Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer’s Disease Cerebrospinal Fluid Biomarker Levels

Tort‐Merino, Adrià; Olives, Jaume; León, María; Peñaloza, Claudia; Valech, Natalia; Santos‐Santos, Miguel A.; Càmara, Estela; Grönholm-Nyman, Petra; Martínez-Lage, Pablo; Fortea, Juan; Molinuevo, José Luís; Sánchez‐Valle, Raquel; Laine, Matti; Rodrı́guez-Fornells, Antoni; Rami, Lorena

doi:10.3233/jad-190046

Cited by 13 publications

(11 citation statements)

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“…This result is consistent with those of other studies reporting a link between performances on episodic memory tests, such as the original FNAME [4], the S-FNAME [8], the PAL CANTAB [1], or the Ancient Farming Equipment Test [43], and biomarkers of AD pathology, either PET imaging or CSF. Moreover, our results are consistent with the findings showing that CSF tau levels are more related to cognitive functioning, mainly memory, than CSF Aβ levels [43][44][45][46][47][48]. Additionally, the Aβ/p-tau ratio, which includes both AD biomarkers, was the CSF measurement that best correlated with performance on FACEmemory®, reinforcing the hypothesis that this test is a diagnostic tool that reflects AD pathology changes [49].…”

Section: Discussionsupporting

confidence: 90%

A computerized version of the Short Form of the Face-Name Associative Memory Exam (FACEmemory®) for the early detection of Alzheimer’s disease

et al. 2020

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Background Computerized neuropsychological tests for early detection of Alzheimer’s disease (AD) have attracted increasing interest. Memory for faces and proper names is a complex task because its association is arbitrary. It implicates associative occipito-temporal cerebral regions, which are disrupted in AD. The short form of the Face-Name Associative Memory Exam (FNAME-12), developed to detect preclinical and prodromal AD, asks individuals to learn the names and occupations associated with 12 faces. The current work advances this field by using voice recognition and touchscreen response format. The purpose of this study is to create the first self-administered episodic memory test, FACEmemory®, by adapting the FNAME-12 for tablet use with voice recognition, touchscreen answers, and automatic scoring. The test was minimally supervised by a psychologist to avoid technological problems during execution and scored manually to assess the reliability of the automatic scoring. The aims of the present study were (1) to determine whether FACEmemory® is a sensitive tool for the detection of cognitive impairment, (2) to examine whether performances on FACEmemory® are correlated with those on the S-FNAME (paper-and-pencil version with 16 images), and (3) to determine whether performances on FACEmemory® are related to AD biomarkers in the cerebrospinal fluid (CSF) (Aβ42, p-tau, and Aβ42/p-tau ratio). Methods FACEmemory® was completed by 154 cognitively healthy (CH) individuals and 122 subjects with mild cognitive impairment, of whom 61 were non-amnestic (naMCI) and 61 amnestic (aMCI). A subsample of 65 individuals completed the S-FNAME, and 65 subjects received lumbar punctures. Results Performance on FACEmemory® was progressively worse from CH to the naMCI and aMCI groups. A cutoff of 31.5 in total FACEmemory® obtained 80.5% and 80.3% sensitivity and specificity values, respectively, for discriminating between CH and aMCI. Automatically corrected FACEmemory® scores were highly correlated with the manually corrected ones. FACEmemory® scores and AD CSF biomarker levels were significantly correlated as well, mainly in the aMCI group. Conclusions FACEmemory® may be a promising memory prescreening tool for detecting subtle memory deficits related to AD. Our findings suggest FACEmemory® performance provides a useful gradation of impairment from normal aging to aMCI, and it is related to CSF AD biomarkers.

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Section: Discussionsupporting

confidence: 90%

A computerized version of the Short Form of the Face-Name Associative Memory Exam (FACEmemory®) for the early detection of Alzheimer’s disease

et al. 2020

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“…Another important point regarding the nature of AFE‐T and its potential application in SCD concerns its neural correlates. Recently, the functional and structural brain correlates of the AFE‐T have been identified in cognitively unimpaired individuals 6,46 as well as in patients 8,47 . These studies have suggested that performance on this task depends on specific brain regions that are typically affected in AD, such as the medial temporal lobe (MTL).…”

Section: Discussionmentioning

confidence: 99%

Accelerated long‐term forgetting in individuals with subjective cognitive decline and amyloid‐β positivity

