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Alzheimer's pathology is associated with altered cognition, brain volume, and plasma biomarker patterns in traumatic encephalopathy syndrome.
Asken, Breton M; Tanner, Jeremy A; Gaynor, Leslie S; VandeVrede, Lawren; Mantyh, William G; Casaletto, Kaitlin B; Staffaroni, Adam M; Fonseca, Corrina; Shankar, Ranjani; Grant, Harli; Smith, Karen; Lago, Argentina Lario; Xu, Haiyan; La Joie, Renaud; Cobigo, Yann; Rosen, Howie; Perry, David C; Rojas, Julio C; Miller, Bruce L; Gardner, Raquel C; Wang, Kevin K W; Kramer, Joel H; Rabinovici, Gil D.
Afiliação
  • Asken BM; Department of Clinical & Health Psychology, 1Florida Alzheimer's Disease Research Center, University of Florida, 1225 Center Drive, Gainesville, FL, 32610, USA. basken8@phhp.ufl.edu.
  • Tanner JA; Department of Neurology, Biggs Institute for Alzheimer's and Neurodegenerative Diseases, South Texas Alzheimer's Disease Research Center, University of Texas Health - San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
  • Gaynor LS; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • VandeVrede L; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Mantyh WG; Department of Neurology, University of Minnesota, PWB 12-100, 516 Delaware Street SE, Minneapolis, MN, 55455, USA.
  • Casaletto KB; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Staffaroni AM; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Fonseca C; Department of Neuroscience, Helen Wills Neuroscience Institute, University of California, 132 Barker Hall MC#3190, Berkeley, CA, 94720, USA.
  • Shankar R; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Grant H; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Smith K; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Lago AL; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Xu H; Department of Surgery, University of Florida, PO Box 100128, Gainesville, FL, 32610, USA.
  • La Joie R; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Cobigo Y; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Rosen H; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Perry DC; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Rojas JC; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Miller BL; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Gardner RC; Sheba Medical Center, Tel Hashomer City of Health, Tel Aviv District, Derech Sheba 2, Ramat Gan, Israel.
  • Wang KKW; Department of Neurobiology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA, 30310, USA.
  • Kramer JH; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
  • Rabinovici GD; Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
Alzheimers Res Ther ; 15(1): 126, 2023 07 21.
Article em En | MEDLINE | ID: mdl-37480088
ABSTRACT

BACKGROUND:

Traumatic encephalopathy syndrome (TES) is a clinical phenotype sensitive but non-specific to underlying chronic traumatic encephalopathy (CTE) neuropathology. However, cognitive symptoms of TES overlap with Alzheimer's disease (AD), and features of AD pathology like beta-amyloid (Aß) plaques often co-occur with CTE, making clinical-to-pathological conclusions of TES diagnoses challenging. We investigated how Alzheimer's neuropathological changes associated with cognition, brain volume, and plasma biomarkers in patients with repetitive head impacts (RHI)/TES, clinical AD, or typically aging controls.

METHODS:

We studied 154 participants including 33 with RHI/TES (age 61.5 ± 11.5, 100% male, 11/33 Aß[ +]), 62 with AD and no known prior RHI (age 67.1 ± 10.2, 48% male, 62/62 Aß[ +]), and 59 healthy controls without RHI (HC; age 73.0 ± 6.2, 40% male, 0/59 Aß[ +]). Patients completed neuropsychological testing (memory, executive functioning, language, visuospatial) and structural MRI (voxel-based morphometry analysis), and provided plasma samples analyzed for GFAP, NfL, IL-6, IFN-γ, and YKL-40. For cognition and plasma biomarkers, patients with RHI/TES were stratified as Aß[ +] or Aß[ -] and compared to each other plus the AD and HC groups (ANCOVA adjusting for age and sex). Differences with at least a medium effect size (Cohen's d > 0.50) were interpreted as potentially meaningful.

RESULTS:

Cognitively, within the TES group, Aß[ +] RHI/TES performed worse than Aß[-] RHI/TES on visuospatial (p = .04, d = 0.86) and memory testing (p = .07, d = 0.74). Comparing voxel-wise brain volume, both Aß[ +] and Aß[ -] RHI/TES had lower medial and anterior temporal lobe volume than HC and did not significantly differ from AD. Comparing plasma biomarkers, Aß[ +] RHI/TES had higher plasma GFAP than HC (p = .01, d = 0.88) and did not significantly differ from AD. Conversely, Aß[ -] RHI/TES had higher NfL than HC (p = .004, d = 0.93) and higher IL-6 than all other groups (p's ≤ .004, d's > 1.0).

CONCLUSIONS:

Presence of Alzheimer's pathology in patients with RHI/TES is associated with altered cognitive and biomarker profiles. Patients with RHI/TES and positive Aß-PET have cognitive and plasma biomarker changes that are more like patients with AD than patients with Aß[ -] RHI/TES. Measuring well-validated Alzheimer's biomarkers in patients with RHI/TES could improve interpretation of research findings and heighten precision in clinical management.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Lesões Encefálicas Traumáticas / Encefalopatia Traumática Crônica Tipo de estudo: Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Alzheimers Res Ther Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Lesões Encefálicas Traumáticas / Encefalopatia Traumática Crônica Tipo de estudo: Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Alzheimers Res Ther Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos