A selection from Stockholm University publication database

• Subjective Impairments in Olfaction and Cognition Predict Dissociated Behavioral Outcomes 

  2022. Nira Cedres (et al.). The journals of gerontology. Series B, Psychological sciences and social sciences

  Article

  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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• Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals

  2022. Nira Cedres (et al.). Neurology 99 (15), e1619-e1629

  Article

  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 Aβ_42/40 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 Aβ_42/40 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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• Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data

  2022. Carla Abdelnour (et al.). Alzheimer's Research & Therapy 14 (1)

  Article

  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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• The interplay between gray matter and white matter neurodegeneration in subjective cognitive decline

  2021. Nira Cedres (et al.). Aging 13 (16), 19963-19977

  Article

  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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Show all publications by Nira Cedres at Stockholm University