AD-Related CSF Biomarkers Across Distinct Levels of Cognitive Impairment: Correlations With Global Cognitive State

Ibarra, Romel; Radanovic, Márcia; Pais, Marcos Vasconcelos; Talib, Leda Leme; Forlenza, Orestes Vicente

doi:10.1177/0891988720944237

Cited by 6 publications

(5 citation statements)

References 53 publications

(98 reference statements)

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“…Another explanation is that an NABD accompanied by substantial axonal neurodegeneration and known to reveal long-term cognitive decline resembling that observed in AD patients should be distinguished from an autoimmune encephalopathy entity. CSF tau protein is known to be interrelated with cognitive functions in AD and other cognitive impairment phases ( 23 ), but so far, no study has investigated its correlation in NABD. As tau protein is elevated when axonal neurodegeneration occurs, it is not surprising that both the long-term and yearly decline of cognitive dysfunction is related to total tau protein.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Total Tau Protein Correlates With Longitudinal, Progressing Cognitive Dysfunction in Anti-Neural Autoantibody-Associated Dementia and Alzheimer’s Dementia: A Case–Control Study

et al. 2022

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BackgroundNeural autoantibody-associated dementia (NABD) is an increasing phenomenon in memory clinics with a high impact on later therapy. Biomarkers are lacking that differentiate this type of dementia from neurodegenerative dementia such as Alzheimer’s dementia (AD). Our aim is to analyze neurodegeneration markers and their relationship to progressing cognitive dysfunction in NABD and AD to test for tools differentiating these two forms of dementia prior to neural autoantibody testing.MethodsIn our retrospective, observational study, we investigated 14 patients with dementia and serum and/or cerebrospinal fluid (CSF) neural autoantibodies as well as 14 patients with AD by relying on recent CSF and clinical criteria for AD. Patient files were checked for psychopathology, neuropsychological test performance, autoimmune indicators, CSF, and MRI results.ResultsOur patient groups did not differ in their psychopathology, autoimmune indicators, or MRI profile. The progression of cognitive dysfunction [as measured by the difference in Mini-Mental State Examination (MMSE) scores since disease onset, and the yearly progression rate (MMSE loss/per year)] did not vary significantly between groups. Total tau protein was significantly higher in AD patients than NABD patients revealing no signs of Alzheimer’s disease pathology in their CSF (p < 0.05). Total tau protein levels in CSF correlated with cognitive decline since disease onset (r = 0.38, p < 0.05) and yearly progression rates (r = 0.56, p < 0.005) in all patients.DiscussionOur results suggest that the progression of cognitive dysfunction as defined by MMSE does not seem to be an appropriate biomarker for distinguishing NABD from AD. However, the total tau protein level in CSF might be a relevant molecular biomarker that can indicate disease pathology and/or progression in both known AD and NABD, which is often accompanied by axonal degeneration. Total tau protein may be an additional diagnostic tool with which to differentiate anti-neural-associated dementia from AD if further research confirms these proof-of-concept findings in larger patient cohorts.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Total Tau Protein Correlates With Longitudinal, Progressing Cognitive Dysfunction in Anti-Neural Autoantibody-Associated Dementia and Alzheimer’s Dementia: A Case–Control Study

et al. 2022

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“…No significant differences in demographic and clinical information were found across the two groups. The AD population was older than the lvPPA population and the two groups comprised more women than men, corresponding to the pathologies’ demography described in the literature [ 50 ]. They had an equivalent cognitive level as shown by the MMSE score ( p = 0.709).…”

Section: Resultsmentioning

confidence: 99%

“…Lumbar punctures allowed the extraction of CSF and measurement of AD relative biomarkers. Measures of β 42-Amyloïd peptide, total tau and phospho-tau protein concentrations were collected [ 49 , 50 ]. The standard for each protein corresponds to 700–1800 pg/mL, 130–6001 pg/mL and 20–60 ng/mL, respectively.…”

Section: Methodsmentioning

confidence: 99%

Logogenic Primary Progressive Aphasia or Alzheimer Disease: Contribution of Acoustic Markers in Early Differential Diagnosis

