| 1. |
- Abdelnour, Carla, et al.
(författare)
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Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data
- 2022
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dementia with Lewy bodies (DLB) includes various core clinical features that result in different phenotypes. In addition, Alzheimer's disease (AD) and cerebrovascular pathologies are common in DLB. All this increases the heterogeneity within DLB and hampers clinical diagnosis. We addressed this heterogeneity by investigating subgroups of patients with similar biological, clinical, and demographic features.Methods: We studied 107 extensively phenotyped DLB patients from the European DLB consortium. Factorial analysis of mixed data (FAMD) was used to identify dimensions in the data, based on sex, age, years of education, disease duration, Mini-Mental State Examination (MMSE), cerebrospinal fluid (CSF) levels of AD biomarkers, core features of DLB, and regional brain atrophy. Subsequently, hierarchical clustering analysis was used to subgroup individuals based on the FAMD dimensions.Results: We identified 3 dimensions using FAMD that explained 38% of the variance. Subsequent hierarchical clustering identified 4 clusters. Cluster 1 was characterized by amyloid-beta and cerebrovascular pathologies, medial temporal atrophy, and cognitive fluctuations. Cluster 2 had posterior atrophy and showed the lowest frequency of visual hallucinations and cognitive fluctuations and the worst cognitive performance. Cluster 3 had the highest frequency of tau pathology, showed posterior atrophy, and had a low frequency of parkinsonism. Cluster 4 had virtually normal AD biomarkers, the least regional brain atrophy and cerebrovascular pathology, and the highest MMSE scores.Conclusions: This study demonstrates that there are subgroups of DLB patients with different biological, clinical, and demographic characteristics. These findings may have implications in the diagnosis and prognosis of DLB, as well as in the treatment response in clinical trials.
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| 2. |
- Cedres, Nira, et al.
(författare)
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Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals
- 2022
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 99:15, s. e1619-e1629
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Several pathologic processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers toward the degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals.Methods The contribution of amyloid and tau pathology was assessed through CSF levels of the Aβ42/40 ratio and phosphorylated tau (p-tau). CSF Aβ38 levels were also measured. Cerebrovascular pathology was assessed using automatic segmentations of WM lesions (WMLs) on MRI. Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE ε4 carriership were also included in the analysis as variables of interest.Results We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals aged 70 years, 51% female). WM lesion burden was the most important contributor to the degeneration of both cholinergic pathways (increase in mean square error [IncMSE] = 98.8% in the external capsule pathway and IncMSE = 93.3% in the cingulum pathway). Levels of Aβ38 and p-tau also contributed to cholinergic WM degeneration, especially in the external capsule pathway (IncMSE = 28.4% and IncMSE = 23.4%, respectively). The Aβ42/40 ratio did not contribute notably to the models (IncMSE<3.0%). APOE ε4 carriers showed poorer integrity in the cingulum pathway (IncMSE = 21.33%). Women showed poorer integrity of the external capsule pathway (IncMSE = 21.55%), which was independent of amyloid status as reflected by the nonsignificant differences in integrity when comparing amyloid-positive vs amyloid-negative women participants (T201 = −1.55; p = 0.123).Discussion In cognitively unimpaired older individuals, WMLs play a central role in the degeneration of cholinergic pathways. Our findings highlight the importance of WM lesion burden in the elderly population, which should be considered in the development of prevention programs for neurodegeneration and cognitive impairment.
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| 3. |
- Cedres, Nira, et al.
(författare)
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Subjective Impairments in Olfaction and Cognition Predict Dissociated Behavioral Outcomes
- 2022
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Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press (OUP). - 1079-5014 .- 1758-5368. ; 78:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Self-rated subjective cognitive decline (SCD) and subjective olfactory impairment (SOI) are associated with objective cognitive decline and dementia. However, their relationship and co-occurrence is unknown. We aimed to (a) describe the occurrence of SOI, SCD and their overlap in the general population; (b) compare SOI and SCD in terms of longitudinal associations with corresponding objective olfactory and cognitive measures; and (c) describe how SOI and SCD may lead to distinct sensory and cognitive outcomes.Methods: Cognitively unimpaired individuals from the third wave of the Swedish population-based Betula study (n = 784, aged 35–90 years; 51% females) were split into self-rated SOI, SCD, overlapping SCD + SOI, and controls. Between-subject and within-subject repeated-measures MANCOVA were used to compare the groups regarding odor identification, cognition, age, sex, and education. Spearman correlation was used to assess the different patterns of association between olfaction and cognition across groups.Results: SOI was present in 21.1%, whereas SCD was present in 9.9% of participants. According to a chi-square analysis, the SCD + SOI overlap (2.7%) is on a level that could be expected if the phenomena were independent. Odor identification in SOI showed decline at the 10-year follow-up (n = 284) and was positively associated with cognition. The SOI and SCD groups showed distinct cognitive-olfactory profiles at follow-up.Conclusions: SOI occur independently of SCD in the population, and these risk factors are associated with different cognitive and olfactory outcomes. The biological causes underlying SOI and SCD, as well as the risk for future cognitive impairment, need further investigation.
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| 4. |
- Cedres, Nira, et al.
