- Email: [email protected]
NON-RESILIENT BRAIN AGING IN ASSOCIATION WITH CARDIOVASCULAR RISK AND WHITE MATTER HYPERINTENSITIES: THE SHIP STUDY
P226
Podium Presentations: Monday, July 25, 2016
Background: Cerebral perivascular spaces are interstitial fluid (ISF)
filled channels that surround penetrating arterioles and draining venules. Enlarged perivascular spaces (ePVS), might represent impaired ISF drainage, and are common in both white matter and basal ganglia. ePVS have previously been associated with markers of small vessel disease, including microbleeds, lacunar infarctions, and white matter hyperintensities (WMH). However, whether regional differences in ePVS are differentially associated with these markers or have clinical relevance remains unclear. Methods: We studied a cohort of 346 patients with multiple diagnostic etiologies (MCI, AD, AD+CVD, AD+VaD) from the Sunnybrook Dementia Study. MRI-derived volumes of WMH, periventricular WMH (pWMH), deep WMH (dWMH), and ePVS volumes were segmented using a validated semi-automated methodology. ePVS were further segmented into: Basal Ganglia (BG), global white matter, and frontal, temporal, parietal, and occipital white matter. Cognitive function was indexed by the dementia rating scale (DRS). Multivariate linear regressions were used to evaluate relationships between regionalized ePVS volumes and primary outcomes. Models were adjusted for age, gender, atrophy, APOE4genotype, vascular risk, MMSE, diagnostic classification, and duration of cognitive impairment. Results: White matter, but not basal ganglia, ePVS were related to global WMH (b¼0.25, p<0.0001), dWMH (b¼0.30, p<0.0001) and pWMH (b¼0.23, p<0.0001) volumes. Global WMH volume was related specifically to ePVS in temporal (b¼0.12, <0.05) and parietal (b¼0.24, p<0.0001) regions. While dWMH volume was related to ePVS in temporal and parietal lobes, pWMH volume was only associated with parietal lobe ePVS. In terms of cognition, basal ganglia ePVS were associated with total and conceptualization subscale scores of the DRS (p<0.05), while white matter ePVS were associated with working memory (p<0.05). Conclusions: This study uniquely identifies a direct relationship between enlarged perivascular spaces in parietal and temporal lobes and WMH burden. These findings may reflect regional white matter vulnerability to impaired ISF drainage. Furthermore, we demonstrate differential associations between: basal ganglia ePVS and DRS total and conceptualization scores; and white matter ePVS with working memory. This study suggests that, across the diagnostic spectrum of cognitive impairment, the location and burden of ePVS may be a useful neuroimaging biomarker of cognitive impairment and small vessel disease. O2-03-02
ARE WHITE MATTER HYPERINTENSITIES A CORE FEATURE OF ALZHEIMER’S DISEASE OR JUST A REFLECTION OF AMYLOID ANGIOPATHY? EVIDENCE FROM THE DOMINANTLY INHERITED ALZHEIMER NETWORK (DIAN)
Seonjoo Lee1, Molly E. Zimmerman2,3, Fawad Viqar2, Atul Narkhede4, Giuseppe Tosto4, Tammie Lee Smith Benzinger5, Daniel S. Marcus6, Alison M. Goate7, Nick C. Fox8, Nigel J. Cairns5,9, David M. Holtzman5, Virginia Buckles10, Bernardino Ghetti11, Eric McDade12, Ralph N. Martins13, Andy J. Saykin11, Colin L. Masters14, John M. Ringman15, Natalie S. Ryan16, Stefan F€orster17, Christoph Laske18, Peter R. Schofield19, Reisa A. Sperling20, Stephen Salloway21, Stephen Correia22, Michael W. Weiner23, Randall Bateman5, John C. Morris5, Clifford R. Jack, Jr,24, Richard Mayeux4, Adam M. Brickman4, 1New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, USA; 2Fordham University, New York, NY, USA; 3Albert Einstein College of Medicine, Bronx, NY, USA; 4 Columbia University, New York, NY, USA; 5Washington University School of Medicine, St. Louis, MO, USA; 6Washington University School of
