%0 Journal Article %J J Alzheimers Dis %D 2018 %T Distribution of Cerebrospinal Fluid Biomarker Profiles in Patients Explored for Cognitive Disorders. %A Paquet, Claire %A Bouaziz-Amar, Elodie %A Cognat, Emmanuel %A Volpe-Gillot, Lisette %A Haddad, Victor %A Mahieux, Florence %A Dekimeche, Siham %A Defontaines, Benedicte %A Chabriat, Hugues %A Belin, Catherine %A Texeira, Antonio %A Goutagny, Stephane %A Questel, Frank %A Azuar, Julien %A Sellier, Pierre-Olivier %A Laplanche, Jean-Louis %A Hugon, Jacques %A Dumurgier, Julien %X

BACKGROUND: CSF Alzheimer's disease (AD) biomarkers allow classifying individuals based on their levels of amyloid and neurodegeneration pathologies.

OBJECTIVE: To investigate the distribution of AD biomarker profiles from patients suffering from cognitive disorders.

METHODS: We analyzed 3001 patients with cognitive disorders and referred by 18 French memory clinics located in and around Paris. Patients were classified as normal, amyloidosis (A+/N-), amyloidosis and neurodegeneration (A+/N+) or suspected non-AD pathophysiology (SNAP), according to their CSF levels of biomarkers. Analysis were performed for the overall population and stratified by gender, age quintiles, and Mini-Mental State Examination (MMSE) score quintiles. Results were compared to previous findings in cohorts of healthy elderly adults.

RESULTS: 37% of the sample were classified as A+/N+, 22% were classified A+/N-, and 15% as SNAP. The A+/N+ profile was associated with female gender, advanced age, and lower MMSE score, while the A+/N-profile was observed more frequently in men and the distribution was stable across age and MMSE. The SNAP profile showed no association with gender or age, was less frequent in patients with lower MMSE, and had a lower repartition than the one previously reported in asymptomatic populations.

CONCLUSIONS: While A+/N+ patients had the clinical characteristics typically observed in AD, A+/N-patients had a different epidemiological pattern (higher frequency in men, no association with advanced age or lower MMSE). The SNAP profile was less frequent than previously reported in the general elderly population, suggesting that this profile is not a frequent cause of memory impairment in this population.

%B J Alzheimers Dis %V 64 %P 889-897 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29966201?dopt=Abstract %R 10.3233/JAD-180240 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults. %A Dumurgier, Julien %A Hanseeuw, Bernard J %A Hatling, Frances B %A Judge, Kelly A %A Schultz, Aaron P %A Chhatwal, Jasmeer P %A Blacker, Deborah %A Sperling, Reisa A %A Johnson, Keith A %A Hyman, Bradley T %A Gómez-Isla, Teresa %X

BACKGROUND: Identifying older adults at risk of cognitive decline represents a challenge as Alzheimer's disease (AD) modifying therapies move toward preclinical stages.

OBJECTIVE: To investigate the relationship between AD biomarkers and subsequent change in cognition in a cohort of cognitively intact older adults.

METHODS: 84 cognitively normal subjects (mean age 72.0 years, 59% women) were recruited through the Massachusetts Alzheimer's Disease Research Center and the Harvard Aging Brain Study and followed over 3 years. Measurements of amyloid-β 1-42 (Aβ42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) in the cerebrospinal fluid (CSF) at study entry were available in all cases. Baseline brain MRI, FDG-PET, and PiB-PET data were available in the majority of participants. Relationship between baseline AD biomarkers and longitudinal change in cognition was assessed using Cox proportional hazard regression and linear mixed models.

RESULTS: 14% participants increased their global Clinical Dementia Rating (CDR) score from 0 to 0.5 during follow-up. A CDR score increase was associated with higher baseline CSF t-Tau and p-Tau181, higher global cortical PiB retention, and lower hippocampal volume. The combination of high CSF t-Tau and low Aβ42 or low hippocampal volume was more strongly related to cognitive outcome than each single biomarker. Higher CSF t-Tau was the only biomarker associated with subsequent decline in MMSE score.

CONCLUSIONS: Baseline CSF t-Tau and p-Tau181, in vivo amyloid load, and hippocampal volume were all independently associated with future decline in cognition. The discriminatory ability of these biomarkers to predict risk of cognitive decline, however, was only modest.

%B J Alzheimers Dis %V 60 %P 1451-1459 %G eng %N 4 %R 10.3233/JAD-170511 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Differential Diagnosis of Dementia with High Levels of Cerebrospinal Fluid Tau Protein. %A Grangeon, Lou %A Paquet, Claire %A Bombois, Stephanie %A Quillard-Muraine, Muriel %A Martinaud, Olivier %A Bourre, Bertrand %A Lefaucheur, Romain %A Nicolas, Gaël %A Dumurgier, Julien %A Gerardin, Emmanuel %A Jan, Mary %A Laplanche, Jean-Louis %A Peoc'h, Katell %A Hugon, Jacques %A Pasquier, Florence %A Maltête, David %A Hannequin, Didier %A Wallon, David %K Adult %K Age of Onset %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Biomarkers %K Creutzfeldt-Jakob Syndrome %K Dementia, Vascular %K Diagnosis, Differential %K Female %K France %K Frontotemporal Dementia %K Humans %K Lewy Body Disease %K Male %K Mental Status Schedule %K Middle Aged %K Phosphorylation %K Retrospective Studies %K Sex Factors %K tau Proteins %X

BACKGROUND: Total Tau concentration in cerebrospinal fluid (CSF) is widely used as a biomarker in the diagnosis of neurodegenerative process primarily in Alzheimer's disease (AD). A particularly high Tau level may indicate AD but may also be associated with Creutzfeldt-Jakob disease (CJD). In such situations little is known about the distribution of differential diagnoses.

