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1.
Front Aging Neurosci ; 16: 1406394, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39170895

RESUMO

Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer's disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging.

2.
Alzheimers Dement (Amst) ; 16(3): e70001, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39183745

RESUMO

INTRODUCTION: We examined the relationship between sedentary behavior (SB), moderate-to-vigorous physical activity (MVPA), and white matter hyperintensity (WMH) volumes, a common magnetic resonance imaging (MRI) marker associated with risk of neurodegenerative disease in middle-aged to older adults. METHODS: We used data from the UK Biobank (n = 14,415; 45 to 81 years) that included accelerometer-derived measures of SB and MVPA, and WMH volumes from MRI. RESULTS: Both MVPA and SB were associated with WMH volumes (ßMVPA = -0.03 [-0.04, -0.01], p < 0.001; ßSB = 0.02 [0.01, 0.03], p = 0.007). There was a significant interaction between SB and MVPA on WMH volumes (ßSB×MVPA = -0.015 [-0.028, -0.001], p SB×MVPA = 0.03) where SB was positively associated with WMHs at low MVPA, and MVPA was negatively associated with WMHs at high SB. DISCUSSION: While this study cannot establish causality, the results highlight the potential importance of considering both MVPA and SB in strategies aimed at reducing the accumulation of WMH volumes in middle-aged to older adults. Highlights: SB is associated with greater WMH volumes and MVPA is associated with lower WMH volumes.Relationships between SB and WMH are strongest at low levels of MVPA.Associations between MVPA and WMH are strongest at high levels of SB.Considering both SB and MVPA may be effective strategies for reducing WMHs.

3.
Neurobiol Aging ; 121: 129-138, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36436304

RESUMO

Homocysteine (Hcy) is a vascular risk factor associated with cognitive impairment and cerebrovascular disease but has also been implicated in Alzheimer's disease (AD). Using multivariate Scaled Subprofile Model (SSM) analysis, we sought to identify a network pattern in structural neuroimaging reflecting the regionally distributed association of plasma Hcy with subcortical gray matter (SGM) volumes and its relation to other health risk factors and cognition in 160 healthy older adults, ages 50-89. We identified an SSM Hcy-SGM pattern that was characterized by bilateral hippocampal and nucleus accumbens volume reductions with relative volume increases in bilateral caudate, pallidum, and putamen. Greater Hcy-SGM pattern expression was associated with greater white matter hyperintensity (WMH) volume, older age, and male sex, but not with other vascular and AD-related risk factors. Mediation analyses revealed that age predicted WMH volume, which predicted Hcy-SGM pattern expression, which, in turn, predicted cognitive processing speed performance. These findings suggest that the multivariate SSM Hcy-SGM pattern may be indicative of cognitive aging, reflecting a potential link between vascular health and cognitive dysfunction in healthy older adults.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Envelhecimento Saudável , Substância Branca , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Homocisteína , Testes Neuropsicológicos , Imageamento por Ressonância Magnética , Encéfalo/patologia , Atrofia/patologia , Cognição , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Doença de Alzheimer/patologia
4.
Neuroimage ; 258: 119353, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35667639

RESUMO

Cognitive reserve (CR) has been introduced to explain individual differences in susceptibility to cognitive or functional impairment in the presence of age or pathology. We developed a deep learning model to quantify the CR as residual variance in memory performance using the Structural Magnetic Resonance Imaging (sMRI) data from a lifespan healthy cohort. The generalizability of the sMRI-based deep learning model was tested in two independent healthy and Alzheimer's cohorts using transfer learning framework. Structural MRIs were collected from three cohorts: 495 healthy adults (age: 20-80) from RANN, 620 healthy adults (age: 36-100) from lifespan Human Connectome Project Aging (HCPA), and 941 adults (age: 55-92) from Alzheimer's Disease Neuroimaging Initiative (ADNI). Region of interest (ROI)-specific cortical thickness and volume measures were extracted using the Desikan-Killiany Atlas. CR was quantified by residuals which subtract the predicted memory from the true memory. Cascade neural network (CNN) models were used to train RANN dataset for memory prediction. Transfer learning was applied to transfer the T1 imaging-based model from source domain (RANN) to the target domains (HCPA or ADNI). The CNN model trained on the RANN dataset exhibited strong linear correlation between true and predicted memory based on the T1 cortical thickness and volume predictors. In addition, the model generated from healthy lifespan data (RANN) was able to generalize to an independent healthy lifespan data (HCPA) and older demented participants (ADNI) across different scanner types. The estimated CR was correlated with CR proxies such education and IQ across all three datasets. The current findings suggest that the transfer learning approach is an effective way to generalize the residual-based CR estimation. It is applicable to various diseases and may flexibly incorporate different imaging modalities such as fMRI and PET, making it a promising tool for scientific and clinical purposes.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Reserva Cognitiva , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Disfunção Cognitiva/diagnóstico por imagem , Progressão da Doença , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Adulto Jovem
5.
Sci Rep ; 11(1): 6600, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758214

