Alzheimer Disease: Ivanoiu A

Ivanoiu A, Cooper JM, Shanks MF, Venneri A. · Neurology Department and Neuropsychological Rehabilitation Unit, University of Louvain, Brussels, Belgium. · Cortex. · Pubmed #15174457 No free full text.

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Adam S, Van der Linden M, Ivanoiu A, Juillerat AC, Bechet S, Salmon E. · Neuropsychology Unit, University of Liège, Belgium. · J Clin Exp Neuropsychol. · Pubmed #17564913 No free full text.

Abstract: The aim of this study was to evaluate the discriminant validity of the RI-48 test, a shorter French version of the Category Cued Recall portion of the Double Memory Test developed initially by Buschke and colleagues (1997), in the diagnosis of mild and very mild Alzheimer disease (AD). The distinctive feature of the RI-48 task is that encoding specificity was increased by adding an immediate cued recall stage at the encoding phase. The results show that the RI-48 task seems to be well adapted to the clinical context and to have good psychometric properties, in particular a lack of a ceiling effect. Moreover, this task appears to be especially well suited for the diagnosis of both mild and very mild AD (sensitivity of 93% and 83.8%). From a more theoretical point of view, this study confirms the importance of optimizing the encoding specificity for the diagnosis of very mild AD, since the more encoding specificity is accentuated, the more discriminating power is increased for the diagnosis of very mild AD.

Vanderstichele H, De Vreese K, Blennow K, Andreasen N, Sindic C, Ivanoiu A, Hampel H, Bürger K, Parnetti L, Lanari A, Padovani A, DiLuca M, Bläser M, Olsson AO, Pottel H, Hulstaert F, Vanmechelen E. · Innogenetics NV, Industriepark Zwijnaarde 7, 9052 Gent, Belgium. · Clin Chem Lab Med. · Pubmed #17163825 No free full text.

Abstract: BACKGROUND: Total tau (T-tau) and beta-amyloid((1-42)) (Abeta(1-42)) levels in cerebrospinal fluid (CSF) can differentiate Alzheimer's disease (AD) from normal aging or depressive pseudo-dementia. Differential diagnosis from dementia with Lewy bodies (DLB) in clinical settings is difficult. METHODS: The analytical performance of the INNOTEST PHOSPHO-TAU(181P) assay was validated in terms of selectivity, sensitivity, specificity, precision, robustness, and stability. Clinical utility of the assay alone, or combined with T-tau and Abeta(1-42), for discrimination of AD (n=94) from patients suffering from DLB (n=60) or from age-matched control subjects (CS) (n=60) was assessed in a multicenter study. RESULTS: CSF concentrations of tau phosphorylated at threonine 181 (P-tau(181P)) in AD was significantly higher than in DLB and CS. Discriminant analysis, a classification tree, and logistic regression showed that P-tau(181P) was the most statistically significant single variable of the three biomarkers for discrimination between AD and DLB. CONCLUSIONS: P-tau(181P) quantification is a robust and reliable assay that may be useful in discriminating AD from DLB.

Rogers TT, Ivanoiu A, Patterson K, Hodges JR. · MRC Cognition and Brain Sciences Unit, Cambridge, England. · Neuropsychology. · Pubmed #16719625 No free full text.

Abstract: Using semantic dementia (SD) as a reference point, the authors assessed semantic memory in four other neurodegenerative disorders: progressive nonfluent aphasia (PNFA), frontal variant frontotemporal dementia (fvFTD), Alzheimer's disease (AD), and posterior cortical atrophy (PCA). Individuals with SD were more impaired than other groups on semantic measures and showed a characteristic pattern across tasks: category fluency (CF) worse than letter fluency (LF), naming worse than comprehension, and visual and verbal comprehension equally affected, suggesting disruption to an amodal semantic system. Individuals with AD demonstrated a similar pattern to a milder degree. Although PNFA, fvFTD, and PCA groups had abnormal scores (relative to controls) on most semantic measures, their differing patterns across measures indicate that the apparent semantic impairment in these conditions is largely secondary to other factors.

Ivanoiu A, Cooper JM, Shanks MF, Venneri A. · Neurology Department and Neuropsychological Rehabilitation Unit, Saint Luc Hospital, University of Louvain, Brussels, Belgium. · Neuropsychologia. · Pubmed #16519908 No free full text.

Abstract: Detailed study of the autobiographical memory (ABM) impairments seen in different forms of degenerative dementia, in particular Alzheimer's disease (AD) and semantic dementia (SD) can inform neuropsychological models of memory. A modified ABM questionnaire which allowed more detailed analysis of episodic and semantic ABM was used to study the pattern of deficits in patients with minimal to mild Alzheimer's disease (AD) and in two patients with mild and moderate semantic dementia (SD). The questionnaire tested both cued and free recall. A group of healthy elderly was also tested. AD patients differed from controls in all measures. There was no clear temporal gradient for episodic ABM, but a modest gradient was observed for semantic ABM. The mild SD patient performed at control level for episodic ABM but showed a deficit within the range of the AD patients for semantic ABM except for the most recent life period. In contrast the moderate SD patient was impaired within the range of the AD patients for both episodic and semantic ABM. The evidence for differential impairment of episodic and semantic ABM retrieval in AD and SD is interpreted as supporting the multiple trace model of memory.