Medicine, Saint Louis, MO, USA; 7Icahn School of Medicine at Mount Sinai, New York, NY, USA; 8University College London, London, United Kingdom; 9 Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA; 10 Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; 11Indiana University School of Medicine, Indianapolis, IN, USA; 12Washington University at St. Louis, St. Louis, MO, USA; 13Sir James McCusker Alzheimer’s Disease Research Unit (Hollywood Private Hospital), Perth, Australia; 14The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; 15Keck School of Medicine at USC, Los Angeles, CA, USA; 16UCL Institute of Neurology, London, United Kingdom; 17Technische Universit€at M€unchen, Munich, Germany; 18Department of Psychiatry and Psychotherapy, University of T€ubingen, T€ubingen, Germany; 1919. Neuroscience Research Australia and University of New South Wales, Sydney, Australia; 20Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 21Butler Hospital & Alpert Medical School of Brown University, Providence, RI, USA; 22Brown University, Providence, RI, USA; 23 University of California, San Francisco, San Francisco, CA, USA; 24Mayo Clinic, Rochester, MN, USA. Contact e-mail: [email protected] Background: We previously established that white matter hyperin-
tensities (WMH) volume is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer’s disease (AD) up to 20 years prior to expected symptom onset. One potential explanation is that WMH are, in part, a reflection of cerebral amyloid angiopathy (CAA). We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between mutation status and WMH in individuals from DIAN. Methods: The study comprised participants (n¼175, mean age¼41.05, 57% women) from DIAN, including 112(64%) with a mutation that results in AD and 63(36%) first-degree relatives who were non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent’s symptom onset age from the participant’s age. Baseline MRI data were analyzed for WMH volume and for cerebral microbleeds, a radiological marker of CAA. We examined WMH differences between carriers and non-carriers with respect to EYO, differences between carriers and non-carriers in presence of microbleeds, and tested whether the association between WMH and mutation status is dependent on the presence of microbleeds. Results: Mutation carriers were more likely to have a microbleed than non-carriers(20% vs. 6%, p<0.05) and individuals with microbleeds had higher WMH volume than those without(p<0.05). Total WMH volume was increased in mutation carriers up to 20 years prior to EYO, after controlling for microbleed status. Total WMH also remained elevated in mutation carriers even after exclusion of individuals with microbleeds. Mediations tests demonstrated that 21% of the association between mutation status and WMH was mediated by presence of microbleeds(p¼0.03) but a significant direct effect of WMH remained (p¼0.02) after controlling for presence of microbleeds. Conclusions: Although there is some co-dependency between WMH and cerebral microbleeds, the observed increases in WMH among mutation carriers is not fully mediated by this marker of cerebral amyloid angiopathy. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid. O2-03-03
NON-RESILIENT BRAIN AGING IN ASSOCIATION WITH CARDIOVASCULAR RISK AND WHITE MATTER HYPERINTENSITIES: THE SHIP STUDY
Mohamad Habes1,2,3, Erus Guray1, Jon B. Toledo4, Tianhao Zhang1, R. N. Bryan1, Deborah Janowitz3, Jimit Doshi1, Bettina von Sarnowski5, Katrin Hegenscheid6, Henry Voelzke2, Ulf Schminke5, Wolfgang Hoffmann2,7, Hans J. Grabe3,7, Christos Davatzikos1, 1Center for
Podium Presentations: Monday, July 25, 2016 Biomedical Image Computing and Analytics / University of Pennsylvania, Philadelphia, PA, USA; 2Institute for Community Medicine / University of Greifswald, Greifswald, Germany; 3Department of Psychiatry / University of Greifswald, Greifswald, Germany; 4Institute on Aging / University of Pennsylvania, Philadelphia, PA, USA; 5Department of Neurology / University of Greifswald, Greifswald, Germany; 6Department of Radiology / University of Greifswald, Greifswald, Germany; 7German Center for Neurodegenerative Diseases (DZNE), Greifswald, Germany. Contact e-mail: [email protected] Background: Previous studies have shown associations between
