Authors: Polcher, Alexandra | Frommann, Ingo | Koppara, Alexander | Wolfsgruber, Steffen | Jessen, Frank | Wagner, Michael
Article Type: Research Article
Abstract: Background: There is a need for more sensitive neuropsychological tests to detect subtle cognitive deficits emerging in the preclinical stage of Alzheimer’s disease (AD). Associative memory is a cognitive function supported by the hippocampus and affected early in the process of AD. Objective: We developed a short computerized face-name associative recognition test (FNART) and tested whether it would detect memory impairment in memory clinic patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Methods: We recruited 61 elderly patients with either SCD (n = 32) or MCI (n = 29) and 28 healthy controls (HC) and compared performance on FNART, …self-reported cognitive deterioration in different domains (ECog-39), and, in a reduced sample (n = 46), performance on the visual Paired Associates Learning of the CANTAB battery. Results: A significant effect of group on FNART test performance in the total sample was found (p < 0.001). Planned contrasts indicated a significantly lower associative memory performance in the SCD (p = 0.001, d = 0.82) and MCI group (p < 0.001, d = 1.54), as compared to HCs, respectively. The CANTAB-PAL discriminated only between HC and MCI, possibly because of reduced statistical power. Adjusted for depression, performance on FNART was significantly related to ECog-39 Memory in SCD patients (p = 0.024) but not in MCI patients. Conclusions: Associative memory is substantially impaired in memory clinic patients with SCD and correlates specifically with memory complaints at this putative preclinical stage of AD. Further studies will need to examine the predictive validity of the FNART in SCD patients with regard to longitudinal (i.e., conversion to MCI/AD) and biomarker outcomes. Show more
Keywords: Alzheimer’s disease, associative memory, cognition, early detection, hippocampus, mild cognitive impairment, neuropsychological tests, recognition, subjective cognitive decline
DOI: 10.3233/JAD-160637
Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 1185-1196, 2017
Authors: Koppara, Alexander | Frommann, Ingo | Polcher, Alexandra | Parra, Mario A. | Maier, Wolfgang | Jessen, Frank | Klockgether, Thomas | Wagner, Michael
Article Type: Research Article
Abstract: Background: Feature binding is a sensitive and specific cognitive marker for Alzheimer’s disease (AD). Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are clinical categories associated with an increased risk for AD. Objective: To investigate whether the SCD and MCI group are impaired with regard to feature binding. Methods: The feature binding test was administered to memory clinic patients with either SCD (n = 19, mean MMSE: 29.2) or with MCI (n = 23, mean MMSE: 26.5), and to a group of healthy controls (HC, n = 23, mean MMSE: 29.0). Participants were assessed with the CERAD Plus neuropsychological test battery. Cognitive …performance of the three groups was compared by ANCOVA with age, gender and education as covariates and planned contrasts. Results: Groups differed in the binding condition. Planned contrasts showed significant differences in adjusted means between HC and SCD (p = 0.003), as well as between HC and MCI (p < 0.0001). Discussion: The feature binding task detects subtle cognitive impairments in participants with SCD, who are unimpaired in traditional neuropsychological testing. This corroborates the use of feature binding tests in preclinical AD studies and suggests that specific cognitive deficits can be found in SCD. Future studies incorporating AD biomarkers and longitudinal follow-up are needed to further establish the clinical utility of feature binding. Show more
Keywords: Alzheimer’s disease, early detection, feature binding, mild cognitive impairment, subjective cognitive decline
DOI: 10.3233/JAD-150105
Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S161-S170, 2015
Authors: Wolfsgruber, Steffen | Polcher, Alexandra | Koppara, Alexander | Kleineidam, Luca | Frölich, Lutz | Peters, Oliver | Hüll, Michael | Rüther, Eckart | Wiltfang, Jens | Maier, Wolfgang | Kornhuber, Johannes | Lewczuk, Piotr | Jessen, Frank | Wagner, Michael
Article Type: Research Article
Abstract: Background: There is very limited data on the prevalence of abnormal cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline (SCD). Objective: To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment (MCI) from the same cohort. Methods: We analyzed prospective data from memory clinic patients of the German Competence Network Dementia cohort with a baseline diagnosis of SCD (n = 82) or MCI (n = 134), …distinguished by actuarial neuropsychological MCI criteria (“Jak-Bondi criteria”). Risk of clinical progression during 3-year follow-up was evaluated with Cox-Proportional-Hazard models. Results: Prevalence of abnormal values in CSF markers of tau-mediated neurodegeneration (67.8% versus 46.3%) but not of amyloid deposition (40.3% versus 35.4%) was significantly higher in MCI compared to SCD. The rate of incident AD dementia (26.1% versus 12.2%) was also significantly higher in MCI. In SCD, additional 22% progressed to MCI during follow-up. Combined amyloid/tau abnormality was the strongest predictor of clinical progression in both groups. Conclusion: High prevalence of biomarker abnormality and clinical progression, together with the predictive value of CSF biomarkers, in memory clinic patients with SCD support the validity and usefulness of this condition as a “pre-MCI” at risk stage of AD. Show more
