Linking CSF and cognition in Alzheimer's disease: Reanalysis of clinical data

Guhra, M.; Thomas, Christine; Boedeker, Sebastian; Kreisel, Stefan H.; Drießen, Martin; Beblo, Thomas; Ohrmann, Patricia; Toepper, Max

doi:10.1016/j.exger.2015.11.008

Cited by 7 publications

(6 citation statements)

References 63 publications

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“…Knowledge regarding the relationship between core CSF biomarkers and cognition remains incomplete. Overall, Aβ 42 and T-tau appear to associate with memory and executive functions in some studies [61,62], although results have not been consistent in terms of which cognitive domains they are associated with, which particular tests are most suitable and the strength of relationships in different clinical stages [61,63,64]. However, the levels of core CSF marker have shown evidence of reaching a plateau early in the clinical course of the disease and are therefore not considered ideal for tracking the progression of disease at later stages [65].…”

Section: Discussionmentioning

confidence: 93%

Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions

et al. 2020

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Background: Neuroinflammation has gained increasing attention as a potential contributing factor in the onset and progression of Alzheimer's disease (AD). The objective of this study was to examine the association of selected cerebrospinal fluid (CSF) inflammatory and neuronal degeneration markers with signature CSF AD profile and cognitive functions among subjects at the symptomatic pre-and early dementia stages. Methods: In this cross-sectional study, 52 subjects were selected from an Icelandic memory clinic cohort. Subjects were classified as having AD (n = 28, age = 70, 39% female, Mini-Mental State Examination [MMSE] = 27) or non-AD (n = 24, age = 67, 33% female, MMSE = 28) profile based on the ratio between CSF total-tau (T-tau) and amyloid-β 1-42 (Aβ 42) values (cut-off point chosen as 0.52). Novel CSF biomarkers included neurofilament light (NFL), YKL-40, S100 calciumbinding protein B (S100B) and glial fibrillary acidic protein (GFAP), measured with enzyme-linked immunosorbent assays (ELISAs). Subjects underwent neuropsychological assessment for evaluation of different cognitive domains, including verbal episodic memory, non-verbal episodic memory, language, processing speed, and executive functions. Results: Accuracy coefficient for distinguishing between the two CSF profiles was calculated for each CSF marker and test. Novel CSF markers performed poorly (area under curve [AUC] coefficients ranging from 0.61 to 0.64) compared to tests reflecting verbal episodic memory, which all performed fair (AUC > 70). LASSO regression with a stability approach was applied for the selection of CSF markers and demographic variables predicting performance on each cognitive domain, both among all subjects and only those with a CSF AD profile. Relationships between CSF markers and cognitive domains, where the CSF marker reached stability selection criteria of > 75%, were visualized with scatter plots. Before calculations of corresponding Pearson's correlations coefficients, composite scores for cognitive domains were adjusted for age and education. GFAP correlated with executive functions (r = − 0.37, p = 0.01) overall, while GFAP correlated with processing speed (r = − 0.68, p < 0.001) and NFL with verbal episodic memory (r = − 0.43, p = 0.02) among subjects with a CSF AD profile.

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Section: Discussionmentioning

confidence: 93%

Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions

et al. 2020

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“…Overall, Aβ 42 and T-tau appear to associate with memory and executive functions in some studies [62,63], although results have not been consistent in terms of which cognitive domains they are associated with, which particular tests are most suitable and the strength of relationships in different clinical stages [62,64,65]. However, the levels of core CSF marker have shown evidence of reaching a plateau early in the clinical course of the disease and are therefore not considered ideal for tracking the progression of disease at later stages [66].…”

Section: Discussionmentioning

confidence: 93%

Association of glial and neuronal degeneration markers with Alzheimer‘s disease cerebrospinal fluid profile and cognitive functions

