- Email: [email protected]
Rate of decline in ADNI normal controls with evidence of amyloid burden
S126
Oral O3-02: Neuropsychology
Additionally, beta-amyloid area levels were highly associated with clinical dementia (P < 0.005), whereas CERAD plaque scores were not (P ¼ 0.22) Conclusions: In the oldest-old, APOE2 was associated with increased CERAD plaque staging, but not increased beta-amyloid percent area. This lower level of percent area may reflect lower total beta-amyloid and may be responsible for the APOE2 carriers’ decreased risk of dementia, despite high CERAD plaque staging. Conversely, APOE4 carriers have both increased CERAD plaque staging and total beta-amyloid, which may be associated with their increased risk of clinical dementia. Therefore, findings from APOE2 carriers highlight the poor relationship between CERAD staging and cognition, and suggest that other measures of total beta-amyloid are more related to cognition in this age group. Consequently, the neuropathological criteria for AD may need to be reevaluated in this age group. O3-01-07
RATE OF DECLINE IN ADNI NORMAL CONTROLS WITH EVIDENCE OF AMYLOID BURDEN
Michael Donohue1, Anthony Gamst1, Ron Thomas1, Jim Brewer1, Michael Weiner2, Paul Aisen1, 1University of California San Diego, San Diego, CA, USA; 2University of California San Diego, San Francisco, CA, USA. Contact e-mail: [email protected] Background: Amyloid beta 1-42 peptide (Abeta) has been shown to differentiate normal elderly controls (NC) from Alzheimer’s Disease (AD). We explore whether changes in measures of volumetric MRI, resting glucose metabolism (FDG-PET), or cognitive or functional assessments within NCs are also predicted by evidence of amyloid deposition in the brain. We explore the feasibility of randomized interventions in amyloid positive (Abeta+) NCs to detect a 50% improvement in 2-year amyloid specific decline. Methods: We stratify the ADNI NC cohort by established PIB and CSF Abeta cutoffs, and estimate the 2-year rate of change in vMRI hippocampus, vMRI entorhinal cortex, FDG-PET posterior cingulated, RAVLT, FAQ, and MMSE. Using the difference between Abeta+ and Abeta- change from baseline as estimates of Abeta related decline, we estimate the required sample size necessary to detect a 50% improvement in a proof-of-concept randomized study in an Abeta+ cognitively normal cohort. We use linear mixed-models to estimate rates change. Results: The Abeta- group was slightly younger (75.13 (SD ¼ 5.27) vs 76.83 (5.23) years, p ¼ 0.086), so age was included as a covariate. A low proportion of Abeta- were ApoE4 carriers (7/76 ¼ 9% versus 21/46 ¼ 46%; p < 0.001), and a lower proportion converted to MCI within 2-years (2/76 ¼ 3% vs 4/46 ¼ 9%; p ¼ 0.133). The effect of Abeta on decline was significant for MMSE (p ¼ 0.007), hippocampus (p ¼ 0.010), and FAQ (p ¼ 0.026); and the rate of decline in Abeta+ was significant for hippocampus (p < 0.001), entorhinal (p < 0.001), MMSE (p ¼ 0.024), and FAQ (p ¼ 0.025). It would require N ¼ 187 (hippocampus), N ¼ 279 (MMSE), and N ¼ 613 (FAQ) subjects per arm to achieve 80% power (5% alpha) to detect a 50% reduction in amyloid specific decline in a hypothetical 2-year randomized, placebo controlled study in Abeta+ NCs (6-month visit intervals). Conclusions: There was a highly significant rate of vMRI change in Abeta+. Change in FDG-PET was not as pronounced. Surprisingly, we also found a significant (p < 0.05) rate of FAQ and MMSE change. Furthermore, the difference between amyloid+ and amyloid- was significant for hippocampus, FAQ and MMSE (p < 0.05), while the difference in entorhinal and FDG-PET was not.