RESUMO

The cortical control of gait and mobility involves multiple brain regions. Therefore, one could speculate that the association between specific spatial patterns of cortical thickness may be differentially associated with different mobility domains. To test this possibility, 115 healthy participants aged 27-82 (mean 60.5 ± 13.8) underwent a mobility assessment (usual-walk, dual-task walk, Timed Up and Go) and MRI scan. Ten mobility domains of relatively simple (e.g., usual-walking) and complex tasks (i.e., dual task walking, turns, transitions) and cortical thickness of 68 ROIs were extracted. All associations between mobility and cortical thickness were controlled for age and gender. Scaled Subprofile Modelling (SSM), a PCA-regression, identified thickness patterns that were correlated with the individual mobility domains, controlling for multiple comparisons. We found that lower mean global cortical thickness was correlated with worse general mobility (r = - 0.296, p = 0.003), as measured by the time to complete the Timed Up and Go test. Three distinct patterns of cortical thickness were associated with three different gait domains during simple, usual-walking: pace, rhythm, and symmetry. In contrast, cortical thickness patterns were not related to the more complex mobility domains. These findings demonstrate that robust and topographically distinct cortical thickness patterns are linked to select mobility domains during relatively simple walking, but not to more complex aspects of mobility. Functional connectivity may play a larger role in the more complex aspects of mobility.


Assuntos
Marcha , Córtex Motor/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Conectoma , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
6.
Brain Behav ; 11(1): e01954, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33210446

RESUMO

INTRODUCTION: Past studies have found that healthy aging has a significant effect on the organization and function of networks in the human brain. Many of these studies have examined how functional connectivity during one task or at rest is affected by aging; however, few studies have systematically examined how the effect of age on functional connectivity may vary as a function of choice of in-scanner task. METHODS: The present study included healthy adults between the ages of 20 and 80 and examined a variety of metrics of functional connectivity during performance of 11 in-scanner tasks, falling into 4 cognitive domains: vocabulary, processing speed, fluid reasoning, and episodic memory. Functional connectivity was assessed at three levels: average correlations within and between 10 networks, system segregation (sensorimotor vs. association networks), and whole-brain graph theory metrics (global efficiency and modularity). RESULTS: Results showed that the effect of age on these metrics differed as a function of task-for example, age had a more consistent effect on functional connectivity metrics computed during fluid reasoning tasks; however, there was less of an effect of age on functional connectivity metrics computed during tasks of episodic memory. Further, some of these measures showed relationships with behavioral performance on the in-scanner task, with different networks playing a role in the different cognitive domains. CONCLUSION: These findings suggest that while aging may be generally associated with reductions in within- and between-network connectivity, system segregation, global efficiency, and modularity, the magnitude and presence of these effects varies by in-scanner task.


Assuntos
Imageamento por Ressonância Magnética , Rede Nervosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Cognição , Humanos , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Adulto Jovem
7.
Front Aging Neurosci ; 11: 234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31555124

RESUMO

Recent studies have found a deleterious effect of age on a wide variety of measures of functional connectivity, and some hints at a relationship between connectivity at rest and cognitive functioning. However, few studies have combined multiple functional connectivity methods, or examined them over a wide range of adult ages, to try to uncover which metrics and networks seem to be particularly sensitive to age-related decline across the adult lifespan. The present study utilized multiple resting state functional connectivity methods in a sample of adults from 20-80 years old to gain a more complete understanding of the effect of aging on network function and integrity. Whole-brain results showed that aging results in weakening average within-network connectivity, lower system segregation and local efficiency, and higher participation coefficient. Network-level results suggested that nearly every primary sensory and cognitive network faces some degree of age-related decline, including reduced within-network connectivity, higher network-based participation coefficient, and reduced network-level local efficiency. Further, some of these connectivity metrics showed relationships with cognitive performance. Thus, these results suggest that a multi-method analysis of functional connectivity data may be critical to capture the full effect of aging on the health of brain networks.

