- Email: [email protected]
P4-114
S548
Poster P4:: Wednesday Posters P4-113
CLINICOPATHOLOGIC AND BIOCHEMICAL OVERLAP OF FRONTOTEMPORAL DEGENERATION, CORTICOBASAL DEGENERATION AND PROGRESSIVE SUPRANUCLEAR PALSY: THE LILLE-BAILLEUL FRENCH COHORT
Vincent Deramecourt1, Ste´phanie Bombois1, Claude-Alain Maurage2, Florence Lebert1, Andre´ Delacourte3, Florence Pasquier1, 1Memory Clinic, University Hospital, Lille, France; 2Department of Neuropathology, University Hospital, Lille, France; 3INSERM U815, Lille, France. Contact e-mail: [email protected]
P4-112
IS EARLY FRONTOTEMPORAL DEMENTIA A DEMENTIA?
Mario F. Mendez, Aaron McMurtray, Eliot A. Licht, Ronald E. Saul, Bruce L. Miller, University of California, Los Angeles, Los Angeles, CA, USA. Contact e-mail: [email protected] Background: In the absence of a biomarker, the diagnosis of frontotemporal dementia (FTD) depends on recognizing the neuropsychiatric symptoms of this disease. The traditional model of cognitive loss of Alzheimer’s disease (AD) may not apply in the beginning stages of FTD, when patients have predominant behavioral symptoms. Patients with early FTD often lack the multiple cognitive impairments or memory loss necessary to meet established criteria (DSM-IV or ICD-10) for dementia. Objective: To determine whether patients with FTD meet criteria for dementia on presentation within two years of onset of their disease. Methods: We reviewed all patients meeting Consensus Criteria for FTD (Neary et al, 1998) and having corroborative frontal or frontotemporal changes on functional neuroimaging (either PET or SPECT). All FTD patients in this study presented for evaluation in universitybased neurological clinics. All patients were within two years of onset of their first symptoms. This study included only the behavioral variant of frontotemporal lobar degeneration and excluded patients with primary progressive aphasia or semantic dementia. All patients underwent initial neurobehavioral and neuropsychological testing at baseline and again at two years. Results: On initial presentation, 23 (36.5%) patients met all core criteria for FTD and were diagnosed with the disorder; an additional 40 patients met all core criteria at two years from the initial presentation. Of these 63 patients eventually diagnosed with FTD, none met criteria (DSM-IV or ICD-10) for dementia at baseline by neurobehavioral or neuropsychological testing, and 43 (68.3%) met dementia criteria at two years from the initial presentation. Most FTD patients initially lacked sufficient memory and other cognitive deficits to characterize as “dementia.” Conclusion: FTD is often difficult to diagnose. Patients with FTD present with subtle personality or behavioral changes rather than cognitive deficits typical of AD. Although neuropsychological studies report abnormalities in frontal-executive functions and language, with less impaired memory and visuospatial skills than AD, the non-cognitive behavioral changes are actually the earliest and most characteristic features of FTD. This report suggests that early FTD defies the neuropsychological model of dementia and that clinicians need better diagnostic tools for recognizing this neuropsychiatric disorder.