O3-01-08
FAMILY HISTORY, DEMOGRAPHICS, AND GENETIC CHARACTERISTICS OF SYMPTOMATIC AND NON-SYMPTOMATIC SUBJECTS WITH NEUROPATHOLOGICAL ALZHEIMER’S DISEASE IN THE NATIONAL ALZHEIMER’S COORDINATING CENTER (NACC) DATASETS
Leslie E. Phillips1, Dawn P. Gill1, Catherine M. Roe2, Thomas D. Koepsell1, Walter A. Kukull1, John C. Morris2, 1National Alzheimer’s Coordinating Center, Seattle, WA, USA; 2Washington University in St. Louis, St. Louis, MO, USA. Contact e-mail: [email protected] Background: Greater education and older age have been associated with decreased cognitive impairment in the presence of neuropathology consistent
with Alzheimer’s disease (AD). To date, no published studies have sought to comprehensively characterize the family history, demographics, and genetic characteristics of persons who were not clinically-demented in life but who showed neuropathological features consistent with Alzheimer’s disease (AD) at autopsy. Methods: We studied 2,033 subjects who had neuropathologic features consistent with AD. We compared 126 subjects without clinically-detectable dementia (NONDEM) to the remaining 1,907 subjects with dementia (DEM). Deaths occurred within 18 months of subjects’ clinical evaluation at one of 32 Alzheimer’s Disease Centers in the U.S. All subjects had AD-consistent neuropathology, defined as one or more of the following neuropathologic features: Braak Stage >¼ 3 plus frequent neuritic plaques, NIA/Reagan intermediate or high, CERAD or Khachaturian consistent with AD, and/or primary pathologic diagnosis of AD. We conducted a stratified analysis using Mantel-Haenszel (M-H) odds ratios (OR) to control for ADC and identify characteristics that differentiate DEM subjects (those with both clinical dementia and neuropathological signs of AD) from NONDEM subjects (those with only neuropathological signs of AD). Results: Compared to NONDEM subjects, DEM subjects were more like to carry the APOE4 allele (M-H OR ¼ 2.94;95% CI, 1.85 to 4.66), more likely to have a first-degree relative with a history of dementia (M-H OR ¼ 1.79; 95% CI, 1.16 to 2.77), less likely to have completed a high school or greater education (M-H OR ¼ 0.33; 95% CI, 0.21 to 0.55), and were less likely to be age 82 years or older at last clinical assessment (M-H OR ¼ 0.28; 95% CI, 0.18 to 0.44). We observed no significant differences between NONDEM and DEM subjects by subject’s sex. Conclusions: The degree to which patients express clinical manifestations of AD neuropathology may be influenced by several demographic characteristics as well as family history and APOE status. Identifying demographic and genetic characteristics associated with clinical robustness to neuropathologic changes may advance understanding of factors that influence the slope of cognitive decline and help identify potential interventions aimed at slowing cognitive impairment. Funding: National Institute on Aging Grant (U01 AG016976) to National Alzheimer’s Coordinating Center
TUESDAY, JULY 13, 2010 ORAL O3-02 NEUROPSYCHOLOGY O3-02-01
SUBJECTIVE MEMORY COMPLAINERS IN THE AIBL COHORT: HYPERVIGILANCE AMONGST THE WORRIED WELL, OR INDIVIDUALS AT INCREASED RISK OF ALZHEIMER’S DISEASE?
Jonathan Foster1, Uma Jha2, Belinda Brown1, Greg Savage3, Kathryn Ellis4, David Darby5, Nicola Lautenschlager4, Paul Maruff4, Cassandra Szoeke4, Kevin Taddei1, Vanessa Ward1, Mark Rodrigues1, Rebecca Lachovitzki1, Mira Rimajova1, Nat Lenzo6, Andrew Campbell7, Christopher Rowe4, Victor Villemagne8, Tania Taddei1, James Lui1, Colin Masters4, David Ames4, Ralph Martins1, 1Edith Cowan University, Joondalup, Australia; 2Shenton College, Shenton Park, Australia; 3Macquarie University, Sydney, Australia; 4University of Melbourne, Melbourne, Australia; 5University of Mebourne, Melbourne, Australia; 6Notre Dame University, Fremantle, Australia; 7Royal Perth Hospital, Perth, Australia; 8University of Melbourne, Melbourne, Australia. Contact e-mail: [email protected] Background: The significance of subjective memory complaints in older adults is controversial. We sought to clarify this issue in this study. Methods: We examined the relationship between memory complaints, neuropsychological capacity, mood, diagnostic status and clinically significant brain amyloid deposition (PIB PET) in the Australian Imaging, Biomarker and Lifestyle (AIBL) cohort (Ellis et al., 2009) of 1112 participants over the age of 60 studied i) at baseline and ii) 18 months later. We focused on subjective memory complainers (MCs: n ¼ 318) and subjective non-memory complainers (NMCs: n ¼ 311) from among the healthy controls enrolled at baseline in this cohort. Results: Statistically significant differences in neuropsychological capacity were observed at baseline between MC and NMC
