Enhancing the Sensitivity of Memory Tests: Reference Data for the Free and Cued Selective Reminding Test and the Logical Memory Task from Cognitively Healthy Subjects with Normal Alzheimer’s Disease Cerebrospinal Fluid Biomarker Levels (original) (raw)
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Journal of Neuropsychology, 2015
Amnestic mild cognitive impairment (aMCI) patients carry a greater risk of conversion to Alzheimer's disease (AD). Therefore, the International Working Group (IWG) on AD aims to consider some cases of aMCI as symptomatic prodromal AD. The core diagnostic marker of AD is a significant and progressive memory deficit, and the Free and Cued Selective Reminding Test (FCSRT) was recommended by the IWG to test memory in cases of possible prodromal AD. This study aims to investigate whether the performance on the FCSRT would enhance the ability to predict conversion to AD in an aMCI group. A longitudinal study was conducted on 88 aMCI patients, and neuropsychological tests were analysed on the relative risk of conversion to AD. During follow-up (23.82 months), 33% of the aMCI population converted to AD. An impaired FCSRT TR was significantly associated with the risk of conversion to dementia, with a mean time to conversion of 25 months. The FCSRT demonstrates utility for detecting AD at its prodromal stage, thus supporting its use as a valid clinical marker. Among all types of dementia, Alzheimer's disease (AD) is the most common, comprising about 50 to 80% of all the dementia cases. It is an area of significant health concern in the elderly and has become one of the leading causes of death in modern society (Corey-Bloom, 2004; Ferri et al., 2005). AD diagnosis is generally supported by clinical history, neurological examination, and neuropsychological evidence of cognitive dysfunction, especially in the memory domain (American Psychiatric Association, 2000; McKhann et al., 1984, 2011). The clinical interest in establishing an early diagnosis has led to the concept of a transitional state between normal ageing and dementia (i.e., prodromal AD). This stage is widely known as amnestic mild cognitive impairment (aMCI; Petersen et al., 1999) and
Frontiers in Aging Neuroscience
We investigated whether amyloid-β (Aβ) and tau affected cognition in cognitively normal (CN) individuals, and whether norms for neuropsychological tests based on biomarker-negative individuals would improve early detection of dementia. We included 907 CN individuals from 8 European cohorts and from the Alzheimer's disease Neuroimaging Initiative. All individuals were aged above 40, had Aβ status and neuropsychological data available. Linear mixed models were used to assess the associations of Aβ and tau with five neuropsychological tests assessing memory (immediate and delayed recall of Auditory Verbal Learning Test, AVLT), verbal fluency (Verbal Fluency Test, VFT), attention and executive functioning (Trail Making Test, TMT, part A and B). All test except the VFT were associated with Aβ status and this influence was augmented by age. We found no influence of tau on any of the cognitive tests. For the AVLT Immediate and Delayed recall and the TMT part A and B, we calculated norms in individuals without Aβ pathology (Aβ-norms), which we validated in an independent memory-clinic cohort by comparing their predictive accuracy to published norms. For memory tests, the Aβ-norms rightfully Bos et al.
Dementia and Geriatric Cognitive Disorders Extra, 2014
Background/Aims: Dementia is a worldwide public health problem and there are several diagnostic tools for its assessment. The aim of this study was to evaluate the performance of the Memory Alteration Test (M@T) to discriminate between patients with early Alzheimer's disease (AD), patients with amnestic mild cognitive impairment (a-MCI), and subjects with a cognitively healthy status (CHS). Methods: The discriminative validity was assessed in a sample of 90 patients with AD, 45 patients with a-MCI, and 180 subjects with CHS. Clinical, functional, and cognitive studies were independently performed in a blinded fashion and the gold standard diagnosis was established by consensus on the basis of these results. The test performance was assessed by means of a receiver operating characteristic curve analysis as area under the curve (AUC). Results: M@T mean scores were 17.7 (SD = 5.7) in AD, 30.8 (SD = 2.3) in a-MCI, and 44.5 (SD = 3.1) in CHS. A cutoff score of 37 points had a sensiti...