Background: Frontotemporal lobar degeneration (FTLD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) share striking clinical and pathological features. Some authors use the term Pick Complex to encompass these neurodegenerative diseases. Objective(s): To study the overlap of FTLD, CBD and PSP in our cohort. Methods: We studied the clinical, neuropsychological, neuro-imaging, neuropathological and biochemical data of 12 autopsy-proven cases of DFT, PPA, CBD and PSP followed at the Lille-Bailleul Memory Clinic. Results: Clinical diagnoses were PSP (n⫽2), CBD (n⫽2), primary progressive aphasia (n⫽1), progressive anarthria (n⫽1), semantic dementia (n⫽1), frontotemporal dementia (FTD) (n⫽2) and FTD with motor neuron disease (n⫽1). Post mortem analysis showed a diagnosis of dementia lacking distinctive histology (DLDH) (n⫽5), PSP (n⫽2), CBD (n⫽2), Pick’s disease (n⫽1), FTLD with motor neuron degeneration (n⫽1) and mixed Alzheimer’s and Parkinson’s pathology (n⫽1). All cases shared important clinical and neuropsychological features. All clinical diagnoses were confirmed by post mortem analysis with the exception of 2 cases of CBD (mixed Alzheimer’s and Parkinson’s pathology and DLDH). Morphological and functional neuro-imaging helped in the establishment of clinical diagnosis but failed to predict neuropathology. Presence or absence of tau-positive inclusion is unpredictable in DFT. Some syndromes are better correlated with underlying pathology than others. CBD and progressive aphasia should be considered as clinical syndromes rather than clinicopathological entities. Conclusions: At the present time, multidisciplinary confrontation of clinical, neuropathological and biochemical data is still the only way to make a formal and precise diagnosis of neurodegenerative disease. Further studies are needed, including biomarker techniques, to understand in a better way the nosology of FTLD. P4-114
AUTOSOMAL DOMINANT FRONTOTEMPORAL DEMENTIA LINKED TO CHROMOSOME 3, FTD3: RECENT CLINICAL AND MOLECULAR FINDINGS
Suzanne G. Lindquist1,2, Hans Brændgaard3, Anne Nørremølle2, Kirsten Svenstrup2, Lis Hasholt2, Jørgen E. Nielsen1,2, 1Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen Ø, Denmark; 2 Department of Medical Biochemistry and Genetics, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; 3Department of Neurology, Århus University Hospital, Århus, Denmark. Contact e-mail: [email protected] Background: Frontotemporal dementia, which is the third most common neurodegenerative dementia syndrome, is genetically heterogenous. Previously, a Danish family with FTD linked to chromosome 3 (FTD3) was described and a mutation in the CHMP2B gene encoding a component of the endosomal ESCRTIII complex identified in all affected family members. Objective(s): We present clinical features and the finding of the same FTD3 mutation in the CHMP2B gene in a patient with frontotemporal dementia without known relation to the previously reported family. Results: The proband developed symptoms of dementia at the age of 50. His behavior and personality changed, he became increasingly aggressive and apathetic, and his spontaneous speech declined early in the disease course. His symptoms have been rapidly
Poster P4:: Wednesday Posters progressive and he is currently in a full-time care facility, less than two years after onset of symptoms. His mother developed early-onset dementia and was in full-time care from the age of 54, and a sister of the proband was diagnosed with frontotemporal dementia at the age of 59. A cerebral CT scan of the proband showed frontotemporal and central atrophy, and a PET scan showed frontal, temporal and parietal hypoperfusion. MMSE score at referral was 24/30. Neuropsychological examination revealed massive impairment of frontal and temporoparietal functions. Direct DNA sequencing of exon 6 of the CHMP2B gene showed that the patient had the characteristic G-to-C transition which has previously been described in the FTD3 family. In the previously reported FTD3 family, seven asymptomatic at risk individuals have been tested after genetic counselling and the mutation has been found in one of these individuals. Conclusions: We present recent findings in FTD3, including the detection of the mutation in a patient with no known relation to the previously reported FTD3 family. Most likely, the patient represents a previously unknown branch of the family. P4-115
