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17 results on '"Freeze, Whitney M"'

1. Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART

Author

Ehrenberg, Alexander J, Kelberman, Michael A, Liu, Kathy Y, Dahl, Martin J, Weinshenker, David, Falgàs, Neus, Dutt, Shubir, Mather, Mara, Ludwig, Mareike, Betts, Matthew J, Winer, Joseph R, Teipel, Stefan, Weigand, Alexandra J, Eschenko, Oxana, Hämmerer, Dorothea, Leiman, Marina, Counts, Scott E, Shine, James M, Robertson, Ian H, Levey, Allan I, Lancini, Elisa, Son, Gowoon, Schneider, Christoph, Van Egroo, Maxime, Liguori, Claudio, Wang, Qin, Vazey, Elena M, Rodriguez‐Porcel, Federico, Haag, Lena, Bondi, Mark W, Vanneste, Sven, Freeze, Whitney M, Yi, Yeo‐Jin, Maldinov, Mihovil, Gatchel, Jennifer, Satpati, Abhijit, Babiloni, Claudio, Kremen, William S, Howard, Robert, Jacobs, Heidi IL, and Grinberg, Lea T

Subjects
Neurosciences, Dementia, Acquired Cognitive Impairment, Alzheimer's Disease, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Neurological, Humans, Alzheimer Disease, Brain, Biomarkers, Disease Progression, Clinical Sciences, Geriatrics
Abstract

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.

Published
2023

5. White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed

Author

Freeze, Whitney M., Freeze, Whitney M., Jacobs, Heidi I. L., de Jong, Joost J., Verheggen, Inge C. M., Gronenschild, Ed H. B. M., Palm, Walter M., Hoff, Erik I., Wardlaw, Joanna M., Jansen, Jacobus F. A., Verhey, Frans R., Backes, Walter H., Freeze, Whitney M., Freeze, Whitney M., Jacobs, Heidi I. L., de Jong, Joost J., Verheggen, Inge C. M., Gronenschild, Ed H. B. M., Palm, Walter M., Hoff, Erik I., Wardlaw, Joanna M., Jansen, Jacobus F. A., Verhey, Frans R., and Backes, Walter H.

Abstract

Blood-brain barrier (BBB) leakage is considered an important underlying process in both cerebral small vessel disease (cSVD) and Alzheimer's disease (AD). The objective of this study was to examine associations between BBB leakage, cSVD, neurodegeneration, and cognitive performance across the spectrum from normal cognition to dementia. Leakage was measured with dynamic contrast-enhanced magnetic resonance imaging in 80 older participants (normal cognition, n = 32; mild cognitive impairment, n 34; clinical AD-type dementia, n = 14). Associations between leakage and white matter hyperintensity (WMH) volume, hippocampal volume, and cognition (information processing speed and memory performance) were examined with multivariable linear regression and mediation analyses. Leakage within the gray and white matter was positively associated with WMH volume (gray matter, p = 0.03; white matter, p = 0.01). A negative association was found between white matter BBB leakage and information processing speed performance, which was mediated by WMH volume. Leakage was not associated with hippocampal volume. WMH pathology is suggested to form a link between leakage and decline of information processing speed in older individuals with and without cognitive impairment. (C) 2019 Elsevier Inc. All rights reserved.

Published
2020

6. Histopathological correlates of haemorrhagic lesions on ex vivo magnetic resonance imaging in immunized Alzheimer's disease cases

Author

Scherlek, Ashley A., Kozberg, Mariel G., Nicoll, James A. R., Perosa, Valentina, Freeze, Whitney M., van der Weerd, Louise, Bacskai, Brian J., Greenberg, Steven M., Frosch, Matthew P., Boche, Delphine, and van Veluw, Susanne J.

