- Email: [email protected]
P1-142 Who volunteers for long-term clinical trials?
Poster Session PI : Diagnosis and Disease Progression - Others
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fiber ceils. In AD lenses, A[~ and metal co-localize in supranuclear and deep cortical lens fiber cell cytoplasm. In vitro, metal chelation blocks Al3-potentiated lens protein aggregation and light scattering. A[3 binds and co-immunoprecipitates with alphaB-crystallin, an abundant cytosolic lens structural protein also upregulated in AD brain. A~ and alphaB-crystallin co-localize in cytosolic microaggregates in AD lenses and co-immunopurify from AD brain. Lens pathology in Tg2576 mice can be detected and imaged using conventional and novel optical insmamentation. Conclusions: [3-APP gene expression and protein processing are altered during lens epithelial to fiber cell terminal differentiation. These factors may contribute to cytoplasmic A~ accumulation in AD lens supranuclear fiber cells. A[~ interacts with other cytosolic lens proteins and promotes metal-dependent protein aggregation and light scattering. AD-associated lens pathology may have potential as an early AD biomarker.
dictated sentences. The group with low education level showed poorer performance than the other, and deficits in oral comprehension of words, serial writing and graphic denomination were also observed for this group. Although the most compromised linguistic tasks, in this stage, were the ones depending on memory, especially working memory/phonological loop and semantic memory or semantic buffer, specific disorders of linguistic processing were observed in the initial stages of the disease and school grade have contributed to worsen the deficits. Conclusions: We strongly believe that early language evaluation may corroborate in understanding compromised cognitive-linguistic skills and may help in counseling for communication facilitating strategies during the disease's course.
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~ W H O
VOLUNTEERS FOR LONG-TERM CLINICAL TRIALS?
VALIDATION O F A M O D E L TO ASSESS L O N G - T E R M DISEASE P R O G R E S S I O N IN A L Z H E I M E R ' S DISEASE PATIENTS TREATED W I T H RIVASTIGMINE
Lindy E. Harrell*, Edward Zamrini, Nickie Burst, Alfred Batolucci. University of Alabama at Birmingham, Birmingham, AL, USA. Contact e-mail: [email protected]
Brett Hanber* 1, Sean Candrilli 1, Edward H. Snyder 2, Christopher R. McBumey 2. I Research Triangle Institute, Chapel Hill, NC, USA; 2Novartis Pharmaceuticals, East Hanover, NJ, USA. Contact e-mail: abhauber@ rti.org
Background: Little is know about who volunteers for longitudinal study
Background: There is a lack of data linking the progression of Alzheimer's
in Alzheimer's Disease Research Centers (ADRC). Objective(s): To try to answer this question we examined some of the demographics of normal older subjects and patients with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) participating in a NIA funded ADRC. Methods: Chi-square analysis was used to compare groups. Results: Of 345 patients, 177 suffered from AD, 63 from MCI and 105 were normals. Of these 63% and 65% were female AD and MCI patients while 74% were female normals (p < 0.003). Mean age was higher in the AD group (73 + 8.6 SD) when compared to both MCI (68 =t= 8.5) and normals (64 4- 7.4) (p90 2%) than MCI (11%; 48%; 32%; 8%; 2%) and normals (33%; 38%; 26%; 3%; 0%)(p < 0.0001). Family history of dementia was similar among all groups (postive history: AD 66%; MCI 59%; normals 56%). Depression was more common in normals (23%) than AD (6%) or MCI (2%)(p < 0.0001). At initial evaluation none of the groups had signs or symptoms of Parkinsonism. Conclusions: These findings suggest that normal older individuals who volunteer for research tend to be female and younger than AD patients. Further MCI patients are also younger than AD pateints. Those with a family history appear to vohinteer at higher rates than those without family history. These results suggest that age and depression need to be taken into consideration when performing statistical analysis.
disease (AD) symptoms with long-term consequences for both domestic and institutional care burdens. One method of rectifying this is to use modeling techniques that allow extrapolation of cost savings and decreases in caregiver time over the long term, based on pooled data from large, multicenter studies with cholinesterase inhibitors. Objective(s): To validate the use of an existing model of AD progression for the estimation of long-term cost savings with the cholinesterase inhibitor, rivasfigmine, using pooled data from long-term, open-label clinical studies. Methods: A previous model of AD progression utilized data from two pivotal clinical trials (overall n = 1333) assessing the efficacy and safety of rivastigmine over 180 days. With disease progression measured as decline on the MiniMental Status Evaluation (MMSE), various stages of AD were defined as intervals on this scale. Extrapolated survival analyses then evaluated the impact of treatment in delaying the onset of more severe disease states using a Weibull parametric hazard method. To validate this model, data from open-label rivastigmine extension studies up to 720 days were treated similarly. Survival probabilities in the 180-day and 720-day cohorts were compared using Wilcoxon Rank-Sum tests. Results: The final open-label study analysis included data from 1814 patients (mean age, 72.6 years; mean (-4-SD) baseline MMSE score, 19.65 -t- 4.62 points). Patients were followed up for 812.5 + 497.3 days, and the mean total change in MMSE score was -5.41 =t= 6.22 points. Predicted survival probabilities from the pivotal trial data set were lower than those from the open-label analysis at 180, 360, 540 and 720 days. Significant differences were seen at 540 and 720 days (p < 0.01 and p < 0.0001, respectively). Conclusions: Although the 720-day open-label analysis serves to validate the original pivotal trial model, the original model appears conservative, predicting a more rapid rate of cognitive decline in rivastigmine-treated patients. These results indicate that patients with mild to moderate AD treated with rivastigmine remain in less severe stages of AD for longer periods of time, and incur lower treatment costs than originally predicted.
