- Email: [email protected]
WWII COMBAT EXPOSURE IS NOT ASSOCIATED WITH LATE-LIFE COGNITIVE DECLINE, DEMENTIA, NEUROPATHOLOGIC ALZHEIMER’S DISEASE, OR OTHER NEUROPATHOLOGIC ABNORMALITIES: THE HONOLULOU-ASIA AGING STUDY (HAAS)
P186
Podium Presentations: Sunday, July 24, 2016
correlation coefficient between predicted and observed cognitive scores indicates that predicted cognitive changes over 8 years is close to observed ones. For example, for patients with mild cognitive impairment (MCI) at baseline and stable until dropout, disenrollment, or death, the correlation coefficient between predicted and observed scores is 0.82. For patients who are normal at baseline but transition to Alzheimer dementia, the correlation coefficient is 0.73. Conclusions: We tested the feasibility of a machine learning algorithm to discern patterns of long-term cognitive change, and then to predict ADAS-Cog scores and annual changes over 8 years. We are in the process of revising our methods with the goal of translating our research method to settings in which data relevant to cognitive status and decline are less rich than ADNI in high-salience predictive power.
Figure 1. We aim to individualize prediction of long-term cognitive changes overtime. The figure demonstrates a case study of such an individualized prediction, integrating many currently known risk factors.
years (range 79-102). Average age at military induction was 25 years. Combat experiences were categorized as negligible (n¼244, 4% with service related disability), mild or moderate (n¼76, 14% with disability), or as intense and protracted (n¼219, 49% with service connected disabilities). Dementia or severe cognitive impairment was identified by screening with the Cognitive Abilities and Screening Instrument (CASI) with follow-up dementia assessments. Brain autopsies were completed for 106 decedents for whom combat information was available. Analyses utilized multivariate logistic and linear regression methods controlling for birth year, age at death, education, and ApoE 4 zygosity. Results: Among the 539 men with combat exposure information, 15% developed severe cognitive impairment or dementia, 23% became moderately impaired, and 62% remained unimpaired. No significant associations of combat exposure were observed with longevity (age at death), dementia, cognitive impairment, or any of the following neuropathologic abnormalities measured at autopsy: Braak stage, neocortical NFT and amyloid plaque counts, vascular amyloid, A-beta accumulation in the striata (by Thal staining), large infarcts, lacunar infarcts, microinfarcts, Lewy bodies, hippocampal sclerosis, generalized brain atrophy, or temporally remote subdural hematoma. Conclusions: Among Japanese-American veterans who survived to late life, WWII combat experiences appear to be unrelated to dementia or its common neuropathologic correlates. O1-06-03
PROTEOMIC ANALYSIS OF EXTRACELLULAR VESICLES IN ALZHEIMER’S DISEASE CEREBROSPINAL FLUID
Davide Chiasserini1, Tim Schelfhorst2, Pier Luigi Orvietani1, Sander R. Piersma2, Thang V. Pham2, Stefano Giovagnoli1, Lucilla Parnetti1, Connie R. Jimenez2, 1University of Perugia, Perugia, Italy; 2VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: [email protected] Figure 2. Examples of stable and changing cognitive patterns from our ADNI study. The figure demonstrates comparison between predicted and observed ADAS-Cog scores over time for MCI->MCI (left panel) and NL->AD (right panel) subgroups averaged over individuals. O1-06-02
WWII COMBAT EXPOSURE IS NOT ASSOCIATED WITH LATE-LIFE COGNITIVE DECLINE, DEMENTIA, NEUROPATHOLOGIC ALZHEIMER’S DISEASE, OR OTHER NEUROPATHOLOGIC ABNORMALITIES: THE HONOLULOU-ASIA AGING STUDY (HAAS)