Eloïse

Plonka

Arslan

et al. 2022

Life

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The logopenic variant of Primary Progressive Aphasia (lvPPA), a syndromic disorder centered on language impairment, often presents variable underlying neurodegenerative pathologies such as Alzheimer Disease (AD). Actual language assessment tests and lumbar puncture, focused on AD diagnosis, cannot precisely distinguish the symptoms, or predict their progression at onset time. We analyzed acoustic markers, aiming to discriminate lvPPA and AD as well as the influence of AD biomarkers on acoustic profiles at the beginning of the disease. We recruited people with AD (n = 8) and with lvPPA (n = 8), with cerebrospinal fluid biomarker profiles determined by lumbar puncture. The participants performed a sentence repetition task that allows assessing potential lvPPA phonological loop deficits. We found that temporal and prosodic markers significantly differentiate the lvPPA and AD group at an early stage of the disease. Biomarker and acoustic profile comparisons discriminated the two lvPPA subgroups according to their biomarkers. For lvPPA with AD biomarkers, acoustic profile equivalent to an atypical AD form with a specific alteration of the phonological loop is shown. However, lvPPA without AD biomarkers has an acoustic profile approximating the one for DLFT. Therefore, these results allow us to classify lvPPA differentially from AD based on acoustic markers from a sentence repetition task. Furthermore, our results suggest that acoustic analysis would constitute a clinically efficient alternative to refused lumbar punctures. It offers the possibility to facilitate early, specific, and accessible neurodegenerative diagnosis and may ease early care with speech therapy, preventing the progression of symptoms.

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“…This discrepancy could be due to different sensitivity in the assays used in the two studies (a fully automated Lumipulse assay (Fujirebio, Inc.) in the present study and an enzyme-linked immunosorbent assay (ELISA) assay (ADx; Sutphen et al, 2015) in the previous study), or differences in study participants. Correlations between behavioral measures and either CSF Aβ42 or CSF Tau are common in the literature (Ibarra et al, 2021; Milà-Alomà et al, 2020). Finally, Gollan and colleagues reported that the oldest-old participants with the most AD-like biomarkers produced the most autocorrect errors (Gollan, Smirnov, et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Autocorrection if→of function words in reading aloud: A novel marker of Alzheimer’s risk.

Gollan¹,

Stasenko²,

Li³

et al. 2023

Neuropsychology

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Objective: The present study investigated cognitive mechanisms underlying the ability to stop “autocorrect” errors elicited by unexpected words in a read-aloud task, and the utility of autocorrection for predicting Alzheimer’s disease (AD) biomarkers. Method: Cognitively normal participants (total n = 85; n = 64 with cerebrospinal fluid [CSF] biomarkers) read aloud six short paragraphs in which 10 critical target words were replaced with autocorrect targets, for example, The player who scored that final [paint] for the local team reported [him] experience. Autocorrect targets either replaced the most expected/dominant completion (i.e., point) or a less expected/nondominant completion (i.e., basket), and within each paragraph half of the autocorrect targets were content words (e.g., point/paint) and half were function words (e.g., his/him). Participants were instructed to avoid autocorrecting. Results: Participants produced more autocorrect errors in paragraphs with dominant than with nondominant targets, and with function than with content targets. Cognitively normal participants with high CSF Tau/Aβ42 (i.e., an AD-like biomarker profile) produced more autocorrect total errors than those below the Tau/Aβ42 threshold, an effect also significant with dominant-function targets alone (e.g., saying his instead of him). A logistic regression model with dominant-function errors and age showed errors as the stronger predictor of biomarker status (sensitivity 83%; specificity 85%). Conclusions: Difficulty stopping autocorrect errors is associated with biomarkers indicating preclinical AD, and reveals promise as a diagnostic tool. Greater vulnerability of function over content words to autocorrection in individuals with AD-like biomarkers implicates monitoring and attention (rather than semantic processing) in the earliest of cognitive changes associated with AD risk.

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AD-Related CSF Biomarkers Across Distinct Levels of Cognitive Impairment: Correlations With Global Cognitive State

Cited by 6 publications

References 53 publications

Cerebrospinal Fluid Total Tau Protein Correlates With Longitudinal, Progressing Cognitive Dysfunction in Anti-Neural Autoantibody-Associated Dementia and Alzheimer’s Dementia: A Case–Control Study

Cerebrospinal Fluid Total Tau Protein Correlates With Longitudinal, Progressing Cognitive Dysfunction in Anti-Neural Autoantibody-Associated Dementia and Alzheimer’s Dementia: A Case–Control Study

Logogenic Primary Progressive Aphasia or Alzheimer Disease: Contribution of Acoustic Markers in Early Differential Diagnosis

Autocorrection if→of function words in reading aloud: A novel marker of Alzheimer’s risk.

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