| 51. |
- Pereira, Joana B., et al.
(författare)
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Association between cerebrospinal fluid and plasma neurodegeneration biomarkers with brain atrophy in Alzheimer's disease
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 58, s. 14-29
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation and deposition of amyloid-β (Aβ) peptides into plaques is an early event in Alzheimer's disease (AD), which is followed by different aspects of neurodegeneration that can be measured in the cerebrospinal fluid (CSF) or plasma using neurofilament light (NFL), neurogranin (Ng), total Tau (T-Tau), and phosphorylated tau (P-Tau) levels. The relationship between these biomarkers and regional brain atrophy across the different stages of AD remains largely unexplored. In this study, we assessed whether NFL, Ng, T-Tau, and P-Tau levels in CSF and NFL in plasma are associated with cortical thinning and subcortical volume loss in cognitively normal, mild cognitive impairment, and AD subjects with and without Aβ pathology. Our main findings showed that CSF NFL levels were associated with brain atrophy in all groups, but plasma NFL only correlated with atrophy in symptomatic cases. In contrast, Ng was associated with regional brain atrophy only in individuals with Aβ pathology. Altogether, our main findings suggest that Ng is strongly associated with Aβ pathology, whereas NFL is more unspecific.
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| 52. |
- Pereira, Joana B., et al.
(författare)
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Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson's disease
- 2020
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 139
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD. Methods: We included 106 non-demented PD patients, 19 PD dementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing. After 4.2 ± 1.8 years, 20 non-demented PD patients were diagnosed with dementia (PD-dementia converters), whereas the rest of PD patients remained non-demented (stable-PD). We compared MRI volumes of the medial septum/diagonal band (Ch1/Ch2) and nucleus basalis of Meynert (Ch4) between groups. Cox regression analyses were applied to test whether Ch1/Ch2 or Ch4 atrophy could predict future dementia and linear mixed models assessed their association with cognitive decline. Results: Compared to controls, we found reduced Ch4 baseline volumes in PD-dementia converters (p =.003) and those who already had PDD (p <.001) but not in stable-PD. Over time, there was a greater loss in Ch1/Ch2 volumes in PD-dementia converters and PDD compared to the other groups (p =.004). Baseline and longitudinal Ch4 volumes were associated with cognition (p <.002) and longitudinal Ch4 atrophy predicted future dementia (p =.009). Conclusions: Atrophy of Ch4 precedes and predicts future dementia in PD and is followed by changes in Ch1/Ch2, reflecting a posterior-anterior pattern of basal forebrain atrophy. This pattern could be used to track the spread of cholinergic degeneration and identify patients at risk of developing dementia.
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| 53. |
- Peter, Moa G., et al.
(författare)
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Lifelong olfactory deprivation-dependent cortical reorganization restricted to orbitofrontal cortex
- 2023
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Ingår i: Human Brain Mapping. - 1065-9471 .- 1097-0193. ; 44:18, s. 6459-6470
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Tidskriftsartikel (refereegranskat)abstract
- Prolonged sensory deprivation has repeatedly been linked to cortical reorganization. We recently demonstrated that individuals with congenital anosmia (CA, complete olfactory deprivation since birth) have seemingly normal morphology in piriform (olfactory) cortex despite profound morphological deviations in the orbitofrontal cortex (OFC), a finding contradictory to both the known effects of blindness on visual cortex and to the sparse literature on brain morphology in anosmia. To establish whether these unexpected findings reflect the true brain morphology in CA, we first performed a direct replication of our previous study to determine if lack of results was due to a deviant control group, a confound in cross sectional studies. Individuals with CA (n = 30) were compared to age and sex matched controls (n = 30) using voxel- and surface-based morphometry. The replication results were near identical to the original study: bilateral clusters of group differences in the OFC, including CA atrophy around the olfactory sulci and volume increases in the medial orbital gyri. Importantly, no group differences in piriform cortex were detected. Subsequently, to assess any subtle patterns of group differences not detectable by our mass-univariate analysis, we explored the data from a multivariate perspective. Combining the newly collected data with data from the replicated study (CA = 49, control = 49), we performed support vector machine classification based on gray matter volume. In line with the mass-univariate analyses, the multivariate analysis could accurately differentiate between the groups in bilateral OFC, whereas the classification accuracy in piriform cortex was at chance level. Our results suggest that despite lifelong olfactory deprivation, piriform (olfactory) cortex is morphologically unaltered and the morphological deviations in CA are confined to the OFC.
