Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer's disease
(2021) In Translational Psychiatry 11(1).- Abstract
Mild behavioral impairment (MBI) is suggested as risk marker for neurodegenerative diseases, such as Alzheimer's disease (AD). Recently, pathologic tau deposition in the brain has been shown closely related to clinical manifestations, such as cognitive deficits. Yet, associations between tau pathology and MBI have rarely been investigated. It is further debated if MBI precedes cognitive deficits in AD. Here, we explored potential mechanisms by which MBI is related to AD, this by studying associations between MBI and tau in preclinical AD. In all, 50 amyloid-β-positive cognitively unimpaired subjects (part of the BioFINDER-2 study) underwent MBI-checklist (MBI-C) to assess MBI, and the Alzheimer's Disease Assessment Scale - Cognitive... (More)
Mild behavioral impairment (MBI) is suggested as risk marker for neurodegenerative diseases, such as Alzheimer's disease (AD). Recently, pathologic tau deposition in the brain has been shown closely related to clinical manifestations, such as cognitive deficits. Yet, associations between tau pathology and MBI have rarely been investigated. It is further debated if MBI precedes cognitive deficits in AD. Here, we explored potential mechanisms by which MBI is related to AD, this by studying associations between MBI and tau in preclinical AD. In all, 50 amyloid-β-positive cognitively unimpaired subjects (part of the BioFINDER-2 study) underwent MBI-checklist (MBI-C) to assess MBI, and the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) delayed word recall (ADAS-DR) to assess episodic memory. Early tau pathology was determined using tau-PET ([18F]RO948 retention in entorhinal cortex/hippocampus) and cerebrospinal fluid (CSF) P-tau181. Regression models were used to test for associations. We found that higher tau-PET signal in the entorhinal cortex/hippocampus and CSF P-tau181 levels were associated with higher MBI-C scores (β = 0.010, SE = 0.003, p = 0.003 and β = 1.263, SE = 0.446, p = 0.007, respectively). When MBI-C and ADAS-DR were entered together in the regression models, tau-PET (β = 0.009, p = 0.009) and CSF P-tau181 (β = 0.408, p = 0.006) were predicted by MBI-C, but not ADAS-DR. We conclude that in preclinical AD, MBI is associated with tau independently from memory deficits. This denotes MBI as an important early clinical manifestation related to tau pathology in AD.
(Less)
- author
- organization
-
- Clinical Memory Research (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Clinical Sciences, Helsingborg
- Regeneration in Movement Disorders (research group)
- Neurology, Lund
- Neuroradiology (research group)
- Diagnostic Radiology, (Lund)
- WCMM-Wallenberg Centre for Molecular Medicine
- Brain Injury After Cardiac Arrest (research group)
- publishing date
- 2021-01-26
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Translational Psychiatry
- volume
- 11
- issue
- 1
- article number
- 76
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:33500386
- scopus:85099860453
- ISSN
- 2158-3188
- DOI
- 10.1038/s41398-021-01206-z
- language
- English
- LU publication?
- yes
- id
- acd26f7d-e9da-40a2-ab14-732223540080
- date added to LUP
- 2021-02-03 09:42:51
- date last changed
- 2025-01-24 06:01:27
@article{acd26f7d-e9da-40a2-ab14-732223540080, abstract = {{<p>Mild behavioral impairment (MBI) is suggested as risk marker for neurodegenerative diseases, such as Alzheimer's disease (AD). Recently, pathologic tau deposition in the brain has been shown closely related to clinical manifestations, such as cognitive deficits. Yet, associations between tau pathology and MBI have rarely been investigated. It is further debated if MBI precedes cognitive deficits in AD. Here, we explored potential mechanisms by which MBI is related to AD, this by studying associations between MBI and tau in preclinical AD. In all, 50 amyloid-β-positive cognitively unimpaired subjects (part of the BioFINDER-2 study) underwent MBI-checklist (MBI-C) to assess MBI, and the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) delayed word recall (ADAS-DR) to assess episodic memory. Early tau pathology was determined using tau-PET ([18F]RO948 retention in entorhinal cortex/hippocampus) and cerebrospinal fluid (CSF) P-tau181. Regression models were used to test for associations. We found that higher tau-PET signal in the entorhinal cortex/hippocampus and CSF P-tau181 levels were associated with higher MBI-C scores (β = 0.010, SE = 0.003, p = 0.003 and β = 1.263, SE = 0.446, p = 0.007, respectively). When MBI-C and ADAS-DR were entered together in the regression models, tau-PET (β = 0.009, p = 0.009) and CSF P-tau181 (β = 0.408, p = 0.006) were predicted by MBI-C, but not ADAS-DR. We conclude that in preclinical AD, MBI is associated with tau independently from memory deficits. This denotes MBI as an important early clinical manifestation related to tau pathology in AD.</p>}}, author = {{Johansson, Maurits and Stomrud, Erik and Insel, Philip S. and Leuzy, Antoine and Johansson, Per Mårten and Smith, Ruben and Ismail, Zahinoor and Janelidze, Shorena and Palmqvist, Sebastian and van Westen, Danielle and Mattsson-Carlgren, Niklas and Hansson, Oskar}}, issn = {{2158-3188}}, language = {{eng}}, month = {{01}}, number = {{1}}, publisher = {{Nature Publishing Group}}, series = {{Translational Psychiatry}}, title = {{Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer's disease}}, url = {{http://dx.doi.org/10.1038/s41398-021-01206-z}}, doi = {{10.1038/s41398-021-01206-z}}, volume = {{11}}, year = {{2021}}, }