Abstract

Haemorrhagic amyloid-related imaging abnormalities on MRI are frequently observed adverse events in the context of amyloid β immunotherapy trials in patients with Alzheimer’s disease. The underlying histopathology and pathophysiological mechanisms of haemorrhagic amyloid-related imaging abnormalities remain largely unknown, although coexisting cerebral amyloid angiopathy may play a key role. Here, we used ex vivo MRI in cases that underwent amyloid β immunotherapy during life to screen for haemorrhagic lesions and assess underlying tissue and vascular alterations. We hypothesized that these lesions would be associated with severe cerebral amyloid angiopathy. Ten cases were selected from the long-term follow-up study of patients who enrolled in the first clinical trial of active amyloid β immunization with AN1792 for Alzheimer’s disease. Eleven matched non-immunized Alzheimer’s disease cases from an independent brain brank were used as ‘controls’. Formalin-fixed occipital brain slices were imaged at 7 T MRI to screen for haemorrhagic lesions (i.e. microbleeds and cortical superficial siderosis). Samples with and without haemorrhagic lesions were cut and stained. Artificial intelligence-assisted quantification of amyloid β plaque area, cortical and leptomeningeal cerebral amyloid angiopathy area, the density of iron and calcium positive cells and reactive astrocytes and activated microglia was performed. On ex vivo MRI, cortical superficial siderosis was observed in 5/10 immunized Alzheimer’s disease cases compared with 1/11 control Alzheimer’s disease cases (κ = 0.5). On histopathology, these areas revealed iron and calcium positive deposits in the cortex. Within the immunized Alzheimer’s disease group, areas with siderosis on MRI revealed greater leptomeningeal cerebral amyloid angiopathy and concentric splitting of the vessel walls compared with areas without siderosis. Moreover, greater density of iron-positive cells in the cortex was associated with lower amyloid β plaque area and a trend towards increased post-vaccination antibody titres. This work highlights the use of ex vivo MRI to investigate the neuropathological correlates of haemorrhagic lesions observed in the context of amyloid β immunotherapy. These findings suggest a possible role for cerebral amyloid angiopathy in the formation of haemorrhagic amyloid-related imaging abnormalities, awaiting confirmation in future studies that include brain tissue of patients who received passive immunotherapy against amyloid β with available in vivo MRI during life.

Published
2022

7. Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer's Disease

Author

Drenthen, Gerhard S, Backes, Walter H, Freeze, Whitney M, Jacobs, Heidi I. L., Verheggen, Inge C. M., van Boxtel, Martin P. J., Hoff, Erik I., Verhey, Frans R., Jansen, Jacobus F A, Drenthen, Gerhard S, Backes, Walter H, Freeze, Whitney M, Jacobs, Heidi I. L., Verheggen, Inge C. M., van Boxtel, Martin P. J., Hoff, Erik I., Verhey, Frans R., and Jansen, Jacobus F A

Abstract

BACKGROUND: Though mediotemporal lobe volume changes are well-known features of Alzheimer's disease (AD), grey matter volume changes may be distributed throughout the brain. These distributed changes are not independent due to the underlying network structure and can be described in terms of a structural covariance network (SCN).OBJECTIVE: To investigate how the cortical brain organization is altered in AD we studied the mutual connectivity of hubs in the SCN, i.e., the rich-club.METHODS: To construct the SCNs, cortical thickness was obtained from structural MRI for 97 participants (normal cognition, n = 37; mild cognitive impairment, n = 41; Alzheimer-type dementia, n = 19). Subsequently, rich-club coefficients were calculated from the SCN, and related to memory performance and hippocampal volume using linear regression.RESULTS: Lower rich-club connectivity was related to lower memory performance as well as lower hippocampal volume.CONCLUSION: Therefore, this study provides novel evidence of reduced connectivity in hub areas in relation to AD-related cognitive impairments and atrophy.