Lon R. White1,2,3,4, Emy A. Willis3, Margaret Mackintosh5, Lenore J. Launer6, Steven D. Edland7, 1National Institute on Aging, NIH, Bethesda, MD, USA; 2University of Washington School of Medicine, Seattle, WA, USA; 3Pacific Health Research and Education Institute, Honolulu, HI, USA; 4John A Burns School of Medicine, Honolulu, HI, USA; 5Pacific Health Research and Education Institute, Honolulu, HI, USA; 6National Institute on Aging, Bethesda, MD, USA; 7University of California at San Diego, San Diego, CA, USA. Contact e-mail: [email protected] Background: Emotional and physical trauma in early or middle
adult life have been proposed as factors influencing late life cognitive decline, Alzheimer’s disease, and longevity. Methods: The HAAS cohort included 3734 Japanese-American men, of whom 879 had served in WWII, including 539 who provided descriptions of their combat experiences. More than 77% died during the 20 year course of the study. Average age at death was 88.8
Background: Cerebrospinal fluid (CSF) contains different types of extracellular vesicles (EVs) with undisclosed biomarker potential for neurodegenerative diseases1. Here we isolated EVs from pooled CSF samples coming from control subjects (CTRL) and patients diagnosed with probable Alzheimer’s disease (AD). We then characterized the EV proteome using high resolution tandem mass spectrometry (LC-MS/MS) and bioinformatic analysis. Our aim was to compare the EVs proteome in AD patients and controls, to highlight candidate biomarkers to be further validated. Methods: CSF samples were obtained from the biobank of the University Hospital of Perugia. Two CSF pools were constructed, the AD pool was composed of patients diagnosed with probable AD and with a CSF profile indicative of AD (n¼30). The CTRL CSF pool was built from 30 subjects who underwent CSF tapping for diagnostic reasons and, after evaluation, they were found free of any cognitive impairment or any neurodegenerative disease. All the control subjects had a negative AD biomarker profile. EV isolation and proteomic analysis were carried out as previously described1, two replicates were run for each sample. Results: About 800 proteins were consistently identified in all the CSF EV samples. CSF EVs proteome was enriched in heat shock proteins, tetraspanins and endosomal trafficking proteins. Furthermore, CSF EVs were highly enriched in brain-derived proteins including several Intraflagellar Transport Proteins expressed in the choroid plexus, possibly showing that CSF EVs are in part derived from the tissue
Podium Presentations: Sunday, July 24, 2016
correlation coefficient between predicted and observed cognitive scores indicates that predicted cognitive changes over 8 years is close to observed ones. For example, for patients with mild cognitive impairment (MCI) at baseline and stable until dropout, disenrollment, or death, the correlation coefficient between predicted and observed scores is 0.82. For patients who are normal at baseline but transition to Alzheimer dementia, the correlation coefficient is 0.73. Conclusions: We tested the feasibility of a machine learning algorithm to discern patterns of long-term cognitive change, and then to predict ADAS-Cog scores and annual changes over 8 years. We are in the process of revising our methods with the goal of translating our research method to settings in which data relevant to cognitive status and decline are less rich than ADNI in high-salience predictive power.
Figure 1. We aim to individualize prediction of long-term cognitive changes overtime. The figure demonstrates a case study of such an individualized prediction, integrating many currently known risk factors.
