- Email: [email protected]
Cerebrospinal fluid from patients with Synucleinopathies promotes in vitro -synuclein fibril formation
Poster Presentations P4 and finally died 17 years after onset. Dominant behavioral features were apathy, inertia, emotional blunting, dietary changes and self neglect. The two others, aged 52 and 60 at onset, rapidly developed severe behavioral troubles with disinhibition and compulsive behavior at foreground. They died 3 and 5 years later respectively. Although patients had various combinations of vascular risk factors their brain MRI only showed mild vascular modifications. There was neither significant frontotemporal atrophy nor hypometabolism. Pathological examination showed isolated chronic ischemic changes: severe arteriolosclerosis, perivascular spaces dilatations and microinfarcts in the frontal white matter and basal ganglia, and moderate myelin loss. Conclusions: These three cases illustrate that isolated subcortical microvascular pathology may underlie atypical presentation of bvFTD including the long lasting, slowly progressive variant. These observations also support the revised diagnosis criteria for bvFTD (international bvFTD criteria consortium, 2010) which require both functional decline and imaging results consistent with bvFTD to meet criteria for a probable diagnosis. P4-141
CLINICAL AND PATHOLOGIC PHENOTYPE OF DEMENTIA AFTER TRAUMATIC BRAIN INJURY (TBI)
Nasreen Sayed*1, Ramon Diaz-Arrastia1, 1University of Texas Southwestern Medical Center, Dallas, Texas, United States. Background: TBI is associated with an increased risk of dementia. Studies in retired athletes exposed to multiple concussions have identified the syndrome of chronic traumatic encephalopathy (CTE). CTE differs from AD clinically in that it presents at an earlier age and is associated with more prevalent mood and behavior disturbances. Pathologically, CTE is a taupathy with modest amyloid pathology. This study was undertaken to determine whether dementia occurring after TBI in non-athletes is similar to CTE. Methods: Data from the National Alzheimer’s Coordinating Center (NACC) was analyzed. Categorical data was analyzed using Fisher’s exact test or the Chi-square test, and continuous data was analyzed using either Student’s t-test for parametric data, or Mann-Whitney test for non-parametric data. Results: 877 demented individuals who had sustained TBI were identified. Of these, 567 had brief loss of consciousness (LOC), 248 had extended LOC, and 62 had chronic deficit of dysfunction. TBI with chronic deficit or dysfunction was associated with increased risk of dementia (OR 3.1, p < 0.0001). There was no increased risk of dementia with TBI resulting in brief or extended LOC. Comparing the 62 patients with TBI associated with chronic deficit of dysfunction with a matched group of patients with probable AD, the age of onset of dementia was no different. Dementia associated with TBI was more likely to be associated with depression, agitation, irritability, and personality changes (ORs 1.9 - 2.3, p < 0.05 for each comparison). Motor disorders were more common in the TBI group (ORs 2.9 - 6.9, p < 0.01 for each comparison). eizures were much more common in the TBI group (OR 45.2, p < 0.0001). Pathologic data was available from 16 demented patients with a history of TBI. None were diagnosed with taupathy. The neuritic plaque score and the prevalence of amyloid angiopathy were lower than in non-TBI cases. Conclusions: TBI with chronic deficit or dysfunction is associated with an increased risk of dementia. The clinical phenotype of dementia in these patients is distinct from CTE, but may represent an endophenotype within the AD spectrum. P4-142
CEREBROSPINAL FLUID FROM PATIENTS WITH SYNUCLEINOPATHIES PROMOTES IN VITRO -SYNUCLEIN FIBRIL FORMATION
