| 1. |
- Aspli, Klaus Thanke, et al.
(author)
-
CSF, Blood, and MRI Biomarkers in Skogholt’s Disease - A Rare Neurodegenerative Disease in a Norwegian Kindred
- 2023
-
In: Brain Sciences. - 2076-3425. ; 13:11
-
Journal article (peer-reviewed)abstract
- Skogholt’s disease is a rare neurological disorder that is only observed in a small Norwegian kindred. It typically manifests in adulthood with uncharacteristic neurological symptoms from both the peripheral and central nervous systems. The etiology of the observed cerebral white matter lesions and peripheral myelin pathology is unclear. Increased cerebrospinal fluid (CSF) concentrations of protein have been confirmed, and recently, very high concentrations of CSF total and phosphorylated tau have been detected in Skogholt patients. The symptoms and observed biomarker changes in Skogholt’s disease are largely nonspecific, and further studies are necessary to elucidate the disease mechanisms. Here, we report the results of neurochemical analyses of plasma and CSF, as well as results from the morphometric segmentation of cerebral magnetic resonance imaging. We analyzed the biomarkers Aβ1––42, Aβ1–40, Aβx–38, Aβx–40, Aβx–42, total and phosphorylated tau, glial fibrillary acidic protein, neurofilament light chain, platelet-derived growth factor receptor beta, and beta-trace protein. All analyzed CSF biomarkers, except neurofilament light chain and Aβ1/x–42, were increased several-fold. In blood, none of these biomarkers were significantly different between the Skogholt and control groups. MRI volumetric segmentation revealed decreases in the ventricular, white matter, and choroid plexus volumes in the Skogholt group, with an accompanying increase in white matter lesions. The cortical thickness and subcortical gray matter volumes were increased in the Skogholt group. Pathophysiological changes resulting from choroidal dysfunction and/or abnormal CSF turnover, which may cause the increases in CSF protein and brain biomarker levels, are discussed.
|
|
| 2. |
- Eliassen, Ingvild Vøllo, et al.
(author)
-
Regression-Based Cognitive Change Norms Applied in Biochemically Defined Predementia Alzheimer’s Disease
- 2023
-
In: Neuropsychology. - : American Psychological Association (APA). - 0894-4105 .- 1931-1559. ; 37:1
-
Journal article (peer-reviewed)abstract
- Objective: We aim to develop 2-year cognitive change norms for adults ages 41–84 for six cognitive tests, and to evaluate these norms in groups with AD biomarkers. Background: Practice effects are common in repeated neuropsychological testing. Not accounting for practice effects may obscure cognitive decline in early Alzheimer’s disease (AD). Method: We developed standardized regression-based change norms from normative samples consisting of healthy controls from the Dementia Disease Initiation study (n = 125), the Trønderbrain study (n = 57), and the Gothenburg mild cognitive impairment (MCI) study (n = 65). Norms were applied in a sample with cognitive symptoms (subjective cognitive decline or MCI) and AD cerebrospinal fluid (CSF) biomarkers (n = 246), classified according to the A/T/N system. Results: The change norms adjusted for pertinent demographics and practice effects. The group with cognitive complaints displayed a trend toward cognitive decline compared to the normative group, with the A+T/N+ subgroup showing the most marked decline. This was observed in tests of episodic memory and cognitive flexibility/divided attention. Conclusions: We present 2-year cognitive change norms for adults between 41 and 84 years, adjusted for practice and demographics. A web-based change norm calculator is provided.
|
|
| 3. |
- Gonzalez-Ortiz, Fernando, 1990, et al.
(author)
-
Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer's disease.
- 2024
-
In: Nature communications. - 2041-1723. ; 15:1
-
Journal article (peer-reviewed)abstract
- Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer's disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n=1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ ("A") and neurodegeneration ("N") abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aβ-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aβ therapies.
|
|
| 4. |
- Nordengen, Kaja, et al.
(author)
-
Longitudinal cerebrospinal fluid measurements show glial hypo- and hyperactivation in predementia Alzheimer's disease.
