMOGRAPHIC AND BEHAVIORAL MARKERS
Barry Reisberg, Ricardo Osorio, Asif Khan, Carol Torossian, Kamalika Roy, Istvan Boksay, Ohnmar Thwin, Naveen Khanzada, Pawan Kumar, Melanie Shulman, Iryna Lobach, New York University School of Medicine, New York, New York, United States. Background: Pre-MCI, Subjective Cognitive Impairment (SCI) has been associated with worsening to MCI and AD (Jessen et al., Arch Gen Psychiatry, 2010). In our study (Reisberg, et al., Alzheimer’s & ~ greater risk of deDementia, 2010 1), persons with SCI had a 4.5 A— cline to MCI or dementia over 7-years, than subjects with no-cognitive impairment (NCI). There have apparently been no studies of SCI remission. Such studies might be of great relevance for AD prevention. Methods: Subjects from our published 7-year outcome study 1 were selected if they had: (1) SCI at baseline; (2) a follow-up (F/U) conducted from 1.5-3.0 years post baseline; and (3) no significant comorbidities. From 166 SCI subjects at baseline, 98 fulfilled the criteria (for sociodemographics see Table). Outcome was defined dichotomously as: remission (NCI status at F/U) or non-remission (SCI, MCI or dementia at F/U). Sociodemographic, clinical-behavioral, mental status, and psychometric predictors of outcome at baseline, were examined using the Wilcoxon procedure. Results: 8 subjects, 12.25%, remitted to an NCI status at F/U; 87.75% did not remit. Of the latter, at F/U, 68 subjects manifested SCI, 20 MCI, and 2 mild dementia. At baseline, subjects who remitted were younger (57.4 6 8.2 years) than non-remitters (68.0 6 8.3 years) (P<0.01). No baseline differences in outcome were noted for gender or education. Baseline Brief Cognitive Rating