| 31. |
- Rolstad, Sindre, 1976, et al.
(author)
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Cerebrospinal fluid biomarkers mirror rate of cognitive decline.
- 2013
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In: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 34:4, s. 949-56
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Journal article (peer-reviewed)abstract
- The ability to predict future decline in cognitive systems using the cerebrospinal fluid (CSF) biomarkers 42 amino acid form of amyloid-β (Aβ42) and total tau (T-tau) is not fully understood. In a clinical sample ranging from cognitively healthy to dementia (n = 326), linear regression models were performed in order to investigate the ability of CSF biomarkers to predict cognitive decline in all cognitive domains from baseline to 2-year follow-up. Gender, age, and years of education were included as covariates. In patients with subjective cognitive impairment, T-tau had a small impact on executive functions (r2 = 0.07). T-tau had a small to moderate influence (r2 = 0.06-0.11) on all cognitive functions with the exception of visuospatial functions in patients with mild cognitive impairment (MCI). In patients with dementia, the impact of T-tau was large (r2 = 0.29) on semantic memory. Aβ42 had a small effect (r2 = 0.07) on speed and executive functions in MCI. In patients with dementia, Aβ42 had a moderate influence (r2 = 0.13-0.24) on semantic and verbal working memory/fluency. Our results speak in favor of the notion that CSF biomarkers reflect the rate of cognitive decline across the continuum of cognitive impairment from healthy to dementia. CSF predicted subsequent decline in more cognitive domains among MCI cases, but the impact was most pronounced in patients with dementia.
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| 32. |
- Rolstad, Sindre, 1976, et al.
(author)
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Cognitive Performance and Cerebrospinal Fluid Biomarkers of Neurodegeneration: A Study of Patients with Bipolar Disorder and Healthy Controls
- 2015
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Journal article (peer-reviewed)abstract
- The purpose of the present study was to investigate if cerebrospinal fluid (CSF) biomarkers of neurodegeneration are associated with cognition in bipolar disorder and healthy controls, respectively. CSF concentrations of total and phosphorylated tau, amyloid beta (A beta) 1-42, ratios of A beta 42/40 and A beta 42/38, soluble amyloid precursor protein alpha and beta, and neurofilament light chain protein were analyzed in relation to neuropsychological performance in 82 euthymic bipolar disorder patients and 71 healthy controls. Linear regression models were applied to account for performance in five cognitive domains using the CSF biomarkers. In patients, the CSF biomarkers explained a significant proportion of the variance (15-36%, p =. 002 -<. 0005) in all cognitive domains independently of age, medication, disease status, and bipolar subtype I or II. However, the CSF biomarkers specifically mirroring Alzheimer-type brain changes, i.e., P-tau and A beta 1-42, did not contribute significantly. In healthy controls, CSF biomarkers did not explain the variance in cognitive performance. Selected CSF biomarkers of neurodegenerative processes accounted for cognitive performance in persons with bipolar disorder, but not for healthy controls. Specifically, the ratios of A beta 42/40 and A beta 42/38 were consistently associated with altered cognitive performance.
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| 33. |
- Rolstad, Sindre, 1976, et al.
(author)
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Cognitive reserve in relation to abeta42 in patients converting from MCI to dementia - a follow-up report.
- 2009
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:2, s. 110-5
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Journal article (peer-reviewed)abstract
- The concept of the cognitive reserve (CR) hypothesizes that premorbid factors such as education enable compensation for the manifestation of brain pathology. Accordingly, pathology should be more prominent in individuals with higher CR before becoming clinically apparent. Previously, we found that patients subsequently converting to dementia with higher CR had lower concentrations of amyloid beta 42 (abeta42) as compared to patients with lower CR. However, the interaction between time, biomarkers, neuropsychological performance and CR is yet to be established. OBJECTIVE: To study the relation between biomarkers, neuropsychological performance and CR longitudinally. METHOD: A mixed between-within subject analysis of variance was performed for longitudinal analysis. Paired t tests were used for within group comparisons. RESULTS: Patients with higher CR (n = 15) had significantly lower concentrations of abeta42 at both time points compared to those with medium (n = 23) and lower CR (n = 28). Also, abeta42 concentrations decreased significantly from baseline to follow-up in patients with higher and medium CR. Groups performed comparably on neuropsychological tests. CONCLUSION: This study provides further support for the applicability of abeta42 as a substitute for pathology in relation to CR. Also, abeta42 reflects the disease progression in patients with higher and medium CR.
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| 34. |
- Rolstad, Sindre, 1976, et al.