OBJECTIVE: Our study aimed to describe the different diagnoses encountered in clinical practice for patients with dementia and CSF Tau levels over 1000 pg/ml. We studied the p-Tau/Tau ratio to specify its ability to distinguish AD from CJD.

METHODS: Patients (n = 202) with CSF Tau levels over 1000 pg/ml were recruited in three memory clinics in France. All diagnoses were made using the same diagnostic procedure and criteria.

RESULTS: Patients were diagnosed with AD (n = 148, 73.2%), mixed dementia (n = 38, 18.8%), CJD, vascular dementia (n = 4, 2.0% for each), Lewy body dementia, and frontotemporal dementia (n = 3, 1.5% for each). Dispersion of CSF Tau levels clearly showed an overlap between all diagnoses. Using the p-Tau/Tau ratio suggestive of CJD (<0.075), all CJD patients were correctly categorized and only two AD patients were miscategorized. This ratio was highly associated with CJD compared to AD (p < 0.0001).

CONCLUSION: Our study showed that in clinical practice, extremely high CSF Tau levels are mainly related to diagnosis of AD. CJD patients represent a minority. Our results support a sequential interpretation algorithm for CSF biomarkers in dementia. High CSF Tau levels should alert clinicians to check the p-Tau/Tau ratio to consider a probable diagnosis of CJD.

%B J Alzheimers Dis %V 51 %P 905-13 %8 2016 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/26890785?dopt=Abstract %R 10.3233/JAD-151111 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Primary Progressive Aphasia in the Network of French Alzheimer Plan Memory Centers. %A Magnin, Eloi %A Démonet, Jean-François %A Wallon, David %A Dumurgier, Julien %A Troussière, Anne-Cécile %A Jager, Alain %A Duron, Emmanuelle %A Gabelle, Audrey %A de la Sayette, Vincent %A Volpe-Gillot, Lisette %A Tio, Gregory %A Evain, Sarah %A Boutoleau-Bretonnière, Claire %A Enderle, Adeline %A Mouton-Liger, François %A Robert, Philippe %A Hannequin, Didier %A Pasquier, Florence %A Hugon, Jacques %A Paquet, Claire %X

BACKGROUND: Few demographical data about primary progressive aphasia (PPA) are available, and most knowledge regarding PPA is based on tertiary centers' results.

OBJECTIVE: Our aims were to describe demographical characteristics of the PPA population in a large sample of PPA patients from the network of French Alzheimer plan memory centers (Sample 1), and to describe the stratification of cerebrospinal fluid (CSF) biomarkers in two different samples of PPA patients (Samples 2 and 3).

METHODS: All registered PPA patients in the French Alzheimer's disease (AD) databank (Sample 1: n = 2,035) and a subsample (Sample 2: n = 65) derived from a multicentric prospective cohort with CSF biomarker analysis were analyzed. A multicentric retrospective cohort from language expert tertiary centers (Sample 3: n = 97) with CSF biomarker analysis was added. Sample 3 was added to replicate the CSF results of the Sample 2 and to evaluate repartition of AD pathology in the three variant of PPA according to the latest classification.

RESULTS: Non-Fluent/Agrammatic, Logopenic, and Unclassifiable PPA patients (NF/A-Logo-Unclass PPA) were older and more frequent than Semantic PPA patients (2.2 versus 0.8/100,000 inhabitants; p < 0.00001). Male predominance occurred after the age of 80 (p < 0.00001). A higher level of education was observed in the PPA population compared to a typical amnesic AD group. No demographical significant difference between PPA due to AD and not due to AD was observed. The Logopenic variant was most frequent with 85% of AD CSF biomarker profiles (35% in NF/A PPA; 20% in Semantic PPA).

CONCLUSION: PPA occurs also in an elderly population, especially in male patients over 80. CSF biomarkers are useful to stratify PPA. The epidemiology of PPA should be further investigated to confirm gender and cognitive reserve role in PPA to better understand the factors and mechanisms leading to this language-predominant deficit during neurodegenerative diseases.

%B J Alzheimers Dis %V 54 %P 1459-1471 %8 2016 Oct 18 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27589533?dopt=Abstract %R 10.3233/JAD-160536 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Time Orientation and 10 Years Risk of Dementia in Elderly Adults: The Three-City Study. %A Dumurgier, Julien %A Dartigues, Jean-François %A Gabelle, Audrey %A Paquet, Claire %A Prevot, Magali %A Hugon, Jacques %A Tzourio, Christophe %X

Time disorientation is commonly observed in dementia, however very little is known about the pathological significance of minor time errors in community-dwelling population. Our objective was to investigate the relationship between time orientation and risk of dementia in a population of older adults. Analyses relies on 8611 dementia-free subjects from the Three-City Study, France. Participants were followed up for 10 years for incident dementia. Time orientation was assessed by asking for the date, the day of the week, the month, the season and the year. At baseline, 905 subjects made at least one error in time orientation. During 57,073 person-years of follow-up, 827 participants developed dementia. After controlling for age, gender and education level, subjects with one error in time had a greater risk of dementia (hazard ratio [HR] 1.44 [1.18-1.77]), while those with at least 2 errors had a more than three-fold increased risk (HR 3.10 [1.98-4.83]). This association was particularly marked for the diagnosis of probable Alzheimer's disease. Time disorientation was associated with an increased risk of dementia in a large population of cognitively normal older people followed during up to 10 years and should not be underestimated in clinical setting.

%B J Alzheimers Dis %V 53 %P 1411-8 %8 2016 Jul 01 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27392864?dopt=Abstract %R 10.3233/JAD-160295