Teitsdottir

Jónsdóttir

Lund

et al. 2020

Preprint

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Abstract Background Neuroinflammation has gained increasing attention as a potential contributing factor in the onset and progression of Alzheimer‘s disease (AD). The objective of this study was to examine the association of selected cerebrospinal fluid (CSF) inflammatory and neuronal degeneration markers with signature CSF AD profile and cognitive functions among subjects at the symptomatic pre- and early dementia stages. Methods In this cross-sectional study, 52 subjects were selected from an Icelandic memory clinic cohort. Subjects were classified as having CSF AD (n=28, age=67, 33% female, Mini-mental state examination [MMSE]=28) or non-AD (n=24, age=70, 39% female, MMSE=27) profile based on the ratio between CSF total-tau (T-tau) and amyloid-β 1‐42 (Aβ 42 ) values (cut-off point chosen as 0.52). Novel CSF biomarkers included Neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B) and Glial fibrillary acidic protein (GFAP), measured with enzyme-linked immunosorbent assay (ELISA). Subjects underwent a neuropsychological assessment for evaluation of different cognitive domains including verbal episodic memory, non-verbal memory, language, processing speed and executive functions. Results Accuracy for distinguishing between the two CSF profiles was calculated for each CSF marker and cognitive domain. Verbal episodic memory performed the best overall (Area under curve [AUC]=0.80), with AUCs for CSF markers ranging from 0.61 to 0.64. For estimation of the relationships between CSF markers and cognitive domains (adjusted for age and education), Pearson‘s correlation and ridge regression analyses were performed. The ratio between NFL and YKL-40 levels correlated higher with verbal episodic memory score (r=-0.51, p <0.001) compared to single protein levels (NFL: r=-0.26, p =0.06; YKL-40: r=0.18, p =0.20). The correlation was also higher among those with CSF AD profile (r=-0.67, p <0.001) compared to those without (r=-0.46, p =0.03). GFAP levels showed weak correlation with executive functions scores (r=-0.37, p =0.007). Among those with a CSF AD profile, both S100B (r=-0.45, p =0.02) and GFAP (0.68, p <0.001) levels correlated with processing speed scores. Conclusions The novel CSF markers NFL, YKL-40 and GFAP show potential as markers for cognitive decline among individuals with core AD pathology at the symptomatic pre- and early stages of dementia.

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“…Different combinations of these markers as the ratios between Aβ 42 and t-tau or between Aβ 42 and Aβ 40 peptides can even slightly increase diagnostic accuracy. Particularly Aβ 42 and t-tau are associated with the cognitive key symptoms of AD [138] and can predict conversion to AD dementia in patients with mild cognitive impairment (MCI) [139, 140]. …”

Section: Neurocognitive Changes Associated With Alzheimer’s Diseasementioning

confidence: 99%

Dissociating Normal Aging from Alzheimer’s Disease: A View from Cognitive Neuroscience

Toepper

2017

JAD

Self Cite

140

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Both normal aging and Alzheimer’s disease (AD) are associated with changes in cognition, grey and white matter volume, white matter integrity, neural activation, functional connectivity, and neurotransmission. Obviously, all of these changes are more pronounced in AD and proceed faster providing the basis for an AD diagnosis. Since these differences are quantitative, however, it was hypothesized that AD might simply reflect an accelerated aging process. The present article highlights the different neurocognitive changes associated with normal aging and AD and shows that, next to quantitative differences, there are multiple qualitative differences as well. These differences comprise different neurocognitive dissociations as different cognitive deficit profiles, different weights of grey and white matter atrophy, and different gradients of structural decline. These qualitative differences clearly indicate that AD cannot be simply described as accelerated aging process but on the contrary represents a solid entity.

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Linking CSF and cognition in Alzheimer's disease: Reanalysis of clinical data

Cited by 7 publications

References 63 publications

Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions

Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions

Association of glial and neuronal degeneration markers with Alzheimer‘s disease cerebrospinal fluid profile and cognitive functions

Dissociating Normal Aging from Alzheimer’s Disease: A View from Cognitive Neuroscience

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