Oral O3-02: Neuropsychology
Additionally, beta-amyloid area levels were highly associated with clinical dementia (P < 0.005), whereas CERAD plaque scores were not (P ¼ 0.22) Conclusions: In the oldest-old, APOE2 was associated with increased CERAD plaque staging, but not increased beta-amyloid percent area. This lower level of percent area may reflect lower total beta-amyloid and may be responsible for the APOE2 carriers’ decreased risk of dementia, despite high CERAD plaque staging. Conversely, APOE4 carriers have both increased CERAD plaque staging and total beta-amyloid, which may be associated with their increased risk of clinical dementia. Therefore, findings from APOE2 carriers highlight the poor relationship between CERAD staging and cognition, and suggest that other measures of total beta-amyloid are more related to cognition in this age group. Consequently, the neuropathological criteria for AD may need to be reevaluated in this age group. O3-01-07
RATE OF DECLINE IN ADNI NORMAL CONTROLS WITH EVIDENCE OF AMYLOID BURDEN
Michael Donohue1, Anthony Gamst1, Ron Thomas1, Jim Brewer1, Michael Weiner2, Paul Aisen1, 1University of California San Diego, San Diego, CA, USA; 2University of California San Diego, San Francisco, CA, USA. Contact e-mail: [email protected] Background: Amyloid beta 1-42 peptide (Abeta) has been shown to differentiate normal elderly controls (NC) from Alzheimer’s Disease (AD). We explore whether changes in measures of volumetric MRI, resting glucose metabolism (FDG-PET), or cognitive or functional assessments within NCs are also predicted by evidence of amyloid deposition in the brain. We explore the feasibility of randomized interventions in amyloid positive (Abeta+) NCs to detect a 50% improvement in 2-year amyloid specific decline. Methods: We stratify the ADNI NC cohort by established PIB and CSF Abeta cutoffs, and estimate the 2-year rate of change in vMRI hippocampus, vMRI entorhinal cortex, FDG-PET posterior cingulated, RAVLT, FAQ, and MMSE. Using the difference between Abeta+ and Abeta- change from baseline as estimates of Abeta related decline, we estimate the required sample size necessary to detect a 50% improvement in a proof-of-concept randomized study in an Abeta+ cognitively normal cohort. We use linear mixed-models to estimate rates change. Results: The Abeta- group was slightly younger (75.13 (SD ¼ 5.27) vs 76.83 (5.23) years, p ¼ 0.086), so age was included as a covariate. A low proportion of Abeta- were ApoE4 carriers (7/76 ¼ 9% versus 21/46 ¼ 46%; p < 0.001), and a lower proportion converted to MCI within 2-years (2/76 ¼ 3% vs 4/46 ¼ 9%; p ¼ 0.133). The effect of Abeta on decline was significant for MMSE (p ¼ 0.007), hippocampus (p ¼ 0.010), and FAQ (p ¼ 0.026); and the rate of decline in Abeta+ was significant for hippocampus (p < 0.001), entorhinal (p < 0.001), MMSE (p ¼ 0.024), and FAQ (p ¼ 0.025). It would require N ¼ 187 (hippocampus), N ¼ 279 (MMSE), and N ¼ 613 (FAQ) subjects per arm to achieve 80% power (5% alpha) to detect a 50% reduction in amyloid specific decline in a hypothetical 2-year randomized, placebo controlled study in Abeta+ NCs (6-month visit intervals). Conclusions: There was a highly significant rate of vMRI change in Abeta+. Change in FDG-PET was not as pronounced. Surprisingly, we also found a significant (p < 0.05) rate of FAQ and MMSE change. Furthermore, the difference between amyloid+ and amyloid- was significant for hippocampus, FAQ and MMSE (p < 0.05), while the difference in entorhinal and FDG-PET was not.