8.
J Cogn Neurosci ; 31(4): 607-622, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30605005

RESUMO

Research on the cognitive neuroscience of aging has identified myriad neurocognitive processes that are affected by the aging process, with a focus on identifying neural correlates of cognitive function in aging. This study aimed to test whether internetwork connectivity among six cognitive networks is sensitive to age-related changes in neural efficiency and cognitive functioning. A factor analytic connectivity approach was used to model network interactions during 11 cognitive tasks grouped into four primary cognitive domains: vocabulary, perceptual speed, fluid reasoning, and episodic memory. Results showed that both age and task domain were related to internetwork connectivity and that some of the connections among the networks were associated with performance on the in-scanner tasks. These findings demonstrate that internetwork connectivity among several cognitive networks is not only affected by aging and task demands but also shows a relationship with task performance. As such, future studies examining internetwork connectivity in aging should consider multiple networks and multiple task conditions to better measure dynamic patterns of network flexibility over the course of cognitive aging.


Assuntos
Envelhecimento/fisiologia , Conectoma , Memória Episódica , Rede Nervosa/fisiologia , Percepção/fisiologia , Análise e Desempenho de Tarefas , Pensamento/fisiologia , Vocabulário , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Adulto Jovem
9.
Neurology ; 86(21): 2006-9, 2016 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-27164681

RESUMO

OBJECTIVE: The brain reserve hypothesis links larger maximal lifetime brain growth (MLBG, estimated with intracranial volume [ICV]) with lower risk for cognitive decline/dementia. We examined whether larger MLBG is also linked to less physical disability progression over 5 years in a prospective sample of treatment-naive patients with multiple sclerosis (MS). METHODS: Physical disability was measured with the Expanded Disability Status Scale (EDSS) at baseline and 5-year follow-up in 52 treatment-naive Serbian patients with MS. MRI measured disease burden (cerebral atrophy, T2 lesion volume) and MLBG: a genetically determined, premorbid (established during adolescence, stable thereafter) patient characteristic estimated with ICV (adjusted for sex). Logistic regression tested whether MLBG (smaller vs larger) predicts disability progression (stable vs worsened) independently of disease burden. RESULTS: Disability progression was observed in 29 (55.8%) patients. Larger MLBG predicted lower risk for progression (odds ratio 0.13, 95% confidence interval 0.02-0.78), independently of disease burden. We also calculated absolute change in EDSS scores, and observed that patients with smaller MLBG showed worse EDSS change (0.91 ± 0.71) than patients with larger MLBG (0.42 ± 0.87). CONCLUSIONS: Larger MLBG was linked to lower risk for disability progression in patients with MS over 5 years, which is the first extension of the brain reserve hypothesis to physical disability. MLBG (ICV) represents a clinically available metric that may help gauge risk for future disability in patients with MS, which may advance the science and practice of early intervention. Potential avenues for future research are discussed.


Assuntos
Encéfalo/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Adulto , Atrofia , Encéfalo/crescimento & desenvolvimento , Avaliação da Deficiência , Progressão da Doença , Feminino , Seguimentos , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Modelos Neurológicos , Esclerose Múltipla/fisiopatologia , Tamanho do Órgão , Risco
10.
Ann Neurol ; 79(6): 1014-25, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27129740

RESUMO

OBJECTIVE: We examined the association of nutrient intake with microstructural white matter integrity, and the role of white matter integrity in the association between nutrient consumption and cognition. METHODS: This cross-sectional analysis included 239 elderly (age ≥ 65 years) participants of a multiethnic cohort. White matter integrity was measured with fractional anisotropy (FA) from diffusion tensor magnetic resonance imaging. Nutrient patterns were derived from principal component analysis based on energy-adjusted intake of 24 selected nutrients. Generalized linear models were used to assess the association between nutrient patterns and mean FA of 26 white matter tracts. Mediation analysis was used to determine whether FA mediates the nutrient-cognition relationship. All models were adjusted for age at time of scan, gender, ethnicity, education, caloric intake, and apolipoprotein genotype. RESULTS: Among the identified 6 nutrient patterns, 1 (nutrient pattern 6, characterized by high intakes of Ω-3 and Ω-6 polyunsaturated fatty acids and vitamin E) was positively associated with FA. Those with the highest tertile of nutrient pattern 6 score had a mean of 0.01 (p = 0.01) higher FA value than those with the lowest tertile, similar to the effect of a 10-year decrease in age (b for age = -0.001, p = 0.01). FA mediated the relationship between nutrient pattern 6 and memory, language, visuospatial and speed/executive function, and mean cognitive scores. INTERPRETATION: Our study suggests that older adults consuming more polyunsaturated fatty acids and vitamin E rich foods had better white matter integrity, and that maintaining white matter microstructural integrity might be a mechanism for the beneficial role of diet on cognition. Ann Neurol 2016;79:1014-1025.


Assuntos
Cognição , Alimentos , Substância Branca , Idoso de 80 Anos ou mais , Anisotropia , Estudos Transversais , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Neuroimagem , Testes Neuropsicológicos
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