Tort‐Merino

Valech

Laine

et al. 2021

Int J Geriat Psychiatry

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Objectives We studied a sample of cognitively unimpaired individuals, with and without subjective cognitive decline (SCD), in order to investigate accelerated long‐term forgetting (ALF) and to explore the relationships between objective and subjective cognitive performance and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. Methods Fifty‐two individuals were included and SCD was quantified through the Subjective Cognitive Decline Questionnaire (SCD‐Q), using its validated cutoff to classify participants as Low SCD‐Q (n = 21) or High SCD‐Q (n = 31). These groups were further subdivided according to the presence or absence of abnormal levels of CSF Aβ42. Objective cognitive performance was assessed with the Ancient Farming Equipment Test (AFE‐T), a new highly‐demanding test that calls for acquisition and retention of novel object/name pairs and allows measuring ALF over a 6‐month period. Results The High SCD‐Q group showed a significantly higher free forgetting rate at 3 months compared to the Low SCD‐Q (F [1,44] = 4.72; p < 0.05). When stratifying by amyloid status, High SCD‐Q/Aβ+ showed a significantly lower performance than High SCD‐Q/Aβ–on the final free and cued learning scores (F [1,27] = 6.44, p < 0.05 and F [1,27] = 7.51, p < 0.05, respectively), the 1‐week free and cued recall (F [1,24] = 4.49; p < 0.05 and F [1,24] = 7.10; p < 0.01, respectively), the 1‐week cued forgetting rate (F [1,24] = 5.13; p < 0.05), and the 3‐month cued recall (F [1,24] = 4.27; p < 0.05). Linear regression analyses showed that higher SCD‐Q scores were associated with higher forgetting rates on the AFE‐T (β = −0.212; p < 0.05). Conclusions It is possible to detect ALF in individuals with high SCD ratings, appearing especially in those with abnormal CSF Aβ42 levels. Both in research and the clinical field, there is an increasing need of using more demanding cognitive measures, such as the AFE‐T, for identifying and tracking the earliest cognitive changes in these populations.

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“…More recent studies have demonstrated that this particular cognitive profile in MCI is compatible with positive AD biomarkers [26,27,28,29,30], as well as abnormal neural connectivity [31,32,33] and cerebral perfusion patterns [34] during memory encoding tasks. Moreover, declines in memory encoding have been predicted in amyloid-positive cognitively-normal individuals [35,36,37] alongside downstream tau increases [38,39,40,41], as well as in patients with subjective cognitive complaint with positive AD biomarkers [42]. Abnormal cortical activity has also been observed in genetic carriers during memory encoding tasks [43,44], supporting the thesis of a preference of AD pathology for cortical areas devoted to memory processing and, more precisely, those involved in encoding and retrieval of newly learned information.…”

Section: Introductionmentioning

confidence: 83%

Speech pause distribution as an early marker for Alzheimer’s disease

Pastoriza-Domínguez

Torre

Diéguez-Vide

et al. 2022

Speech Communication

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Background: Pause duration analysis is a common feature in the study of discourse in Alzheimer's disease (AD) and may also be helpful for its early detection. However, studies involving patients at the preclinical stage of mild cognitive impairment (MCI) have yielded varying results.Objectives: To characterize the probability density distribution of speech pause duration in AD, two multi-domain amnestic MCI patients (with memory encoding deficits, a-mdMCI-E, and only with retrieval impairment, a-mdMCI-R) and healthy control groups (HC) and to check if there are significant differences between them. To discuss the potential of those findings in clinical practice.Method: 112 picture-based oral narratives were manually transcribed and annotated for the automatic extraction of pause durations and their subsequent logconversion. We consider different probability distributions to fit speech pause duration truncating shorter ranges taking into account latest statistical findings to avoid inherent methodological uncertainties present in them.Results: Lognormal distribution (LND) explains the distribution of pause duration in speech for all groups, and its fitted parameters (µ,σ ) followed a gradation from the group with shorter durations and a higher tendency to produce short pauses (HC) to the group with longer pause durations and a considerably higher tendency to produce long pauses with more variance (AD). Importantly, a-mdMCI-E produced significantly longer pauses with greater variability than their a-mdMCI-R counterparts (α = 0.05) across all groups of study. Conclusion:We characterize and report significant differences at group level in the speech pause distribution across all groups of study that could be used to design tools and experiments for early prediction of AD progression.

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Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer’s Disease Cerebrospinal Fluid Biomarker Levels

Cited by 13 publications

References 70 publications

A computerized version of the Short Form of the Face-Name Associative Memory Exam (FACEmemory®) for the early detection of Alzheimer’s disease

A computerized version of the Short Form of the Face-Name Associative Memory Exam (FACEmemory®) for the early detection of Alzheimer’s disease

Accelerated long‐term forgetting in individuals with subjective cognitive decline and amyloid‐β positivity

Speech pause distribution as an early marker for Alzheimer’s disease

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