(author)
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Cognitive reserve lessens the burden of white matter lesions on executive functions in bipolar disorder
- 2016
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In: Psychological Medicine. - : Cambridge University Press (CUP). - 0033-2917 .- 1469-8978. ; 46:15, s. 3095-3104
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Journal article (peer-reviewed)abstract
- Background. The concept of cognitive reserve (CR) hypothesizes that intellectually stimulating activities provide resilience against brain pathology/disease. Whereas brain abnormalities and cognitive impairment are frequently reported in bipolar disorder (BD), it is unknown whether the impact of brain alterations can be lessened by higher CR in BD. Method. We tested if higher CR would reduce the influence of total volumes of deep white matter hypointensities (WMH), ventricular cerebrospinal fluid (CSF), and prefrontal cortex on memory, executive, and attention/speed functions in patients with BD (n = 75). Linear regression models with interaction terms for CR and brain volumes were applied to directly test if CR reduces the influence of brain pathology on cognitive domains. Results. CR reduced the influence of total volumes of deep WMH (beta=-0.38, Q = 0.003) and ventricular CSF (beta = -41, Q = 006) on executive functions. Conclusions. The interactions between CR and total volumes of deep WMH/ventricular CSF appear to account for executive functioning in BD. The results suggest that the concept of CR is applicable in BD. Higher reserve capacity in BD alters the relationship between brain pathology and clinical presentation.
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| 35. |
- Rolstad, Sindre, 1976, et al.
(author)
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CSF neuroinflammatory biomarkers in bipolar disorder are associated with cognitive impairment.
- 2015
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In: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. - : Elsevier BV. - 1873-7862. ; 25:8, s. 1091-1098
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Journal article (peer-reviewed)abstract
- Persistent cognitive impairment in the euthymic state of bipolar disorder is increasingly recognized. Mounting evidence also suggests an association between neuroinflammation and cognitive dysfunction. The purpose of this study was to test if cerebrospinal fluid (CSF) markers of neuroinflammation could account for cognitive impairment in bipolar disorder. Hierarchical linear regression models were applied to account for performance in five cognitive domains using CSF neuroinflammatory biomarkers as predictors in patients with bipolar disorder type I and II (N=78). The associations between these biomarkers and cognition were further tested in healthy age- and sex-matched controls (N=86). In patients with bipolar disorder, the CSF biomarkers accounted for a significant proportion of the variance in executive functions (42.8%, p=<.0005) independently of age, medication, disease status, and bipolar subtype. The microglial marker YKL-40 had a high impact (beta=-.99), and was the only biomarker that contributed individually. CSF biomarkers were not associated with cognitive performance in healthy controls. The CSF neuroinflammation biomarker YKL-40 is associated with executive performance in euthymic bipolar disorder, but not in healthy controls.
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| 36. |
- Rolstad, Sindre, 1976, et al.
(author)
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Differential Impact of Neurofilament Light Subunit on Cognition and Functional Outcome in Memory Clinic Patients with and without Vascular Burden
- 2015
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 45:3, s. 873-881
-
Journal article (peer-reviewed)abstract
- The neurofilament light (NF-L) subunit is mainly expressed in large-caliber myelinated axons, and elevated concentrations in the cerebrospinal fluid (CSF) are correlated with damage to white matter and subcortical regions. Because the correlation between NF-L and cognition and functional impairment is largely unknown, we investigated associations in patients (n = 622) with (n = 199) and without (n = 423) vascular burden in subjective cognitive impairment (SCI, n = 168), mild cognitive impairment (MCI, n = 261), and dementia (n = 193). Patients were staged according to disease severity and the presence/absence of cerebrovascular disease. CSF amyloid-beta(1-42) (A beta(1-42))was included in all models due to its concomitant influence on vascular and primary etiology. Linear regression was used to assess associations between NF-L and A beta(1-42) and five cognitive domains of a comprehensive neuropsychological battery as well as with functional impairment using the Clinical Dementia Rating. Changes in these outcomes at the 2-year follow-up were also evaluated. In SCI and MCI patients with vascular burden, higher NF-L concentrations were associated with baseline cognitive performance (beta = -0.38 to -0.58) and executive decline (beta = -0.44). Lower A beta(1-42) levels were associated with worse cognitive performance in dementia (beta = 0.46 to 0.51). In MCI and dementia patients without vascular burden, higher NF-L (beta = -0.30 to -0.34) and lower A beta(1-42) concentrations (beta = 0.30) were associated with reduced cognitive performance. Higher NF-L concentrations (beta = -0.26) were associated with functional decline in patients with vascular burden. CSF NF-L is associated with cognition in patients with and without vascular etiology. These associations were greater in pre-dementia phases in those with vascular etiology and vice versa in those without vascular burden.
