PASSED: Brain atrophy in non-demented individuals in a long-term longitudinal study from two independent cohorts

dc.contributor.authorHaas, Anna-Lena
dc.contributor.authorOlm, Pauline
dc.contributor.authorUtz, Janine
dc.contributor.authorSiegmann, Eva-Maria
dc.contributor.authorSpitzer, Philipp
dc.contributor.authorFlorvaag, Anna
dc.contributor.authorSchmidt, Manuel Alexander
dc.contributor.authorDoerfler, Arnd
dc.contributor.authorLewczuk, Piotr
dc.contributor.authorKornhuber, Johannes
dc.contributor.authorMaler, Juan Manuel
dc.contributor.authorOberstein, Timo Jan
dc.date.accessioned2023-03-20
dc.date.available2023-10-09T21:00:23Z
dc.date.created2023
dc.date.issued2023-03-20
dc.description.abstractIntroduction Alzheimer’s disease (AD) is indicated by a decrease in amyloid beta 42 (Aβ42) level or the Aβ42/Aβ40 ratio, and by increased levels of Tau with phosphorylated threonine at position 181 (pTau181) in cerebrospinal fluid (CSF) years before the onset of clinical symptoms. However, once only pTau181 is increased, cognitive decline in individuals with subjective or mild cognitive impairment is slowed compared to individuals with AD. Instead of a decrease in Aβ42 levels, an increase in Aβ42 was observed in these individuals, leading to the proposal to refer to them as nondemented subjects with increased pTau-levels and Aβ surge with subtle cognitive deterioration (PASSED). In this study, we determined the longitudinal atrophy rates of AD, PASSED, and Biomarker-negative nondemented individuals of two independent cohorts to determine whether these groups can be distinguished by their longitudinal atrophy patterns or rates. Methods Depending on their CSF-levels of pTau 181 (T), total Tau (tTau, N), Aβ42 or ratio of Aβ42/Aβ40 (A), 185 non-demented subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and 62 non-demented subjects from Erlangen AD cohort were assigned to an ATN group (A–T–N–, A–T+N±, A+T–N±and A+T+N±) and underwent T1-weighted structural magnetic resonance imaging (sMRI). Longitudinal grey matter (GM) atrophy patterns were assessed with voxel-based morphometry (VBM) using the cat12 toolbox on spm12 (statistical parametric mapping) of MRI scans from individuals in the ADNI cohort with a mean follow-up of 2 and 5 years, respectively. The annualized atrophy rate for individuals in the Erlangen cohort was determined using region of interest analysis (ROI) in terms of a confirmatory analysis. Results In the A–T+N± group, VBM did not identify any brain region that showed greater longitudinal atrophy than the A+T+N±, A+T+N± or biomarker negative control group. In contrast, marked longitudinal atrophy in the temporal lobe was evident in the A+T–N± group compared with A+T–N±  and biomarker-negative subjects. The ROI in the angular gyrus identified by VBM analysis of the ADNI cohort did not discriminate better than the hippocampal volume and atrophy rate between AD and PASSED in the confirmatory analysis. Discussion In this study, nondemented subjects with PASSED did not show a unique longitudinal atrophy pattern in comparison to nondemented subjects with AD. The nonsignificant atrophy rate compared with controls suggests that increased pTau181-levels without concomitant amyloidopathy did not indicate a neurodegenerative disorder.en
dc.identifier.citationFrontiers in Aging Neuroscience 15 (2023): 1121500. <https://www.frontiersin.org/articles/10.3389/fnagi.2023.1121500/full>
dc.identifier.doihttps://doi.org/10.3389/fnagi.2023.1121500
dc.identifier.issn1663-4365
dc.identifier.opus-id21870
dc.identifier.urihttps://open.fau.de/handle/openfau/21870
dc.identifier.urnurn:nbn:de:bvb:29-opus4-218704
dc.language.isoen
dc.publisherFrontiers Media S.A.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjectmagnetic resonance imaging
dc.subjectmedial temporal lobe
dc.subjecttau proteins/cerebrospinal fluid
dc.subjectamyloid beta-peptides/cerebrospinal fluid
dc.subjectSNAP
dc.subjectATN classification
dc.subjectAlzheimer disease/physiopathology
dc.subjectlongitudinal studies
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titlePASSED: Brain atrophy in non-demented individuals in a long-term longitudinal study from two independent cohortsen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.date.prevpublished2023-02-22
local.document.articlenumber1121500
local.journal.titleFrontiers in Aging Neuroscience
local.journal.volume15
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.importimport
local.subject.sammlungUniversität Erlangen-Nürnberg / Eingespielte Open Access Artikel / Eingespielte Open Access Artikel 2023
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