FRONTOTEMPORAL DEGENERATION WITH UBIQUINATED INCLUSIONS: A CASE REPORT OF A FAMILY WITH CORTICOBASAL SYNDROME AND PROMINENT PARIETAL DEGENERATION
Najeeb Qadi, Ian RA Mackenzie, Emily S. Dwosh, Howard H. Feldman, University of British Columbia, Vancouver, BC, Canada. Contact e-mail: [email protected] Background: Frontotemporal lobar degeneration with ubiquinated inclusions (FTLD-U) was first described in patients with motor neuron disease and dementia but has recently been recognized as the most common pathology in cases of frontotemporal dementia (FTD). A significant proportion of cases are familial with the pattern of inheritance often being autosomal dominant. Several recent reports suggest that the spectrum of clinical disease associated with this pattern of pathology has not yet been fully appreciated. Objective: To describe a family with autosomal dominant FTD and corticobasal syndrome and autopsy confirmed FTLD-U with severe parietal lobe involvement. Methods: This family was identified and investigated at the UBC Clinic for Alzheimer Disease and Related Disorders. There are five affected members in two generations. Detailed clinical evaluations were performed on two affected sisters, one of whom eventually came to autopsy. Results: The age of onset was 60 and 63 years. Both developed characteristic features of FTD with non-fluent aphasia that progressed to mutism and behavioral changes that included apathy, emotional flatness and socially inappropriate behavior. Additional clinical features, consistent with a corticobasal syndrome, included slowness in mental processing, early, severe asymmetric apraxia (R⬎L), impairment in acquiring motor sequences, rigidity and alien hand phenomena. Neuroimaging showed asymmetric (L⬎R) degeneration of the frontal, temporal and parietal lobes. Disease duration was 5 and 8 years, respectively. Post mortem examination demonstrated cerebral atrophy that most severely affected the parietal lobes (L⬎R). There were typical microscopic features of FTLD-U with ubiquitin-positive, tau-, synuclein-negative neuronal cytoplasmic inclusions and neurites in the upper layers of neocortex and hippocampal dentate granule layer. Although all areas of neocortex were involved, the parietal cortex showed the most severe degeneration and most abundant ubiquitin pathology. The striatum and substantia nigra were also extensively involved. Also present were numerous ubiquitin-positive lentiform neuronal intranuclear inclusions, of the type most characteristic of autosomal dominant FTLD-U. Genetic screening for tau mutations was negative. Conclusions: This family demonstrates that FTLD-U may significantly involve the parietal lobes and cause a corticobasal syndrome.
P4-116
S549 FRONTOTEMPORAL LOBAR DEGENERATION WITH UBIQUITIN-POSITIVE INCLUSIONS: DEMOGRAPHICS AND SURVIVAL ANALYSIS OF CLINICAL SUBGROUPS
