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Association of Cere...
Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals
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- Cedres, Nira (author)
- Stockholm University,Karolinska Institute,Stockholms universitet,Perception och psykofysik,Karolinska Institutet, Sweden
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- Ferreira, Daniel (author)
- Karolinska Institute,Karolinska Institutet,Mayo Clinic Minnesota
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- Nemy, Milan (author)
- Karolinska Institutet,Czech Technical University in Prague
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- Machado, Alejandra (author)
- Karolinska Institute,Karolinska Institutet
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- Pereira, Joana B. (author)
- Karolinska Institute,Lund University,Lunds universitet,Karolinska Institutet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Shams, Sara (author)
- Karolinska Institute
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- Wahlund, Lars-Olof (author)
- Karolinska Institute,Karolinska Institutet
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- Zettergren, Anna (author)
- Sahlgrenska Academy,Sahlgrenska University Hospital
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- Stepankova, Olga (author)
- Czech Technical University in Prague
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- Vyslouzilova, Lenka (author)
- Czech Technical University in Prague
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- Eriksdotter, Maria (author)
- Karolinska Institutet,Karolinska University Hospital
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- Teipel, Stefan (author)
- Universitätsmedizin Rostock,German Center for Neurodegenerative Diseases (DZNE), Rostock
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- Grothe, Michel J. (author)
- University Hospital Virgen del Rocío,German Center for Neurodegenerative Diseases (DZNE), Rostock,University of Seville
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- Blennow, Kaj (author)
- Sahlgrenska Academy,Sahlgrenska University Hospital
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- Zetterberg, Henrik (author)
- University College London,Sahlgrenska University Hospital,Sahlgrenska Academy,Hong Kong Center for Neurodegenerative Diseases
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- Schöll, Michael (author)
- University of Gothenburg,Sahlgrenska University Hospital,University College London
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- Kern, Silke (author)
- Sahlgrenska Academy,Sahlgrenska University Hospital
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- Skoog, Ingmar (author)
- Sahlgrenska University Hospital,Sahlgrenska Academy
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- Westman, Eric (author)
- Karolinska Institute,Karolinska Institutet,King's College London
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(creator_code:org_t)
- 2022
- 2022
- English.
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In: Neurology. - 0028-3878 .- 1526-632X. ; 99:15, s. e1619-e1629
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Abstract
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- Background and Objectives Several pathologic processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers toward the degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals.Methods The contribution of amyloid and tau pathology was assessed through CSF levels of the Aβ42/40 ratio and phosphorylated tau (p-tau). CSF Aβ38 levels were also measured. Cerebrovascular pathology was assessed using automatic segmentations of WM lesions (WMLs) on MRI. Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE ε4 carriership were also included in the analysis as variables of interest.Results We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals aged 70 years, 51% female). WM lesion burden was the most important contributor to the degeneration of both cholinergic pathways (increase in mean square error [IncMSE] = 98.8% in the external capsule pathway and IncMSE = 93.3% in the cingulum pathway). Levels of Aβ38 and p-tau also contributed to cholinergic WM degeneration, especially in the external capsule pathway (IncMSE = 28.4% and IncMSE = 23.4%, respectively). The Aβ42/40 ratio did not contribute notably to the models (IncMSE<3.0%). APOE ε4 carriers showed poorer integrity in the cingulum pathway (IncMSE = 21.33%). Women showed poorer integrity of the external capsule pathway (IncMSE = 21.55%), which was independent of amyloid status as reflected by the nonsignificant differences in integrity when comparing amyloid-positive vs amyloid-negative women participants (T201 = −1.55; p = 0.123).Discussion In cognitively unimpaired older individuals, WMLs play a central role in the degeneration of cholinergic pathways. Our findings highlight the importance of WM lesion burden in the elderly population, which should be considered in the development of prevention programs for neurodegeneration and cognitive impairment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- psykologi
- Psychology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Neurology
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- By the author/editor
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Cedres, Nira
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Ferreira, Daniel
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Nemy, Milan
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Machado, Alejand ...
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Pereira, Joana B ...
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Shams, Sara
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show more...
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Wahlund, Lars-Ol ...
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Zettergren, Anna
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Stepankova, Olga
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Vyslouzilova, Le ...
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Eriksdotter, Mar ...
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Teipel, Stefan
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Grothe, Michel J ...
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Blennow, Kaj
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Zetterberg, Henr ...
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Schöll, Michael
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Kern, Silke
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Skoog, Ingmar
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Westman, Eric
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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Neurology
- By the university
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Stockholm University
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Karolinska Institutet
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Lund University