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| 54. |
- Peter, Moa G., et al.
(författare)
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Morphological changes in secondary, but not primary, sensory cortex in individuals with life-long olfactory sensory deprivation
- 2020
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 218
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with congenital sensory deprivation usually demonstrate altered brain morphology in areas associated with early processing of the absent sense. Here, we aimed to establish whether this also applies to individuals born without a sense of smell (congenital anosmia) by comparing cerebral morphology between 33 individuals with isolated congenital anosmia and matched controls. We detected no morphological alterations in the primary olfactory (piriform) cortex. However, individuals with anosmia demonstrated gray matter volume atrophy in bilateral olfactory sulci, explained by decreased cortical area, curvature, and sulcus depth. They further demonstrated increased gray matter volume and cortical thickness in the medial orbital gyri; regions closely associated with olfactory processing, sensory integration, and value-coding. Our results suggest that a lifelong absence of sensory input does not necessarily lead to morphological alterations in primary sensory cortex and extend previous findings with divergent morphological alterations in bilateral orbitofrontal cortex, indicating influences of different developmental processes.
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| 55. |
- Peter, Moa G., et al.
(författare)
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Normal Olfactory Functional Connectivity Despite Lifelong Absence of Olfactory Experiences
- 2021
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 31:1, s. 159-168
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Tidskriftsartikel (refereegranskat)abstract
- Congenital blindness is associated with atypical morphology and functional connectivity within and from visual cortical regions; changes that are hypothesized to originate from a lifelong absence of visual input and could be regarded as a general (re) organization principle of sensory cortices. Challenging this is the fact that individuals with congenital anosmia (lifelong olfactory sensory loss) display little to no morphological changes in the primary olfactory cortex. To determine whether olfactory input from birth is essential to establish and maintain normal functional connectivity in olfactory processing regions, akin to the visual system, we assessed differences in functional connectivity within the olfactory cortex between individuals with congenital anosmia (n=33) and matched controls (n=33). Specifically, we assessed differences in connectivity between core olfactory processing regions as well as differences in regional homogeneity and homotopic connectivity within the primary olfactory cortex. In contrast to congenital blindness, none of the analyses indicated atypical connectivity in individuals with congenital anosmia. In fact, post-hoc Bayesian analysis provided support for an absence of group differences. These results suggest that a lifelong absence of olfactory experience has a limited impact on the functional connectivity in the olfactory cortex, a finding that indicates a clear difference between sensory modalities in how sensory cortical regions develop.
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| 56. |
- Peter, Moa G., et al.
(författare)
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Seeing Beyond Your Nose? The Effects of Lifelong Olfactory Sensory Deprivation on Cerebral Audio-visual Integration
- 2021
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 472, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Lifelong auditory and visual sensory deprivation have been demonstrated to alter both perceptual acuity and the neural processing of remaining senses. Recently, it was demonstrated that individuals with anosmia, i.e. complete olfactory sensory deprivation, displayed enhanced multisensory integration performance. Whether this ability is due to a reorganization of olfactory processing regions to focus on cross-modal multisensory information or whether it is due to enhanced processing within multisensory integration regions is not known. To dissociate these two outcomes, we investigated the neural processing of dynamic audio-visual stimuli in individuals with congenital anosmia and matched controls (both groups, n = 33) using functional magnetic resonance imaging. Specifically, we assessed whether the previously demonstrated multisensory enhancement is related to cross-modal processing of multisensory stimuli in olfactory associated regions, the piriform and olfactory orbitofrontal cortices, or enhanced multisensory processing in established multisensory integration regions, the superior temporal and intraparietal sulci. No significant group differences were found in the a priori hypothesized regions using region of interest analyses. However, exploratory whole-brain analysis suggested higher activation related to multisensory integration within the posterior superior temporal sulcus, in close proximity to the multisensory region of interest, in individuals with congenital anosmia. No group differences were demonstrated in olfactory associated regions. Although results were outside our hypothesized regions, combined, they tentatively suggest that enhanced processing of audio-visual stimuli in individuals with congenital anosmia may be mediated by multisensory, and not primary sensory, cerebral regions.
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| 57. |
- Pitti, Helda, et al.