Ivanoiu A, Sindic CJ. · The Neurology Department Memory Clinic and Neurochemistry Laboratory, Saint Luc University Hospital, Catholic University of Louvain, Brussels, Belgium. · Neurocase. · Pubmed #15804922 No free full text.

Abstract: Cerebrospinal fluid (CSF) TAU protein and Amyloid beta42 were able to distinguish between 28 mild cognitive impairment (MCI) patients and both 38 normal aged and 17 anxious and depressed elderly patients, with good sensitivity/specificity when the two measures were combined. These biological markers are independent predictors of the presence of Alzheimer disease (AD), in addition to memory performance. Low Amyloid beta42 level was predictor of a fast progression of MCI patients to full blown dementia. The TAU protein level tended to correlate with memory performance, presumably in relation with the extent of the bilateral medio-temporal damage in early AD.

Ivanoiu A, Adam S, Van der Linden M, Salmon E, Juillerat AC, Mulligan R, Seron X. · Department of Neurology, Memory Clinic and Neuropsychological Rehabilitation Center, Saint Luc University Hospital, University of Louvain, 10 Avenue Hippocrate, 1200 Brussels, Belgium. · J Neurol. · Pubmed #15654553 No free full text.

Abstract: Free delayed recall is considered the memory measure with the greatest sensitivity for the early diagnosis of dementia. However, its specificity for dementia could be lower, as deficits other than those of pure memory might account for poor performance in this difficult and effortful task. Cued recall is supposed to allow a better distinction between poor memory due to concurrent factors and impairments related to the neurodegenerative process. The available cued recall tests suffer from a ceiling effect. This is a prospective, longitudinal study aiming to assess the utility of a new memory test based on cued recall that avoids the ceiling effect in the early diagnosis of Alzheimer's disease (AD). Twenty-five patients with mild cognitive impairment (MCI), 22 probable AD patients (NINCDS-ADRDA) at a mild stage, 22 elderly patients with subjective memory complaints (SMC) and 38 normal age-matched controls took part in the study. The patients underwent a thorough cognitive evaluation and the recommended screening procedure for the diagnosis of dementia. All patients were re-examined 12-18 months later. A newly devised delayed cued recall test using semantic cues (The RI48 Test) was compared with three established memory tests: the Ten Word-List Recall from CERAD, the "Doors" and the "Shapes" Tests from "The Doors and People Test Battery". Forty-four % of the MCI patients fulfilled criteria for probable AD at follow-up. The RI48 Test classified correctly 88% of the MCI and SMC participants and was the best predictor of the status of MCI and mild AD as well as the outcome of the MCI patients. Poor visual memory was the second best predictor of those MCI patients who evolved to AD. A cued recall test which avoids the ceiling effect is at least as good as the delayed free recall tests in the early detection of AD.

Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP, Bancher C, Cras P, Wiltfang J, Mehta PD, Iqbal K, Pottel H, Vanmechelen E, Vanderstichele H. · Innogenetics NV, Ghent, Belgium. · Neurology. · Pubmed #10331678 No free full text.

Abstract: OBJECTIVE: To evaluate CSF levels of beta-amyloid(1-42) (Abeta42) alone and in combination with CSF tau for distinguishing AD from other conditions. METHODS: At 10 centers in Europe and the United States, 150 CSF samples from AD patients were analyzed and compared with 100 CSF samples from healthy volunteers or patients with disorders not associated with pathologic conditions of the brain (CON), 84 patients with other neurologic disorders (ND), and 79 patients with non-Alzheimer types of dementia (NAD). Sandwich ELISA techniques were used on site for measuring Abeta42 and tau. RESULTS: Median levels of Abeta42 in CSF were significantly lower in AD (487 pg/mL) than in CON (849 pg/mL; p = 0.001), ND (643 pg/mL; p = 0.001), and NAD (603 pg/mL; p = 0.001). Discrimination of AD from CON and ND was significantly improved by the combined assessment of Abeta42 and tau. At 85% sensitivity, specificity of the combined test was 86% (95% CI: 81% to 91%) compared with 55% (95% CI: 47% to 62%) for Abeta42 alone and 65% (95% CI: 58% to 72%) for tau. The combined test at 85% sensitivity was 58% (95% CI: 47% to 69%) specific for NAD. The APOE e4 gene load was negatively correlated with Abeta42 levels not only in AD but also in NAD. CONCLUSIONS: The combined measure of CSF Abeta42 and tau meets the requirements for clinical use in discriminating AD from normal aging and specific neurologic disorders.