Ging-Yuek R. Hsiung, Ian Mackenzie, Caroline Lindholm, Howard Feldman, University of British Columbia, Vancouver, BC, Canada. Contact e-mail: [email protected] Background: Frontotemporal lobar degeneration with ubiquitin-immunoreactive, tau-negative inclusions (FTLD-U) was first recognized as the characteristic pathology in patients with motor neuron disease (MND) and dementia, but was subsequently found to be the most common cause of frontotemporal dementia (FTD). Most previous studies have evaluated clinically defined groups of FTD patients with various underlying pathologies. Clinical features specific to FTLD-U have not yet been well defined. Objective(s): To characterize the demographics and survival pattern of clinical subgroups in pathologically confirmed FTLD-U. Methods: Cases of FTLD-U were identified from recent autopsies and by retrospective review and re-evaluation of cases from our departmental archives. Medical records were reviewed and analyzed. In some cases, additional information was obtained from living family members. Results: Fifty cases with FTLD-U were divided into three clinical subgroups: 23 with dementia only, 9 with MND only, and 18 with both MND and dementia (MND-D). A definite family history was noted in 22 patients (44 %) from 16 unrelated families. There was an overall male predominance (1.6 M: 1 F) that remained constant among all clinical subgroups, and was particularly evident in sporadic cases (2.1 M: 1 F). The mean age of onset (61 ⫹/- 9 years) was similar in all clinical subgroups. Eight cases (16%) presented after age 70. While both familial and sporadic cases could present with dementia, MND, or both, most (95%) of the familial cases had developed dementia during their course of illness (p⫽0.03). Survival was significantly longer in females than males (7 vs. 4 years respectively, p⫽0.04). Patients with only dementia had a longer median survival (5 years) than those with only MND (1 year), or MND-D (4 years) (p⫽0.002). In each clinical subgroup, there was a trend for familial cases to have an earlier disease onset and shorter duration than sporadic cases. Conclusions: A sizable proportion of patients with FTLD-U presents after age of 70. While some patients have only MND symptoms, the majority developed dementia symptoms during their clinical course, especially those with a positive family history. The co-existence of MND pathology decreases survival, while female sex is associated with longer survival. P4-117
EXTENDING THE NEUROPATHOLOGICAL SPECTRUM OF FRONTOTEMPORAL LOBAR DEGENERATIONS: A REVIEW OF 833 PROSPECTIVELY ASSESSED DEMENTIA CASES
Lea Tenenholz Grinberg1,2, Rajka M. Liscic3,2, Tu Pang-hsien2, Daniel McKeel2, Deborah Carter2, Lisa Marie Taylor-Reinwald2, John C. Morris2, Nigel J. Cairns2, 1University of Sao Paulo, Sao Paulo, Brazil; 2Washington University in St Louis, St Louis, MO, USA; 3 Institute for Medical Research and Occupational Health, Zagreb, Croatia. Contact e-mail: [email protected] Background: Frontotemporal lobar degenerations (FTLDs) are clinically and neuropathologically heterogeneous and may account for 5-10% of dementias. Advances in immunohistochemistry, biochemistry, and genetics have helped to define and continue to broaden the spectrum of neurodegenerative diseases that are FTLDs. Objectives: To determine the pathological spectrum and frequency of FTLDs in a cohort of individuals assessed at the Washington University Alzheimer’s Disease Research Center (WUADRC). Methods: Review of 833 prospectively assessed dementia cases (Clinical Dementia Rating ⱖ 0.5) between 1988 and 2005 at the WUADRC and selection of cases with a neuropathological diagnosis of FTLD according to established and other neuropathological criteria. Brain tissue was processed and blocks taken according to the protocols of the WUADRC Neuropathology Core. Immunohistochemistry was performed
Poster P4:: Wednesday Posters P4-113
CLINICOPATHOLOGIC AND BIOCHEMICAL OVERLAP OF FRONTOTEMPORAL DEGENERATION, CORTICOBASAL DEGENERATION AND PROGRESSIVE SUPRANUCLEAR PALSY: THE LILLE-BAILLEUL FRENCH COHORT
Vincent Deramecourt1, Ste´phanie Bombois1, Claude-Alain Maurage2, Florence Lebert1, Andre´ Delacourte3, Florence Pasquier1, 1Memory Clinic, University Hospital, Lille, France; 2Department of Neuropathology, University Hospital, Lille, France; 3INSERM U815, Lille, France. Contact e-mail: [email protected]
P4-112
IS EARLY FRONTOTEMPORAL DEMENTIA A DEMENTIA?