Mie Hirohata*1, Kenjiro Ono2, Akiyoshi Morinaga2, Tokuhei Ikeda2, Masahito Yamada2, 1Department of Neurology and Neurobiology of Aging, Graduate School of Medical Science, Kanazawa Univ, Kanazawa, Ishikawa, Japan; 2Department of Neurology and Neurobiology of Aging Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan. Background: The aggregation of a-synuclein (aS) in the central nervous system (CNS) is the hallmarkof multiple system atrophy (MSA) and Lewy body diseases including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) (a-synucleinopathies). Although aS has beenconsidered an intracellular
S753
protein, extracellular aS was detected in PD, DLB, andnormal subjects in recent human cerebrospinal fluid (CSF) studies. Previously, we reported that CSF from DLB and Alzheimer’sdisease patients promote in vitro aS aggregation. Here, we hypothesizethat patients with a-synucleinopathies (MSA, DLB and PD) may have a CNSenvironment favorable for aS aggregation. Methods: We examined the influence of CSF from patients with MSA (n ¼ 20), DLB (n ^ C using ¼ 8), andPD (n ¼ 10) on in vitro aS fibril formation at pH 7.5 and 37A fluorescence spectroscopy with thioflavinS, compared with those with hereditary spinocerebellar ataxia (hSCA) (n ¼ 16), and tension-typeheadache (n ¼ 7). By electron microscopic analyses, section analysis wasperformed measuring the width of individual fibrils, and an average was obtained. Spearman’s rank correlations were calculated to determine the relationship betweenthe final levels of ThS fluorescence after incubation with MSA-, DLB-, PD-, or hSCA-CSF, thelength of the illness, the age of patients, and the CSF levels of total proteinor albumin. Results: Thefinal fluorescence level of MSA-group was the highest of all, but did notproceeded to equilibrium much more rapidly than other groups. CSF from MSApatients (MSA-CSF) promoted aS fibril (faS) formation more strongly than PD-, hSCA-, orheadache-CSF. a-Synucleinopathies-CSF promoted faS formation significantly more than non-a-Synucleinopathies-CSF,and MSA-CSF promoted than LBD (PD and DLB)- or PD-CSF. By electronmicroscopic analyses, the width of faS formed in MSA-CSF was significantly greater than others. The final fluorescencelevels after incubation with MSA-, DLB-, PD-, or hSCA-CSF showed no significantcorrelation with the age, CSF-total protein, or CSF-albumin. Conclusions: aSynucleinopathies-CSF, particularly MSA-CSF, promoted aS fibril formation. MSA may have a CSF environment particularly favorable for faS formation.
P4-143
CHANGES IN EATING HABITS IN FRONTOTEMPORAL DEMENTIA
Angela Iragorri*1, Liliana Rosas1, Diana Matallana2, Carlos Filizzola2, 1 Universidad Javeriana, Bogota, Colombia; 2Universidad Javeriana, Bogota, Colombia. Background: Previous studies suggest that changes in eating habits are present in 80% of patients with frontotemporal dementia (FTD) diagnosis and may be the initial clinical manifestation and may increase the probability of death. Additionally, some patients have swallowing problems, which may indicate disease progressionand brainstem dysfunction. Methods: Thirty eight patients with FTD diagnosis were recruited at The Memory Clinic of the San Ignacio Hospital at the Javeriana University in Bogota, Colombia. With the objective of identify the changes in eating habits, we used a semi-structured interview and some clinical scales: the Columbia University Scale for psychopathology in Alzheimer Disease, and the Frontal Behavioral Inventory (Kertesz). Results: We found that 86,8% of patients report any change in eating habits; the more frequent disorders were hyporexia (45%, n ¼ 17) and overeating (34 %, n ¼ 13). > In our sample of patients with PPA (n ¼ 11), the most frequent changes in the eating habit were overeating (54.5%, n ¼ 6), taste and olfaction problems (27.3% n ¼ 3) and hyporexia (18.2% n ¼ 2). In patients with SD (n ¼ 6) hyporexia was more frequent (66,7%, n ¼ 4), and restrictive patterns were found in 33,3% of patients (n ¼ 2). In patients with frontal variant of FTD (n ¼ 17) hyporexia was the more common disorder (52,9%); overeating was present in 35,3% n ¼ 6 and 23,5 % (n ¼ 4) showed taste and olfaction problems. In patients with other variants of FTD, dysphagia for liquids and solids was as common as hyporexia (n ¼ 4). Conclusions: Changes in eating habits are common in patients with FTD diagnosis. In PPA patients overeating is more common, whereas in SD patients hyporexia is more frequent, and in other variants of FTD dysphagia is as common as hyporexia. P4-144