white matter hyperintensities (WMH) and increased risk of dementia, which might be affected from common factors such as vascular risk and age. We sought to investigate the association of WMH burden and cardiovascular risk with brain atrophy patterns related to brain aging (BA) and to Alzheimer disease (AD), in the general population, leveraging state of the art pattern analysis methods. Methods: We quantified WMH burden through automated segmentation in a large population-based sample (n¼2,367) covering a wide age (range 20-90 years, median¼53 years), from the Study of Health in Pomerania, Germany. Using machine learning methods, we calculated two indices summarizing brain atrophy: i) the SPARE-BA index to quantify age-related brain atrophy, and ii) the SPARE-AD index, previously developed to capture ADlike atrophy patterns. Framingham cardiovascular disease risk score (CVD-RS) was used to summarize individual risk profile. We used two linear regression models, in which WMH and CVDRS were independent variables, and SPARE-AD and SPARE-BA scores were dependent variables respectively, after adjusting for age, gender and education level. Results: BA was associated with atrophy in regions such as the frontal lobe, putamen amygdala and insula. BA patterns of atrophy were overlapping to some extend with, but notably deviating from, AD-like patterns of atrophy. WMH were associated with gray matter atrophy in regions such as anterior temporal, frontal lobe and hippocampus. Linear regression models showed that higher WMH burden was significantly associated with SPARE-BA, as well as with SPARE-AD scores (P<0.0001 for both). CVD-RS was significantly associated with SPARE-BA score (P<0.0001), but not with SPARE-AD score (P¼0.087). We found that high and low WMH burden groups in age older than 60 years, defined as subjects with age-adjusted WMH volume above 70th percentile and below 30thpercentile respectively, displayed brain age differences that would correspond in average to 4.6 years of additional aging. Conclusions: Our results
P227
Table 1 Linear regression model with WMH volume, and CVD-RS as independent variables and SPARE-BA as dependent variable. Results are adjusted for age, gender and education. Factor SPARE-BA SHIP participants n¼2,367 Estimate White matter hyperintensities volume0 Framingham cardiovascular disease risk score
S.E.
P-value (factor)
-0.052
0.005
<0.0001*
-0.029&
0.006
<0.0001*
$
R2 ¼ 0.69 * Significance at level P < 0.05, S.E: Standard Error. Values in mm3 are transformed using cubic root function. $ A lesion volume increase of 1mm leads to 3.5 months of additional brain aging approximately (transformed WMH volume range was [0-30.3], standard deviation¼4.6, median¼4.7). & A 1 unit increase of CVD-RS leads to 1.9 months of brain aging atrophy approximately (CVD-RS range was [-5,27], standard deviation¼6.4, median¼ll). Table 2 Linear regression model with WMH volume, and CVD-RS as independent variables and SPARE-AD as dependent variable. Results are adjusted for age, gender and education. Factor SPARE-AD SHIP participants n¼2,367 Estimate White matter hyperintensities volume , mm Framingham cardiovascular disease risk score, arbitrary units
S.E.
P-value (factor)
0.039
0.004
<0.0001*
-0.008
0.005
0.087
R2 ¼ 0.194 * Significance at level P < 0.05, S.E: Standard Error, Values are transformed using cubic root function.
revealed that WMH and cardiovascular risk are additive factors that might accelerate the brain aging process. WMH are also associated with AD-like atrophy patterns in the general population. Preventive strategies against WMH and cardiovascular risk could help to delay brain aging. O2-03-04
BASELINE NORMAL APPEARING WHITE MATTER STRUCTURAL INTEGRITY AND CEREBRAL BLOOD FLOW CAN PREDICT WHITE MATTER HYPERINTENSITY EXPANSION OVER TIME: A VOXEL-WISE ANALYSIS
Nutta-on Promjunyakul1, David Lahna1, Jeff A. Kaye1,2,3, Hiroko H. Dodge1,2,3,4, William D. Rooney1, Deniz Erten-Lyons1,5, Lisa C. Silbert1, 1Oregon Health & Science University, Portland, OR, USA; 2 NIA-Layton Aging & Alzheimer’s Disease Center, Portland, OR, USA; 3 Oregon Center for Aging & Technology (ORCATECH), Portland, OR, USA; 4University of Michigan, Ann Arbor, MI, USA; 5NIA-Layton Aging and Alzheimer’s Disease Center, Portland, OR, USA. Contact e-mail: [email protected] Background: White matter hyperintensity (WMH) penumbra is the Figure 1.