(författare)
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The interplay between gray matter and white matter neurodegeneration in subjective cognitive decline
- 2021
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589 .- 1945-4589. ; 13:16, s. 19963-19977
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the interplay between gray matter (GM) and white matter (WM) neurodegeneration in subjective cognitive decline (SCD), including thickness across the whole cortical mantle, hippocampal volume, and integrity across the whole WM.Methods: We included 225 cognitively unimpaired individuals from a community-based cohort. Subjective cognitive complaints were assessed through 9 questions covering amnestic and non-amnestic cognitive domains. In our cohort, 123 individuals endorsed from one to six subjective cognitive complaints (i.e. they fulfilled the diagnostic criteria for SCD), while 102 individuals reported zero complaints. GM neurodegeneration was assessed through measures of cortical thickness across the whole mantle and hippocampal volume. WM neurodegeneration was assessed through measures of mean diffusivity (MD) across the whole WM skeleton. Mediation analysis and multiple linear regression were conducted to investigate the interplay between the measures of GM and WM neurodegeneration.Results: A higher number of complaints was associated with reduced hippocampal volume, cortical thinning in several frontal and temporal areas and the insula, and higher MD across the WM skeleton, with a tendency to spare the occipital lobe. SCD-related cortical thinning and increased MD were associated with each other and jointly contributed to complaints, but the contribution of cortical thinning to the number of complaints was stronger.Conclusions: Neurodegeneration processes affecting the GM and WM seem to be associated with each other in SCD and include brain areas other than those typically targeted by Alzheimer's disease. Our findings suggest that SCD may be a sensitive behavioral marker of heterogeneous brain pathologies in individuals recruited from the community.
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| 5. |
- Corujo-Bolaños, Graciela, et al.
(författare)
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The block design subtest of the Wechsler adult intelligence scale as a possible non-verbal proxy of cognitive reserve
- 2023
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365 .- 1663-4365. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the potential of the Block design subtest of the Wechsler Adults Intelligence Scale as a non-verbal proxy of cognitive reserve.Method: A total of 391 cognitively unimpaired participants were included in this study. The association between the Block design subtest and the Information subtest (an established verbal proxy of cognitive reserve) from the WAIS, as well as the association of the two subtests with a Cognitive Reserve Questionnaire (CRQ) were tested. In addition, multiple linear regression models were conducted to investigate the association of the Block design and Information subtests with cognitive performance. The capacity of the Block design subtest to minimize the negative effect of an older age over cognitive performance was also assessed and this effect was compared with that of the Information subtest. The four cognitive domains included were: verbal memory, visual–visuospatial memory, executive-premotor functions and processing speed.Results: The Block design subtest correlated positively with both the Information subtest and the CRQ. A statistically significant association was observed between the Block design subtest and all four cognitive domains. Higher scores in the Block design subtest minimized the negative effect of aging on the cognitive domains of visual–visuospatial memory and executive-premotor functions, in a similar way to the results obtained for the Information subtest.Conclusion: The Block design subtest is significantly correlated with two established proxies of cognitive reserve: it correlates with cognitive performance and high scores in Block design have the capacity to minimize the negative effect of an older age on cognitive performance. Therefore, the results suggest that the corrected Block design subtest could be considered as a non-verbal proxy of cognitive reserve.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Zapater-Fajari, Mariola, et al.
(författare)
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Biomarkers of Alzheimer's Disease and Cerebrovascular Disease in Relation to Depressive Symptomatology in Individuals With Subjective Cognitive Decline
- 2024
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 79:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Subjective cognitive decline (SCD) has gained recent interest as a potential harbinger of neurodegenerative diseases such as Alzheimer's disease (AD) and cerebrovascular disease (CVD). In addition, SCD can be related to depressive symptomatology. However, the association between AD and CVD biomarkers, depressive symptomatology, and SCD is still unclear. We investigated the association of AD and CVD biomarkers and depressive symptomatology with SCD in individuals with subjective memory complaints (SCD-memory group) and individuals with subjective concentration complaints (SCD-concentration group). Methods We recruited a population-based cohort of 217 individuals (all aged 70 years, 53% female participants, 119 SCD-memory individuals, 23 SCD-concentration individuals, and 89 controls). AD and CVD were assessed through cerebrospinal fluid levels of the A beta 42/40 ratio and phosphorylated tau, and white matter signal abnormalities on magnetic resonance imaging, respectively. Associations between biomarkers, depressive symptomatology, and SCD were tested via logistic regression and correlation analyses. Results We found a significant association between depressive symptomatology with SCD-memory and SCD-concentration. Depressive symptomatology was not associated with AD and CVD biomarkers. Both the phosphorylated tau biomarker and depressive symptomatology predicted SCD-memory, and the A beta 42/40 ratio and depressive symptomatology predicted SCD-concentration. Conclusions The role of depressive symptomatology in SCD may differ depending on the stage within the spectrum of preclinical AD (as determined by amyloid-beta and tau positivity), and does not seem to reflect AD pathology. Our findings contribute to the emerging field of subclinical depressive symptomatology in SCD and clarify the association of different types of subjective complaints with distinct syndromic and biomarker profiles.
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