O3-01-08
FAMILY HISTORY, DEMOGRAPHICS, AND GENETIC CHARACTERISTICS OF SYMPTOMATIC AND NON-SYMPTOMATIC SUBJECTS WITH NEUROPATHOLOGICAL ALZHEIMER’S DISEASE IN THE NATIONAL ALZHEIMER’S COORDINATING CENTER (NACC) DATASETS
Leslie E. Phillips1, Dawn P. Gill1, Catherine M. Roe2, Thomas D. Koepsell1, Walter A. Kukull1, John C. Morris2, 1National Alzheimer’s Coordinating Center, Seattle, WA, USA; 2Washington University in St. Louis, St. Louis, MO, USA. Contact e-mail: [email protected] Background: Greater education and older age have been associated with decreased cognitive impairment in the presence of neuropathology consistent
with Alzheimer’s disease (AD). To date, no published studies have sought to comprehensively characterize the family history, demographics, and genetic characteristics of persons who were not clinically-demented in life but who showed neuropathological features consistent with Alzheimer’s disease (AD) at autopsy. Methods: We studied 2,033 subjects who had neuropathologic features consistent with AD. We compared 126 subjects without clinically-detectable dementia (NONDEM) to the remaining 1,907 subjects with dementia (DEM). Deaths occurred within 18 months of subjects’ clinical evaluation at one of 32 Alzheimer’s Disease Centers in the U.S. All subjects had AD-consistent neuropathology, defined as one or more of the following neuropathologic features: Braak Stage >¼ 3 plus frequent neuritic plaques, NIA/Reagan intermediate or high, CERAD or Khachaturian consistent with AD, and/or primary pathologic diagnosis of AD. We conducted a stratified analysis using Mantel-Haenszel (M-H) odds ratios (OR) to control for ADC and identify characteristics that differentiate DEM subjects (those with both clinical dementia and neuropathological signs of AD) from NONDEM subjects (those with only neuropathological signs of AD). Results: Compared to NONDEM subjects, DEM subjects were more like to carry the APOE4 allele (M-H OR ¼ 2.94;95% CI, 1.85 to 4.66), more likely to have a first-degree relative with a history of dementia (M-H OR ¼ 1.79; 95% CI, 1.16 to 2.77), less likely to have completed a high school or greater education (M-H OR ¼ 0.33; 95% CI, 0.21 to 0.55), and were less likely to be age 82 years or older at last clinical assessment (M-H OR ¼ 0.28; 95% CI, 0.18 to 0.44). We observed no significant differences between NONDEM and DEM subjects by subject’s sex. Conclusions: The degree to which patients express clinical manifestations of AD neuropathology may be influenced by several demographic characteristics as well as family history and APOE status. Identifying demographic and genetic characteristics associated with clinical robustness to neuropathologic changes may advance understanding of factors that influence the slope of cognitive decline and help identify potential interventions aimed at slowing cognitive impairment. Funding: National Institute on Aging Grant (U01 AG016976) to National Alzheimer’s Coordinating Center
TUESDAY, JULY 13, 2010 ORAL O3-02 NEUROPSYCHOLOGY O3-02-01
SUBJECTIVE MEMORY COMPLAINERS IN THE AIBL COHORT: HYPERVIGILANCE AMONGST THE WORRIED WELL, OR INDIVIDUALS AT INCREASED RISK OF ALZHEIMER’S DISEASE?
Jonathan Foster1, Uma Jha2, Belinda Brown1, Greg Savage3, Kathryn Ellis4, David Darby5, Nicola Lautenschlager4, Paul Maruff4, Cassandra Szoeke4, Kevin Taddei1, Vanessa Ward1, Mark Rodrigues1, Rebecca Lachovitzki1, Mira Rimajova1, Nat Lenzo6, Andrew Campbell7, Christopher Rowe4, Victor Villemagne8, Tania Taddei1, James Lui1, Colin Masters4, David Ames4, Ralph Martins1, 1Edith Cowan University, Joondalup, Australia; 2Shenton College, Shenton Park, Australia; 3Macquarie University, Sydney, Australia; 4University of Melbourne, Melbourne, Australia; 5University of Mebourne, Melbourne, Australia; 6Notre Dame University, Fremantle, Australia; 7Royal Perth Hospital, Perth, Australia; 8University of Melbourne, Melbourne, Australia. Contact e-mail: [email protected] Background: The significance of subjective memory complaints in older adults is controversial. We sought to clarify this issue in this study. Methods: We examined the relationship between memory complaints, neuropsychological capacity, mood, diagnostic status and clinically significant brain amyloid deposition (PIB PET) in the Australian Imaging, Biomarker and Lifestyle (AIBL) cohort (Ellis et al., 2009) of 1112 participants over the age of 60 studied i) at baseline and ii) 18 months later. We focused on subjective memory complainers (MCs: n ¼ 318) and subjective non-memory complainers (NMCs: n ¼ 311) from among the healthy controls enrolled at baseline in this cohort. Results: Statistically significant differences in neuropsychological capacity were observed at baseline between MC and NMC