Clinical characteristics of patients with suspected Alzheimer’s disease within a CSF Aß-ratio grey zone

Abstract Background The AT(N) research framework for Alzheimer's disease (AD) remains unclear on how to best deal with borderline cases. Our aim was to characterise patients with suspected AD with a borderline Aß1-42/Aß1-40 ratio in cerebrospinal fluid. Methods We analysed retrospective data fr...

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Main Authors: Dariia Yosypyshyn, Domantė Kučikienė, Inez Ramakers, Jörg B. Schulz, for the Alzheimer’s Disease Neuroimaging Initiative, Kathrin Reetz, Ana Sofia Costa
Format: Article
Language:English
Published: BMC 2023-08-01
Series:Neurological Research and Practice
Subjects:
Online Access:https://doi.org/10.1186/s42466-023-00262-8
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author Dariia Yosypyshyn
Domantė Kučikienė
Inez Ramakers
Jörg B. Schulz
for the Alzheimer’s Disease Neuroimaging Initiative
Kathrin Reetz
Ana Sofia Costa
author_facet Dariia Yosypyshyn
Domantė Kučikienė
Inez Ramakers
Jörg B. Schulz
for the Alzheimer’s Disease Neuroimaging Initiative
Kathrin Reetz
Ana Sofia Costa
author_sort Dariia Yosypyshyn
collection DOAJ
description Abstract Background The AT(N) research framework for Alzheimer's disease (AD) remains unclear on how to best deal with borderline cases. Our aim was to characterise patients with suspected AD with a borderline Aß1-42/Aß1-40 ratio in cerebrospinal fluid. Methods We analysed retrospective data from two cohorts (memory clinic cohort and ADNI) of patients (n = 63) with an Aß1-42/Aß1-40 ratio within a predefined borderline area—Q1 above the validated cut-off value(grey zone). We compared demographic, clinical, neuropsychological and neuroimaging features between grey zone patients and patients with low Aß1-42 (normal Aß ratio but pathological Aß1-42, n = 42) and patients with AD (pathological Aß, P-Tau, und T-Tau, n = 80). Results Patients had mild cognitive impairment or mild dementia and a median age of 72 years. Demographic and general clinical characteristics did not differ between the groups. Patients in the grey zone group were the least impaired in cognition. However, they overlapped with the low Aß1-42 group in verbal episodic memory performance, especially in delayed recall and recognition. The grey zone group had less severe medial temporal atrophy, but mild posterior atrophy and mild white matter hyperintensities, similar to the low Aß1-42 group. Conclusions Patients in the Aß ratio grey zone were less impaired, but showed clinical overlap with patients on the AD continuum. These borderline patients may be at an earlier disease stage. Assuming an increased risk of AD and progressive cognitive decline, careful consideration of clinical follow-up is recommended when using dichotomous approaches to classify Aß status.
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spelling doaj.art-a204332cd2d44f14a28bfff3d82d789c2023-08-06T11:28:11ZengBMCNeurological Research and Practice2524-34892023-08-015111110.1186/s42466-023-00262-8Clinical characteristics of patients with suspected Alzheimer’s disease within a CSF Aß-ratio grey zoneDariia Yosypyshyn0Domantė Kučikienė1Inez Ramakers2Jörg B. Schulz3for the Alzheimer’s Disease Neuroimaging InitiativeKathrin Reetz4Ana Sofia Costa5Department of Neurology, University Hospital RWTH AachenDepartment of Neurology, University Hospital RWTH AachenDepartment of Neurology, University Hospital RWTH AachenDepartment of Neurology, University Hospital RWTH AachenDepartment of Neurology, University Hospital RWTH AachenDepartment of Neurology, University Hospital RWTH AachenAbstract Background The AT(N) research framework for Alzheimer's disease (AD) remains unclear on how to best deal with borderline cases. Our aim was to characterise patients with suspected AD with a borderline Aß1-42/Aß1-40 ratio in cerebrospinal fluid. Methods We analysed retrospective data from two cohorts (memory clinic cohort and ADNI) of patients (n = 63) with an Aß1-42/Aß1-40 ratio within a predefined borderline area—Q1 above the validated cut-off value(grey zone). We compared demographic, clinical, neuropsychological and neuroimaging features between grey zone patients and patients with low Aß1-42 (normal Aß ratio but pathological Aß1-42, n = 42) and patients with AD (pathological Aß, P-Tau, und T-Tau, n = 80). Results Patients had mild cognitive impairment or mild dementia and a median age of 72 years. Demographic and general clinical characteristics did not differ between the groups. Patients in the grey zone group were the least impaired in cognition. However, they overlapped with the low Aß1-42 group in verbal episodic memory performance, especially in delayed recall and recognition. The grey zone group had less severe medial temporal atrophy, but mild posterior atrophy and mild white matter hyperintensities, similar to the low Aß1-42 group. Conclusions Patients in the Aß ratio grey zone were less impaired, but showed clinical overlap with patients on the AD continuum. These borderline patients may be at an earlier disease stage. Assuming an increased risk of AD and progressive cognitive decline, careful consideration of clinical follow-up is recommended when using dichotomous approaches to classify Aß status.https://doi.org/10.1186/s42466-023-00262-8Alzheimer’s diseaseCognitive impairmentMemory clinicATNBiomarkersValidation
spellingShingle Dariia Yosypyshyn
Domantė Kučikienė
Inez Ramakers
Jörg B. Schulz
for the Alzheimer’s Disease Neuroimaging Initiative
Kathrin Reetz
Ana Sofia Costa
Clinical characteristics of patients with suspected Alzheimer’s disease within a CSF Aß-ratio grey zone
Neurological Research and Practice
Alzheimer’s disease
Cognitive impairment
Memory clinic
ATN
Biomarkers
Validation
title Clinical characteristics of patients with suspected Alzheimer’s disease within a CSF Aß-ratio grey zone
title_full Clinical characteristics of patients with suspected Alzheimer’s disease within a CSF Aß-ratio grey zone
title_fullStr Clinical characteristics of patients with suspected Alzheimer’s disease within a CSF Aß-ratio grey zone
title_full_unstemmed Clinical characteristics of patients with suspected Alzheimer’s disease within a CSF Aß-ratio grey zone
title_short Clinical characteristics of patients with suspected Alzheimer’s disease within a CSF Aß-ratio grey zone
title_sort clinical characteristics of patients with suspected alzheimer s disease within a csf ass ratio grey zone
topic Alzheimer’s disease
Cognitive impairment
Memory clinic
ATN
Biomarkers
Validation
url https://doi.org/10.1186/s42466-023-00262-8
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