Keywords: Alzheimer’s disease, cerebrospinal fluid, mild cognitive impairment, subjective cognitive decline
DOI: 10.3233/JAD-161252
Citation: Journal of Alzheimer's Disease, vol. 58, no. 3, pp. 939-950, 2017
Authors: Polcher, Alexandra | Wolfsgruber, Steffen | Peters, Oliver | Frölich, Lutz | Wiltfang, Jens | Kornhuber, Johannes | Hüll, Michael | Rüther, Eckart | Lewczuk, Piotr | Maier, Wolfgang | Jessen, Frank | Wagner, Michael
Article Type: Research Article
Abstract: Background: Consideration of many tests from different cognitive domains in defining mild cognitive impairment (MCI) is clinical routine, but guidelines for a neuropsychological operationalization of MCI are lacking. Objective: Among different operational MCI criteria, to identify those which are best in predicting either conversion to dementia, or a biomarker profile indicative for Alzheimer’s disease (AD). Methods: Memory clinic patients without dementia (N = 558; mean age = 66; up to 3 years of follow-up; n = 360 with baseline CSF biomarkers) were included in an observational study using most liberal criteria of cognitive impairment. Four operational definitions of MCI were retrospectively applied: 1) amnestic …MCI (CERAD word list delayed recall), 2) CERAD total score, 3) comprehensive criteria and 4) base rate corrected CERAD. We compared their accuracy in predicting incident all-cause dementia or AD dementia within three years, or a concurrent CSF Aβ42 /tau-ratio indicative of AD. Results: The four definitions overlapped considerably, classified 35–58% of the original sample as impaired and were associated with markedly increased PPVs regarding incident all-cause dementia (39–46% versus 26% of the original sample), AD dementia and AD biomarker positivity. The base rate corrected MCI definition had the highest prognostic accuracy. Conclusion: he operational criteria examined seem suitable to specify MCI in memory clinic settings, as they identify subjects at high risk of clinical progression. Depending on the neuropsychological battery in use, one or several of these criteria could help to calibrate the clinical judgment of test results, reduce false-positive decisions, and define risk-enriched groups for clinical trials. Show more
Keywords: Alzheimer’s disease, biomarker, cognition, conversion, dementia, diagnosis, DSM-5 mild NCD, mild cognitive impairment, prognosis
DOI: 10.3233/JAD-215548
Citation: Journal of Alzheimer's Disease, vol. 88, no. 4, pp. 1663-1678, 2022
Authors: Teipel, Stefan J. | Metzger, Coraline D. | Brosseron, Frederic | Buerger, Katharina | Brueggen, Katharina | Catak, Cihan | Diesing, Dominik | Dobisch, Laura | Fliebach, Klaus | Franke, Christiana | Heneka, Michael T. | Kilimann, Ingo | Kofler, Barbara | Menne, Felix | Peters, Oliver | Polcher, Alexandra | Priller, Josef | Schneider, Anja | Spottke, Annika | Spruth, Eike J. | Thelen, Manuela | Thyrian, René J. | Wagner, Michael | Düzel, Emrah | Jessen, Frank | Dyrba, Martin | the DELCODE study group
Article Type: Research Article
Abstract: Background: Alterations of intrinsic networks from resting state fMRI (rs-fMRI) have been suggested as functional biomarkers of Alzheimer’s disease (AD). Objective: To determine the diagnostic accuracy of multicenter rs-fMRI for prodromal and preclinical stages of AD. Methods: We determined rs-fMRI functional connectivity based on Pearson’s correlation coefficients and amplitude of low-frequency fluctuation in people with subjective cognitive decline, people with mild cognitive impairment, and people with AD dementia compared with healthy controls. We used data of 247 participants of the prospective DELCODE study, a longitudinal multicenter observational study, imposing a unified fMRI acquisition protocol across sites. We determined cross-validated discrimination …accuracy based on penalized logistic regression to account for multicollinearity of predictors. Results: Resting state functional connectivity reached significant cross-validated group discrimination only for the comparison of AD dementia cases with healthy controls, but not for the other diagnostic groups. AD dementia cases showed alterations in a large range of intrinsic resting state networks, including the default mode and salience networks, but also executive and language networks. When groups were stratified according to their CSF amyloid status that was available in a subset of cases, diagnostic accuracy was increased for amyloid positive mild cognitive impairment cases compared with amyloid negative controls, but still inferior to the accuracy of hippocampus volume. Conclusion: Even when following a strictly harmonized data acquisition protocol and rigorous scan quality control, widely used connectivity measures of multicenter rs-fMRI do not reach levels of diagnostic accuracy sufficient for a useful biomarker in prodromal stages of AD. Show more
Keywords: diagnostic accuracy, functional MRI, multicenter, subjective cognitive decline, contstartabstract
DOI: 10.3233/JAD-180106
Citation: Journal of Alzheimer's Disease, vol. 64, no. 3, pp. 801-813, 2018
