- Email: [email protected]
PERSISTENT BRAIN NEUROIMAGING AND NEUROCOGNITIVE ABNORMALITIES IN MILITARY VETERANS WHO EXPERIENCED BLAST MILD TRAUMATIC BRAIN INJURY IN IRAQ AND AFGHANISTAN
P294
Oral Sessions: O5-03: Epidemiology: New Trends in Alzeimer’s Disease Incidence and Life Course Approach
whereby AD-like structural brain changes and neuropsychological deficits develop in TBI, with possible relevance to treatment and rehabilitation. O5-02-06
PERSISTENT BRAIN NEUROIMAGING AND NEUROCOGNITIVE ABNORMALITIES IN MILITARY VETERANS WHO EXPERIENCED BLAST MILD TRAUMATIC BRAIN INJURY IN IRAQ AND AFGHANISTAN
Elaine R. Peskind1, Eric C. Petrie1, Kathleen F. Pagulayan1, Vasily Yarnykh2, Donna J. Cross2, Todd Richards2, Murray A. Raskind2, Jing Zhang3, Thomas Montine2, Satoshi Minoshima2, 1VA Puget Sound Health Care System, Seattle, Washington, United States; 2University of Washington, Seattle, Washington, United States; 3University of Washington School of Medicine, Seattle, Washington, United States. Contact e-mail: [email protected] Background: Traumatic brain injury (TBI) is the best established risk factor for Alzheimer’s disease (AD) in late life. Repetitive mild TBIs, "concussions," can produce chronic traumatic encephalopathy (CTE, the former "dementia puglistica") with tau-containing neurofibrillary tangles histologically indistinguishable from AD. Given that mild TBI from explosive blast is the "signature injury" of the wars in Iraq and Afghanistan, we asked if combat Veterans who had experienced repetitive mild TBIs in these conflicts demonstrated structural and/or functional brain abnormalities on four neuroimaging modalities, subtle cognitive impairment on neuropsychologic evaluation, or neurodegeneration biomarkers in cerebrospinal fluid (CSF). Methods: Subjects included a deployed Veteran group with a history of blast concussion mild TBI (n¼54); a deployed Veteran group with no (lifetime) history of TBI (n¼25); and civilian controls with no history of concussion (n¼67). Both Veteran groups received a neuropsychological test battery, brain FDG-PET scan, and both structural MRI for diffusion tensor imaging (DTI) and macromolecular proton fraction (MPF) mapping and functional MRI (resting state and task-based) scans, and lumbar punctures for CSF collection. Civilians received only FDG-PET or lumbar puncture. Results: Mild TBI Veterans compared to Veteran controls demonstrated functional and/or structural abnormalities on all neuroimaging modalities in multiple brain regions. Abnormalities were most pronounced on MPF mapping. Subtle cognitive abnormalities were detected by the more demanding neurocognitive tasks of working memory, prospective memory and processing speed. Unexpectedly, the Veteran controls compared to civilian community controls had decreased glucose metabolic activity on FDG-PET in cerebellum, pons, thalamus medial temporal lobe and both Veteran groups had an increased ratio of CSF phosphorylated tau to total tau concentrations. Conclusions: Years after returning from combat deployments in Iraq and Afghanistan, functional and structural brain abnormalities on multiple neuroimaging modalities and cognitive deficits are detectable in military Veterans exposed to mild TBIs. FDG-PET abnormalities and CSF tau abnormalities in deployed Veterans without TBI history suggest possible brain effects from environmental exposures. Longitudinal follow-up studies of these Veterans would clarify blast mild TBI effects on risks for CTE and AD.
Background: Brain tissue loss is not determined in any single time period, but results from the complex interplay of exposures during critical periods throughout life. The "fetal origins of adult disease" hypothesis proposes that an unfavorable intrauterine environment, deduced from small birthsize, may induce permanent changes in fetal brains. These changes in combination with effects of (cardiovascular) exposures during adult life may condition the later risk of brain atrophy. In this study we investigated the combined effect of small birth-size and mid-life hypertension on late-life brain volumes. Methods: Archived records of birth weight and height were abstracted for 1348 subjects who participated in the Reykjavik Study (RS) (mean age 5066) and were re-examined as part of the AGES-RS (mean age 7565). The Ponderal index (PI) was calculated as an indicator of fetal growth status using birth weight and birth length (kg/m 3). Low PI was defined as the lowest tertile (<24.3 kg/m 3). Mid-life hypertension, assessed as part of the RS, was defined as high blood pressure (BP>140/90mmHg) and/or use of antihypertensive treatment. Brain MRI was acquired in the AGES-RS exam, and brain volumes were quantified by computer algorithm. Results: At mid-life 35% of the population had hypertension. Adjusting for total intracranial volume, demographics, and education, the combination of small birth-size (low PI) and presence of mid-life hypertension was associated with smaller late-life brain volumes. Compared with the reference group (high PI/no mid-life hypertension), individuals with low PI and mid-life hypertension had 5.9 mL (95% CI 0.2, 11.9) smaller total brain volume (Figure) and 3.8mL (95% CI 0.7, 7.0) smaller white matter volume. P-values for interaction (’more than additive’) between PI and mid-life hypertension were >0.10. PI was not associated with gray matter volume or white matter lesion volume. Conclusions: In this population-based cohort of older subjects, the combined additive effect of small birth size and hypertension at mid-life resulted in significantly smaller total brain and white matter volumes later in life. These results show both preand post-natal factors affect brain tissue volume in late-life. Both these factors can be modified, but efforts should begin early in life.