Mario F. Mendez, Aaron McMurtray, Eliot A. Licht, Ronald E. Saul, Bruce L. Miller, University of California, Los Angeles, Los Angeles, CA, USA. Contact e-mail: [email protected] Background: In the absence of a biomarker, the diagnosis of frontotemporal dementia (FTD) depends on recognizing the neuropsychiatric symptoms of this disease. The traditional model of cognitive loss of Alzheimer’s disease (AD) may not apply in the beginning stages of FTD, when patients have predominant behavioral symptoms. Patients with early FTD often lack the multiple cognitive impairments or memory loss necessary to meet established criteria (DSM-IV or ICD-10) for dementia. Objective: To determine whether patients with FTD meet criteria for dementia on presentation within two years of onset of their disease. Methods: We reviewed all patients meeting Consensus Criteria for FTD (Neary et al, 1998) and having corroborative frontal or frontotemporal changes on functional neuroimaging (either PET or SPECT). All FTD patients in this study presented for evaluation in universitybased neurological clinics. All patients were within two years of onset of their first symptoms. This study included only the behavioral variant of frontotemporal lobar degeneration and excluded patients with primary progressive aphasia or semantic dementia. All patients underwent initial neurobehavioral and neuropsychological testing at baseline and again at two years. Results: On initial presentation, 23 (36.5%) patients met all core criteria for FTD and were diagnosed with the disorder; an additional 40 patients met all core criteria at two years from the initial presentation. Of these 63 patients eventually diagnosed with FTD, none met criteria (DSM-IV or ICD-10) for dementia at baseline by neurobehavioral or neuropsychological testing, and 43 (68.3%) met dementia criteria at two years from the initial presentation. Most FTD patients initially lacked sufficient memory and other cognitive deficits to characterize as “dementia.” Conclusion: FTD is often difficult to diagnose. Patients with FTD present with subtle personality or behavioral changes rather than cognitive deficits typical of AD. Although neuropsychological studies report abnormalities in frontal-executive functions and language, with less impaired memory and visuospatial skills than AD, the non-cognitive behavioral changes are actually the earliest and most characteristic features of FTD. This report suggests that early FTD defies the neuropsychological model of dementia and that clinicians need better diagnostic tools for recognizing this neuropsychiatric disorder.
Background: Frontotemporal lobar degeneration (FTLD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) share striking clinical and pathological features. Some authors use the term Pick Complex to encompass these neurodegenerative diseases. Objective(s): To study the overlap of FTLD, CBD and PSP in our cohort. Methods: We studied the clinical, neuropsychological, neuro-imaging, neuropathological and biochemical data of 12 autopsy-proven cases of DFT, PPA, CBD and PSP followed at the Lille-Bailleul Memory Clinic. Results: Clinical diagnoses were PSP (n⫽2), CBD (n⫽2), primary progressive aphasia (n⫽1), progressive anarthria (n⫽1), semantic dementia (n⫽1), frontotemporal dementia (FTD) (n⫽2) and FTD with motor neuron disease (n⫽1). Post mortem analysis showed a diagnosis of dementia lacking distinctive histology (DLDH) (n⫽5), PSP (n⫽2), CBD (n⫽2), Pick’s disease (n⫽1), FTLD with motor neuron degeneration (n⫽1) and mixed Alzheimer’s and Parkinson’s pathology (n⫽1). All cases shared important clinical and neuropsychological features. All clinical diagnoses were confirmed by post mortem analysis with the exception of 2 cases of CBD (mixed Alzheimer’s and Parkinson’s pathology and DLDH). Morphological and functional neuro-imaging helped in the establishment of clinical diagnosis but failed to predict neuropathology. Presence or absence of tau-positive inclusion is unpredictable in DFT. Some syndromes are better correlated with underlying pathology than others. CBD and progressive aphasia should be considered as clinical syndromes rather than clinicopathological entities. Conclusions: At the present time, multidisciplinary confrontation of clinical, neuropathological and biochemical data is still the only way to make a formal and precise diagnosis of neurodegenerative disease. Further studies are needed, including biomarker techniques, to understand in a better way the nosology of FTLD. P4-114
AUTOSOMAL DOMINANT FRONTOTEMPORAL DEMENTIA LINKED TO CHROMOSOME 3, FTD3: RECENT CLINICAL AND MOLECULAR FINDINGS
