Hippocampus shape across the healthy lifespan and its relationship with cognition

Bussy, Aurélie; Plitman, Eric; Tullo, Stephanie; Salaciak, Alyssa; Bedford, Saashi A.; Farzin, Sarah; Béland, Marie-Lise; Valiquette, Vanessa; Kazazian, Christina; Tardif, Christine; Devenyi, Gabriel A.; Chakravarty, M. Mallar

doi:10.1101/2020.10.30.362921

Cited by 3 publications

(3 citation statements)

References 128 publications

(174 reference statements)

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“…The use of NMF in this study enables a multimodal fusion and dimensionality reduction simultaneously, though unlike similar techniques such as Principal Component Analysis, exact quantification of variance explained is unavailable. Finally, we focus this analysis on the neocortical grey matter which captures a distributed set of brain regions, but this decision makes our study blind to the role of the hippocampus and subcortical structures, both of which have been shown to be heavily involved in brain aging (Bartsch & Wulff, 2015; Bussy, Patel, et al, 2021; Bussy, Plitman, et al, 2021; Fjell, McEvoy, et al, 2014; Tamnes et al, 2013; Tullo et al, 2019; Walhovd et al, 2011). Re-examining this research question using macro- and micro-structural measures of these structures (similar to our previous work in healthy young adults (R Patel et al, 2020…”

Section: Discussionmentioning

confidence: 99%

Individual variation in brain structural-cognition relationships in aging

Mackay

Jansen²,

Devenyi

et al. 2021

Preprint

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While all individuals are susceptible to age-related cognitive decline, significant inter- and intra-individual variability exists. However, the sources of this variation remain poorly understood. Here, we examined the association between 30-year trajectories of cognitive decline and multimodal indices of brain microstructure and morphology in older age. We used the Whitehall II Study, an extensively characterised cohort using 3T brain magnetic resonance images acquired at older age (mean age = 69.52 4.9) and 5 repeated cognitive performance assessments between mid-life (mean age = 53.2 4.9 years) and late-life (mean age = 67.7 4.9). Using non-negative matrix factorization, we identified 10 brain microstructural components that integrate measures of cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities. We observed two modes of variance that describe the association between cognition and brain microstructure. The first describes variations in 5 microstructural components associated with low mid-life performance across multiple cognitive domains, decline in reasoning abilities, but a relative maintenance of lexical and semantic fluency from mid-to-late life. The second describes variations in 5 microstructural components that are associated with low mid-life performance in lexical fluency, semantic fluency and short-term memory performance, but a retention of abilities in multiple domains from mid-to-late life. The extent to which a subject loads onto a latent variables predicts their future cognitive performance 3.2 years later (mean age = 70.87 4.9). This data-driven approach highlights a complex pattern of brain-behavior relationships, wherein the same individuals express both decline and maintenance in function across cognitive domains and in brain structural features.

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Section: Discussionmentioning

confidence: 99%

Individual variation in brain structural-cognition relationships in aging

Mackay

Jansen²,

Devenyi

et al. 2021

Preprint

Self Cite

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“…The values in the behavior matrices were z‐scored along each column prior to performing PLS (i.e., z‐score the values of each behavior score across all subjects). Each LV was tested statistically using permutation testing and bootstrap resampling following a similar protocol (detailed in the Supplementary methods) as in previous studies (Anthony Randal McIntosh & Lobaugh, 2004 ; Zeighami et al, 2017 ; Patel et al, 2020 ; Bussy et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia

Bussy

Levy

Best

et al. 2023

Human Brain Mapping

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Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule‐associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello‐subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first‐degree relatives of known symptomatic carriers. Voxel‐wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello‐subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.

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“…Each LV was tested statistically using permutation testing following a similar protocol (detailed in the Supplementary methods) as in previous studies [44][45][46][47][48][49] . Secondly, the degree to which each brain and behaviour variable contributes to these LVs was tested using a bootstrap resampling technique detailed in the Supplementary methods (BSR threshold of…”

Section: Partial Least Squaresmentioning

confidence: 99%

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia

Bussy

Levy

Cupo

et al. 2021

Preprint

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Recent studies have suggested that cerebellar and subcortical structures are impacted early in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the clinical contribution of the structures involved in the cerebello-subcortical circuitry has been understudied in FTD given their potentially central role in cognition and behaviour processes. The present study aims to investigate whether there is an association between the atrophy of the cerebellar and subcortical structures, and neuropsychiatric symptoms (using the revised version of the Cambridge Behavioral Inventory, CBI-R) across genetic mutations and whether this association starts during the preclinical phase of the disease. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative (GENFI) including mutation carriers (n=608) and non-carrier first-degree relatives of known symptomatic carriers (n= 375). Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed using deformation based morphometry (DBM) and partial least squares analyses (PLS) were used to link morphometry and behavioural symptoms. Our univariate results suggest that in this group of primarily presymptomatic subjects, volume loss in subcortical and cerebellar structure was primarily a function of aging, with only the C9orf72 group showing more pronounced volume loss in the thalamus compared to the non-carrier individuals. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to all neuropsychiatric symptoms from the CBI-R, with significant overlap in brain/behaviour patterns, but also specificity for each genetic group. The biggest differences were in the extent of the cerebellar involvement (larger extent in C9orf72 group) and more prominent amygdalar contribution in the MAPT group. Finally, our findings demonstrated that C9orf72 and MAPT brain scores were related to estimated years before the age of symptom onset (EYO) in a second order relationship highlighting a steeper brain score decline 20 years before expected symptom onset, while GRN brain scores were related to age and not EYO. Overall, these results demonstrated the important role of the subcortical structures and especially of the cerebellum in genetic FTD symptom expression.

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Hippocampus shape across the healthy lifespan and its relationship with cognition

Cited by 3 publications

References 128 publications

Individual variation in brain structural-cognition relationships in aging

Individual variation in brain structural-cognition relationships in aging

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia

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