normal appearing white matter (NAWM) surrounding WMH that
Podium Presentations: Monday, July 25, 2016
Background: Cerebral perivascular spaces are interstitial fluid (ISF)
filled channels that surround penetrating arterioles and draining venules. Enlarged perivascular spaces (ePVS), might represent impaired ISF drainage, and are common in both white matter and basal ganglia. ePVS have previously been associated with markers of small vessel disease, including microbleeds, lacunar infarctions, and white matter hyperintensities (WMH). However, whether regional differences in ePVS are differentially associated with these markers or have clinical relevance remains unclear. Methods: We studied a cohort of 346 patients with multiple diagnostic etiologies (MCI, AD, AD+CVD, AD+VaD) from the Sunnybrook Dementia Study. MRI-derived volumes of WMH, periventricular WMH (pWMH), deep WMH (dWMH), and ePVS volumes were segmented using a validated semi-automated methodology. ePVS were further segmented into: Basal Ganglia (BG), global white matter, and frontal, temporal, parietal, and occipital white matter. Cognitive function was indexed by the dementia rating scale (DRS). Multivariate linear regressions were used to evaluate relationships between regionalized ePVS volumes and primary outcomes. Models were adjusted for age, gender, atrophy, APOE4genotype, vascular risk, MMSE, diagnostic classification, and duration of cognitive impairment. Results: White matter, but not basal ganglia, ePVS were related to global WMH (b¼0.25, p<0.0001), dWMH (b¼0.30, p<0.0001) and pWMH (b¼0.23, p<0.0001) volumes. Global WMH volume was related specifically to ePVS in temporal (b¼0.12, <0.05) and parietal (b¼0.24, p<0.0001) regions. While dWMH volume was related to ePVS in temporal and parietal lobes, pWMH volume was only associated with parietal lobe ePVS. In terms of cognition, basal ganglia ePVS were associated with total and conceptualization subscale scores of the DRS (p<0.05), while white matter ePVS were associated with working memory (p<0.05). Conclusions: This study uniquely identifies a direct relationship between enlarged perivascular spaces in parietal and temporal lobes and WMH burden. These findings may reflect regional white matter vulnerability to impaired ISF drainage. Furthermore, we demonstrate differential associations between: basal ganglia ePVS and DRS total and conceptualization scores; and white matter ePVS with working memory. This study suggests that, across the diagnostic spectrum of cognitive impairment, the location and burden of ePVS may be a useful neuroimaging biomarker of cognitive impairment and small vessel disease. O2-03-02
ARE WHITE MATTER HYPERINTENSITIES A CORE FEATURE OF ALZHEIMER’S DISEASE OR JUST A REFLECTION OF AMYLOID ANGIOPATHY? EVIDENCE FROM THE DOMINANTLY INHERITED ALZHEIMER NETWORK (DIAN)
Seonjoo Lee1, Molly E. Zimmerman2,3, Fawad Viqar2, Atul Narkhede4, Giuseppe Tosto4, Tammie Lee Smith Benzinger5, Daniel S. Marcus6, Alison M. Goate7, Nick C. Fox8, Nigel J. Cairns5,9, David M. Holtzman5, Virginia Buckles10, Bernardino Ghetti11, Eric McDade12, Ralph N. Martins13, Andy J. Saykin11, Colin L. Masters14, John M. Ringman15, Natalie S. Ryan16, Stefan F€orster17, Christoph Laske18, Peter R. Schofield19, Reisa A. Sperling20, Stephen Salloway21, Stephen Correia22, Michael W. Weiner23, Randall Bateman5, John C. Morris5, Clifford R. Jack, Jr,24, Richard Mayeux4, Adam M. Brickman4, 1New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, USA; 2Fordham University, New York, NY, USA; 3Albert Einstein College of Medicine, Bronx, NY, USA; 4 Columbia University, New York, NY, USA; 5Washington University School of Medicine, St. Louis, MO, USA; 6Washington University School of