Suzanne G. Lindquist1,2, Hans Brændgaard3, Anne Nørremølle2, Kirsten Svenstrup2, Lis Hasholt2, Jørgen E. Nielsen1,2, 1Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen Ø, Denmark; 2 Department of Medical Biochemistry and Genetics, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; 3Department of Neurology, Århus University Hospital, Århus, Denmark. Contact e-mail: [email protected] Background: Frontotemporal dementia, which is the third most common neurodegenerative dementia syndrome, is genetically heterogenous. Previously, a Danish family with FTD linked to chromosome 3 (FTD3) was described and a mutation in the CHMP2B gene encoding a component of the endosomal ESCRTIII complex identified in all affected family members. Objective(s): We present clinical features and the finding of the same FTD3 mutation in the CHMP2B gene in a patient with frontotemporal dementia without known relation to the previously reported family. Results: The proband developed symptoms of dementia at the age of 50. His behavior and personality changed, he became increasingly aggressive and apathetic, and his spontaneous speech declined early in the disease course. His symptoms have been rapidly
Poster P4:: Wednesday Posters progressive and he is currently in a full-time care facility, less than two years after onset of symptoms. His mother developed early-onset dementia and was in full-time care from the age of 54, and a sister of the proband was diagnosed with frontotemporal dementia at the age of 59. A cerebral CT scan of the proband showed frontotemporal and central atrophy, and a PET scan showed frontal, temporal and parietal hypoperfusion. MMSE score at referral was 24/30. Neuropsychological examination revealed massive impairment of frontal and temporoparietal functions. Direct DNA sequencing of exon 6 of the CHMP2B gene showed that the patient had the characteristic G-to-C transition which has previously been described in the FTD3 family. In the previously reported FTD3 family, seven asymptomatic at risk individuals have been tested after genetic counselling and the mutation has been found in one of these individuals. Conclusions: We present recent findings in FTD3, including the detection of the mutation in a patient with no known relation to the previously reported FTD3 family. Most likely, the patient represents a previously unknown branch of the family. P4-115
FRONTOTEMPORAL DEGENERATION WITH UBIQUINATED INCLUSIONS: A CASE REPORT OF A FAMILY WITH CORTICOBASAL SYNDROME AND PROMINENT PARIETAL DEGENERATION
Najeeb Qadi, Ian RA Mackenzie, Emily S. Dwosh, Howard H. Feldman, University of British Columbia, Vancouver, BC, Canada. Contact e-mail: [email protected] Background: Frontotemporal lobar degeneration with ubiquinated inclusions (FTLD-U) was first described in patients with motor neuron disease and dementia but has recently been recognized as the most common pathology in cases of frontotemporal dementia (FTD). A significant proportion of cases are familial with the pattern of inheritance often being autosomal dominant. Several recent reports suggest that the spectrum of clinical disease associated with this pattern of pathology has not yet been fully appreciated. Objective: To describe a family with autosomal dominant FTD and corticobasal syndrome and autopsy confirmed FTLD-U with severe parietal lobe involvement. Methods: This family was identified and investigated at the UBC Clinic for Alzheimer Disease and Related Disorders. There are five affected members in two generations. Detailed clinical evaluations were performed on two affected sisters, one of whom eventually came to autopsy. Results: The age of onset was 60 and 63 years. Both developed characteristic features of FTD with non-fluent aphasia that progressed to mutism and behavioral changes that included apathy, emotional flatness and socially inappropriate behavior. Additional clinical features, consistent with a corticobasal syndrome, included slowness in mental processing, early, severe asymmetric apraxia (R⬎L), impairment in acquiring motor sequences, rigidity and alien hand phenomena. Neuroimaging showed asymmetric (L⬎R) degeneration of the frontal, temporal and parietal lobes. Disease duration was 5 and 8 years, respectively. Post mortem examination demonstrated cerebral atrophy that most severely affected the parietal lobes (L⬎R). There were typical microscopic features of FTLD-U with ubiquitin-positive, tau-, synuclein-negative neuronal cytoplasmic inclusions and neurites in the upper layers of neocortex and hippocampal dentate granule layer. Although all areas of neocortex were involved, the parietal cortex showed the most severe degeneration and most abundant ubiquitin pathology. The striatum and substantia nigra were also extensively involved. Also present were numerous ubiquitin-positive lentiform neuronal intranuclear inclusions, of the type most characteristic of autosomal dominant FTLD-U. Genetic screening for tau mutations was negative. Conclusions: This family demonstrates that FTLD-U may significantly involve the parietal lobes and cause a corticobasal syndrome.