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| 37. |
- Rolstad, Sindre, 1976, et al.
(author)
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High Education May Offer Protection Against Tauopathy in Patients with Mild Cognitive Impairment.
- 2010
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In: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 21:1, s. 221-8
-
Journal article (peer-reviewed)abstract
- The concepts of brain and cognitive reserve stem from the observation that premorbid factors (e.g., education) result in variation in the response to brain pathology. Potential early influence of reserve on pathology, as assessed using the cerebrospinal fluid biomarkers total tau and amyloid-beta{42}, and cognition was explored in mild cognitive impairment (MCI) patients who remained stable over a two-year period. A total of 102 patients with stable MCI grouped on the basis of educational level were compared with regard to biomarker concentrations and cognitive performance. Stable MCI patients with higher education had lower concentrations of t-tau as compared to those with lower education. Also, educational level predicted a significant proportion of the total variance in t-tau concentrations. Our results suggest that higher education may offer protection against tauopathy.
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| 38. |
- Rolstad, Sindre, 1976, et al.
(author)
-
Polymorphisms of BDNF and CACNA1C are not associated with cognitive functioning in bipolar disorder or healthy controls.
- 2016
-
In: Cognitive neuropsychiatry. - : Informa UK Limited. - 1464-0619 .- 1354-6805. ; 21:3, s. 271-8
-
Journal article (peer-reviewed)abstract
- The cause of cognitive dysfunction in bipolar disorder (BD) is not well understood. BDNF and CACNA1C are two susceptibility genes for the disorder that have also been reported to be associated with cognitive deficits in the disorder, but the studies have been small and with conflicting results. We therefore attempted to replicate an association between cognitive dysfunction with the most commonly studied single nucleotide polymorphisms rs6265 and rs1006737.
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| 39. |
- Rolstad, Sindre, 1976, et al.
(author)
-
Polymorphisms of dopamine pathway genes NRG1 and LMX1A are associated with cognitive performance in bipolar disorder
- 2015
-
In: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 17:8, s. 859-868
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Journal article (peer-reviewed)abstract
- LIM homeobox transcription factor 1, alpha (LMX1A) and neuregulin 1 (NRG1) are susceptibility genes for schizophrenia that have been implicated in the dopaminergic pathway and have been associated with altered cognitive functioning. We hypothesized that single nucleotide polymorphisms (SNPs) in LMX1A and NRG1 would be associated with cognitive functioning in bipolar disorder.
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| 40. |
- Rolstad, Sindre, 1976
(author)
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The reserve concept in patients with Mild Cognitive Impairment – new approaches
- 2010
-
Doctoral thesis (other academic/artistic)abstract
- The concept of reserve stems from the observation that premorbid factors, e.g. education, result in variation in the response to any kind of brain pathology. As subjects with higher reserve tolerate more neuropathology, symptomatic expression of pathology is delayed. It is thus predicted that neuropathology should be more pronounced in those with higher reserve as compared to those with lower at the same level of clinical severity. Most research within the reserve paradigm has been conducted on patients with established diagnoses, mainly Alzheimer’s disease, but knowledge on the modifying effects of reserve in preclinical, Mild Cognitive Impairment (MCI), and early phases of dementia is limited. The main purpose was to investigate if use of cerebrospinal fluid (CSF) biomarkers, would enable studies of reserve in earlier phases. Specifically, the 42 amino acid form of beta-amyloid (abeta42), mirroring amyloid plaques depositions, and CSF total tau (t-tau), reflecting axonal degeneration, were used as surrogate measures for neuropathology. Another purpose was to explore if patients with higher reserve diverge from patients with intermediate and lower reserve in terms of CSF pathology, and cognitive functioning in various disease phases. As premorbid intelligence Quotient (IQ), cognitive functioning prior to manifest disease, may be a better proxy for reserve than education, the final objective was to construct a test for assessment of premorbid IQ in Swedish. In summary, we found that patients with higher reserve were distinguishable from those with intermediate and lower reserve with regards to abeta42 pathology, but not clinical manifestations. The incongruence between pathology and clinical outcome indicates compensation for neuropathology. We also found that abeta42 may be sensitive to disease progress when taking level of reserve into account. Patients with higher reserve with stable MCI had lower concentrations of CSF t-tau, but comparable abeta42 concentrations. This finding may either indicate a true protective effect for education, or suggests that higher education promotes cognitive stimulation resulting in better axonal integrity. Also, a test for assessment of premorbid IQ, NART-SWE, was successfully constructed and found to have satisfactory psychometric properties. The results of these studies may contribute to earlier identification, and consequentially treatment of patients with higher reserve at risk for dementia.
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