Medicine, Saint Louis, MO, USA; 7Icahn School of Medicine at Mount Sinai, New York, NY, USA; 8University College London, London, United Kingdom; 9 Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA; 10 Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; 11Indiana University School of Medicine, Indianapolis, IN, USA; 12Washington University at St. Louis, St. Louis, MO, USA; 13Sir James McCusker Alzheimer’s Disease Research Unit (Hollywood Private Hospital), Perth, Australia; 14The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; 15Keck School of Medicine at USC, Los Angeles, CA, USA; 16UCL Institute of Neurology, London, United Kingdom; 17Technische Universit€at M€unchen, Munich, Germany; 18Department of Psychiatry and Psychotherapy, University of T€ubingen, T€ubingen, Germany; 1919. Neuroscience Research Australia and University of New South Wales, Sydney, Australia; 20Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 21Butler Hospital & Alpert Medical School of Brown University, Providence, RI, USA; 22Brown University, Providence, RI, USA; 23 University of California, San Francisco, San Francisco, CA, USA; 24Mayo Clinic, Rochester, MN, USA. Contact e-mail: [email protected] Background: We previously established that white matter hyperin-
tensities (WMH) volume is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer’s disease (AD) up to 20 years prior to expected symptom onset. One potential explanation is that WMH are, in part, a reflection of cerebral amyloid angiopathy (CAA). We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between mutation status and WMH in individuals from DIAN. Methods: The study comprised participants (n¼175, mean age¼41.05, 57% women) from DIAN, including 112(64%) with a mutation that results in AD and 63(36%) first-degree relatives who were non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent’s symptom onset age from the participant’s age. Baseline MRI data were analyzed for WMH volume and for cerebral microbleeds, a radiological marker of CAA. We examined WMH differences between carriers and non-carriers with respect to EYO, differences between carriers and non-carriers in presence of microbleeds, and tested whether the association between WMH and mutation status is dependent on the presence of microbleeds. Results: Mutation carriers were more likely to have a microbleed than non-carriers(20% vs. 6%, p<0.05) and individuals with microbleeds had higher WMH volume than those without(p<0.05). Total WMH volume was increased in mutation carriers up to 20 years prior to EYO, after controlling for microbleed status. Total WMH also remained elevated in mutation carriers even after exclusion of individuals with microbleeds. Mediations tests demonstrated that 21% of the association between mutation status and WMH was mediated by presence of microbleeds(p¼0.03) but a significant direct effect of WMH remained (p¼0.02) after controlling for presence of microbleeds. Conclusions: Although there is some co-dependency between WMH and cerebral microbleeds, the observed increases in WMH among mutation carriers is not fully mediated by this marker of cerebral amyloid angiopathy. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid. O2-03-03
NON-RESILIENT BRAIN AGING IN ASSOCIATION WITH CARDIOVASCULAR RISK AND WHITE MATTER HYPERINTENSITIES: THE SHIP STUDY
Mohamad Habes1,2,3, Erus Guray1, Jon B. Toledo4, Tianhao Zhang1, R. N. Bryan1, Deborah Janowitz3, Jimit Doshi1, Bettina von Sarnowski5, Katrin Hegenscheid6, Henry Voelzke2, Ulf Schminke5, Wolfgang Hoffmann2,7, Hans J. Grabe3,7, Christos Davatzikos1, 1Center for
Podium Presentations: Monday, July 25, 2016 Biomedical Image Computing and Analytics / University of Pennsylvania, Philadelphia, PA, USA; 2Institute for Community Medicine / University of Greifswald, Greifswald, Germany; 3Department of Psychiatry / University of Greifswald, Greifswald, Germany; 4Institute on Aging / University of Pennsylvania, Philadelphia, PA, USA; 5Department of Neurology / University of Greifswald, Greifswald, Germany; 6Department of Radiology / University of Greifswald, Greifswald, Germany; 7German Center for Neurodegenerative Diseases (DZNE), Greifswald, Germany. Contact e-mail: [email protected] Background: Previous studies have shown associations between