Memory Correlates of Alzheimer's Disease Cerebrospinal Fluid Markers: A Longitudinal Cohort Study
Journal of Alzheimer's disease : JAD, 2017
Performance on episodic, semantic, and working memory tests is impaired in Alzheimer's disease (AD)-type dementia, but it is unclear which type of memory test is most strongly associated with early AD biomarkers in cerebrospinal fluid (CSF), and most useful for monitoring disease progression. To examine the association between amyloid-β 1-42 (Aβ42) and tau in CSF with performance on different memory domains at baseline, and how these CSF markers are related with memory decline. We included 263 individuals with normal cognition, mild cognitive impairment, AD-type dementia, and non-AD dementia from the European EDAR study. Assessment included CSF Aβ42 and t-tau analyses with INNO-BIA AlzBio3 Luminex assay, the CERAD wordlist learning and delayed recall, animal fluency test, and the CANTAB Paired Associates Learning (PAL) and Spatial Working Memory tasks. Follow-up assessments were performed within 3 years after baseline. At baseline, decreased CSF Aβ42 correlated most strongly wit...
Neurological Sciences
Introduction To assess the diagnostic accuracy of the free and cued selective reminding test (FCSRT) for the development of Alzheimer's disease (AD) in people with mild cognitive impairment (MCI). Methods We enrolled 187 consecutive MCI outpatients from a memory clinic that were evaluated at baseline and every 6 to 12 months through an extensive clinical and neuropsychological protocol. For each test, measures of diagnostic accuracy were obtained. To improve the overall specificity of the neuropsychological battery, we also used the diagnostic tests in parallel combination. The association between FCSRT indexes and AD was tested through proportional hazard regression models with other dementia subtypes as competing event. Laplace regression was used to model time-toAD diagnosis as a function of FCSRT indexes. Results The area under the curve of the FCSRT indexes ranged from 0.69 (95% CI: 0.62-0.76) to 0.76 (95% CI: 0.70-0.82). The specificity peaked up to 100% when we combined the category fluency test with the delayed total recall index of the FCSRT. Participants who tested positive at the FCSRT, as compared with those with negative tests, presented a twofold to fivefold higher risk of developing AD (median follow-up time 2.5 years; p < 0.001) and were diagnosed with AD 2-3 years earlier (p < 0.001). Discussion The FCSRT assessment suite shows the best predictive performance in detecting AD in people with MCI. These findings might help to reliably and timely identify people at higher risk of AD that is crucial both for properly selecting participants to clinical trials and to fine tune an effective and patient-centered care.
Cns Spectrums, 2010
Objective: Aim of the study was to investigate the influence of cerebrospinal fluid (CSF), amyloid β 42 (Aβ 42 ), phosphorylated tau 181 (ptau), and total tau (t-tau) on cognitive functioning. Methods: We analyzed the ability of the CSF biomarkers Aβ 42 , p-tau, and t-tau to predict the results on the Cambridge Cognitive Examination-Revised (CAMCOG-R), a cognitive screening test that assesses multiple cognitive domains, in 65 memory clinic patients (73.1±8.2 years) (n=30 probable Alzheimer's disease [AD], n=7 possible AD, n=12 non-AD dementia, n=16 mild cognitive impairment).