(författare)
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Cerebrovascular damage in subjective cognitive decline : A systematic review and meta-analysis
- 2022
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Ingår i: Ageing Research Reviews. - : Elsevier Ireland Ltd. - 1568-1637 .- 1872-9649. ; 82
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Tidskriftsartikel (refereegranskat)abstract
- Background: Subjective cognitive decline (SCD) has been postulated as an early marker of Alzheimer’s Disease (AD) but it can also be associated to other non-AD pathologies such as Vascular Dementia (VaD). Nevertheless, there is scarce data about SCD as a potential harbinger of cerebrovascular pathology. Thus, we conducted a systematic review and meta-analysis on the association between SCD and cerebrovascular damage measured by neuroimaging markers.Method: This study was performed following the PRISMA guidelines. The search was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin to December 8th, 2021. Primary studies including cognitively unimpaired adults with SCD and neuroimaging markers of cerebrovascular damage (i.e., white matter signal abnormalities, WMSA) were selected. Qualitative synthesis and meta-analysis of studies with a case-control design was performed.Results: Of 241 articles identified, 21 research articles were selected. Eight case-control studies were included for the meta-analysis. A significant overall effect-size was observed for the mean WMSA burden in SCD relative to controls, where the WMSA burden was higher in SCD.Conclusion: Our findings show the potential usefulness of SCD as a harbinger of cerebrovascular disease in cognitively healthy individuals. Further research is needed in order to elucidate the role of SCD as a preclinical marker of vascular cognitive impairment.
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| 58. |
- Poulakis, Konstantinos, et al.
(författare)
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Fully bayesian longitudinal unsupervised learning for the assessment and visualization of AD heterogeneity and progression
- 2020
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Ingår i: Aging. - : IMPACT JOURNALS LLC. - 1945-4589. ; 12:13, s. 12622-12647
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Tidskriftsartikel (refereegranskat)abstract
- Tau pathology and brain atrophy are the closest correlate of cognitive decline in Alzheimer's disease (AD). Understanding heterogeneity and longitudinal progression of atrophy during the disease course will play a key role in understanding AD pathogenesis. We propose a framework for longitudinal clustering that simultaneously: 1) incorporates whole brain data, 2) leverages unequal visits per individual, 3) compares clusters with a control group, 4) allows for study confounding effects, 5) provides cluster visualization, 6) measures clustering uncertainty. We used amyloid-beta positive AD and negative healthy subjects, three longitudinal structural magnetic resonance imaging scans (cortical thickness and subcortical volume) over two years. We found three distinct longitudinal AD brain atrophy patterns: one typical diffuse pattern (n=34, 47.2%), and two atypical patterns: minimal atrophy (n=23 31.9%) and hippocampal sparing (n=9, 12.5%). We also identified outliers (n=3, 4.2%) and observations with uncertain classification (n=3, 4.2%). The clusters differed not only in regional distributions of atrophy at baseline, but also longitudinal atrophy progression, age at AD onset, and cognitive decline. A framework for the longitudinal assessment of variability in cohorts with several neuroimaging measures was successfully developed. We believe this framework may aid in disentangling distinct subtypes of AD from disease staging.
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| 59. |
- Rodriguez-Hernandez, Marta A., et al.
(författare)
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Degeneration of the cholinergic system in individuals with subjective cognitive decline : A systematic review
- 2024
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Ingår i: Neuroscience and Biobehavioral Reviews. - 0149-7634 .- 1873-7528. ; 157
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Forskningsöversikt (refereegranskat)abstract
- BackgroundSubjective cognitive decline (SCD) is a risk factor for future cognitive impairment and dementia. It is uncertain whether the neurodegeneration of the cholinergic system is already present in SCD individuals. We aimed to review the current evidence about the association between SCD and biomarkers of degeneration in the cholinergic system. MethodOriginal articles were extracted from three databases: Pubmed, Web of Sciences, and Scopus, in January 2023. Two researchers screened the studies independently.ResultsA total of 11 research articles were selected. SCD was mostly based on amnestic cognitive complaints. Cholinergic system biomarkers included neuroimaging markers of basal forebrain volume, functional connectivity, transcranial magnetic stimulation, or biofluid. The evidence showed associations between basal forebrain atrophy, poorer connectivity of the cholinergic system, and SCDConclusionsDegenerative changes in the cholinergic system can be present in SCD. Subjective complaints may help when identifying individuals with brain changes that are associated with cognitive impairment. These findings may have important implications in targeting individuals that may benefit from cholinergic-target treatments at very early stages of neurodegenerative diseases.
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| 60. |
- Rydberg Sterner, Therese, et al.
(författare)
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The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
- 2019
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
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Tidskriftsartikel (refereegranskat)abstract
- To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
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