white matter hyperintensities (WMH) and increased risk of dementia, which might be affected from common factors such as vascular risk and age. We sought to investigate the association of WMH burden and cardiovascular risk with brain atrophy patterns related to brain aging (BA) and to Alzheimer disease (AD), in the general population, leveraging state of the art pattern analysis methods. Methods: We quantified WMH burden through automated segmentation in a large population-based sample (n¼2,367) covering a wide age (range 20-90 years, median¼53 years), from the Study of Health in Pomerania, Germany. Using machine learning methods, we calculated two indices summarizing brain atrophy: i) the SPARE-BA index to quantify age-related brain atrophy, and ii) the SPARE-AD index, previously developed to capture ADlike atrophy patterns. Framingham cardiovascular disease risk score (CVD-RS) was used to summarize individual risk profile. We used two linear regression models, in which WMH and CVDRS were independent variables, and SPARE-AD and SPARE-BA scores were dependent variables respectively, after adjusting for age, gender and education level. Results: BA was associated with atrophy in regions such as the frontal lobe, putamen amygdala and insula. BA patterns of atrophy were overlapping to some extend with, but notably deviating from, AD-like patterns of atrophy. WMH were associated with gray matter atrophy in regions such as anterior temporal, frontal lobe and hippocampus. Linear regression models showed that higher WMH burden was significantly associated with SPARE-BA, as well as with SPARE-AD scores (P<0.0001 for both). CVD-RS was significantly associated with SPARE-BA score (P<0.0001), but not with SPARE-AD score (P¼0.087). We found that high and low WMH burden groups in age older than 60 years, defined as subjects with age-adjusted WMH volume above 70th percentile and below 30thpercentile respectively, displayed brain age differences that would correspond in average to 4.6 years of additional aging. Conclusions: Our results
P227
Table 1 Linear regression model with WMH volume, and CVD-RS as independent variables and SPARE-BA as dependent variable. Results are adjusted for age, gender and education. Factor SPARE-BA SHIP participants n¼2,367 Estimate White matter hyperintensities volume0 Framingham cardiovascular disease risk score
S.E.
P-value (factor)
-0.052
0.005
<0.0001*
-0.029&
0.006
<0.0001*
$
R2 ¼ 0.69 * Significance at level P < 0.05, S.E: Standard Error. Values in mm3 are transformed using cubic root function. $ A lesion volume increase of 1mm leads to 3.5 months of additional brain aging approximately (transformed WMH volume range was [0-30.3], standard deviation¼4.6, median¼4.7). & A 1 unit increase of CVD-RS leads to 1.9 months of brain aging atrophy approximately (CVD-RS range was [-5,27], standard deviation¼6.4, median¼ll). Table 2 Linear regression model with WMH volume, and CVD-RS as independent variables and SPARE-AD as dependent variable. Results are adjusted for age, gender and education. Factor SPARE-AD SHIP participants n¼2,367 Estimate White matter hyperintensities volume , mm Framingham cardiovascular disease risk score, arbitrary units
S.E.
P-value (factor)
0.039
0.004
<0.0001*
-0.008
0.005
0.087
R2 ¼ 0.194 * Significance at level P < 0.05, S.E: Standard Error, Values are transformed using cubic root function.
revealed that WMH and cardiovascular risk are additive factors that might accelerate the brain aging process. WMH are also associated with AD-like atrophy patterns in the general population. Preventive strategies against WMH and cardiovascular risk could help to delay brain aging. O2-03-04
BASELINE NORMAL APPEARING WHITE MATTER STRUCTURAL INTEGRITY AND CEREBRAL BLOOD FLOW CAN PREDICT WHITE MATTER HYPERINTENSITY EXPANSION OVER TIME: A VOXEL-WISE ANALYSIS
Nutta-on Promjunyakul1, David Lahna1, Jeff A. Kaye1,2,3, Hiroko H. Dodge1,2,3,4, William D. Rooney1, Deniz Erten-Lyons1,5, Lisa C. Silbert1, 1Oregon Health & Science University, Portland, OR, USA; 2 NIA-Layton Aging & Alzheimer’s Disease Center, Portland, OR, USA; 3 Oregon Center for Aging & Technology (ORCATECH), Portland, OR, USA; 4University of Michigan, Ann Arbor, MI, USA; 5NIA-Layton Aging and Alzheimer’s Disease Center, Portland, OR, USA. Contact e-mail: [email protected] Background: White matter hyperintensity (WMH) penumbra is the Figure 1.
normal appearing white matter (NAWM) surrounding WMH that