Biomarker validation of a cued recall memory deficit in prodromal Alzheimer disease
Neurology, 2012
Objective: To compare cued recall measures with other memory and nonmemory tests regarding their association with a biomarker profile indicative of Alzheimer disease (AD) in CSF among patients with mild cognitive impairment (MCI). Methods: Data were obtained by the German Dementia Competence Network. A total of 185 memory clinic patients fulfilling broad criteria for MCI (1 SD deficit in memory tests or in nonmemory tests) were assessed with an extended neuropsychological battery, which included the Free and Cued Selective Reminding Test (FCSRT), the word list learning task from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-NP), and the Logical Memory (LM) paragraph recall test from the Wechsler Memory Scale-Revised. CSF was obtained from all patients. Results: A total of 74 out of 185 subjects with MCI (40%) had a CSF profile consistent with AD (A 1-42 /tau ratio; CSF ADϩ group). FCSRT measures reflecting both free and cued recall discriminated best between CSF ADϩ and CSF ADϪ patients, and significantly improved CSF AD classification accuracy, as compared with CERAD delayed recall and LM delayed recall. Conclusions: Cued recall deficits are most closely associated with CSF biomarkers indicative of AD in subjects with MCI. This novel finding complements results from prospective clinical studies and provides further empirical support for cued recall as a specific indicator of prodromal AD, in line with recently proposed research criteria. Neurology ® 2012;78:379-386 GLOSSARY AD ϭ Alzheimer disease; aMCI ϭ amnestic mild cognitive impairment; CERAD-NP ϭ Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery; DCN ϭ Dementia Competence Network; ERC ϭ entorhinal cortex; FCSRT ϭ Free and Cued Selective Reminding Test; LM ϭ Logical Memory; MCI ϭ mild cognitive impairment; PHC ϭ parahippocampal cortex. Abnormal processing of the -amyloid peptide, giving rise to amyloid depositions in the brain and subsequent neuronal loss, is an early event in the pathophysiology of Alzheimer disease (AD). 1 Increased CSF tau protein, not specific for AD, reflects neuronal injury and loss and is assumed to occur in temporal succession, before cognitive and finally functional impairment occur. The ratio of (reduced) CSF A 1-42 and (increased) CSF tau has been established as a signature both sensitive and specific to AD. 2,3 An impairment of episodic memory is generally considered as a core requirement for defining mild cognitive impairment (MCI) due to AD. 4,5 Since recall deficits can be caused by conditions different from AD (e.g., depression, or frontotemporal lobar degeneration), the
Journal of the International Neuropsychological Society : JINS, 2016
Relatively few studies have investigated relationships between performance on clinical memory measures and indexes of underlying neuropathology related to Alzheimer's disease (AD). This study investigated predictive relationships between Free and Cued Selective Reminding Test (FCSRT) cue efficiency (CE) and free-recall (FR) measures and brain amyloid levels, hippocampal volume (HV), and regional cortical thickness. Thirty-one older controls without memory complaints and 60 patients presenting memory complaints underwent the FCSRT, amyloid imaging using [F18]-flutemetamol positron emission tomography, and surface-based morphometry (SBM) using brain magnetic resonance imaging. Three groups were considered: patients with high (Aβ+P) and low (Aβ- P) amyloid load and controls with low amyloid load (Aβ- C). Aβ+P showed lower CE than both Aβ- groups, but the Aβ- groups did not differ significantly. In contrast, FR discriminated all groups. SBM analyses revealed that CE indexes were cor...
Memory Markers In The Continuum Of The Alzheimer’s Clinical Syndrome
2022
BACKGROUND: The individual and complementary value of the Visual Short-Term Memory Binding Test (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT) as markers to trace the AD continuum was investigated. It was hypothesised that the VSTMBT would be an early indicator while the FCSRT would inform on imminent progression. METHODS: Healthy older adults (n=70) and patients with Mild Cognitive Impairment (MCI) (n=80) were recruited and followed up between 2012 and 2017. Participants with at least two assessments points entered the study. Using baseline and follow up assessments four groups were defined: Older adults how were healthy (HOA), with very mild cognitive but not functional impairment (eMCI), and with MCI who did and did not convert to dementia (MCI Converters and non-Converters). RESULTS: Only the VSTMBT predicted group membership in the very early stages (HOA vs eMCI). As the disease progressed, the FCSRT became a strong predictor excluding the VSTMB from the models...