Published
2022

8. Histopathological correlates of haemorrhagic lesions on ex vivo magnetic resonance imaging in immunized Alzheimer’s disease cases

Author

Scherlek, Ashley A., primary, Kozberg, Mariel G., additional, Nicoll, James A. R., additional, Perosa, Valentina, additional, Freeze, Whitney M., additional, van der Weerd, Louise, additional, Bacskai, Brian J., additional, Greenberg, Steven M., additional, Frosch, Matthew P., additional, Boche, Delphine, additional, and van Veluw, Susanne J., additional

Published
2022
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10. Linking APOE-epsilon 4, blood-brain barrier dysfunction, and inflammation to Alzheimer's pathology

Author

Riphagen, Joost M., Ramakers, Inez H.G.M., Freeze, Whitney M., Pagen, Linda H.G., Hanseeuw, Bernard J., Verbeek, M.M., Verhey, F.R.J., Jacobs, Heidi I.L., Riphagen, Joost M., Ramakers, Inez H.G.M., Freeze, Whitney M., Pagen, Linda H.G., Hanseeuw, Bernard J., Verbeek, M.M., Verhey, F.R.J., and Jacobs, Heidi I.L.

Abstract

Contains fulltext : 214075.pdf (Publisher’s version ) (Open Access)

Published
2020

13. White Matter Hyperintensities Potentiate Hippocampal Volume Reduction in Non-Demented Older Individuals with Abnormal Amyloid-beta

Author

Freeze, Whitney M., Freeze, Whitney M., Jacobs, Heidi I. L., Gronenschild, Ed H., Jansen, Jacobus F. A., Burgmans, Saartje, Aalten, Pauline, Clerx, Lies, Vos, Stephanie J., van Buchem, Mark A., Barkhof, Frederik, van der Flier, Wiesje M., Verbeek, Marcel M., Rikkert, Marcel Olde, Backes, Walter H., Verhey, Frans R., LeARN Project, Freeze, Whitney M., Freeze, Whitney M., Jacobs, Heidi I. L., Gronenschild, Ed H., Jansen, Jacobus F. A., Burgmans, Saartje, Aalten, Pauline, Clerx, Lies, Vos, Stephanie J., van Buchem, Mark A., Barkhof, Frederik, van der Flier, Wiesje M., Verbeek, Marcel M., Rikkert, Marcel Olde, Backes, Walter H., Verhey, Frans R., and LeARN Project

Abstract

Cerebral small vessel disease (cSVD) and amyloid-beta (A beta) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and A beta have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. A beta pathologywas assessed as cerebrospinal fluid-derived A beta(1-42) levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and A beta on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal A beta and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, A beta and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF A beta(42) levels, but not in individuals with normal CSF A beta(42) levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal A beta levels are at an increased risk of accelerated disease progression when concomitant cSVD is present.

Published
2017

14. Imaging markers associated with the development of post-stroke depression and apathy: Results of the Cognition and Affect after Stroke – a Prospective Evaluation of Risks study

Author

Douven, Elles, primary, Staals, Julie, additional, Freeze, Whitney M, additional, Schievink, Syenna HJ, additional, Hellebrekers, Danique MJ, additional, Wolz, Robin, additional, Jansen, Jacobus FA, additional, van Oostenbrugge, Robert J, additional, Verhey, Frans RJ, additional, Aalten, Pauline, additional, and Köhler, Sebastian, additional

Published
2019
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17. In vivo imaging of gadolinium-based contrast agent leakage in patients with cerebral amyloid angiopathy

Author

van den Brink, Hilde, Kozberg, Mariel G, Makkinejad, Nazanin, Kirsch, John, Freeze, Whitney M, Viswanathan, Anand, and van Veluw, Susanne J

Abstract

Blood-brain barrier (BBB) leakage is hypothesized to be an early step in the pathophysiology of cerebral amyloid angiopathy (CAA), possibly preceding vessel wall breakdown and hemorrhage. This study aims (1) to measure BBB leakage in vivo in the parenchyma and at the level of the leptomeningeal blood vessels in patients with CAA without lobar intracerebral hemorrhage compared to controls and (2) to study the relationship between BBB leakage and neuroimaging markers of CAA severity.

Published
2024
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