THURSDAY, JULY 17, 2014 ORAL SESSIONS O5-03 EPIDEMIOLOGY: NEW TRENDS IN ALZEIMER’S DISEASE INCIDENCE AND LIFE COURSE APPROACH O5-03-01
BIRTH WEIGHT, MID-LIFE HYPERTENSION, AND LATE-LIFE BRAIN TISSUE LOSS: A LIFE-COURSE APPROACH
Majon Muller1, Sigurdur Sigurdsson2, Olafur Kjartansson3, Ingibjorg Gunnarsdottir4, Inga Thorsdottir4, Mark van Buchem1, Vilmundur Gudnason5, Lenore Launer6, 1Leiden University Medical Center, Leiden, Netherlands; 2Icelandic Heart Association, Kopavagur, Iceland; 3 Landspitali University Hospital, Reykjavik, Iceland; 4University of Iceland, Reykjavik, Iceland; 5Icelandic Heart Association, Kopavogur, Iceland; 6National Institute on Aging, Bethesda, Maryland, United States. Contact e-mail: [email protected]
Figure. Mean (SE) total brain volumes (mL) for combined categories of ponderal index (PI: low vs. high) and mid-life hypertension (HT: present vs. absent) in 1,348 subjects. Volumes were adjusted for age, sex, education, and late-life intracranial volume. *P<0.05. O5-03-02
KNOWLEDGE, STIGMA, AND ATTITUDES ABOUT ALZHEIMER’S DISEASE AMONG HISPANIC OLDER ADULTS AND THEIR CAREGIVERS
Jim Sherry1, Yanira Cruz2, 1George Washington University, Washington, D.C., United States; 2National Hispanic Council on Aging, Washington, D.C., United States. Contact e-mail: [email protected]
Oral Sessions: O5-03: Epidemiology: New Trends in Alzeimer’s Disease Incidence and Life Course Approach
whereby AD-like structural brain changes and neuropsychological deficits develop in TBI, with possible relevance to treatment and rehabilitation. O5-02-06
PERSISTENT BRAIN NEUROIMAGING AND NEUROCOGNITIVE ABNORMALITIES IN MILITARY VETERANS WHO EXPERIENCED BLAST MILD TRAUMATIC BRAIN INJURY IN IRAQ AND AFGHANISTAN
Elaine R. Peskind1, Eric C. Petrie1, Kathleen F. Pagulayan1, Vasily Yarnykh2, Donna J. Cross2, Todd Richards2, Murray A. Raskind2, Jing Zhang3, Thomas Montine2, Satoshi Minoshima2, 1VA Puget Sound Health Care System, Seattle, Washington, United States; 2University of Washington, Seattle, Washington, United States; 3University of Washington School of Medicine, Seattle, Washington, United States. Contact e-mail: [email protected] Background: Traumatic brain injury (TBI) is the best established risk factor for Alzheimer’s disease (AD) in late life. Repetitive mild TBIs, "concussions," can produce chronic traumatic encephalopathy (CTE, the former "dementia puglistica") with tau-containing neurofibrillary tangles histologically indistinguishable from AD. Given that mild TBI from explosive blast is the "signature injury" of the wars in Iraq and Afghanistan, we asked if combat Veterans who had experienced repetitive mild TBIs in these conflicts demonstrated structural and/or functional brain abnormalities on four neuroimaging modalities, subtle cognitive impairment on neuropsychologic evaluation, or neurodegeneration biomarkers in cerebrospinal fluid (CSF). Methods: Subjects included a deployed Veteran group with a history of blast concussion mild TBI (n¼54); a deployed Veteran group with no (lifetime) history of TBI (n¼25); and civilian controls with no history of concussion (n¼67). Both Veteran groups received a neuropsychological test battery, brain FDG-PET scan, and both structural MRI for diffusion tensor imaging (DTI) and macromolecular proton fraction (MPF) mapping and functional MRI (resting state and task-based) scans, and lumbar punctures for CSF collection. Civilians received only FDG-PET or lumbar puncture. Results: Mild TBI Veterans compared to Veteran controls demonstrated functional and/or structural abnormalities on all neuroimaging modalities in multiple brain regions. Abnormalities were most pronounced on MPF mapping. Subtle cognitive abnormalities were detected by the more demanding neurocognitive tasks of working memory, prospective memory and processing speed. Unexpectedly, the Veteran controls compared to civilian community controls had decreased glucose metabolic activity on FDG-PET in cerebellum, pons, thalamus medial temporal lobe and both Veteran groups had an increased ratio of CSF phosphorylated tau to total tau concentrations. Conclusions: Years after returning from combat deployments in Iraq and Afghanistan, functional and structural brain abnormalities on multiple neuroimaging modalities and cognitive deficits are detectable in military Veterans exposed to mild TBIs. FDG-PET abnormalities and CSF tau abnormalities in deployed Veterans without TBI history suggest possible brain effects from environmental exposures. Longitudinal follow-up studies of these Veterans would clarify blast mild TBI effects on risks for CTE and AD.
