| 11. |
- Mattsson, Niklas, et al.
(författare)
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Effects of APOE ε4 on neuroimaging, cerebrospinal fluid biomarkers, and cognition in prodromal Alzheimer's disease
- 2018
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 71, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), but its importance for the clinical and biological heterogeneity in AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD patients (44 APOE ε4-negative and 107 APOE ε4-positive) from the BioFINDER study. We tested cognition, 18F-flutemetamol β-amyloid (Aβ) positron emission tomography, cerebrospinal fluid biomarkers of Aβ tau and neurodegeneration, and magnetic resonance imaging of white matter pathology and brain structure. Despite having similar cortical Aβ-load and baseline global cognition (mini mental state examination), APOE ε4-negative prodromal AD had more nonamnestic cognitive impairment, higher cerebrospinal fluid levels of Aβ-peptides and neuronal injury biomarkers, more white matter pathology, more cortical atrophy, and faster decline of mini mental state examination, compared to APOE ε4-positive prodromal AD. The absence of APOE ε4 is associated with an atypical phenotype of prodromal AD. This suggests that APOE ε4 may impact both the diagnostics of AD in early stages and potentially also effects of disease-modifying treatments.
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| 12. |
- Santillo, Alexander Frizell, et al.
(författare)
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Diffusion Tensor Tractography versus Volumetric Imaging in the Diagnosis of Behavioral Variant Frontotemporal Dementia
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7, s. e66932-
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Tidskriftsartikel (refereegranskat)abstract
- MRI diffusion tensor imaging (DTI) studies of white matter integrity in behavioral variant frontotemporal dementia have consistently shown involvement of frontal and temporal white matter, corresponding to regional loss of cortical volume. Volumetric imaging has a suboptimal sensitivity as a diagnostic tool and thus we wanted to explore if DTI is a better method to discriminate patients and controls than volumetric imaging. We examined the anterior cingulum bundle in 14 patients with behavioral variant frontotemporal dementia and 22 healthy controls using deterministic manual diffusion tensor tractography, and compared DTI parameters with two measures of cortical atrophy, VBM and cortical thickness, of the anterior cingulate cortex (ACC). Statistically significant changes between patients and controls were detected in all DTI parameters, with large effect sizes. ROC-AUC was for the best DTI parameters: 0.92 (fractional anisotropy) to 0.97 (radial diffusivity), 0.82 for the best cortical parameter, VBM of the ACC. Results from the AUC were confirmed with binary logistic regression analysis including demographic variables, but only for fractional anisotropy and mean diffusivity. Ability to classify patient/nonpatient status was significantly better for mean diffusivity vs. VBM (p = 0.031), and borderline significant for fractional anisotropy vs. VBM (p = 0.062). The results indicate that DTI could offer advantages in comparison with the assessment of cortical volume in differentiating patients with behavioral variant frontotemporal dementia and controls.
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| 13. |
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| 14. |
- Skillbäck, Tobias, et al.
(författare)
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Sex differences in CSF biomarkers for neurodegeneration and blood-brain barrier integrity.
- 2021
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Ingår i: Alzheimer's & dementia. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- As cerebrospinal fluid (CSF) neurofilament light protein (NfL) and the CSF/serum albumin ratio (QAlb) are used in the clinical routine, the impact of demographic factors on these biomarkers is important to understand.Participants were derived from two Swedish samples: the population-based H70 Study (n = 308, age 70) and a clinical routine cohort (CSF NfL, n = 8995, QAlb, n = 39252, age 0 to 95). In the population-based study, QAlb and NfL were examined in relation to sex, cardiovascular risk factors, and cerebral white matter lesions (WMLs). In the clinical cohort, QAlb and NfL sex differences were tested in relation to age.Men had higher QAlb and NfL concentrations and had higher QAlb and NfL concentrations from adolescence throughout life. NfL was not related to WML, but QAlb correlated positively with WMLs.The CSF NfL sex difference could not be explained by vascular pathology. Future studies should consider using different reference limits for men and women.
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| 15. |
- Spotorno, Nicola, et al.
(författare)
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Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia
- 2020
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo, especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process.
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| 16. |
- Zhang, Yi, et al.
(författare)
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Acceleration of hippocampal atrophy in a non-demented elderly population : the SNAC-K study
- 2010
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Ingår i: International psychogeriatrics. - 1041-6102 .- 1741-203X. ; 22:1, s. 14-25
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Brain atrophy in Alzheimer's disease (AD) includes not only AD-specific brain atrophy but also the atrophy induced by normal aging. Atrophy of the hippocampus has been one diagnostic marker of AD, but it was also found to emerge in healthy adults, along with increasing age. It was reported that the important age when age-related shrinkage of the hippocampus starts was around the mid-40s. The aim is to study the aging atrophy speed and acceleration of brain atrophy in a cross-sectional database, to identify the age at which acceleration of hippocampal atrophy starts in non-demented elderly persons.METHODS: 544 subjects (aged 60-97 years; 318 female and 226 male) were recruited into the MRI study by using a subsample of an epidemiological sample of 3363 healthy non-demented elderly people (over 60 years of age). Hippocampus and ventricle sizes were measured.RESULTS: The normalized volumes (by intracranial volume, ICV) of the hippocampus in males were smaller than those in females. The right hippocampus was larger than the left. The expansion of the lateral ventricles (2.80% per year in males, 2.95% in females) and third ventricle (1.58% and 2.28%, respectively) was more marked than the hippocampal shrinkage (0.68% and 0.79%, respectively). The suggested age at which acceleration of hippocampal atrophy starts is 72 years.CONCLUSIONS: Males present smaller hippocampus volumes (normalized by ICV) than females; however, females are more vulnerable to hippocampal atrophy in a non-demented elderly population. An acceleration of hippocampal atrophy may emerge and start around 72 years of age in a non-demented elderly population.
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