- 2023
-
In: Journal of neuroinflammation. - 1742-2094. ; 20:1
-
Journal article (peer-reviewed)abstract
- Brain innate immune activation is associated with Alzheimer's disease (AD), but degrees of activation may vary between disease stages. Thus, brain innate immune activation must be assessed in longitudinal clinical studies that include biomarker negative healthy controls and cases with established AD pathology. Here, we employ longitudinally sampled cerebrospinal fluid (CSF) core AD, immune activation and glial biomarkers to investigate early (predementia stage) innate immune activation levels and biomarker profiles.We included non-demented cases from a longitudinal observational cohort study, with CSF samples available at baseline (n=535) and follow-up (n=213), between 1 and 6years from baseline (mean 2.8years). We measured Aβ42/40 ratio, p-tau181, and total-tau to determine Ab (A+), tau-tangle pathology (T+), and neurodegeneration (N+), respectively. We classified individuals into these groups: A-/T-/N-, A+/T-/N-, A+/T+ or N+, or A-/T+ or N+. Using linear and mixed linear regression, we compared levels of CSF sTREM2, YKL-40, clusterin, fractalkine, MCP-1, IL-6, IL-1, IL-18, and IFN-γ both cross-sectionally and longitudinally between groups. A post hoc analysis was also performed to assess biomarker differences between cognitively healthy and impaired individuals in the A+/T+ or N+ group.Cross-sectionally, CSF sTREM2, YKL-40, clusterin and fractalkine were higher only in groups with tau pathology, independent of amyloidosis (p<0.001, A+/T+ or N+ and A-/T+ or N+, compared to A-/T-/N-). No significant group differences were observed for the cytokines CSF MCP-1, IL-6, IL-10, IL18 or IFN-γ. Longitudinally, CSF YKL-40, fractalkine and IFN-γ were all significantly lower in stable A+/T-/N- cases (all p<0.05). CSF sTREM2, YKL-40, clusterin, fractalkine (p<0.001) and MCP-1 (p<0.05) were all higher in T or N+, with or without amyloidosis at baseline, but remained stable over time. High CSF sTREM2 was associated with preserved cognitive function within the A+/T+ or N+ group, relative to the cognitively impaired with the same A/T/N biomarker profile (p<0.01).Immune hypoactivation and reduced neuron-microglia communication are observed in isolated amyloidosis while activation and increased fractalkine accompanies tau pathology in predementia AD. Glial hypo- and hyperactivation through the predementia AD continuum suggests altered glial interaction with Ab and tau pathology, and may necessitate differential treatments, depending on the stage and patient-specific activation patterns.
|
|
| 5. |
|
|
| 6. |
- Öhman, Fredrik, et al.
(author)
-
Demographically adjusted Rey-Osterrieth Complex Figure Test norms in a Swedish and Norwegian cohort aged 49-77years and comparison with North American norms.
- 2024
-
In: Scandinavian journal of psychology. - 1467-9450. ; 65:2, s. 168-178
-
Journal article (peer-reviewed)abstract
- The Rey-Osterrieth Complex Figure Test (RCFT) is one of the most commonly used neuropsychological tests in Sweden and Norway. However, no publications provide normative data for this population. The objective of this study was to present demographically adjusted norms for a Swedish and Norwegian population and to evaluate these in an independent comparison group.The RCFT was administrated to 344 healthy controls recruited from the Swedish Gothenburg MCI study, the Norwegian Dementia Disease Initiation study, and the Swedish Cardiopulmonary Bioimage Study. Age ranged from 49 to 77years (mean=62.4years, SD=5.0years), and education ranged from 6 to 24years (mean=13.3years, SD=3.0years). Using a regression-based procedure, we investigated the effects of age, sex, and years of education on test performance. We compared and evaluated our Swedish and Norwegian norms with North American norms in an independent comparison group of 145 individuals.In healthy controls, age and education were associated with performance on the RCFT. When comparing normative RCFT performance in an independent comparison group, North American norms generally overestimated immediate and delayed recall performance. In contrast, our Swedish and Norwegian norms appear to better take into account factors of age and education.We presented demographically adjusted norms for the RCFT in a Swedish and Norwegian sample. This is the first normative study of the RCFT that presents normative data for this population. In addition, we showed that North American norms might produce inaccurate normative estimations in an independent comparison group.
|
|