years (range 79-102). Average age at military induction was 25 years. Combat experiences were categorized as negligible (n¼244, 4% with service related disability), mild or moderate (n¼76, 14% with disability), or as intense and protracted (n¼219, 49% with service connected disabilities). Dementia or severe cognitive impairment was identified by screening with the Cognitive Abilities and Screening Instrument (CASI) with follow-up dementia assessments. Brain autopsies were completed for 106 decedents for whom combat information was available. Analyses utilized multivariate logistic and linear regression methods controlling for birth year, age at death, education, and ApoE 4 zygosity. Results: Among the 539 men with combat exposure information, 15% developed severe cognitive impairment or dementia, 23% became moderately impaired, and 62% remained unimpaired. No significant associations of combat exposure were observed with longevity (age at death), dementia, cognitive impairment, or any of the following neuropathologic abnormalities measured at autopsy: Braak stage, neocortical NFT and amyloid plaque counts, vascular amyloid, A-beta accumulation in the striata (by Thal staining), large infarcts, lacunar infarcts, microinfarcts, Lewy bodies, hippocampal sclerosis, generalized brain atrophy, or temporally remote subdural hematoma. Conclusions: Among Japanese-American veterans who survived to late life, WWII combat experiences appear to be unrelated to dementia or its common neuropathologic correlates. O1-06-03
PROTEOMIC ANALYSIS OF EXTRACELLULAR VESICLES IN ALZHEIMER’S DISEASE CEREBROSPINAL FLUID
Davide Chiasserini1, Tim Schelfhorst2, Pier Luigi Orvietani1, Sander R. Piersma2, Thang V. Pham2, Stefano Giovagnoli1, Lucilla Parnetti1, Connie R. Jimenez2, 1University of Perugia, Perugia, Italy; 2VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: [email protected] Figure 2. Examples of stable and changing cognitive patterns from our ADNI study. The figure demonstrates comparison between predicted and observed ADAS-Cog scores over time for MCI->MCI (left panel) and NL->AD (right panel) subgroups averaged over individuals. O1-06-02
WWII COMBAT EXPOSURE IS NOT ASSOCIATED WITH LATE-LIFE COGNITIVE DECLINE, DEMENTIA, NEUROPATHOLOGIC ALZHEIMER’S DISEASE, OR OTHER NEUROPATHOLOGIC ABNORMALITIES: THE HONOLULOU-ASIA AGING STUDY (HAAS)
Lon R. White1,2,3,4, Emy A. Willis3, Margaret Mackintosh5, Lenore J. Launer6, Steven D. Edland7, 1National Institute on Aging, NIH, Bethesda, MD, USA; 2University of Washington School of Medicine, Seattle, WA, USA; 3Pacific Health Research and Education Institute, Honolulu, HI, USA; 4John A Burns School of Medicine, Honolulu, HI, USA; 5Pacific Health Research and Education Institute, Honolulu, HI, USA; 6National Institute on Aging, Bethesda, MD, USA; 7University of California at San Diego, San Diego, CA, USA. Contact e-mail: [email protected] Background: Emotional and physical trauma in early or middle
adult life have been proposed as factors influencing late life cognitive decline, Alzheimer’s disease, and longevity. Methods: The HAAS cohort included 3734 Japanese-American men, of whom 879 had served in WWII, including 539 who provided descriptions of their combat experiences. More than 77% died during the 20 year course of the study. Average age at death was 88.8
Background: Cerebrospinal fluid (CSF) contains different types of extracellular vesicles (EVs) with undisclosed biomarker potential for neurodegenerative diseases1. Here we isolated EVs from pooled CSF samples coming from control subjects (CTRL) and patients diagnosed with probable Alzheimer’s disease (AD). We then characterized the EV proteome using high resolution tandem mass spectrometry (LC-MS/MS) and bioinformatic analysis. Our aim was to compare the EVs proteome in AD patients and controls, to highlight candidate biomarkers to be further validated. Methods: CSF samples were obtained from the biobank of the University Hospital of Perugia. Two CSF pools were constructed, the AD pool was composed of patients diagnosed with probable AD and with a CSF profile indicative of AD (n¼30). The CTRL CSF pool was built from 30 subjects who underwent CSF tapping for diagnostic reasons and, after evaluation, they were found free of any cognitive impairment or any neurodegenerative disease. All the control subjects had a negative AD biomarker profile. EV isolation and proteomic analysis were carried out as previously described1, two replicates were run for each sample. Results: About 800 proteins were consistently identified in all the CSF EV samples. CSF EVs proteome was enriched in heat shock proteins, tetraspanins and endosomal trafficking proteins. Furthermore, CSF EVs were highly enriched in brain-derived proteins including several Intraflagellar Transport Proteins expressed in the choroid plexus, possibly showing that CSF EVs are in part derived from the tissue