PRIOR TRANSIENT ISCHEMIC ATTACK (TIA) AND EARLY DEMENTIA AFTER SUBSEQUENT ISCHEMIC STROKE
Agnes Jacquin*1, Olivier Rouaud2, Yannick Bejot3, Corine Aboa-Eboule4, Guy-Victor Osseby2, Thibault Moreau2, Maurice Giroud5, 1Department of Neurology, University hospital of Dijon, France, DIJON, France; 2 Department of Neurology, University hospital of Dijon, DIJON, France;
CLINICAL AND PATHOLOGIC PHENOTYPE OF DEMENTIA AFTER TRAUMATIC BRAIN INJURY (TBI)
Nasreen Sayed*1, Ramon Diaz-Arrastia1, 1University of Texas Southwestern Medical Center, Dallas, Texas, United States. Background: TBI is associated with an increased risk of dementia. Studies in retired athletes exposed to multiple concussions have identified the syndrome of chronic traumatic encephalopathy (CTE). CTE differs from AD clinically in that it presents at an earlier age and is associated with more prevalent mood and behavior disturbances. Pathologically, CTE is a taupathy with modest amyloid pathology. This study was undertaken to determine whether dementia occurring after TBI in non-athletes is similar to CTE. Methods: Data from the National Alzheimer’s Coordinating Center (NACC) was analyzed. Categorical data was analyzed using Fisher’s exact test or the Chi-square test, and continuous data was analyzed using either Student’s t-test for parametric data, or Mann-Whitney test for non-parametric data. Results: 877 demented individuals who had sustained TBI were identified. Of these, 567 had brief loss of consciousness (LOC), 248 had extended LOC, and 62 had chronic deficit of dysfunction. TBI with chronic deficit or dysfunction was associated with increased risk of dementia (OR 3.1, p < 0.0001). There was no increased risk of dementia with TBI resulting in brief or extended LOC. Comparing the 62 patients with TBI associated with chronic deficit of dysfunction with a matched group of patients with probable AD, the age of onset of dementia was no different. Dementia associated with TBI was more likely to be associated with depression, agitation, irritability, and personality changes (ORs 1.9 - 2.3, p < 0.05 for each comparison). Motor disorders were more common in the TBI group (ORs 2.9 - 6.9, p < 0.01 for each comparison). eizures were much more common in the TBI group (OR 45.2, p < 0.0001). Pathologic data was available from 16 demented patients with a history of TBI. None were diagnosed with taupathy. The neuritic plaque score and the prevalence of amyloid angiopathy were lower than in non-TBI cases. Conclusions: TBI with chronic deficit or dysfunction is associated with an increased risk of dementia. The clinical phenotype of dementia in these patients is distinct from CTE, but may represent an endophenotype within the AD spectrum. P4-142
CEREBROSPINAL FLUID FROM PATIENTS WITH SYNUCLEINOPATHIES PROMOTES IN VITRO -SYNUCLEIN FIBRIL FORMATION
Mie Hirohata*1, Kenjiro Ono2, Akiyoshi Morinaga2, Tokuhei Ikeda2, Masahito Yamada2, 1Department of Neurology and Neurobiology of Aging, Graduate School of Medical Science, Kanazawa Univ, Kanazawa, Ishikawa, Japan; 2Department of Neurology and Neurobiology of Aging Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan. Background: The aggregation of a-synuclein (aS) in the central nervous system (CNS) is the hallmarkof multiple system atrophy (MSA) and Lewy body diseases including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) (a-synucleinopathies). Although aS has beenconsidered an intracellular
S753