•
LANGUAGE DISORDERS IN INITIAL STAGES O F
ALZHEIMER'S DISEASE Karin Z. Ortiz*, Paulo E Bertolucci. Universidade Federal de Sao Paulo, Sao Paulo, Brazil. Contact e-mail: [email protected]
Background: Patients with Alzheimer's dementia present cognitive, language and behavioral disorders, which deteriorate as the disease progresses. Memory deficits, however, are the most frequent complaints reported by the family and these are also the most predominant during clinical assessment in the initial stages of the disease. Objective(s): Our purpose, in this study, were to investigate the possibility of identifying early language deficits and to establish the most frequent disorders observed. Methods: Twelve patients diagnosed with Alzheimer's disease were evaluated. All patients scored more than 23 points (average 25,5) at Mini Mental State Exam. School grade varied from incomplete primary school and complete university level and allowed the division into two groups: one with 4 years of education and the other with 17 years of education. Patients have undergone language evaluation using Boston Test and the data obtained was compared to normal subjects data with similar school grade. Results: All patients, independently from school grade, showed language disorders. The group with superior education presented significant deficits only in oral comprehension tasks of higher complexity (oral commands and texts), spelling comprehension, comprehension of read texts, handwriting and
~ r ~
TESTSUSEFUL FOR SCREENING FOR AD RISKIN A DIVERSE SAMPLE
Diana S. Woodruff-Pak* 1,2, Mark L. Moster 2,3, Ole S. Jorgensen4, Hyung W. Pak 2, I Temple University, Philadelphia, PA, USA; 2Albert Einstein Healthcare Network, Philadelphia, PA, USA; 3Wills Eye Hospital, Philadelphia, PA, USA; 4Copenhagen University Hospital, Copenhagen, Denmark. Contact e-mail: pak@ temple.edu
Background: Diversity is increasing in the older adult population in the United States, making those at risk for Alzheimer's disease (AD) a multiracial group. However, data on effective screening and diagnostic tests for racial and cultural minority groups are limited. The overrepresentation of the
S136
fiber ceils. In AD lenses, A[~ and metal co-localize in supranuclear and deep cortical lens fiber cell cytoplasm. In vitro, metal chelation blocks Al3-potentiated lens protein aggregation and light scattering. A[3 binds and co-immunoprecipitates with alphaB-crystallin, an abundant cytosolic lens structural protein also upregulated in AD brain. A~ and alphaB-crystallin co-localize in cytosolic microaggregates in AD lenses and co-immunopurify from AD brain. Lens pathology in Tg2576 mice can be detected and imaged using conventional and novel optical insmamentation. Conclusions: [3-APP gene expression and protein processing are altered during lens epithelial to fiber cell terminal differentiation. These factors may contribute to cytoplasmic A~ accumulation in AD lens supranuclear fiber cells. A[~ interacts with other cytosolic lens proteins and promotes metal-dependent protein aggregation and light scattering. AD-associated lens pathology may have potential as an early AD biomarker.
dictated sentences. The group with low education level showed poorer performance than the other, and deficits in oral comprehension of words, serial writing and graphic denomination were also observed for this group. Although the most compromised linguistic tasks, in this stage, were the ones depending on memory, especially working memory/phonological loop and semantic memory or semantic buffer, specific disorders of linguistic processing were observed in the initial stages of the disease and school grade have contributed to worsen the deficits. Conclusions: We strongly believe that early language evaluation may corroborate in understanding compromised cognitive-linguistic skills and may help in counseling for communication facilitating strategies during the disease's course.
•
~ W H O
VOLUNTEERS FOR LONG-TERM CLINICAL TRIALS?
