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Curr Alzheimer Res. 2018;15(7):691-700. doi: 10.2174/1567205015666180110113238.

Relevance of Follow-Up in Patients with Core Clinical Criteria for Alzheimer Disease and Normal CSF Biomarkers.

Author information

1
University Lille, Inserm U1171, Centre Memoire de Ressources et de Recherche & CNR-MAJ, CHU Lille, F-59000 Lille, France.
2
Centre Memoire de Ressources et de Recherche Paris Nord, Unite d`Histologie et de Biologie du Vieillissement, Groupe Hospitalier Lariboisiere FW Saint-Louis, APHP, Universite Paris Diderot, et INSERM U942, Paris, France.
3
Centre Memoire de Ressources et de Recherche, Departement de Neurologie, Hopital Universitaire Gui de Chauliac, Universite de Montpellier, INSERM U1183, Hopital Saint Eloi, Montpellier, France.
4
Unite de Neuropsychologie et Centre Memoire Ressources Recherche, service de Neurologie, Hopitaux Universitaires de Strasbourg, et Laboratoire ICube, Universite de Strasbourg et CNRS, Strasbourg, France.
5
Centre Memoire de Ressources et de Recherche & CNR-MAJ, INSERM U1079, 76000, Rouen University Hospital, France.
6
Centre Memoire de Ressources et de Recherche, service de Neurologie, CHU de Besancon, France.
7
Laboratoire de Biochimie et de Biologie Moleculaire, Hopitaux Universitaires de Strasbourg, et Laboratoire de Neurosciences Cognitives et Adaptatives, Universite de Strasbourg et CNRS, Strasbourg, France.
8
CHU de Montpellier, Hopital St Eloi Universite de Montpellier and INSERM U1183, IRMB, CRB, Laboratoire de Biochimie Proteomique Clinique, Montpellier, France.
9
Laboratoire de Biochimie & Centre de Recherche Biologique, Hopital Universitaire, Rouen, France.
10
Service de Biochimie et Biologie moleculaire, Hopital Lariboisiere-Fernand Widal, APHP, Universite Paris Diderot, Universite Paris Descartes, Paris, France.
11
University Lille, INSERM, CHU-Lille, Alzheimer & Tauopathies, F-59000 Lille, France.
12
University Lille, CHU-Lille, Centre de Biologie Pathologie UF de Neurobiologie, F-59000 Lille, France.

Abstract

BACKGROUND:

Few patients with a normal cerebrospinal fluid (CSF) biomarker profile fulfill the clinical criteria for Alzheimer disease (AD).

OBJECTIVE:

The aim of this study was to test the hypothesis of misdiagnoses for these patients.

METHOD:

Patients from the e-PLM centers fulfilling the core clinical criteria for probable AD dementia or mild cognitive impairment due to AD (AD-MCI), with normal CSF Aβ1-42, T-tau and P-tau biomarkers and clinical follow-up, were included. Clinical and imaging data were reviewed by an independent board, from baseline (visit with clinical evaluation and CSF analysis) to the end of the follow-up, for a final diagnosis.

RESULTS:

In the e-PLM cohort of 1098 AD patients with CSF analysis, 37 (3.3%) patients (20 with AD dementia core clinical criteria and 17 with AD-MCI core clinical criteria) had normal CSF biomarker profile and a clinical follow-up. All patients presented with episodic memory impairment and 27 (73%) had medial temporal lobe atrophy on MRI-scan. After a median follow-up of 36 months (range 7-74), the final diagnosis was AD MCI or dementia for 9 (24%) patients, and unlikely due to AD for 28 (76%) patients. A misdiagnosis was corrected in 18 (49%) patients (mood disorders, non-AD degenerative dementia, vascular cognitive impairment, alcohol cognitive disorders, temporal epilepsy and hippocampal sclerosis), and 10 (27%) patients had cognitive disorders of undetermined etiology.

CONCLUSION:

AD diagnosis (MCI or dementia) with normal CSF biomarkers is a rare condition. A clinical follow- up is particularly recommended to consider an alternative diagnosis.

KEYWORDS:

Alzheimer disease; biomarker; cerebrospinal fluid; dementia; depression; frontotemporal dementia; mild cognitive impairment; vascular dementia.

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