P4-116
S549 FRONTOTEMPORAL LOBAR DEGENERATION WITH UBIQUITIN-POSITIVE INCLUSIONS: DEMOGRAPHICS AND SURVIVAL ANALYSIS OF CLINICAL SUBGROUPS
Ging-Yuek R. Hsiung, Ian Mackenzie, Caroline Lindholm, Howard Feldman, University of British Columbia, Vancouver, BC, Canada. Contact e-mail: [email protected] Background: Frontotemporal lobar degeneration with ubiquitin-immunoreactive, tau-negative inclusions (FTLD-U) was first recognized as the characteristic pathology in patients with motor neuron disease (MND) and dementia, but was subsequently found to be the most common cause of frontotemporal dementia (FTD). Most previous studies have evaluated clinically defined groups of FTD patients with various underlying pathologies. Clinical features specific to FTLD-U have not yet been well defined. Objective(s): To characterize the demographics and survival pattern of clinical subgroups in pathologically confirmed FTLD-U. Methods: Cases of FTLD-U were identified from recent autopsies and by retrospective review and re-evaluation of cases from our departmental archives. Medical records were reviewed and analyzed. In some cases, additional information was obtained from living family members. Results: Fifty cases with FTLD-U were divided into three clinical subgroups: 23 with dementia only, 9 with MND only, and 18 with both MND and dementia (MND-D). A definite family history was noted in 22 patients (44 %) from 16 unrelated families. There was an overall male predominance (1.6 M: 1 F) that remained constant among all clinical subgroups, and was particularly evident in sporadic cases (2.1 M: 1 F). The mean age of onset (61 ⫹/- 9 years) was similar in all clinical subgroups. Eight cases (16%) presented after age 70. While both familial and sporadic cases could present with dementia, MND, or both, most (95%) of the familial cases had developed dementia during their course of illness (p⫽0.03). Survival was significantly longer in females than males (7 vs. 4 years respectively, p⫽0.04). Patients with only dementia had a longer median survival (5 years) than those with only MND (1 year), or MND-D (4 years) (p⫽0.002). In each clinical subgroup, there was a trend for familial cases to have an earlier disease onset and shorter duration than sporadic cases. Conclusions: A sizable proportion of patients with FTLD-U presents after age of 70. While some patients have only MND symptoms, the majority developed dementia symptoms during their clinical course, especially those with a positive family history. The co-existence of MND pathology decreases survival, while female sex is associated with longer survival. P4-117
EXTENDING THE NEUROPATHOLOGICAL SPECTRUM OF FRONTOTEMPORAL LOBAR DEGENERATIONS: A REVIEW OF 833 PROSPECTIVELY ASSESSED DEMENTIA CASES
Lea Tenenholz Grinberg1,2, Rajka M. Liscic3,2, Tu Pang-hsien2, Daniel McKeel2, Deborah Carter2, Lisa Marie Taylor-Reinwald2, John C. Morris2, Nigel J. Cairns2, 1University of Sao Paulo, Sao Paulo, Brazil; 2Washington University in St Louis, St Louis, MO, USA; 3 Institute for Medical Research and Occupational Health, Zagreb, Croatia. Contact e-mail: [email protected] Background: Frontotemporal lobar degenerations (FTLDs) are clinically and neuropathologically heterogeneous and may account for 5-10% of dementias. Advances in immunohistochemistry, biochemistry, and genetics have helped to define and continue to broaden the spectrum of neurodegenerative diseases that are FTLDs. Objectives: To determine the pathological spectrum and frequency of FTLDs in a cohort of individuals assessed at the Washington University Alzheimer’s Disease Research Center (WUADRC). Methods: Review of 833 prospectively assessed dementia cases (Clinical Dementia Rating ⱖ 0.5) between 1988 and 2005 at the WUADRC and selection of cases with a neuropathological diagnosis of FTLD according to established and other neuropathological criteria. Brain tissue was processed and blocks taken according to the protocols of the WUADRC Neuropathology Core. Immunohistochemistry was performed