protein, extracellular aS was detected in PD, DLB, andnormal subjects in recent human cerebrospinal fluid (CSF) studies. Previously, we reported that CSF from DLB and Alzheimer’sdisease patients promote in vitro aS aggregation. Here, we hypothesizethat patients with a-synucleinopathies (MSA, DLB and PD) may have a CNSenvironment favorable for aS aggregation. Methods: We examined the influence of CSF from patients with MSA (n ¼ 20), DLB (n ^ C using ¼ 8), andPD (n ¼ 10) on in vitro aS fibril formation at pH 7.5 and 37A fluorescence spectroscopy with thioflavinS, compared with those with hereditary spinocerebellar ataxia (hSCA) (n ¼ 16), and tension-typeheadache (n ¼ 7). By electron microscopic analyses, section analysis wasperformed measuring the width of individual fibrils, and an average was obtained. Spearman’s rank correlations were calculated to determine the relationship betweenthe final levels of ThS fluorescence after incubation with MSA-, DLB-, PD-, or hSCA-CSF, thelength of the illness, the age of patients, and the CSF levels of total proteinor albumin. Results: Thefinal fluorescence level of MSA-group was the highest of all, but did notproceeded to equilibrium much more rapidly than other groups. CSF from MSApatients (MSA-CSF) promoted aS fibril (faS) formation more strongly than PD-, hSCA-, orheadache-CSF. a-Synucleinopathies-CSF promoted faS formation significantly more than non-a-Synucleinopathies-CSF,and MSA-CSF promoted than LBD (PD and DLB)- or PD-CSF. By electronmicroscopic analyses, the width of faS formed in MSA-CSF was significantly greater than others. The final fluorescencelevels after incubation with MSA-, DLB-, PD-, or hSCA-CSF showed no significantcorrelation with the age, CSF-total protein, or CSF-albumin. Conclusions: aSynucleinopathies-CSF, particularly MSA-CSF, promoted aS fibril formation. MSA may have a CSF environment particularly favorable for faS formation.
P4-143
CHANGES IN EATING HABITS IN FRONTOTEMPORAL DEMENTIA
Angela Iragorri*1, Liliana Rosas1, Diana Matallana2, Carlos Filizzola2, 1 Universidad Javeriana, Bogota, Colombia; 2Universidad Javeriana, Bogota, Colombia. Background: Previous studies suggest that changes in eating habits are present in 80% of patients with frontotemporal dementia (FTD) diagnosis and may be the initial clinical manifestation and may increase the probability of death. Additionally, some patients have swallowing problems, which may indicate disease progressionand brainstem dysfunction. Methods: Thirty eight patients with FTD diagnosis were recruited at The Memory Clinic of the San Ignacio Hospital at the Javeriana University in Bogota, Colombia. With the objective of identify the changes in eating habits, we used a semi-structured interview and some clinical scales: the Columbia University Scale for psychopathology in Alzheimer Disease, and the Frontal Behavioral Inventory (Kertesz). Results: We found that 86,8% of patients report any change in eating habits; the more frequent disorders were hyporexia (45%, n ¼ 17) and overeating (34 %, n ¼ 13). > In our sample of patients with PPA (n ¼ 11), the most frequent changes in the eating habit were overeating (54.5%, n ¼ 6), taste and olfaction problems (27.3% n ¼ 3) and hyporexia (18.2% n ¼ 2). In patients with SD (n ¼ 6) hyporexia was more frequent (66,7%, n ¼ 4), and restrictive patterns were found in 33,3% of patients (n ¼ 2). In patients with frontal variant of FTD (n ¼ 17) hyporexia was the more common disorder (52,9%); overeating was present in 35,3% n ¼ 6 and 23,5 % (n ¼ 4) showed taste and olfaction problems. In patients with other variants of FTD, dysphagia for liquids and solids was as common as hyporexia (n ¼ 4). Conclusions: Changes in eating habits are common in patients with FTD diagnosis. In PPA patients overeating is more common, whereas in SD patients hyporexia is more frequent, and in other variants of FTD dysphagia is as common as hyporexia. P4-144
PRIOR TRANSIENT ISCHEMIC ATTACK (TIA) AND EARLY DEMENTIA AFTER SUBSEQUENT ISCHEMIC STROKE
Agnes Jacquin*1, Olivier Rouaud2, Yannick Bejot3, Corine Aboa-Eboule4, Guy-Victor Osseby2, Thibault Moreau2, Maurice Giroud5, 1Department of Neurology, University hospital of Dijon, France, DIJON, France; 2 Department of Neurology, University hospital of Dijon, DIJON, France;