VALIDATION O F A M O D E L TO ASSESS L O N G - T E R M DISEASE P R O G R E S S I O N IN A L Z H E I M E R ' S DISEASE PATIENTS TREATED W I T H RIVASTIGMINE
Lindy E. Harrell*, Edward Zamrini, Nickie Burst, Alfred Batolucci. University of Alabama at Birmingham, Birmingham, AL, USA. Contact e-mail: [email protected]
Brett Hanber* 1, Sean Candrilli 1, Edward H. Snyder 2, Christopher R. McBumey 2. I Research Triangle Institute, Chapel Hill, NC, USA; 2Novartis Pharmaceuticals, East Hanover, NJ, USA. Contact e-mail: abhauber@ rti.org
Background: Little is know about who volunteers for longitudinal study
Background: There is a lack of data linking the progression of Alzheimer's
in Alzheimer's Disease Research Centers (ADRC). Objective(s): To try to answer this question we examined some of the demographics of normal older subjects and patients with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) participating in a NIA funded ADRC. Methods: Chi-square analysis was used to compare groups. Results: Of 345 patients, 177 suffered from AD, 63 from MCI and 105 were normals. Of these 63% and 65% were female AD and MCI patients while 74% were female normals (p < 0.003). Mean age was higher in the AD group (73 + 8.6 SD) when compared to both MCI (68 =t= 8.5) and normals (64 4- 7.4) (p90 2%) than MCI (11%; 48%; 32%; 8%; 2%) and normals (33%; 38%; 26%; 3%; 0%)(p < 0.0001). Family history of dementia was similar among all groups (postive history: AD 66%; MCI 59%; normals 56%). Depression was more common in normals (23%) than AD (6%) or MCI (2%)(p < 0.0001). At initial evaluation none of the groups had signs or symptoms of Parkinsonism. Conclusions: These findings suggest that normal older individuals who volunteer for research tend to be female and younger than AD patients. Further MCI patients are also younger than AD pateints. Those with a family history appear to vohinteer at higher rates than those without family history. These results suggest that age and depression need to be taken into consideration when performing statistical analysis.
disease (AD) symptoms with long-term consequences for both domestic and institutional care burdens. One method of rectifying this is to use modeling techniques that allow extrapolation of cost savings and decreases in caregiver time over the long term, based on pooled data from large, multicenter studies with cholinesterase inhibitors. Objective(s): To validate the use of an existing model of AD progression for the estimation of long-term cost savings with the cholinesterase inhibitor, rivasfigmine, using pooled data from long-term, open-label clinical studies. Methods: A previous model of AD progression utilized data from two pivotal clinical trials (overall n = 1333) assessing the efficacy and safety of rivastigmine over 180 days. With disease progression measured as decline on the MiniMental Status Evaluation (MMSE), various stages of AD were defined as intervals on this scale. Extrapolated survival analyses then evaluated the impact of treatment in delaying the onset of more severe disease states using a Weibull parametric hazard method. To validate this model, data from open-label rivastigmine extension studies up to 720 days were treated similarly. Survival probabilities in the 180-day and 720-day cohorts were compared using Wilcoxon Rank-Sum tests. Results: The final open-label study analysis included data from 1814 patients (mean age, 72.6 years; mean (-4-SD) baseline MMSE score, 19.65 -t- 4.62 points). Patients were followed up for 812.5 + 497.3 days, and the mean total change in MMSE score was -5.41 =t= 6.22 points. Predicted survival probabilities from the pivotal trial data set were lower than those from the open-label analysis at 180, 360, 540 and 720 days. Significant differences were seen at 540 and 720 days (p < 0.01 and p < 0.0001, respectively). Conclusions: Although the 720-day open-label analysis serves to validate the original pivotal trial model, the original model appears conservative, predicting a more rapid rate of cognitive decline in rivastigmine-treated patients. These results indicate that patients with mild to moderate AD treated with rivastigmine remain in less severe stages of AD for longer periods of time, and incur lower treatment costs than originally predicted.
•
LANGUAGE DISORDERS IN INITIAL STAGES O F
ALZHEIMER'S DISEASE Karin Z. Ortiz*, Paulo E Bertolucci. Universidade Federal de Sao Paulo, Sao Paulo, Brazil. Contact e-mail: [email protected]
Background: Patients with Alzheimer's dementia present cognitive, language and behavioral disorders, which deteriorate as the disease progresses. Memory deficits, however, are the most frequent complaints reported by the family and these are also the most predominant during clinical assessment in the initial stages of the disease. Objective(s): Our purpose, in this study, were to investigate the possibility of identifying early language deficits and to establish the most frequent disorders observed. Methods: Twelve patients diagnosed with Alzheimer's disease were evaluated. All patients scored more than 23 points (average 25,5) at Mini Mental State Exam. School grade varied from incomplete primary school and complete university level and allowed the division into two groups: one with 4 years of education and the other with 17 years of education. Patients have undergone language evaluation using Boston Test and the data obtained was compared to normal subjects data with similar school grade. Results: All patients, independently from school grade, showed language disorders. The group with superior education presented significant deficits only in oral comprehension tasks of higher complexity (oral commands and texts), spelling comprehension, comprehension of read texts, handwriting and
~ r ~
TESTSUSEFUL FOR SCREENING FOR AD RISKIN A DIVERSE SAMPLE
Diana S. Woodruff-Pak* 1,2, Mark L. Moster 2,3, Ole S. Jorgensen4, Hyung W. Pak 2, I Temple University, Philadelphia, PA, USA; 2Albert Einstein Healthcare Network, Philadelphia, PA, USA; 3Wills Eye Hospital, Philadelphia, PA, USA; 4Copenhagen University Hospital, Copenhagen, Denmark. Contact e-mail: pak@ temple.edu
Background: Diversity is increasing in the older adult population in the United States, making those at risk for Alzheimer's disease (AD) a multiracial group. However, data on effective screening and diagnostic tests for racial and cultural minority groups are limited. The overrepresentation of the