Background: Brain tissue loss is not determined in any single time period, but results from the complex interplay of exposures during critical periods throughout life. The "fetal origins of adult disease" hypothesis proposes that an unfavorable intrauterine environment, deduced from small birthsize, may induce permanent changes in fetal brains. These changes in combination with effects of (cardiovascular) exposures during adult life may condition the later risk of brain atrophy. In this study we investigated the combined effect of small birth-size and mid-life hypertension on late-life brain volumes. Methods: Archived records of birth weight and height were abstracted for 1348 subjects who participated in the Reykjavik Study (RS) (mean age 5066) and were re-examined as part of the AGES-RS (mean age 7565). The Ponderal index (PI) was calculated as an indicator of fetal growth status using birth weight and birth length (kg/m 3). Low PI was defined as the lowest tertile (<24.3 kg/m 3). Mid-life hypertension, assessed as part of the RS, was defined as high blood pressure (BP>140/90mmHg) and/or use of antihypertensive treatment. Brain MRI was acquired in the AGES-RS exam, and brain volumes were quantified by computer algorithm. Results: At mid-life 35% of the population had hypertension. Adjusting for total intracranial volume, demographics, and education, the combination of small birth-size (low PI) and presence of mid-life hypertension was associated with smaller late-life brain volumes. Compared with the reference group (high PI/no mid-life hypertension), individuals with low PI and mid-life hypertension had 5.9 mL (95% CI 0.2, 11.9) smaller total brain volume (Figure) and 3.8mL (95% CI 0.7, 7.0) smaller white matter volume. P-values for interaction (’more than additive’) between PI and mid-life hypertension were >0.10. PI was not associated with gray matter volume or white matter lesion volume. Conclusions: In this population-based cohort of older subjects, the combined additive effect of small birth size and hypertension at mid-life resulted in significantly smaller total brain and white matter volumes later in life. These results show both preand post-natal factors affect brain tissue volume in late-life. Both these factors can be modified, but efforts should begin early in life.
THURSDAY, JULY 17, 2014 ORAL SESSIONS O5-03 EPIDEMIOLOGY: NEW TRENDS IN ALZEIMER’S DISEASE INCIDENCE AND LIFE COURSE APPROACH O5-03-01
BIRTH WEIGHT, MID-LIFE HYPERTENSION, AND LATE-LIFE BRAIN TISSUE LOSS: A LIFE-COURSE APPROACH
Majon Muller1, Sigurdur Sigurdsson2, Olafur Kjartansson3, Ingibjorg Gunnarsdottir4, Inga Thorsdottir4, Mark van Buchem1, Vilmundur Gudnason5, Lenore Launer6, 1Leiden University Medical Center, Leiden, Netherlands; 2Icelandic Heart Association, Kopavagur, Iceland; 3 Landspitali University Hospital, Reykjavik, Iceland; 4University of Iceland, Reykjavik, Iceland; 5Icelandic Heart Association, Kopavogur, Iceland; 6National Institute on Aging, Bethesda, Maryland, United States. Contact e-mail: [email protected]
Figure. Mean (SE) total brain volumes (mL) for combined categories of ponderal index (PI: low vs. high) and mid-life hypertension (HT: present vs. absent) in 1,348 subjects. Volumes were adjusted for age, sex, education, and late-life intracranial volume. *P<0.05. O5-03-02
KNOWLEDGE, STIGMA, AND ATTITUDES ABOUT ALZHEIMER’S DISEASE AMONG HISPANIC OLDER ADULTS AND THEIR CAREGIVERS
Jim Sherry1, Yanira Cruz2, 1George Washington University, Washington, D.C., United States; 2National Hispanic Council on Aging, Washington, D.C., United States. Contact e-mail: [email protected]