scholarly journals Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer’s Disease: Results from the Gothenburg H70 Birth Cohort Studies

2021 ◽  
Vol 79 (1) ◽  
pp. 225-235
Author(s):  
Maya Arvidsson Rådestig ◽  
Johan Skoog ◽  
Henrik Zetterberg ◽  
Jürgen Kern ◽  
Anna Zettergren ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cohort Studies ◽  
Cognitive Performance ◽  
Birth Cohort ◽  
Population Based ◽  
Tau Pathology ◽  
Preclinical Alzheimer’S Disease ◽  
Preclinical Ad

Background: We have previously shown that older adults with preclinical Alzheimer’s disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. Objective: We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. Methods: The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. Results: Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). Conclusion: Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.

scholarly journals Disease progression modelling from preclinical Alzheimer’s disease (AD) to AD dementia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Soo Hyun Cho ◽  
Sookyoung Woo ◽  
Changsoo Kim ◽  
Hee Jin Kim ◽  
Hyemin Jang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Disease Assessment ◽  
Time Interval ◽  
Disease Course ◽  
Preclinical Alzheimer’S Disease ◽  
Apoe Ε4 ◽  
Preclinical Ad ◽  
Cognitive Subscale

AbstractTo characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.

Differential Cued-Stroop Performance in Cognitively Asymptomatic Older Adults with Biomarker-Identified Risk for Alzheimer’s Disease: A Pilot Study

2018 ◽  
Vol 15 (9) ◽  
pp. 820-827 ◽  
Author(s):  
Ryan Van Patten ◽  
Anne M. Fagan ◽  
David A.S. Kaufman
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Stroop Task ◽  
Coefficient Of Variation ◽  
Reaction Times ◽  
Preclinical Alzheimer’S Disease ◽  
Cerebrospinal Fluid Biomarkers ◽  
Accuracy Rates

Background: There exists a need for more sensitive measures capable of detecting subtle cognitive decline due to Alzheimer's disease. Objective: To advance the literature in Alzheimer’s disease by demonstrating that performance on a cued-Stroop task is impacted by preclinical Alzheimer's disease neuropathology. Method: Twenty-nine cognitively asymptomatic older adults completed a computerized, cued-Stroop task in which accuracy rates and intraindividual variability in reaction times were the outcomes of interest. Cerebrospinal fluid biomarkers of Aβ42 and tau were measured and participants were then grouped according to a published p-tau/Aβ42 cutoff reflecting risk for Alzheimer’s disease (preclinical Alzheimer's disease = 14; control = 15). Results: ANOVAs indicated that accuracy rates did not differ between the groups but 4-second delay incongruent color-naming Stroop coefficient of variation reaction times were higher in the preclinical Alzheimer’s disease group compared to the control group, reflecting increased within-person variability. Moreover, partial correlations showed no relationships between cerebrospinal fluid biomarkers and accuracy rates. However, increases in coefficient of variation reaction times correlated with decreased Aβ42 and increases in p-tau and the p-tau/Aβ42 ratio. Conclusion: Results supported the ability of the computerized, cued-Stroop task to detect subtle Alzheimer’s disease neuropathology using a small cohort of cognitively asymptomatic older adults. The ongoing measurement of cued-Stroop coefficient of variation reaction times has both scientific and clinical utility in preclinical Alzheimer’s disease.

scholarly journals Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease

2017 ◽  
Vol 39 (2) ◽  
pp. 971-984 ◽  
Author(s):  
Christine L. Tardif ◽  
Gabriel A. Devenyi ◽  
Robert S. C. Amaral ◽  
Sandra Pelleieux ◽  
Judes Poirier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Preclinical Alzheimer’S Disease ◽  
Cerebrospinal Fluid Biomarkers ◽  
Hippocampal Circuitry

scholarly journals Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid

2019 ◽  
Vol 18 (3) ◽  
pp. 546-560 ◽  
Author(s):  
Alberto Lleó ◽  
Raúl Núñez-Llaves ◽  
Daniel Alcolea ◽  
Cristina Chiva ◽  
Daniel Balateu-Paños ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Synaptic Proteins ◽  
Preclinical Alzheimer’S Disease

scholarly journals Searching for novel cerebrospinal fluid biomarkers of tau pathology in frontotemporal dementia: an elusive quest

2019 ◽  
Vol 90 (7) ◽  
pp. 740-746 ◽  
Author(s):  
Martha S Foiani ◽  
Claudia Cicognola ◽  
Natalia Ermann ◽  
Ione O C Woollacott ◽  
Carolin Heller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Frontotemporal Dementia ◽  
Neurodegenerative Disorder ◽  
The Novel ◽  
Tau Pathology ◽  
Total Tau ◽  
Significant Difference ◽  
T Tau

BackgroundFrontotemporal dementia (FTD) is a pathologically heterogeneous neurodegenerative disorder associated usually with tau or TDP-43 pathology, although some phenotypes such as logopenic variant primary progressive aphasia are more commonly associated with Alzheimer’s disease pathology. Currently, there are no biomarkers able to diagnose the underlying pathology during life. In this study, we aimed to investigate the potential of novel tau species within cerebrospinal fluid (CSF) as biomarkers for tau pathology in FTD.Methods86 participants were included: 66 with a clinical diagnosis within the FTD spectrum and 20 healthy controls. Immunoassays targeting tau fragments N-123, N-mid-region, N-224 and X-368, as well as a non-phosphorylated form of tau were measured in CSF, along with total-tau (T-tau) and phospho-tau (P-tau(181)). Patients with FTD were grouped based on their Aβ42 level into those likely to have underlying Alzheimer’s disease (AD) pathology (n=21) and those with likely frontotemporal lobar degeneration (FTLD) pathology (n=45). The FTLD group was then subgrouped based on their underlying clinical and genetic diagnoses into those with likely tau (n=7) or TDP-43 (n=18) pathology.ResultsSignificantly higher concentrations of tau N-mid-region, tau N-224 and non-phosphorylated tau were seen in both the AD group and FTLD group compared with controls. However, none of the novel tau species showed a significant difference between the AD and FTLD groups, nor between the TDP-43 and tau pathology groups. In a subanalysis, normalising for total-tau, none of the novel tau species provided a higher sensitivity and specificity to distinguish between tau and TDP-43 pathology than P-tau(181)/T-tau, which itself only had a sensitivity of 61.1% and specificity of 85.7% with a cut-off of <0.109.ConclusionsDespite investigating multiple novel CSF tau fragments, none show promise as an FTD biomarker and so the quest for in vivo markers of FTLD-tau pathology continues.

O1-03-03: Olfactory dysfunction may predict Alzheimer's disease related tau pathology in cerebrospinal fluid (CSF)

2015 ◽  
Vol 11 (7S_Part_3) ◽  
pp. P130-P130
Author(s):  
Babette L.R. Reijs ◽  
Inez H.G.B. Ramakers ◽  
Charlotte E. Teunissen ◽  
D.P. Devanand ◽  
Frans R.J. Verhey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Olfactory Dysfunction ◽  
Tau Pathology
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